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Health Technology Assessment 2006; Vol. 10: No.

16
Health Technology Assessment 2006; Vol. 10: No. 16

Systematic review of the effectiveness


and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

HealOzone for the treatment of occlusal pit/fissure caries and root caries
M Brazzelli, L McKenzie, S Fielding, C Fraser,
J Clarkson, M Kilonzo and N Waugh
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Systematic review of the effectiveness
and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

M Brazzelli,1* L McKenzie,2 S Fielding,3 C Fraser,1


J Clarkson,4 M Kilonzo2 and N Waugh3
1
Health Services Research Unit, Institute of Applied Health Sciences,
University of Aberdeen, UK
2
Health Economics Research Unit, Institute of Applied Health Sciences,
University of Aberdeen, UK
3
Department of Public Health, Institute of Applied Health Sciences,
University of Aberdeen, UK
4
Dental Health Services Research Unit, MacKenzie Building, Dundee, UK

* Corresponding author. Current affiliation: Department of Clinical Neurosciences,


University of Edinburgh, Western General Hospital, UK

Declared competing interests of authors: none

Published May 2006

This report should be referenced as follows:

Brazzelli M, McKenzie L, Fielding S, Fraser C, Clarkson J, Kilonzo M, et al. Systematic


review of the effectiveness and cost-effectiveness of HealOzone for the treatment of
occlusal pit/fissure caries and root caries. Health Technol Assess 2006;10(16).

Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE,


Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch) and
Current Contents/Clinical Medicine.
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Health Technology Assessment 2006; Vol. 10: No. 16

Abstract
Systematic review of the effectiveness and cost-effectiveness of
HealOzone for the treatment of occlusal pit/fissure caries and
root caries
M Brazzelli,1* L McKenzie,2 S Fielding,3 C Fraser,1 J Clarkson,4 M Kilonzo2
and N Waugh3
1
Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen, UK
2
Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, UK
3
Department of Public Health, Institute of Applied Health Sciences, University of Aberdeen, UK
4
Dental Health Services Research Unit, MacKenzie Building, Dundee, UK
* Corresponding author. Current affiliation: Department of Clinical Neurosciences, University of Edinburgh,
Western General Hospital, UK

Objectives: To assess the effectiveness and cost- caries and one the effects of HealOzone for the
effectiveness of HealOzone (CurOzone USA Inc., management of root caries. Overall, the quality of the
Ontario, Canada) for the management of pit and fissure studies was modest, with many important
caries, and root caries. The complete HealOzone methodological aspects not reported (e.g. concealment
procedure involves the direct application of ozone gas of allocation, blinding procedures, compliance of
to the caries lesion on the tooth surface, the use of a patients with home treatment). In particular, there
remineralising solution immediately after application of were some concerns about the choice of statistical
ozone and the supply of a patient kit, which consists analyses. In most of the full-text studies analyses were
of toothpaste, oral rinse and oral spray all containing undertaken at lesion level, ignoring the clustering of
fluoride. lesions within patients. The nature of the
Data sources: Electronic databases up to May 2004 methodological concerns was sufficient to raise doubts
(except Conference Papers Index, which were about the validity of the included studies findings.
searched up to May 2002). A quantitative synthesis of results was deemed
Review methods: A systematic review of the inappropriate. On the whole, there is not enough
effectiveness of HealOzone for the management of evidence from published RCTs on which to judge the
tooth decay was carried out. A systematic review of effectiveness of ozone for the management of both
existing economic evaluations of ozone for dental caries occlusal and root caries. The perspective adopted for
was also planned but no suitable studies were the study was that of the NHS and Personal Social
identified. The economic evaluation included in the Services. The analysis, carried out over a 5-year
industry submission was critically appraised and period, indicated that treatment using current
summarised. A Markov model was constructed to management plus HealOzone cost more than current
explore possible cost-effectiveness aspects of management alone for non-cavitated pit and fissure
HealOzone in addition to current management of caries (40.49 versus 24.78), but cost less for non-
dental caries. cavitated root caries (14.63 versus 21.45). Given
Results: Five full-text reports and five studies the limitations of the calculations these figures should
published as abstracts met the inclusion criteria. The be regarded as illustrative, not definitive. It was not
five full-text reports consisted of two randomised possible to measure health benefits in terms of
controlled trials (RCTs) assessing the use of HealOzone quality-adjusted life-years, due to uncertainties around
for the management of primary root caries and two the evidence of clinical effectiveness, and to the fact
doctoral theses of three unpublished randomised trials that the adverse events avoided are transient (e.g. pain
assessing the use of HealOzone for the management of from injection of local anaesthetic, fear of the drill).
occlusal caries. Of the abstracts, four assessed the One-way sensitivity analysis was applied to the model.
effects of HealOzone for the management of occlusal However, owing to the limitations of the economic iii

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Abstract

analysis, this should be regarded as merely speculative. present value of current management remained lower
For non-cavitated pit and fissure caries, the HealOzone than that of the HealOzone comparator (22.65
option was always more expensive than current versus 33.39).
management when the probability of cure using the Conclusions: Any treatment that preserves teeth and
HealOzone option was 70% or lower. For non- avoids fillings is welcome. However, the current
cavitated root caries the costs of the HealOzone evidence base for HealOzone is insufficient to conclude
comparator were lower than those of current that it is a cost-effective addition to the management
management only when cure rates from HealOzone and treatment of occlusal and root caries. To make a
were at least 80%. The costs of current management decision on whether HealOzone is a cost-effective
were higher than those of the HealOzone option alternative to current preventive methods for the
when the cure rate for current management was 40% management of dental caries, further research into its
or lower. One-way sensitivity analysis was also clinical effectiveness is required. Independent RCTs of
performed using similar NHS Statement of Dental the effectiveness and cost-effectiveness of HealOzone
Remuneration codes to those that are used in the for the management of occlusal caries and root caries
industry submission. This did not alter the results for need to be properly conducted with adequate design,
non-cavitated pit fissure caries as the discounted net outcome measures and methods for statistical analyses.

iv
Health Technology Assessment 2006; Vol. 10: No. 16

Contents
List of abbreviations .................................. vii Budget implications to the NHS ............... 37

Executive summary .................................... ix 7 Discussion ................................................... 41


Main results ................................................ 41
1 Aim of the review ...................................... 1 Need for further research .......................... 41

2 Background ................................................ 3 8 Conclusion .................................................. 43


Dental caries ............................................... 3
Current service provision ........................... 7 Acknowledgements .................................... 45
Description of new intervention ................ 11
Key questions .............................................. 12 References .................................................. 47

3 Effectiveness ............................................... 13 Appendix 1 Literature search


Methods for reviewing effectiveness .......... 13 strategies ..................................................... 51
Results ........................................................ 14
Discussion of results and conclusions on Appendix 2 Data extraction form ............. 55
the evidence for and against the
intervention ................................................ 21 Appendix 3 Checklist for the quality
assessment of randomised controlled
4 Systematic review of economic trials ............................................................ 59
evaluations ................................................. 23
Methods ...................................................... 23 Appendix 4 Characteristics of included
Results ........................................................ 23 studies: full-text reports ............................. 61
Review of industry submission ................... 24
Appendix 5 Characteristics of included
5 Economic analysis ...................................... 29 studies: abstracts ......................................... 71
Methods for economic analysis .................. 29
Results ........................................................ 33 Appendix 6 Structure of the economic
Discussion ................................................... 36 model ......................................................... 75

6 Implications for the NHS .......................... 37 Health Technology Assessment reports


National Service Framework ...................... 37 published to date ....................................... 81
Health targets ............................................. 37
Fair access ................................................... 37 Health Technology Assessment
Equity issues ............................................... 37 Programme ................................................ 93

v
Health Technology Assessment 2006; Vol. 10: No. 16

List of abbreviations

ANOVA analysis of variance NICE National Institute for Health


and Clinical Excellence
CDC Centers for Disease Control and
Prevention NPV net present value

CI confidence interval ns not significant

DFS decayed and filled surfaces NS not stated

DMFS decayed, missing and filled ORCA European Organisation for


surfaces Caries Research

DMFT decayed, missing and filled PRCL primary root carious lesion
teeth
QALY quality-adjusted life-years
ECM electrical conductance
measurement QLF quantitative light-induced
fluorescence
FDA Food and Drug Administration
QOTI/FOTI quantitative fibre-optic
GDS General Dental Services transillumination

IADR International Association for RCT randomised controlled trial


Dental Research
SD standard deviation
ITT intention-to-treat
SDR NHS Statement of Dental
NCHS National Centre for Health Remuneration
Statistics
TACT tuned aperture computed
NHANES III USA National Health and tomography
Nutrition Examination Survey
UCD ultrasound caries detector
NHS EED NHS Economic Evaluation
Database USPHS US Public Health Service
criteria

All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or
it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case
the abbreviation is defined in the figure legend or at the end of the table.

vii

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Health Technology Assessment 2006; Vol. 10: No. 16

Executive summary
Background Methods
Dental caries is a chronic disease caused by the Electronic searches were conducted to identify
localised and progressive demineralisation of the published and unpublished studies. The following
hard tissues of the coronal and root surfaces of the databases were searched: MEDLINE (1966 to
teeth. Caries location, development and May 2004), EMBASE (1980 to May 2004),
progression depend on a range of environmental, MEDLINE Extra (17 May 2004), Science Citation
social and genetic factors, and vary greatly among Index (1981 to May 2004), BIOSIS (1985 to
individuals. May 2004), AMED (1985 to May 2004), Cochrane
Library (Issue 2, 2004) National Research Register
Despite the decline in the prevalence of dental (Issue 2, 2004), Current Controlled Trials (18 May
caries observed in the high-income countries 2004), Clinical Trials (18 May 2004), SCI
during the past few decades as a consequence of Proceedings (1991 to May 2004), Conference
the increased availability of fluoride products and Papers Index (1982 to May 2002), ZETOC
improved oral hygiene, dental caries is still a conferences (1993 to May 2004) and IADR
common disease experienced by almost 80% of meeting abstracts (2002 to 2004). Two reviewers
children by the age of 18 years and by almost 90% independently assessed the methodological quality
of adults. of included studies and extracted data. Criteria for
assessment of study quality included method and
The current management of early non-cavitated unit of randomisation, concealment of allocation,
occlusal and root caries, and cavitated root caries, comparability of groups at baseline, blinding
which are still accessible to cleaning, is based on procedures, number of withdrawals/dropouts and
non-operative preventive strategies that include completeness of assessment at follow-up.
information on oral hygiene, dietary advice, use of
topically applied fluorides and application of A systematic review of the effectiveness of
sealants. For cavitated occlusal caries and cavitated HealOzone for the management of tooth decay
root caries that are not easily accessible to was carried out. A systematic review of existing
cleaning, restorative interventions are adopted economic evaluations of ozone for dental caries
(drilling and filling). was also planned but no suitable studies were
identified. The economic evaluation included in
HealOzone (CurOzone USA Inc., Ontario, the industry submission was critically appraised
Canada) has recently been proposed as a novel and summarised.
method for the treatment of dental caries. It is
suggested that HealOzone may reverse, arrest or A Markov model was constructed to explore
slow the progression of dental caries. The possible cost-effectiveness aspects of HealOzone in
complete HealOzone procedure involves the direct addition to current management of dental caries.
application of ozone gas to the caries lesion on the
tooth surface, the use of a remineralising solution
immediately after application of ozone and the Results
supply of a patient kit, which consists of
toothpaste, oral rinse and oral spray all containing Number and quality of studies, and
fluoride. direction of evidence
Five full-text reports and five studies published as
abstracts met the inclusion criteria. Of these, only
Objective one was published in a refereed journal, but it
lacked some study details. The remaining studies
The review aims to assess the effectiveness and cost- were PhD theses, unpublished reports or
effectiveness of HealOzone for the management of conference proceedings. The five full-text reports
pit and fissure caries, and root caries. consisted of two randomised controlled trials
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Executive summary

(RCTs) assessing the use of HealOzone for the reported very high success rates (from 86.6% to
management of primary root caries and two PhD 99% of reversal of caries).
theses of three unpublished randomised trials
assessing the use of HealOzone for the Adding ozone to a fissure sealant did not seem to
management of occlusal caries. Of the five studies produce better sealant retention in occlusal lesions
published as abstracts, four assessed the effects of extending 24 mm into dentine.
HealOzone for the management of occlusal caries
and one the effects of HealOzone for the Data on the use of HealOzone for the treatment of
management of root caries. occlusal lesion in the deciduous dentition were
available from only one unpublished study. An
Overall, the quality of the studies was modest, with overall reduction in clinical severity scores was
many important methodological aspects not reported for non-cavitated occlusal lesions in
reported (e.g. concealment of allocation, blinding primary molars treated with ozone.
procedures, compliance of patients with home
treatment). In particular, there were some On the whole, there is not enough evidence from
concerns about the choice of statistical analyses. In published RCTs on which to judge the
most of the full-text studies analyses were effectiveness of ozone for the management of both
undertaken at lesion level, ignoring the clustering occlusal and root caries.
of lesions within patients. The nature of the
methodological concerns was sufficient to raise Costs
doubts about the validity of the included studies The perspective adopted for the study was that of
findings. A quantitative synthesis of results was the NHS and Personal Social Services. The
deemed inappropriate. analysis, carried out over a 5-year period, indicated
that treatment using current management plus
Summary of benefits HealOzone cost more than current management
Root caries alone for non-cavitated pit and fissure caries
Two studies (one published and one unpublished) (40.49 versus 24.78), but cost less for non-
assessing the use of HealOzone for the cavitated root caries (14.63 versus 21.45). Given
management of primary non-cavitated root caries the limitations of the calculations these figures
reported high success rates for ozone-treated should be regarded as illustrative, not definitive.
lesions and no significant changes in the control
lesions, despite application of topical fluoride. Cost per quality-adjusted life-year
This is puzzling, since topical fluoride is known to It was not possible to measure health benefits in
be effective. Results of cavitated root lesions were terms of quality-adjusted life-years. This was
poorly defined and reported in one of these two mainly due to uncertainties around the evidence
studies. Cavitated lesions did not seem to benefit of clinical effectiveness, and to the fact that the
from ozone application. adverse events avoided are transient (e.g. pain
from injection of local anaesthetic, fear the drill).
One unpublished study showed that fissure
sealants preceded by the application of ozone for Sensitivity analyses
the preventive treatment of non-cavitated root One-way sensitivity analysis was applied to the
lesions were more likely to remain intact (61% model. However, owing to the limitations of the
versus 42%, p < 0.05). economic analysis, this should be regarded as
merely speculative. For non-cavitated pit and
Pit and fissure caries fissure caries, the HealOzone option was always
One unpublished study did not show any more expensive than current management when
significant benefits of HealOzone for the the probability of cure using the HealOzone option
management of non-cavitated pit and fissure was 70% or lower. For non-cavitated root caries the
lesions in the permanent dentition. Similarly, a costs of the HealOzone comparator were lower
small unpublished pilot study did not show any than those of current management only when cure
significant differences between cavitated occlusal rates from HealOzone were at least 80%. The costs
lesions treated with or without ozone, apart from of current management were higher than those of
an improvement in the hardness and visual clinical the HealOzone option when the cure rate for
indices. In contrast, findings from conference current management was 40% or lower.
proceedings (which provide little detail for the
assessment of their methodological quality and One-way sensitivity analysis was also performed
x therefore are of little use in systematic reviews) using similar NHS Statement of Dental
Health Technology Assessment 2006; Vol. 10: No. 16

Remuneration codes to those that are used in the inappropriate. It was done merely to illustrate the
industry submission. This did not alter the results key factors involved in economic modelling. The
for non-cavitated pit fissure caries as the long-term effects of HealOzone are unknown and
discounted net present value of current the assumption that reversed caries remains
management remained lower than that of the inactive may not be reliable.
HealOzone comparator (22.65 versus 33.39).

Recommendations for research


Conclusions
To make a decision on whether HealOzone is a
Any treatment that preserves teeth and avoids cost-effective alternative to current preventive
fillings is welcome. However, the current evidence methods for the management of dental caries,
base for HealOzone is insufficient to conclude that further research into its clinical effectiveness is
it is a cost-effective addition to the management required. Independent RCTs of the effectiveness
and treatment of occlusal and root caries. and cost-effectiveness of HealOzone for the
management of occlusal caries and root caries
Limitations of the calculations need to be properly conducted with adequate
The economic analysis was severely constrained by design, outcome measures and methods for
the uncertainty over clinical effectiveness, and it statistical analyses.
could be argued that such analysis was

xi

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Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 1
Aim of the review
he review aims to assess the effectiveness and USA Inc., Ontario, Canada) for the management
T cost-effectiveness of HealOzone (CurOzone of both pit and fissure caries, and root caries.

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Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 2
Background
Dental caries or inactive/arrested. A lesion that is considered to
be progressive is described as active, whereas a
Aetiology, pathology and prognosis lesion that has stopped further progression is
Dental caries (tooth decay) is a chronic disease described as arrested. This distinction is clinically
caused by the localised and progressive important as arrested lesions do not require any
demineralisation of the hard tissues of the coronal further preventive interventions.
and root surfaces of the teeth. The
demineralisation is caused by the interaction of The occlusal surfaces (pits and fissures) of teeth
acid-producing oral microorganisms (in particular are particularly susceptible to dental caries owing
Streptococcus mutans, Lactobacillus and Actinomyces to their morphological structure (minute
species) with dietary carbohydrates (sugar). dimensions of pits and fissures) and because
microbial plaque is more likely to grow in these
Caries occurs when the natural dynamic balance areas (plaque stagnation). The teeth are more
between mineralisation and demineralisation of prone to plaque stagnation during eruption.
dental tissues is disrupted. The process begins on Occlusal caries is seen more often in molar teeth
the surface of the enamel (outer surface of the than in premolar or anterior teeth.
tooth; see Figure 1). In enamel caries, the lesion
may reverse or arrest by remineralisation. If The incidence of root caries begins at about
remineralisation does not occur, the lesion may 3040 years of age and tends to increase
penetrate the enamel and consequently result in thereafter. Root caries is most prevalent in the
the formation of a cavity, which may progress elderly because when people get older and retain
through the dentine and the pulp of the tooth. In their natural teeth, their gums tend to recede and
the absence of treatment, dental caries may expose the root surfaces. According to the
ultimately destroy the tooth. Caries location, published NHS Plan for Modernising NHS
development and progression are influenced by a
range of environmental, social and genetic factors,
and vary greatly among individuals. In most
individuals dental caries tend to progress slowly Enamel
over time, with lesions often taking more than
2 years to cavitate, although in some it can take a
Dentine
Crown

shorter time. Conversely, some lesions never


cavitate. Pulp containing
blood vessels
According to the anatomical location of carious and nerves
lesions, it is possible to differentiate between Gum (gingiva)
Neck

coronal lesions, which may affect the pits and


fissures or the smooth surfaces of a tooth, and root Bone
lesions, which affect the exposed root cementum
and dentine. Root caries occurs in the same Periodontal
membrane
manner as coronal caries, but demineralisation
Root

begins at a higher pH and it is more common in Cementum


older people. The term primary caries is used to
indicate lesions on the unrestored surfaces of Root canal
teeth, while caries that develops adjacent to a Opening at tip
filling is referred to as recurrent or secondary of root
caries. Hidden caries is a term used to identify
carious lesions in the dentine that are not detected
by visual examination but are large enough to be FIGURE 1 Structure of a sound tooth. Reproduced with
identified radiographically. According to their permission from www.mydr.com.au. Copyright CMPMedica
activity, carious lesions may be classified as active Australia 2005. 3

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Background

Dentistry, nearly 90% of people aged over counselling; and increased access to dental care.
65 years show some signs of gum disease Nevertheless, dental caries is still a common
compared with 14% of 1624 year olds.1 disease, experienced by almost 80% of children by
the age of 18 and by almost 90% of adults.2
Significance in terms of ill-health
Impact on patients quality of life Prevalence in children
Dental caries may have a significant impact on an Since the significant decline in the 1970s and
individuals life. The most common consequences 1980s, it seems that over the past 20 years caries
of untreated lesions are discomfort and pain. prevalence rates have become relatively stable.2
Restorative dental treatments can now be provided The 2003 Childrens Dental Health Survey
pain free, apart from the pain of the local commissioned by the UK Health Departments
anaesthetic injection. However, for some people provides the most recent estimate of the
restorative treatments are associated with fear and prevalence of dentine decay in children in
anxiety, which, may become barriers to dental England and Wales.3 The 2003 survey is the fourth
attendance. Treatment avoidance can subsequently in a series of dental health surveys carried out
lead to further progression of caries which, in every 10 years since 1973. The criteria used in the
turn, may cause more distress and long-term survey to assess dental caries were the following:
complications. Gross decay may lead to
disturbances in eating and sleeping patterns filled decay, otherwise sound: teeth with
because of pain. Psychological distress can arise amalgam, or other fillings that had no cavitated
from the embarrassment and self-consciousness of dentine caries present
having missing or decayed teeth, especially in the obvious decay experience: all teeth with
anterior dentition. Communication problems may cavitated dentine caries, restorations with
ultimately occur as a possible result of tooth loss. cavitated dentine caries, teeth with filled decay
(otherwise sound) and teeth extracted due to
In addition to human cost, dental caries can be caries. The term relates to the DMFT (decayed,
costly for the patients receiving treatment. For missing, and filled teeth) dental decay index.
many patients NHS charges can be expensive,
especially for those who earn just enough to The preliminary findings of this survey indicate
disqualify them from exemption or remission of that:
charges. Moreover, where provision of NHS
dentistry is patchy, patients may have to depend there has not been a substantial change in the
on private dental care. proportion of 5- and 8-year-olds who presented
with obvious decay in the primary (milk) teeth
Impact on the NHS between the 1993 and 2003 dental survey
Treatments for dental care carry considerable costs (Table 1)
for both the NHS and society. NHS General the proportion of filled primary teeth as well as
Dental Services (GDS) data reveal that the total the proportion of the total obvious decay
number of claims in England and Wales for dental experience represented by filled primary teeth
interventions in the financial year 2002/03 was 34 in 5- and 8-year-olds has declined since 1983,
million. Almost half (48%) of claims were for indicating a decline in restorative interventions
treatments requiring no dental intervention (i.e. (Table 1)
examination, simple scaling, X-ray, fissure sealant, the mean number of primary teeth with obvious
topical fluoride). The total number of teeth filled decay has decreased since 1983 in 5- and
was about 19 million, while the number of teeth 8-year-olds (Table 2), but the mean number of
with roots filled was just over one million. Overall, primary teeth with obvious decay among
the total gross fees authorised was 1634 million. children with decay has not changed
The care and treatment for children accounted for considerably since 1993, apart from the decline
27% (461 million) of all gross fees authorised. in the number of filled teeth in the 8-year-olds
(Table 3)
Epidemiology the proportion of 8-, 12- and 15-year-olds with
There has been a significant reduction in dental obvious tooth decay and cavities into dentine in
caries since the 1970s in industrialised countries, permanent teeth has decreased considerably
due to environmental and educational factors such since 1983 (Figures 2 and 3)
as the increased use of fluoride in public water the proportion of filled permanent teeth has
supplies, dentifrices and dental products; declined considerably since 1983 in 12- and
4 improved oral hygiene and prophylaxis; dietary 15-year-olds, but not in 8-year-olds (Figure 4)
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 1 Percentage of children with obvious tooth decay in TABLE 3 Mean number of primary teeth with obvious tooth
primary teeth by age (Childrens Dental Health in the United decay in children with obvious decay experience by age
Kingdom, 2003)3 (Childrens Dental Health in the United Kingdom, 2003)3

Year Year

Tooth condition 1983 1993 2003 Tooth condition 1993 2003

Percentage of children: Mean number of teeth


Obvious decay experience Teeth with cavities into dentine
5-year-olds 50 45 43 5-year-olds 3.1 3.2
8-year-olds 70 61 57 8-year-olds 2.1 2.3
Teeth with cavities into dentine Filled decay (otherwise sound)
5-year-olds 41 40 40 5-year-olds 0.6 0.6
8-year-olds 49 50 50 8-year-olds 1.1 0.9
Filled decay (otherwise sound) Obvious decay experience
5-year-olds 23 15 12 5-year-olds 3.7 3.8
8-year-olds 47 33 26 8-year-olds 3.2 3.2
Filled teeth as a proportion of total obvious decay
experience
5-year-olds 28 17 15 TABLE 4 Proportion of children with obvious tooth decay in
8-year-olds 50 35 28 permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

TABLE 2 Mean number of primary teeth with obvious tooth Year


decay by age (Childrens Dental Health in the United Kingdom,
Tooth condition 1983 1993 2003
2003)3
Percentage of children:
Year Filled teeth as a proportion of total obvious decay
experience
Tooth condition 1983 1993 2003 8-year-olds 58 37 52
12-year-olds 70 58 70
Mean number of teeth
15-year-olds 74 68 77
Teeth with cavities into dentine
5-year-olds 1.3 1.4 1.4
8-year-olds 1.2 1.3 1.3
Filled decay (otherwise sound)
5-year-olds 0.5 0.3 0.2
presented with tooth decay in permanent or
8-year-olds 1.2 0.7 0.5 primary teeth. The proportion of children with
untreated caries in permanent or primary teeth
Obvious decay experience
was 29% for the 68-year-olds and 20% for the
5-year-olds 1.8 1.7 1.6
8-year-olds 2.3 2.0 1.8 15-year-olds (Figure 5).

Dental caries is not evenly distributed across the


child population, with about 26% of children (worst
cases) presenting with 75% of all carious lesions.6
the proportion of the total obvious decay This can be interpreted in the light of the fact that
experience represented by the number of filled dental caries is a disease of lifestyle with strong
permanent teeth in 8-, 12- and 15-year-olds has socio-economic and geographical differences. The
increased since 1993, indicating an increase in use of deprivation categories in the assessment of
restorative interventions (Table 4). Scottish schoolchildren aged 5 years is a good
example of how measures of socio-economic status
These findings are consistent with those found by may correlate with dental caries experience
the USA Third National Health and Nutrition (Figure 6).5 The link between social status and
Examination Survey (NHANES III), Centers for prevalence of caries is also supported by the data
Disease Control and Prevention (CDC), National from the National Childrens Dental Health Survey
Centre for Health Statistics (NCHS)4 and the carried out in the UK in 1993 (Figure 7).7
National Survey of Dental Caries in US School
Children 19861987, where 52% of children aged Prevalence in adults
68 years and 61% of children aged 15 years Fewer prevalence data are available for adults. 5

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Background

100
90
80
70
60 1983
% 50
1993
40
2003
30
20
10
0
8 12 15
Age (years)

FIGURE 2 Proportion of children with obvious decay experience in permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

45
40
35
30
% 25 1983
20 1993
15 2003
10
5
0
8 12 15
Age (years)

FIGURE 3 Proportion of children with cavities into dentine in permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

90
80
70
60
50 1983
%
40 1993
30 2003
20
10
0
8 12 15
Age (years)

6 FIGURE 4 Proportion of children with filled permanent teeth by age (Childrens Dental Health in the United Kingdom, 2003)3
Health Technology Assessment 2006; Vol. 10: No. 16

70 Tooth decay
60 Untreated caries
50
40
%
30
20
10
0
68 15
Age (years)

FIGURE 5 Proportion of children with tooth decay and untreated caries by age (NHANES III)4

5.0
4.5
4.0
Number of DMFT

3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
1 2 3 4 5 6 7
Deprivation categories

FIGURE 6 Caries distribution by socio-economic deprivation categories (DEPCAT) in Scottish schoolchildren aged 5 years.5 DEPCAT 1
= most affluent postcode sections. DECAT 7 = most deprived postcode sectors.

According to the UK 1998 Adult Dental Health surface fillings were found in 43% of people aged
Survey,8 adults had an average of 1.5 decayed or 65 and older.
unsound teeth (teeth with visual or cavitated caries
or those with an unsound restoration) and 55% Similarly, in the USA, NHANES III Phase 1
had at least one decayed or unsound tooth. The found evidence of coronal carious lesions in 94%
numbers of adults with decayed or unsound teeth of the studied population. The mean score for
varied according to the regions surveyed. The decayed and filled surfaces (DFS) on permanent
proportion of dentate adults with tooth decay in teeth in adults was 22.2. Carious lesions were
England, Wales, Scotland and Northern Ireland is found in 23% of all dentate adults and in 47% of
shown in Figure 8. people aged 65 years and over (NHANES III
19981991).4
The mean proportion of filled permanent teeth
ranged from 9% for people aged 1624 years to
39% for people aged 4554 years (Figure 9). Current service provision
Overall, 66% of the adult population showed at Current management of dental caries
least one tooth with a root surface that was Increasing emphasis has been recently dedicated
exposed, worn, decayed or filled. Overall, root to the provision of caries prevention and 7

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Background

3.5
3.0
Number of DMFT

2.5
2.0 I, II, III non-manual
1.5 III manual
1.0 IV, V
0.5
0
12 15
Age (years)

FIGURE 7 Average number of decayed, missing or filled teeth in adolescents in the UK by social class (National Childrens Dental
Health Survey, 1993)7

60

50

40

% 30

20

10

0
England Wales Scotland Northern
Ireland

FIGURE 8 Proportion of adults with decaying or unsound teeth by country (United Kingdom Adult Dental Health Survey, 1998)8

40
35
30
25
% 20
15
10
5
0
1624 2534 3544 4554 5564 65 All

Age (years)

8 FIGURE 9 Mean proportion of filled teeth by age (United Kingdom Adult Dental Health Survey, 1998)8
Health Technology Assessment 2006; Vol. 10: No. 16

management strategies. In particular, attention to However, with the exception of digital radiology,
risk assessment and to preventive non-operative these diagnostic procedures are not widely used in
methods for assisting remineralisation of early dental practice. Some procedures need further
caries has been advocated. Despite the investigation (e.g. QOTI/FOTI, QLF) or further
acknowledged importance for the prevention of development (e.g. UCD) before their use could be
caries, non-operative, preventive treatments are recommended in dental practice. Others are
not fully funded by the NHS at present. Changes prone to false-positive measurements (e.g. small
are likely to be introduced with the amount of plaque identified as a carious lesion by
implementation of the new contract in 2006. DIAGNOdent) or unreliable findings (e.g. because
of inadequate tooth isolation during ECM),10
Efficient management of dental caries depends on which require a careful interpretation and
the knowledge of patients dental and medical sometimes correction by the dentist. In particular,
history and risk assessment, correct identification to the authors knowledge the validity of
of carious lesions and identification of the best DIAGNOdent as an instrument for detecting
treatment options for dental caries. A thorough occlusal caries has yet to be demonstrated in in
dental and medical history provides information vivo studies.
about patients previous experience of dental
caries, number of active lesions and factors that Treatment of early caries (non-cavitated pit and
may affect caries activity (e.g. general oral fissure caries and root caries)
hygiene, diet and sugar intake, exposure to Treatment options for early caries include the
fluoride, salivary flow rate, certain medical following:
conditions and medications). Caries risk
assessment aims at identifying high-risk provision of information about oral hygiene
individuals who may benefit more from preventive dietary assessment and advice
treatments, and low-risk individuals for whom fluoride-delivery methods
restorative treatments could be delayed. Carious application of chlorhexidine
lesions are first identified on the basis of the pit and fissure sealants
findings of the clinical examination (visual recall at regular intervals.
criteria). For visual detection of occlusal caries and
for predicting their activity and severity, the Oral hygiene
ranked scoring system described by Ekstrand and Instructions on oral hygiene aim at improving
colleagues9 is recognised as a valid and reliable personal removal of plaque by toothbrushing.
tool, although mainly used in clinical research. For Regular toothbrushing in children may help to
assessing the extent and severity of root caries the reduce the incidence of caries,11 and children
tactile criteria of soft, leathery and hard on whose level of oral hygiene is good experience less
probing are commonly used in dental practice and decay.12 Despite the lack of evidence on the
dental research. Radiographic investigations (X- effectiveness of oral hygiene instructions,13
rays) have been widely used for decades as an toothbrushing, together with the use of fluoride
adjunct to clinical examination to estimate the toothpaste and the advice of reducing sugar intake,
depth of occlusal lesions into dentine or to is usually recommended in the dental practice for
identify lesions that are hidden from clinical maintaining a good level of oral hygiene.
examination. More recently, other quantitative,
more advanced methods have been proposed for Dietary assessment and advice
the diagnosis of dental caries. These include Evidence from epidemiological and experimental
methods based on: studies indicates that frequent consumption of
fermentable carbohydrates is associated with
digital radiology [e.g. digital image prevalence of dental caries. For some patients the
enhancement, digital subtraction radiography, frequency of intake of a certain type of food may
tuned aperture computed tomography (TACT)] primarily contribute to their caries risk and
visible light [e.g. quantitative fibre-optic modification of this factor may be sufficient to
transillumination (QOTI/FOTI), quantitative change their risk. The dietcaries association is,
light-induced fluorescence (QLF)] however, complex and needs to be evaluated not
laser fluorescence (e.g. DIAGNOdent) only on the basis of the quantity and type of
electrical current [e.g. electrical conductance fermentable carbohydrates consumed, but also
measurement (ECM)] considering several other background factors such
ultrasound [e.g. ultrasound caries detector as age, total food intake, dietary habits, salivary
(UCD)]. flow rate, use and type of medications, and use of 9

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Background

fluoride products. Dietary assessment is usually prevented fraction pooled estimate was 0.46 [95%
recommended in patients with multiple active confidence interval (CI) 0.30 to 0.63, p < 0.0001],
lesions. In contrast, no diet modifications are indicating a substantial benefit and demonstrating
suggested for patients with inactive caries. The that fluoride varnish alone can result in reversal of
dentist, however, may still provide information on early caries. Similarly, the meta-analysis of the
how unhealthy dietary habits may become a three studies assessing the effect of fluoride
problem, especially when associated with a poor varnish on deciduous teeth suggested a 0.33%
level of oral hygiene.14 (95% CI 0.19% to 0.48%, p < 0.0001) reduction in
DMFS. Another recent systematic review26 of
Fluoride-delivery methods selected caries prevention methods reached
Use of fluoride-delivery products and water similar conclusions, demonstrating that there is a
fluoridation are among the factors that have fair body of evidence on the effectiveness of
contributed to the observed progressive fluoride varnish to arrest or reverse non-cavitated
improvement in oral health since the 1970s. carious lesions in permanent teeth. Other fluoride
Evidence indicates that fluoridation of the water products such as fluoride supplements (e.g.
supply is associated with an increased proportion fluoride tablets or drops) are regarded as less
of children without caries and a reduction in the effective methods of delivering fluoride because
number of teeth affected by caries.1,15,16 Topical they rely entirely upon patient compliance. Their
fluoride-delivery methods in the form of use is usually limited to high-risk categories of
toothpastes, mouth rinses, gels or varnishes are children, adults and, particularly, elderly people.27
effective measures to prevent dental caries. Their
effectiveness has been established on evidence Application of chlorhexidine
from randomised trials and more recently from a The effectiveness of chlorhexidine as an
series of Cochrane systematic reviews of antimicrobial for preventing progression of non-
randomised trials.1722 Overall, fluoride toothpaste cavitated caries has yet to be established. Current
is the cheapest and the most widespread method evidence is derived mainly from small studies
to control dental caries.2325 A recent randomised, evaluating the effects of different forms of
double-blind, clinical trial examined the anticaries chlorhexidine (varnish, gel or rinse) in
effectiveness of fluoride dentifrices containing combination with other concomitant preventive
1700, 2200 and 2800 ppm fluoride ion compared measures.26,28
with a 1100 ppm fluoride control toothpaste, in
schoolchildren aged 615 years.24 The 1-year Pit and fissure sealants
results demonstrated significant caries reductions Pits and fissures are sealed to prevent caries
for higher fluoride dentifrices for all tooth development.28 Evidence indicates that caries does
surfaces, but in particular for occlusal surfaces.24 not progress as long as the sealant remains in
The use of fluoride mouth rinses and gels, as an place.29,30 Sealant applications may be suitable for
adjunct to fluoride toothpaste, is usually advised both young children and older patients.31
for individuals at high risk of developing caries. Materials that are currently used to seal a lesion
Fluoride varnish is used to provide fluoride include different types of composite resin and
delivery to specific tooth sites and surfaces and is glass ionomer cement. The resin-based sealants
usually applied at intervals of 3 or 6 months. A are divided into generations according to their
recent systematic review by Marinho and mechanism for polymerisation and their content.
colleagues17 looked at the effectiveness of fluoride The first generation sealants which were activated
varnish in preventing dental caries in children and by ultraviolet light are no longer available and the
adults and commented on the ability of fluoride most recently developed fourth generation
varnish to promote remineralisation of early sealants contain fluoride. The effectiveness of
caries. The included studies also considered non- resin sealants for the prevention of caries in the
cavitated incipient enamel lesions, clinically permanent teeth of children and adolescents was
visible as white spots or discoloured fissures, which demonstrated by Ahovuo-Saloranta and
would be included among those lesions eligible for colleagues32 in a recent Cochrane systematic
ozone application. The treatment effect was review. The review compared second, third and
measured in terms of prevented fraction (mean fourth generation resin-based sealants or glass
increment in caries in controls minus mean ionomer sealants with a control (no sealant) and
increment in fluoride group divided by the mean compared one type of fissure sealant with another
increment in the controls). For the seven studies type. The focus of the review was on prevention,
that contributed to the main meta-analysis, the and the children and adolescents included did not
10 decayed, missing and filled surfaces (DMFS) seem to present with obvious caries. The review
Health Technology Assessment 2006; Vol. 10: No. 16

concluded that resin-based sealants are effective in subsequently manufactured under licence and
preventing caries of the occlusal surfaces of distributed by KaVo-Dental GmbH & Co.
permanent molars. Reduction of caries ranged (Germany) under the name HealOzone. Its use
from 86% at 12 months to 57% at 4854 months. has been pioneered by Professor Edward Lynch
Resin sealant retention was good across studies and his team at Queens University in Belfast,
and sealants were retained completely in 79% and Northern Ireland, and Barts and the London
92% of cases at 12 months. Sealant retention Queen Marys School of Medicine and Dentistry
decreased with time and at 36 months ranged in London, UK. HealOzone is a certified
from 61 to 80%. Evidence on the effects of glass Medical Device [Conformit Europene (CE)
ionomer-based sealants was less convincing. marked] for the management of occlusal pit and
fissure caries, and root caries. According to the
Treatment of cavitated pit and fissure caries and manufacturer, 294 HealOzone units (as at June
root caries 2004) are currently in use in dental practices in
For lesions that have progressed to the stage of the UK and more than one million people have
cavity, restorative interventions are often used to already received HealOzone treatment. The
remove the decayed tissue and fill the cavity to aid HealOzone technology has not yet received Food
plaque control. However, cavitated root lesions and Drug Administration (FDA) approval in the
that are still accessible to cleaning need not always USA.
be filled because cleaning alone can arrest caries.
A number of different materials can be used to The new version of HealOzone (Mark3) was
restore a tooth. These include composite resin, launched in July 2004. According to the
glass ionomer cement and amalgam. Amalgam is manufacturer previous models can be upgraded to
still the material of choice for large restoration of the most recent technical functions.
molar teeth. Root caries are usually restored with
composite resin or glass ionomer cement. HealOzone procedure
According to the NHS Dental Review The HealOzone procedure consists of a package,
20022003,33 in the quarter ending December which includes the application of ozone gas, the
2002 the number of teeth filled was 4,896,951 and use of remineralising agents, a patient kit and
on average one tooth was filled for every two information on oral hygiene. The HealOzone
claims (55%). Overall, restorations showed a device comprises an air filter, a vacuum pump, an
median survival interval to next restorative ozone generator, a handpiece fitted with a sealing
intervention of just over 8 years. The main factors silicone cup and a flexible hose. The silicone cups
associated with different likelihoods of re- are available in a range of five sizes from 3 to
intervention were the age of the patient at the 8 mm in diameter. The HealOzone unit requires
date of restoration, the position of the tooth and high-voltage power to generate ozone from the air
the type/material of restoration.33 and to convert ozone back to oxygen when the
process is completed. The air is exposed to high-
voltage current to generate ozone at a
Description of new intervention concentration of 2100 ppm 10% and passes
through the instrument hose and handpiece. The
Rationale flow of air into the system, the delivery of ozone to
The antimicrobial effects of ozone gas (O3) have the tooth and the removal of ozone from the
been known for many years. Direct application of system after completion of treatment are achieved
ozone gas to the coronal or root tooth surface is by a vacuum pump, which works at an adjustable
claimed to have a sterilising effect. In particular, flow rate of 615 cm3 per minute to maintain the
ozone is claimed to stop the action of the ozone concentration at 2100 ppm.
acidogenic and aciduric micro-organisms
responsible for the tooth decay. It is consequently The procedure usually takes between 20 and 120
alleged to be able to reverse, arrest or slow down seconds per tooth. Immediately after ozone
the progression of dental caries. It is also application the tooth surface is treated with a
maintained that ozone is useful for reducing the remineralising solution (reductant) containing
microbial flora in cavitated lesions, before fillings fluoride, calcium, zinc, phosphate and xylitol
are inserted. dispensed from a 2-ml ampoule. The reductant is
supplied in packs of 100 ampoules. Patients are
Development of HealOzone also supplied with a patient kit, which consists of
The ozone unit for dental use was initially toothpaste, oral rinse and oral spray, all
developed by CurOzone Inc. (Canada) and containing fluoride, calcium, zinc, phosphate and 11

Queens Printer and Controller of HMSO 2006. All rights reserved.


Background

xylitol, and aims to enhance the remineralisation advice, chlorhexidine/fluoride varnish and
process. HealOzone application for the treatment fissure sealant? If so, is it a cost-effective
of non-cavitated lesions is usually repeated at 3 alternative?
and 6 months. There is no clear information on For the management of non-cavitated root
how delivery of ozone at the correct concentration caries, is the HealOzone procedure more
can be ensured by the device. clinically effective than the combination of oral
hygiene, dietary advice and varnish? If so, is it
cost-effective?
Key questions For the management of cavitated caries, how
often, if at all, is HealOzone procedure an
This review aims to answer the following alternative to fillings?
questions: For the management of cavitated caries, does
the application of ozone gas and of a re-
For the management of pit and fissure caries, is mineralising solution to the cavity before
the HealOzone procedure more effective than restoration prolong the life of a filling? If so, is
the combination of oral hygiene, dietary it cost-effective?

12
Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 3
Effectiveness
Methods for reviewing DentalOzone; see Appendix 1 for full details),
were also identified. Reference lists of included
effectiveness studies were also checked for additional study
Search strategy reports.
Initial database searches were undertaken to
identify relevant systematic reviews and other Inclusion and exclusion criteria
evidence-based reports. Several websites were also All citations identified by the search strategy were
consulted to obtain background information. Full assessed for relevance by two reviewers. Copies of
details of the main sources consulted are listed in the full-text, published papers of those considered
Appendix 1. to be relevant were then obtained. It was decided
that studies reported in languages other than
Electronic searches were conducted to identify English would be identified but not included in
published and unpublished studies on the clinical the review.
and cost-effectiveness of ozone therapy for dental
caries. The electronic databases searched are For clinical effectiveness assessment, included
detailed in Table 5. Full details of the search studies were randomised controlled trials (RCTs)
strategies are documented in Appendix 1. It was of ozone treatment (HealOzone) versus at least
anticipated that there was a small body of research one comparator (nil, placebo or active treatment).
available, therefore a sensitive search strategy for Data from studies other than randomised trials
clinical effectiveness studies was undertaken to were collected but not included in the review. The
retrieve all useful information on ozone therapy outcome measures were required to be measures of
for dental caries. Additional searches were carried clinical effectiveness (e.g. reversal/progression of
out for economic data and these are detailed in caries). Only in vivo studies involving human
Chapter 4. In addition, selected conferences subjects were deemed to be suitable for inclusion,
proceedings that were not available electronically while studies reporting in vitro results were
were handsearched. These were International excluded. Studies were also excluded if their
Association for Dental Research (IADR) conference follow-up was less than 6 months or did not report
proceedings for 19992001 and the annual clinically relevant outcome measures.
European Organisation for Caries Research (ORCA)
Congresses 20002003. Research abstracts, Data extraction strategy
published on industry and users websites (KaVo A data abstraction form was designed (Appendix
Dental, CurOzone USA, HealOzone and 2) to collect details from each individual study.

TABLE 5 Electronic databases searched

Database Coverage

MEDLINE/EMBASE/MEDLINE Extra multifile search MEDLINE: 1966 to May Week 1 2004


EMBASE: 1980 to Week 20 2004
MEDLINE: Extra: 17 May 2004
Science Citation Index (SCI) 1981 to 16 May 2004
BIOSIS 1985 to 12 May 2004
AMED 1985 to May 2004
Cochrane Controlled Trials Register (CCTR) Cochrane Library, Issue 2, 2004
National Research Register (NRR) Issue 2, 2004
Current Controlled Trials (CCT) 18 May 2004
Clinical Trials 18 May 2004
SCI Proceedings 1991 to 15 May 2004
Conference Papers Index 1982 to May 2002
ZETOC Conferences 1993 to May 2004
IADR Meetings Abstracts 2002 to 2004
13

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Effectiveness

TABLE 6 Number of screened and selected reports according to database searched

Database searched Number screened Number selected Included studies

MEDLINE/EMBASE/MEDLINE Extra 46 4 1
SCI 38 7 1
BIOSIS 38 1 0
CENTRAL 8 1 0
IADR abstracts 175 43 12
Handsearch 14 2
Websites 15 5
Other databases 26 0 0
Total 331 85 21

These included the type of study design, number 12 questions, which focus on the following
of participants and their characteristics, methodological aspects: method of randomisation,
intervention characteristics, caries information unit of randomisation, concealment of allocation,
including location and severity of lesion, patient comparability of groups at baseline, blinding
outcomes such as reversal/progression of caries, procedures, number of withdrawals/dropouts and
and any reported adverse events. completeness of assessment at follow-up.

In particular, the outcomes sought for the For each question a Yes, No or Unclear answer
included studies were as follows: was required. The quality assessment checklist is
presented in Appendix 3.
(a) Non-cavitated caries

reversal of caries Results


progression of caries
utilisation of dental services (e.g. visits to dental Quantity and quality of research
care units; duration of dental treatment) available
adverse events After removing duplicates a total of 331 reports
patient-centred measures (e.g. patient was identified (Table 6): 78% (257) were abstracts
satisfaction and preference, relief of and 22% (74) were full-text reports. Eighty-five
pain/discomfort) reports (seven full-text papers and 78 abstracts)
quality of life. were selected for full assessment, of which 21
(three full-text papers and 18 abstracts) met the
(b) Cavitated caries predefined criteria for inclusion in the review. In
addition, two reports, both PhD theses, were
time to restorative interventions identified from reference lists. All 23 identified
need for further restorative interventions and reports were written in English.
length of time between restorations
symptoms of pulpal pathology. Number of studies identified
In total, five studies reported in five full-text
Inclusion criteria were assessed independently by papers and 13 abstracts, and five studies reported
two reviewers. Any disagreements were resolved by only as abstracts, met the inclusion criteria for
consensus or referred to a third reviewer. studies of clinical effectiveness. In case of multiple
Reviewers were not blinded to the names of study publications the report with the longest follow-up
authors, institutions or publications. time and/or largest sample size was chosen as the
main source of information.
Quality assessment strategy
Two reviewers assessed the methodological quality Number and type of studies excluded
of all included studies and any disagreements were After identifying duplicates, several studies were
resolved by discussion. The quality assessment of excluded as they did not meet the inclusion
RCTs was formally assessed using a published criteria. The main reasons for exclusion, together
checklist modified by the reviewers for the with the corresponding number of studies
14 purpose of this review.34 The checklist consisted of excluded are listed in Table 7.
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 7 Number of studies and reasons for exclusion

Reason for exclusion Number of studies/abstracts

Follow-up less than 6 months 17


No HealOzone treatment; other experiments involving ozone 14
No measures of clinical effectiveness 6
HealOzone used on extracted teeth (in vitro studies) 4
Evaluation of diagnostic tests for detection of dental caries; no clinical effectiveness 5
measures
Time studies, no clinical effectiveness measures 3
Discussion paper, no comparative information on clinical effectiveness 1
Costs, no clinical effectiveness measures 1
No random allocation 2
Patients attitudes, no effectiveness measures 7
Studies not involving ozone 4

Number and type of studies included The Abu-Nabaa main study37,4550 had four
The five full-text studies consisted of two RCTs treatment groups: ozone plus reductant versus air
assessing the use of HealOzone for the treatment plus reductant, and ozone plus
management of primary root caries one reductant plus sealant versus reductant plus
published trial by Holmes35 and one unpublished sealant only. It involved 90 patients with 254
trial by Baysan and Lynch,36 and two PhD theses lesions.
assessing the use of HealOzone for the
management of pit and fissure caries, one by The Abu-Nabaa pilot study37,51,52 had two
Abu-Nabaa37 reporting two unpublished trials treatment groups: ozone plus reductant versus
and one by Abu-Salem38 reporting one reductant only. It involved eight patients with 34
unpublished trial. lesions.

Root caries studies The Abu-Salem study38 had two treatment groups:
Holmes (2003): this published randomised HealOzone plus reductant versus reductant only. It
trial35,39,40 of management of primary non- recruited 21 patients with 74 lesions, from Belfast
cavitated root caries had two treatment groups: primary schools.
ozone plus reductant plus patient care kit versus
air treatment plus reductant plus patient care kit. Of the five studies published only as abstracts,
This study was set in a general dental practice. four assessed the effects of HealOzone for the
management of occlusal pit and fissure carious
Baysan and Lynch (2004): this unpublished lesions,5356 and one assessed the effects of
randomised trial on cavitated and non-cavitated HealOzone on primary root carious lesions.57
root caries36,4144 had four treatment groups:
ozone plus reductant versus reductant only, and Tabulation of quality of studies, characteristics of
ozone plus sealant versus sealant only. It recruited studies and evidence rating
patients who attended the School of Dentistry in The characteristics of the five full-text studies
Belfast. (type and number of participants and carious
lesions, details of study design, inclusion criteria,
Pit and fissure caries studies characteristics of intervention and main results)
Abu-Nabaa PhD thesis37 included two randomised are shown in Appendix 4.
studies: a main study (Abu-Nabaa, 2003) and a
pilot study (Abu-Nabaa pilot study, 2003), which Method of randomisation was reported in three
are considered separately as they do not include studies.35,37,38 Concealment of allocation was not
the same patient population. The main study specified in any of the included studies. One study
assessed exclusively non-cavitated occlusal lesions, was described as double blind35 and another study
whereas the pilot study included cavitated occlusal stated that outcome assessment was undertaken by
lesions. Patients were recruited from the School of a blinded examiner.38 In particular, the double-
Dentistry in Belfast for both the main and pilot blind study by Holmes was reported to involve
studies. three dentists: the first dentist performed the 15

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Effectiveness

initial assessment of primary root carious lesions; In the majority of the included studies, data
the second randomised the lesions to treatment analysis was conducted at the level of the lesion.
groups; the first then treated and assessed the Holmes used 2 statistics, but did not specify
result without knowing which were given ozone whether they were for related samples (i.e.
and which air, using a modified HealOzone McNemar 2 test). In the Baysan and Lynch
machine; the third dentist independently assessed study no information was provided on the
lesions in 15 patients. The practicality of the choice of statistical test used. In both Abu-Nabaa
entire process is, however, doubtful. Holmes is the studies the unit of analysis was tooth-pair, but
only author of the study and the other assessors it was unclear whether the occurrence of
are neither listed as authors nor acknowledged in multiple pairs of lesions per mouth was taken
the paper. into account. Abu-Salem used a mixed-effects
analysis of variance (ANOVA) with random
It was unclear whether blinding procedures were effects for patient and teeth within patient,
secured in the remaining three included studies. and fixed effects for group and time of
The total number of people in the studies was treatment.
287, with a total of 768 carious lesions. Across the
studies, the ages of the participant groups ranged The characteristics of the five studies published as
from 7 to 82 years. Only three studies provided abstracts are shown in Appendix 5.
information on the gender of the participants.3638
The length of follow-up ranged from 6 to Tabulation of results and assessment of
21 months. effectiveness
The clinical effectiveness results are presented
Each study involved either two or four according to type of carious lesions (root caries
intervention groups. Ozone was always used in results are presented separately from occlusal
combination with other active interventions (i.e. caries results). Within this categorisation studies
ozone plus reductant, ozone plus reductant plus results are presented according to:
patient care kit, ozone plus sealant, ozone plus
reductant plus sealant) and compared to the same type of outcome measures
intervention without ozone or to a sham type of publication (results of full-text studies
procedure (air treatment). The dosage of ozone are presented separately from results of studies
treatment varied between studies. In the Baysan published as conference proceedings)
and Lynch study,36 the Abu-Salem study38 and the type of dentition (treatment results of primary
Abu-Nabaa main study,37 ozone was administered teeth are presented separately from treatment
for 10 seconds, whereas in the Holmes study35 and results of permanent teeth).
the Abu-Nabaa pilot study37 ozone was
administered for 40 seconds. In all studies ozone It was planned to undertake further statistical
applications were repeated at some point before analyses of the data reported in the full-text
the final follow-up. None of the included studies studies and when appropriate to combine them
provided information on the model/version of the quantitatively. However, owing to the limited raw
HealOzone device. data provided, this proved unfeasible. The
p-values of statistical analyses in the results section
The main outcome measure was reversal of are those originally quoted by the studies authors.
caries. This included the proportion of carious However, as the data were not analysed as paired
lesions becoming hard and, for some of the data on a patient basis, their validity and
included studies, the proportion of lesions reliability are open to question.
reversing from leathery to leathery approaching
hard texture, but not necessarily hardening. The Primary root carious lesions
proportion of lesions that deteriorated from Two full-text studies by Holmes35 and Baysan and
leathery to soft was also recorded, although not Lynch36 and one abstract by Lynch and
consistently. Where appropriate the proportion of colleagues57 assessed the use of ozone for the
intact sealants was documented. Changes in the management of primary non-cavitated root
ECM and DIAGNOdent readings were also carious lesions. The Baysan and Lynch study also
reported in the identified studies, but not included the assessment of a non-specified
considered in this review, owing to the number of cavitated root lesions. In the Holmes
unreliability of their measurements (i.e. high-false studies the clinical criteria of soft, leathery and
positive rates) and poor correlation with clinical hard were adopted for the assessment of carious
16 outcomes.58 lesions, whereas in the Baysan and Lynch study
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 8 Results of root carious lesions

Ozone final follow-up Control final follow-up


No. (%) No. (%)

PRCLs becoming hard


Baysan and Lynch, 200436 (12 months)a NR (47) NR (0)
Holmes, 200335 (18 months)b 87/87 (100) 1/87 (1)
PRCLs becoming less severe (from index 2 to 1)
Baysan and Lynch, 200436 (12 months)a NR (52) NR (12)
PRCLs becoming soft
Holmes, 200335 (18 months)b 0/87 (0) 32/87 (37)

NR, not reported (the denominator was not clearly reported in the study, so the number of caries cannot be calculated,
hence only percentages are given).
a
Baysan and Lynch: non-cavitated and cavitated primary root carious lesions.
b
Holmes: non-cavitated primary root carious lesions.

TABLE 9 Results of the Holmes study at each recall visit35

Ozone at follow-up Control at follow-up


No. (%) No. (%)

PRCLs becoming hard


12 months 85/87 (98) 1/87 (1)
18 months 87/87 (100) 1/87 (1)
21 months 81/81 (100) 6/81 (8)
PRCLs remaining leathery
12 months 2/87 (2) 65/87 (75)
18 months 0/87 (0) 54/87 (62)
21 months 0/81 (0) 65/81 (80)
PRCLs becoming soft
12 months 0/87 (0) 21/87 (24)
18 months 0/87 (0) 32/87 (37)
21 months 0/81 (0) 10/81 (12)

lesions were classified according to a five-point between three degrees of leathery seemed rather
severity index as follows: artificial.

0 all hard lesions Change in clinical severity Table 8 shows for each of
1 leathery lesions considered to be small, easily the included studies the proportions of carious
cleanable and approaching a hard texture lesions that according to the studies authors
2 leathery lesions judged to be shallow and reversed (became hard), improved (became less
where the surface of the exposed sound dentine severe) or deteriorated in the ozone-treated group
could be easily maintained plaque free and the control group. The Holmes study35
3 leathery lesions judged to be in surfaces that reported that 100% of ozone-treated primary root
were difficult to maintain plaque free, and large, carious lesions (PRCLs) had reversed by
cavitated leathery lesions where pulpal 18 months, while 37% of PRCLs in the control
integrity was judged to be at risk group had worsened from leathery to soft and 1%
4 all soft lesions. had reversed. However, comparisons of results at
different follow-up points show some
No information was provided on the validity and inconsistencies in the way data were reported
reproducibility of the above severity index, or on (Table 9). In particular, the results at 21 months
how lesions were clinically identified as leathery (published as an abstract) showed an increase in
soft or hard. In particular, the distinction the number of control lesions that stabilised 17

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Effectiveness

(from 54/87 at 18 months to 65/81 at 21 months) improvement rates in the control groups are
and a subsequent decrease in the number of therefore surprising.
control lesions that had become soft (from 32/87
at 18 months to 10/81 at 21 months), indicating Summary: root carious lesions The two full-text
an improvement over time in lesions receiving studies assessing the use of ozone for root carious
treatment other than ozone. No comments on lesions both report very high success rates with
these changes were provided by the authors. ozone and very low improvement rates in the
controls.
In the Baysan and Lynch study,36 47% of the
ozone-treated lesions had arrested by 12 months, Fissure sealants after application of ozone for the
whereas none had become hard in the control preventive treatment of non-cavitated root lesions
group (p < 0.001), and 52% had reversed from are more likely to remain intact (61% versus 42%,
index 2 (leathery) to index 1 (leathery p < 0.05).
approaching hard texture) in the ozone group
compared with 12% of lesions in the control group Pit and fissure carious lesions
(p < 0.001). So, if one combines the approaching The three remaining studies the Abu-Nabaa
hard (from index 2 to 1) and hard lesions (from main study (2003),37 Abu-Nabaa pilot study
index 2 to 0), 99% of lesions improved, as in the (2003)37 and Abu-Salem (2004) study38 assessed
Holmes study. This study included both cavitated the effects of ozone on pit and fissure carious
and non-cavitated root lesions, but results were not lesions. Both Abu-Nabaa studies involved patients
clearly presented according to the type of lesions aged over 12 years with primary lesions in the
and it is unclear how many cavitated and non- permanent posterior teeth, while the Abu-Salem
cavitated lesions were assessed in each study involved children 79 years old with carious
intervention group. Only one figure in the paper lesions in the posterior primary teeth. The
presented results for both types of lesions in the Abu-Nabaa main study and the Abu-Salem study
ozone group: the percentage of cavitated lesions assessed non-cavitated lesions, while the
that had reversed (become hard) decreased from Abu-Nabaa pilot study included lesions with
9.1% at 1 month to 1.4% at 9 months, indicating cavitation.
an increase/progression in the severity of cavitated
root lesions treated with ozone. No statistical Change in clinical severity: permanent dentition
analysis was undertaken by the authors, no Results of full-text studies Tables 10 and 11 illustrate
corresponding data were given for the control the results of the Abu-Nabaa main study.37
group, and no comments on reversal/progression Clinical severity of non-cavitated pit and fissure
of cavitated lesions were provided in the text of lesions was assessed using the criteria described by
the paper. Ekstrand and colleagues (0 = least severe, 1, 2, 3,
4 = most severe).9 The change in severity score is
In addition, the abstract by Lynch and calculated as the score at follow-up minus the
colleagues57 indicated that 80% (48/60) of non- score at baseline. Thus, a negative change
cavitated PRCLs treated with ozone reversed from indicates an improvement, while a positive change
severity index 4 to 3, whereas none of the soft implies a worsening of lesion severity. The mean
lesions in the control group significantly changed, change from baseline in clinical severity score at
and that 94% (189/200) of leathery lesions became 12 months was not significantly different
hard and arrested in the ozone group, whereas (p = 0.112) between the two intervention groups:
those in the control group did not significantly ozone (10 seconds) plus reductant group versus
change. reductant only group (Table 10).

Marginal adaptation of the root sealant The Baysan It was also reported that a greater proportion of
and Lynch study36 also assessed the effects of ozone-treated lesions improved or stabilised
ozone with or without a fissure sealant using the compared with control lesions at all recalls
modified US Public Health Service (USPHS) (Table 11). However, statistical analyses of these
criteria. In the ozone plus sealant group 61% of data were not provided. The relationship between
sealants were retained compared with 42% in the clinical severity score and the need for future
sealant only group (p < 0.05) at 12 months. fillings was not explained.

It is worth noticing that both groups had the No significant difference in the clinical severity
same other active interventions such as reductant, score was found between the ozone and control
18 patient care kits and sealants. The very low groups in the Abu-Nabaa main study. The
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 10 Mean change in clinical severity score of pit/fissure lesions from baseline (Abu-Nabaa main study)37

Ozone group Control group p-Value


Change in clinical severity score (n = 106) (n = 106)

Mean change from baseline 0.283 0.443 0.112


Standard deviation 0.64 0.74
Standard error 0.06 0.07

TABLE 11 Percentage of pit/fissure lesions that improved, remained stable, or increased in clinical severity at each recall visit (Abu-
Nabaa main study)37

Month(s) of Treatment Decreased severity Stable Increased severity


follow-up group (improvement) (worsening)

1 Ozone 11.4% 74.6% 14.0%


Control 5.3% 81.6% 13.2%
3 Ozone 17.7% 63.9% 18.5%
Control 8.4% 73.1% 17.6%
6 Ozone 10.8% 55.9% 33.3%
Control 5.9% 59.8% 34.3%
9 Ozone 7.8% 57.8% 34.5%
Control 6.9% 56.0% 37.1%
12 Ozone 7.4% 56.5% 36.1%
Control 5.6% 48.6% 45.8%

reported proportions of lesions improved, This study was only a pilot study, which did not
stabilised and deteriorated appeared similar add much to the results of the Abu-Nabaa main
between groups, but no statistical analyses were study.37
undertaken and the clinical relevance of these
findings was not explained in terms of fillings Results of abstracts The abstracts gave little detail of
avoided. studies, their methodology could not be easily
assessed and therefore their findings must be
Abu-Nabaa pilot study In the Abu-Nabaa pilot interpreted with caution. They are included here
study,37 17 lesions (with cavitation) were treated for completeness and as a guide to emerging
with ozone plus reductant and 17 reserved as research.
controls (reductant only) in eight patients.
Outcomes were measured using Ekstrand and Three abstracts compared pit and fissure lesions
colleagues clinical index9 as well as the following receiving ozone (at different concentrations) with
clinical indices: hardness index (hard, leathery, pit and fissure lesions receiving no-ozone
soft), visual index (sound, arrested, active), treatment.5456 Their results are presented in
cavitation score (1 = no cavitation, Table 13. The proportion of lesions reported as
2 = microcavitation, 3 = frank cavitation), colour clinically reversed, the extent of which was not
index (normal, yellow, light brown, grey, dark specified, ranged from 86.6 to 99% in the ozone-
brown, black), frosted enamel measure (mm), treated groups. All studies reported that no
stained enamel measure (mm) and perceived significant clinical changes were observed in the
treatment need index (e.g. requiring no control group, but no numerical information was
intervention, requiring preventive resin given.
restoration, requiring drilling and filling).
Thirteen lesions in the treatment group and 12 Another abstract53 compared the use of ozone
lesions in the control group were assessed at versus conventional treatment in 35 patients, each
6 months. Lesions treated with ozone showed a with two occlusal lesions extending
significant reduction in the hardness and visual radiographically 24 mm into dentine. The
indices (Table 12). No significant differences authors defined the occlusal lesions as non-
between groups were found for any other indices cavitated, but lesions 24 mm into dentine on
or for the Ekstrand clinical index (p > 0.05). radiographs are likely to have small cavities that 19

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Effectiveness

TABLE 12 Number of pit/fissure lesions showing a reduction in the clinical indices at 6 months (Abu-Nabaa pilot study)37

Colour index

Hardness indexa Visual indexb Cavitation scorec Darkerd Lightere Perceived


treatment needf

Treatment 11/13 (84.6%) 8/13 (61.5%) 6/13 (46.2%) 3/13 (23.1%) 2/13 (15.4%) 12/13 (92%)
Control 4/12 (33.3%) 1/12 (8.3%) 5/12 (41.7%) 2/12 (16.7%) 6/12 (50%) 9/12 (75%)
p-Value <0.05 <0.05 ns 0.084 (ns) 0.16 (ns)
a
The proportion of lesions becoming hard
b
The proportion of lesions with increasing score
c
The proportion of lesions with reduction in cavity score
d
The proportion of darker lesions
e
The proportion of lighter lesions
f
The proportion of lesions with a reduced treatment need

TABLE 13 Reversal of pit/fissure caries: findings from abstracts

Ozone at follow-up Control at follow-up


No. (%) No. (%)

Holmes 200354 (12 months) 1918/1937 (99) 0/427 (0)


Hamid, 200355 (6 months) 80/92 (86.9) 0/92 (0)
Megighian and Bertolini, 200456 (6 months) p < 0.05 0/80 (0)
(220 lesions treated)

trap plaque and are likely to progress unless only presented graphically. The graph showed a
cleaned thoroughly. The ozone-treated lesions steady increase in the mean change from baseline
received ozone for 40 seconds and application of a clinical severity scores for the control group,
glass ionomer preventive sealing, which was compared with an initial slight decrease and a
subsequently replaced with a posterior composite subsequent levelling in the ozone group at
at 3 months. The control lesions received 12 months. The overall changes in the clinical
conventional drilling and filling (posterior severity scores9 were analysed using a mixed-
composite). All the ozone-treated lesions were effects ANOVA. This analysis assumed that
reported to have reversed at 3 months. Six patients and teeth within patients had a random
complaints (17.1%) of postoperative sensitivity were effect, while group and time of treatment had a
reported after conventional drilling and filling at fixed effect. There was overall little reduction in
6 months compared with none after ozone clinical severity scores in the ozone-treated group,
treatment (p < 0.05). Postoperative sensitivity is, while an overall increase was observed in the
however, a measure commonly used to assess large control group. There was a statistically significant
carious lesions and it is questionable whether it effect of treatment upon clinical severity scores
should be used for early carious lesions. Moreover, with time (p < 0.01).
complaints of postoperative sensitivity after
occlusal restorations are rare. Sealant retention The Abu-Nabaa main study37
also assessed the use of ozone for 10 seconds with
Clinical reversal of caries: primary dentition One and without a fissure sealant. No sealants were
full-text study assessed the use of ozone for the reported to be lost in either the ozone plus sealant
treatment of non-cavitated primary posterior teeth group or the sealant-only group. The percentage
in children aged 79 years.38 Occlusal lesions were of partial loss in the ozone plus sealant group at
assigned to receive ozone for 10 seconds followed 12 months was 32.7%, and in the sealant-only
by a reductant or a reductant only. The proportion group was 29.8%, with no significant differences
of lesions that improved, remained stable or between groups (this indicates similar rates of
deteriorated in each intervention group was not reinterventions between groups for repairing
20 provided and the clinical severity findings were partial sealant loss).
Health Technology Assessment 2006; Vol. 10: No. 16

Discussion of results and multilevel modelling procedures would need to


be used.
conclusions on the evidence for
and against the intervention Baysan and Lynch36 stated that statistical tests
Only a limited number of RCTs (five full-text were used, but they did not specify which
reports and five studies reported as abstracts) were particular tests. Holmes used 2 tests, but did not
available for assessing the effects of ozone for the specify whether they were McNemar 2 tests.
management of root carious lesions and pit and Abu-Nabaa37 (main and pilot studies) recognised
fissure carious lesions. Of these only one was the fact that there were pairs of teeth. However, in
published in a refereed journal, but lacked some some cases there were multiple pairs of teeth per
study details, while the remaining studies were person and it is not clear whether this was taken
derived from PhD theses, unpublished reports or into account. Abu-Salem38 used analysis of
conference proceedings. All full-text studies with variance for a mixed effects model. This type of
the exception of the Holmes study were conducted analysis is hierarchical in nature, with one
by the same research team that developed the component for the patients and one for the tooth
procedure, led by Professor Lynch of Queens within the patient. However, as not enough
University, but Holmes was at one time part of the information was provided by the author it was not
same group, having done his PhD in Belfast. The possible to determine whether the statistical
methodological quality varied across studies and analysis was conducted appropriately.
information on method of randomisation,
concealment of allocation, blinding procedures For primary non-cavitated root caries both the
and statistical methods was lacking in many of Holmes study35 and the Baysan and Lynch study36
them. Therefore, interpretation of studies results reported high success rates for ozone-treated
was not straightforward. A quantitative synthesis of lesions compared with control lesions. However,
results was not feasible owing to the differences the lack of reversal of caries among controls
among studies regarding intervention, dosage of receiving conventional treatment (reductant)
ozone and outcome measures. known to be efficacious is puzzling.

Cavitated root lesions did not seem to benefit


There were some concerns over the from ozone application, showing indeed a
appropriateness of the methods of analysis negative effect over time, but no formal statistical
adopted by study investigators. All studies in this analysis was presented.
review were of a hierarchical structure, although
not necessarily treated as such for analysis. Treatment results of pit and fissure caries of
Specific types of analysis are required when data permanent teeth were not consistent across
have a hierarchical structure. The hierarchy occurs studies. The Abu-Nabaa main study did not show
as smaller units, such as lesions or teeth, are any significant differences between non-cavitated
clustered together within a larger unit, the patient. lesions treated with or without ozone. Similarly,
In most studies included in this review, the the Abu-Nabaa pilot study,37 which included
statistical analysis was carried out at the lesion lesions with cavitation, did not demonstrate any
level. However, two lesions within one patient are significant effect of ozone apart from an
not strictly independent, so analysis at the lesion improvement in the hardness and visual clinical
level is inappropriate. A more suitable statistical indices. In contrast, results from conference
analysis takes into account the hierarchical proceedings (methodologically less reliable)
clustering of lesions within a subject.59 provided very high success rates (from 86.6% to
100% of reversal of caries).
In the simple case of two lesions per person, one
receiving control and one receiving the ozone Data on the use of ozone for the treatment
treatment, paired data are produced. In this case, of primary teeth were available from only one
the appropriate paired analysis would be a study, which suggested an overall reduction in
McNemar 2 test for dichotomous data, clinical severity scores for non-cavitated occlusal
a Wilcoxon signed rank test for ordinal data and lesions in primary molars treated with ozone
a paired t-test for continuous data. The choice of (p < 0.01).38
statistical tests that ignore the pairing of the data
is more conservative and may fail to detect The adjunct of ozone to a fissure sealant produced
important differences found by paired analysis.59 a better sealant retention in root carious lesions
In the case of more than two lesions per subject, (61% of sealant retention versus 42%, p < 0.05),36 21

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Effectiveness

but not in pit and fissure carious lesions (32.7% Important subgroup differences
versus 29.8%).37 There are not enough data on which to assess the
effects of ozone on cavitated caries in the
On the whole, and despite the differences permanent dentition (both occlusal caries and root
reported in some studies (e.g. Holmes), there are caries) or on non-cavitated occlusal caries in the
as yet insufficient published full-text studies (only deciduous dentition (only one study involved
one refereed journal article) to provide convincing children with primary teeth38). No data are
evidence on the effectiveness of ozone for the available on cavitated occlusal caries in deciduous
management of caries. teeth, secondary caries or high-risk patient
categories.
This review was done independently of the
Cochrane systematic review on ozone therapy for Adverse effects of intervention
the treatment of dental caries,60 which concluded None of the studies reported any adverse events in
that at present there is no reliable evidence on the the intervention group.
effectiveness of ozone applications to arrest or
reverse the decay process. The present version of
the Cochrane review does not include the Holmes
(2003) and Abu-Salem (2004) studies.

22
Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 4
Systematic review of economic evaluations
Methods results
summary of effectiveness and costs (point
Search strategies estimate and, if reported, range or standard
In addition to the electronic searches and deviation)
handsearches detailed in Chapter 3, a search of summary of cost-effectiveness/utility (point
the NHS Economic Evaluation Database (NHS estimate and, if reported, range or standard
EED) and the Health Management Information deviation)
Consortium was undertaken for economic sensitivity analysis
evaluations of ozone for dental caries. Details of conclusions as reported by the authors of the
the searches are provided in Appendix 1. study.

Studies that reported both costs and outcomes of Quality assessment


HealOzone compared with any of the comparators A single economist assessed the quality of included
were sought. The manufacturers submission to the studies using a published checklist.61 The
National Institute for Health and Clinical questions were set out on a standard form
Excellence (NICE) was also scanned for relevant generated before the review.
economic evidence.
Data synthesis
Inclusion and exclusion criteria Data from included studies were assessed and
To be included, studies needed to compare summarised by a single economist, and
HealOzone with any of the existing comparators interpreted alongside the results of the systematic
in terms of their costs and effectiveness. Studies review of effectiveness so that conclusions could be
reported in languages other than English were drawn on the relative efficiency of HealOzone
identified from the literature searches, but would compared with alternative treatments.
not be included in the review unless a structured
abstract was available from NHS EED. A single
economist assessed all abstracts for relevance. Full- Results
text papers were then obtained for all studies that
appeared potentially relevant and were formally The search revealed no published economic
assessed for relevance. evaluations of HealOzone. One published trial was
found which discussed the costs and effectiveness
Data abstraction of the management of primary root caries with
The following data were extracted for each HealOzone.35 However, since the cost information
included study: is limited to estimates of the total cost of dentistry,
with no detail of costs and consequences of the
study characteristics: alternatives, the study did not meet all of the
research question methodological criteria listed in Table 14 to be
study design classified as an economic evaluation and therefore
comparison was not further reviewed. Two abstracts
setting concerning studies on the costs and benefits of
basis of costing HealOzone for dental caries were found, but did
characteristics of the study population or of the not provide sufficient details of study design or
populations that formed the basis of data used data for the purpose of this review.62,63 However,
in a modelling exercise: the industry submission from KaVo Dental (August
numbers receiving or randomised to each 2004) provided an economic evaluation. The
intervention remainder of this section provides a summary and
dates to which data of effectiveness and costs critique of that submission.
relate
duration of follow-up for both effectiveness and The unpublished industry submission from KaVo
costs Dental Ltd, UK (KaVo: Clinical and cost 23

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Systematic review of economic evaluations

TABLE 14 Quality assessment of the economic evaluation presented in the industry submission by KaVo

Quality component Assessment and comments

1. Was a well-defined question posed in an answerable form? Yes


2. Was a comprehensive description of the competing Yes: current treatments were defined as:
alternatives given (i.e. can you tell who did what, to NC-PFC: sealants
whom, where and how often)? C-PFC: glass ionomer, composite resin and amalgam
restoration
RC: glass ionomer and composite resin restoration
3. Was there evidence that the programmes effectiveness Limited owing to short follow-up of included studies and
had been established? inability to compare/combine results from more than one
study owing to differences in study characteristics. None
of the studies used specifically considered C-PFC,
although the model does include such effectiveness data
based on assumptions outlined in the following critique
4. Were all the important and relevant costs and Yes: the base-case analysis assumes that the capital
consequences for each alternative identified? cost of HealOzone is borne by dental practices. This
assumption is varied for sensitivity analysis
5. Were costs and consequences measured accurately in Yes
appropriate physical units?
6. Were costs and consequences valued credibly? Not always: see critique of QALY estimation
7. Were costs and consequences adjusted for differential Yes: a discount rate of 3.5% was used
timing?
8. Was an incremental analysis of costs and consequences Yes: see critique
of alternatives performed?
9. Was allowance made for uncertainty in the estimates of Yes
costs and consequences?
10. Did the presentation and discussion of study results Yes
include all issues of concern to users?

C-PCF, cavitated pit and fissure caries; NC-PCF, non-cavitated pit and fissure caries; QALY, quality-adjusted life-year;
RC, root caries.

effectiveness of HealOzone for the treatment and Summary of the industry submission
management of dental caries, 2004) included an The submission by KaVo included a cost-
economic model of HealOzone compared with effectiveness analysis over a 5-year time horizon of
current treatment for non-cavitated pit and fissure HealOzone treatment versus current management
caries, cavitated pit and fissure caries, and root for non-cavitated pit and fissure caries, cavitated
caries. Both a base-case and a probabilistic analysis pit and fissure caries, and cavitated root caries.
were included. The submission comprised both a The current management treatments were defined
text document and supporting Excel spreadsheets. as follows:

Table 14 provides a summarised assessment of the non-cavitated pit and fissure caries: sealants
KaVo industry submission based on the ten critical cavitated pit and fissure caries: glass ionomer,
appraisal components.61 composite resin and amalgam fillings
root caries glass ionomer and composite resin
restorations.
Review of industry submission
These comparators were identified from the
The first part of this section provides a summary expert opinion of four dentists. The submission
of the methods and results from the economic does not consider preventive treatments such as
evaluation of HealOzone reported in the industry oral hygiene or advice on diet along with surface
submission. This is followed by a critical review of applications of fluoride and sealants as a
24 the evaluation. comparator. The intervention with HealOzone is
Health Technology Assessment 2006; Vol. 10: No. 16

defined as an initial treatment with HealOzone for either non-cavitated pit and fissure caries,
followed by 12 weeks of treatment with cavitated pit and fissure caries or root caries that
mineralising toothpaste, oral rinse and spray, with would be suitable for treatment with HealOzone.
the possible addition of restorative treatments. An This survey also asked dentists to estimate the
opinion survey of 243 dentists practising proportion of HealOzone-treated teeth that would
HealOzone treatment was used to estimate the require some restorative treatment either at the
proportion of teeth that would require additional time of HealOzone treatment or sometime
restorative treatment at the same time as the afterwards. These restorative treatments were
HealOzone application or at any time defined similarly to current management
subsequently, but only 48 provided usable treatments for each caries type.
responses.
The unit cost of HealOzone treatment was based
Effectiveness data were obtained from a review of on the cost of patient consumables and dentists
published evidence for HealOzone and the time (in practice, a dentist is remunerated by a fee
current management of dental caries. Clinical per item of service as listed in the SDR and these
outcomes included caries progression and reversal. fees are intended to reflect the costs incurred by
dental practices). Using the results of a
Costs included those of comparators plus costs of questionnaire survey of dentists who use
rerestorations avoided. The costs of each current HealOzone in their own dental practice the
treatment comparator were estimated from estimated unit cost for a course of HealOzone-
published data for the treatments defined above. treatment was then adjusted to reflect the
All cost data were estimated from the perspective estimated percentages of HealOzone-treated teeth
of the NHS and were presented in UK pounds that would require additional restorative
sterling () at 2003 prices. Their method was to treatment. On the basis of responses to this
translate the treatments into relevant treatment questionnaire an additional cost of restoration
codes listed in the Statement of Dental (using current management in addition to
Remuneration (SDR codes)64 and then to use HealOzone) was applied to 44% of non-cavitated
GDS65 data to identify the total annual numbers of pit and fissure caries, 84% of cavitated pit and
such treatments. These data are presented fissure caries and 47% of root caries.
separately for patients aged less than 18 years and
those aged 18 years and over. The same source The cost to the NHS of HealOzone also took into
(GDS) gives annual total treatment costs which, account the proportion of treatment fees paid by
when combined with annual treatment numbers, the NHS rather than by patients as described
gave a unit cost per treatment item. These figures above for current treatment costs. The unit cost
were adjusted to take account of SDR codes for a course of HealOzone procedure was based on
relating to more than one tooth and more than an assumption of more than one HealOzone
one type of caries. The unit cost estimates do not application per course of treatment. The model
appear to differentiate between primary used a mean of 2.5 HealOzone applications per
restorations on virgin tooth surfaces and course of treatment (range 14). This was based
secondary restorations, the latter being outside the on data from KaVo Dental.
scope of the study since these would be unsuitable
for treatment with HealOzone. Finally, these unit An additional cost was added to reflect the
cost estimates were adjusted to reflect the fact that weighted average cost per tooth year of
patients under 18 years receive free NHS dental rerestorations avoided. This was based on data
care and those aged 18 years and over pay 80% of from a study that reported the average cost per
their NHS dental fees, unless they are eligible for tooth year of restoration in teeth previously filled
free treatment. It was assumed that the dental with amalgam or composite resin for each type of
practice and not the NHS would fund the capital caries over 5 and 10 years. When calculating the
cost and running cost of the actual HealOzone cost of rerestorations avoided the costs of the
device. original restoration are removed to avoid double
counting.66
Using these unit cost estimates the industry model
assesses the annual cost to the NHS for each The model uses rates of caries progression and
comparator. To estimate the annual cost to the regression taken from a variety of unpublished
NHS of the HealOzone comparator the industry and published clinical studies. The mean values
submission carried out a survey of dentists to for annual rates of caries progression for the
estimate the proportion of teeth currently treated current treatments assumed in the industry 25

Queens Printer and Controller of HMSO 2006. All rights reserved.


Systematic review of economic evaluations

submission, along with the study reference from caries reversal per 100 cases treated with
which these values were obtained, are: non- HealOzone were reported, with an estimated NHS
cavitated pit and fissure caries 0%,67 cavitated pit cost case of per caries reversal of 7.38, again for
and fissure caries 4.9%,6870 and root caries all caries types.
3.9%.68,69
The estimated minimum utility gain (at 0.095) to
The progression rates cited for HealOzone were achieve a cost per QALY of 30,000 was found to
all 0%, taken from studies with follow-up of be for the use of HealOzone for root caries
321 months.35,40,42,44,53,71,72 treatment. This was estimated using alternative
cost-effectiveness acceptability thresholds based on
Caries reversal rates for non-HealOzone varying the length of time over which a utility gain
treatments were assumed to be zero. The industry was accrued.
submission does cite a 15% reversal rate found in
a study reporting the use of varnish Sensitivity analysis indicated that the main drivers
(chlorhexidine), but this value was excluded from of cost and cost-effectiveness were numbers of
the industry submission on the grounds that such teeth treated per treatment session and the
varnish is not cited in the SDR codes. Rates of numbers of treatments per course of therapy.
caries reversal in teeth treated with HealOzone Multivariate analysis revealed that despite
were derived from 11 studies with follow-up times uncertainty around the cost of HealOzone,
ranging from 3 to 21 months. The annualised HealOzone would be likely to be cost-effective
mean values used for base-case analysis were: non- over a 10-year follow-up period.
cavitated pit and fissure caries 93.3%,53,55 cavitated
pit and fissure caries 79.0%,7277 and root caries The report also discusses the wider implications to
84.5%.35,40,42,44,57,71 the NHS, impact on patient health and equity
issues. The results of the economic evaluation are
Although no evidence was available to estimate used to estimate the budget impact to the NHS
underlying QALY scores, the industry submission from the use of HealOzone technology for all
model estimated alternative cost per QALY caries treatment of all eligible teeth. The figures
thresholds of between 10,000 and 40,000 include both initial treatment costs and the
assuming quality of life benefits from 1 day to estimated costs of rerestorations avoided. On this
1 month. The assumptions for QALY estimates basis, an annual net incremental cost of 48.1
were utility gains of 0.01, 0.02, 0.05 and 0.1 for million in year 1, reducing to 11.8 million by
restorations avoided. year 5, was estimated for HealOzone. These
results assume that the capital and running
The model was run to provide results using base- costs of the HealOzone device are funded by
case data. The deterministic base-case analysis dental practices, with no contribution from the
used mean values from the minimum and NHS apart from the fee for service. If the
maximum values inputted for each parameter. exchequer provided additional funds for the
Both one-way analysis and multivariate sensitivity device this would cost the NHS an additional
analysis were also conducted. Stochastic analysis 110.4 million, assuming one device per dental
was conducted using Monte Carlo simulation over practice in England and Wales. Additional
10,000 cycles. Random numbers were used to annual servicing costs are estimated at 10.8
select data inputs from those provided. million.

Results Although the evaluation does not include patient


The average baseline figure estimated in the health as an outcome in the model, the results
industry model, across all caries types, for the include a brief description of possible effects on
incremental cost to the NHS per tooth treated patient health, based on studies of patient
with HealOzone was 6.24. Allowing for the cost attitudes to dental treatment.
of rerestorations avoided (see earlier description),
the net incremental cost per tooth treated with Equity issues are also briefly discussed in the
HealOzone was minus 9.70. The industry model results. The report cites evidence suggesting a link
also resulted in an estimated NHS cost of 61 per between caries incidence and deprivation, and
case of caries progression avoided (for all caries that deprived populations would be one group less
types) using a 5-year model time horizon, and likely to benefit from HealOzone technology as
assuming up to 35 cases per 1000 avoided per long as it is only available through private dental
26 year (152 over 5 years). An estimated 846 cases of treatment.
Health Technology Assessment 2006; Vol. 10: No. 16

Critique of industry submission practices would be offset by lowering subsequent


On the whole, the economic evaluation submitted fees paid to dentists for the associated therapy.
by KaVo Ltd is based on reasonable economic
evaluation methodology. Nevertheless, a number Estimates of caries progression and reversal rates
of concerns can be raised relating to the choice of were extracted from a range of studies of varying
comparators and the quality of data used to degrees of quality, including published and
parameterise the economic model. unpublished RCTs, conference abstracts and PhD
theses. Some of the limitations of these data
The comparators used in the industry submission sources are discussed in Chapter 3. Caries
for non-cavitated caries were based on restorative progression rates for current management were
treatment of caries. The evaluation did not extracted from studies that did not include
consider preventive measures for early caries. HealOzone as a comparator and the patient mix
However, the management of non-cavitated caries may be different. Caries progression rates for
rarely requires fillings, as it is now well established HealOzone were estimated from studies with
that preventive treatments for early lesions can be follow-up periods from as little as 3 months, all of
effective in reversing and arresting further which claimed a 0% caries progression rate. Other
progression of caries. Furthermore, HealOzone studies show higher caries progression rates.
has been cited as being most effective in the role Selecting the most favourable studies biases the
of prevention and early management of lesions.78 results.
It would therefore have been appropriate for the
industry model to include conservative treatments Rates of caries reversal with current management
aimed at ensuring reversal of early caries as were assumed to be zero despite a 15% reversal
additional comparators for non-cavitated caries. rate being reported in one study. This rate was
excluded from the analysis on the grounds that it
The HealOzone comparator includes an was associated with the application of
assumption about the proportions of teeth that chlorhexidine varnish and this was assumed by the
would require additional treatment to HealOzone authors of the industry report not to be a standard
treatment alone. These assumptions are taken NHS dental treatment. However, dentists
from a survey of 243 dentists who currently use commonly rank application of varnish among
HealOzone, of whom only 48 provided usable treatments for sensitive cementum or dentine
responses. Given the absence of robust, objective (code 3631 in the SDR).
clinical data, options to obtain relevant model
parameter values are limited. Nonetheless, such Source data for caries reversal associated with the
data are potentially biased and unreliable and the use of HealOzone came from 14 studies, three of
considerable uncertainty would be reduced if which had follow-up of less than 3 months. Only
actual clinical evidence were to exist. This was a the latter were included in the sensitivity analysis.
non-randomised survey of opinion and cannot The remaining 11 studies differed in design and
therefore be interpreted as having a strong quality. For non-cavitated pit and fissure caries
evidence source. It does not appear that any effectiveness data were extracted from studies with
random selection process was used to recruit 36-month follow-up.53,55 For cavitated pit and
dentists for the survey, and therefore it is unclear fissure caries, despite finding no available
whether any attempt was made to obtain a evidence, data from five studies were used in the
balanced opinion. model. The assumption used to justify this is the
following:
The industry evaluation of implications to the
NHS includes an assumption about the numbers None of the available studies specifically describes
of teeth suitable for treatment with HealOzone. the treatment of cavitated pit and fissure caries. In the
These figures were again estimated from absence of such detail, the studies presented in this
section refer to carious lesions, which are deemed to
information taken from a survey of dentists who
require drilling and filling. While non-cavitated caries
are users of HealOzone.
may be treated in this way, drilling and filling is the
conventional treatment for cavitated caries and it is
The assumption concerning the funding of the therefore assumed that these studies included a
capital cost of providing a HealOzone device in proportion of cavitated caries. (KaVo Dental, 2004).
dental surgeries was that this would not affect the
fee for service. In reality, however, it would be A further concern is that, although the industry
expected that any additional contribution by the submission report does acknowledge the limitation
NHS towards capital costs incurred by dental of combining data from more than one study, 27

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Systematic review of economic evaluations

given the disparity in inclusion/exclusion criteria the figures used should be interpreted with care.
and other study characteristics, the reversal rates Realistically, such data could only be obtained
and progression rates used as the mean rates for from the outcomes of a long-term study of the
base-case analysis were calculated using the results effectiveness of the relevant comparators. QALY
from more than one study. estimates are included in the economic evaluation,
but are not based on quality of life data. Instead,
Estimates of the cost of rerestorations avoided assumptions concerning the amount of utility gain
are based on a number of assumptions and the and duration of gain were used to derive QALY
report does acknowledge the absence of thresholds. Given the short duration of any
published data for rates of future rerestorations. potential intermittent change in quality of life,
Instead, the model uses published data for the along with the high degree of uncertainty
average cost per tooth year of rerestoration in surrounding any estimates of QALY scores, the
teeth previously filled with amalgam or additional information value of such QALY
composite resin over 5 and 10 years (KaVo thresholds is dubious.
industry submission, 2004). It is unclear in the
report exactly how estimates of the numbers of Although the economic evaluation in the industry
future rerestorations would be avoided as a submission is well presented, the choice of
result of HealOzone treatment, although the comparator is questionable and considerable
report does provide estimates for the cost of such uncertainty surrounds many of the parameter
rerestorations avoided. Given the considerable values used in the model. Therefore, their results
uncertainty surrounding the rate of rerestorations, overestimate the benefits of HealOzone.

28
Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 5
Economic analysis
iven the current state of the clinical management of dental caries. A Markov model is
G effectiveness evidence, with little published in
full in peer-reviewed journals, it could be argued
composed of a set of defined health states among
which a patient can move over successive periods
that economic analysis is premature. However, and is run using a hypothetical cohort of patients.
NICE always requests some attempt at economic The model incorporates both the logical and
appraisal, if only to clarify the data deficits. temporal sequences of treatment, including the
Therefore, the following analysis has been events that follow from the initial treatment
produced more as illustrative modelling than as procedure and the outcomes for the patient that
hard evidence. are associated with each possible scenario or
clinical pathway. Transition probabilities are used
to allow patients to move within and between
Methods for economic analysis these states of health. A patient can only be in one
state of health at any time and can only make one
The economic evaluation aimed to assess the cost- transition per cycle. A relevant period is chosen
effectiveness of HealOzone relative to the for the length of a cycle and the cycles then link
alternative interventions for the treatment of both together to form a Markov chain. The length of
occlusal pit and fissure caries and root caries. As cycle used in this study was 1 year. When the
identified in the previous section, economic model is run over the defined number of cycles, a
evaluations of HealOzone versus conventional discounted net present value (NPV) for the cost of
treatments of dental caries were virtually non- an intervention is calculated, determined by the
existent at the time of this review. This section occurrence of different states and the length of
provides an economic evaluation using cost- time in various states.
effectiveness analysis and presents economic
models of the treatment of non-cavitated pit and The models were designed to estimate a typical
fissure caries, and root caries. They compare patients costs and outcomes for the alternative
current management versus current management treatments over a 5-year period. A 5-year time
plus HealOzone. The results over the extended horizon was chosen to facilitate comparison with
period must be qualified by the fact that follow-up the results from the industry model. Figure 10
data on HealOzone are limited to 2 years. The summarises the basic structure of the model.
results reported in this section should be Similar models were developed to carry out the
interpreted on the understanding that they analysis for non-cavitated pit and fissure caries,
entirely depend on the model parameters and and non-cavitated root caries
assumptions made. The authors recommend that
the model be rerun in the future if evidence on Non-cavitated pit and fissure caries
clinical effectiveness is published. The model for non-cavitated pit and fissure caries
compares current management strategies (i.e.
Markov model framework watchful waiting, oral hygiene/removal of plaque,
This section presents a description of the Markov fluoride applications and sealants) versus the same
model developed for the assessment, and of the strategy plus HealOzone.
parameters that were common across all models.
Key parameters specific to each model and Non-cavitated root caries
results are then presented separately for each The model for non-cavitated root caries compares
comparator. The section concludes with a current management strategies (i.e. removal of
summary of the results for all comparators and of plaque, topical fluorides, chlorhexidine and a
the factors deemed to be most critical in affecting sealant) versus the same strategy plus HealOzone.
the results.
Model pathways
Markov modelling techniques were used to assess The pathways for each model were developed in
the cost-effectiveness of HealOzone plus current accordance with the protocol for the assessment
management, relative to the standard current along with expert opinion from members of a 29

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Economic analysis

Early caries initial


treatment

Current management (watchful Current management plus


waiting, oral hygiene/plaque HealOzone
removal, fluoride, sealants)

Reversal of caries Reversal of caries


Progression of caries

Initial treatment
Tooth filled repeated

Progression of caries Reversal of caries

Tooth filled

FIGURE 10 Model for primary non-cavitated pit and fissure caries

local dental school. All models have simplified 5-year timescale of the model, and that a typical
clinical event pathways, but are designed to reflect filling would last longer than 5 years, no states
those clinical events of importance to the beyond filling were included. It was assumed that
evaluation (Figures 1518 in Appendix 6). once a tooth was cured it remained in a cured state
for the rest of the 5 years. TREEAGE DATA 4.0
Non-cavitated pit and fissure caries and root software (TREEAGE Software, 2001) was used to
caries construct the model.
Following initial treatment carious lesions may
either reverse or not reverse. Lesions that do not Estimation of parameters
show reversal of caries progression after the initial Probabilities
intervention require additional treatment. This is a The time horizon considered in the Markov model
further application of the initial preventive/non- was a maximum of 5 years. The outcome
restorative treatment or a restorative treatment (i.e. considered in the economic evaluation was the
drilling and filling). In those receiving further numbers of carious lesions cured. The main
preventive/non-restorative treatments, caries can probabilities used in the model were the rates of
again be reversed or treated with filling (Figure 10). reversal (cure) of caries. These rates were derived
The event pathway is split into two mutually from the effectiveness study (Chapter 3) and
exclusive events, the reversal (cure) of caries and consultation with dental practitioners. The
no reversal of caries. The arrows between these probability of cure rates (Table 15) obtained from
states represent the possible transitions between the effectiveness studies and used in the first run
them. Movement between the different states is of the economic model were: HealOzone 0.074
governed by the transition probabilities, such as (7.4%) for the non-cavitated pit and fissure
the chance of the caries reversing. The absorbing caries37 and 0.98 (98%)35 for the non-cavitated
state in this model is a tooth with a filling. While root caries. The rates used for current
30 this is not an absorbing state in reality, given the management were 0.056 (5.6%)37 for non-
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 15 Probabilities used in the economic model

Intervention Probability Source

HealOzone cure rate (non-cavitated pit fissures) 0.074 Table 11, Chapter 3
Current management cure rate (non-cavitated pit fissures) 0.056 Table 11, Chapter 3
HealOzone cure rate (non-cavitated root caries) 0.98 Table 9, Chapter 3
Current management cure rate (non-cavitated root caries) 0.01 Table 9, Chapter 3
Percentage being retreated with initial treatment 0.50 Discussions with expert
Percentage being retreated with filling 0.50 Discussions with expert

TABLE 16 Unit cost per itema

Type Current treatment (SDR code) Cost ()

Non-cavitated pit and fissure caries


Hygiene/diet advice (0601) 7.70
Chlorhexidine gel/varnish or fluoride varnish (3631) 4.60
Fissure sealant (0701) 6.95
Total (sum of above) 19.25
Non-cavitated root caries
Hygiene/diet advice (0601) 7.70
Chlorhexidine gel/varnish or fluoride varnish (3631) 4.60
Total (sum of above) 12.30
Cavitated pit and fissure caries
Sealant only (1441) 6.95
Composite resin (1442) 9.80
Glass-ionomer (1443) 10.55
Amalgam (1401 or 1421) 7.15
(posterior)
14.15
(anterior)
Total (average of above) 16.98
HealOzone (No SDR code) 20
(estimate)
a
Costs are those that would be incurred by the NHS and exclude patient contributions to dental fees. Further details of
cost calculations are presented in Appendix 6.

cavitated pit and fissure caries and 0.01(1%) for Costs


non-cavitated root caries.35 These values, which The perspective adopted for the study is that of
are highly favourable to HealOzone, were different the NHS and Personal Social Services. The unit
to those used in the industry model, which costs of dental treatments were taken directly from
aggregated data from a number of studies, some cost data published by the NHS.65 Table 16
of which did not meet the inclusion criteria provides details of the different treatments with
specified in this review. In the absence of any corresponding codes from the NHS SDR for each
alternative information, it was assumed for the treatment item. Unit costs are listed for each
purposes of the model that, following initial treatment item and represent the fee paid by the
treatment, there was a 0.50 (50%) chance of NHS to the dentist for each item of service.
subsequent treatment being the same treatment as
the initial one received or a filling. Resource-use data were identified from existing
literature, reports from manufacturers and advice
The root caries cure rates are taken from the from experts in this field. Based on existing
Holmes study,54 the results of which seem evidence and clinical opinion, patients were
puzzling; they reflect a best possible case for assumed to visit the dentist every 6 months. Cost
HealOzone. data were measured in pounds sterling () for the 31

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Economic analysis

TABLE 17 Weighted average costs used in the modela

Cost ()

Intervention Under 18 Over 18 Weighted

Current management
Non-cavitated pit and fissure caries 19.25 7.70 9.02
Non-cavitated root caries 12.30 4.92 6.09

Current management plus HealOzone


Non-cavitated pit and fissure caries 39.25 15.70 20.03
Non-cavitated root caries 32.30 12.92 17.10

Restorative interventions
Filling 19.67 7.87 12.75
a
Costs are those that would be incurred by the NHS excluding patient contributions to dental fees.

year 2004. As specified by the guidelines for In the absence of separate effectiveness data for
conducting health technology assessment, cost- adults and children it was decided to combine all
effectiveness results should reflect the present age groups for the base-case analysis. A two-stage
value of the stream of costs and benefit accruing process was required to weight the unit costs to
over the time horizon of the analysis.79 To make represent a mixed population of adults and
the analysis consistent with the model used in the children. Further details of the stages involved in
industry submission the analysis was carried out the cost calculations are reported in Appendix 6.
over a period of 5 years. An annual discount rate Published statistics65 indicate that adults and
of 3.5% was applied to both costs and benefits children do not receive similar proportions of each
accrued, the rate currently specified in the HTA treatment item among the different treatment
guidelines.79 items listed in Table 16. The first stage was
therefore to calculate the percentage mix of
The per-item fee for service paid by the NHS was children and adults for each identified SDR
used as a proxy for costs to the NHS of current component of the treatment. These proportions
management. Under the current NHS dental were then weighted by the amount that the NHS
system patients pay 80% of the dentists fee, with contributed using the figures described earlier, at
the remaining 20% being paid by the exchequer 100% of the amount of a claim per child and 40%
(except that there is a maximum charge for a per adult. Following this two-stage weighting
course of dental treatment of 366). Some process, the adjusted costs to the NHS used in the
patients, including all those less than 18 years old, model were 9.02 for the non-cavitated pit and
are entitled to free treatment and the exchequer fissure caries and 6.09 for non-cavitated root
pays the full cost of treatment. Recent figures caries, and a filling was estimated at 12.75.
report that 25% of all claims for patients aged 18 Details of the costs are included in Table 17.
years and over were exempt from patient
charges.65 The other 75% of claims for patients The costs of HealOzone were calculated using the
aged 18 and over therefore include a patient existing NHS methods and information from the
contribution at 80% of the amount of the claim manufacturer. Most of the studies indicated that
and an NHS contribution of 20%. Taking these HealOzone treatment is given at the start, and
data into account, the average net NHS repeated at 3 and 6 months. The cost of
contribution equates to 40% [25% + (20% of HealOzone therefore took into account that
75%)] of any NHS dental claim for patients aged patients could receive between one and three
18 and over. As children (persons under 18 years applications. The cost of HealOzone treatment
of age) are exempt from paying NHS dental also included that of current management as
treatment fees, the full cost of all claims for those HealOzone was considered as an additional
less than 18 years old was used as the cost to the treatment and not as a stand-alone treatment. The
NHS. The data used in the industry model weighted average cost of current management
indicated that the NHS contribution to those aged plus HealOzone treatment used in the model was
32 18 and over was 52%. 20.03 for non-cavitated pit and fissure caries and
Health Technology Assessment 2006; Vol. 10: No. 16

17.10 for non-cavitated root caries. These values HealOzone and 0.01% were filled. The present
were not similar to those used in the industry authors remain sceptical about these results.
model as they focused on costs and benefits to the
NHS in England and Wales as a whole, rather Sensitivity analysis
than on costs and benefits faced by the average There was very little suitable evidence on the
patient. effectiveness of the HealOzone comparator. One-
way sensitivity analysis was applied to the model to
Quality of life assess the robustness of the results to variations in
It was not possible to measure health benefits in the underlying data. The probability of caries
terms of QALYs. This was mainly because the being cured was varied for each comparator
adverse events avoided are transient: a few separately, using the baseline cure rate for the
seconds pain from injection of local anaesthetic; alternative comparator. These results indicated
the anxiety/fear of having a drill and numbness that when higher probability cure rates were used
until the local anaesthesia wears off. the proportion of teeth filled was lower at
12 months. These results were similar to those of
Sensitivity analysis the Cochrane review by Ahovuo-Saloranta and
As every economic analysis contains some degree colleagues.32 However, as the focus of the
of uncertainty, imprecision or methodological Cochrane review was on the prevention of dental
controversy, and this one more than most, a decay in the permanent teeth of children and
sensitivity analysis was performed. Given the adolescents, the extrapolation of its results to an
limited effectiveness data for estimating rates of adult population with dental caries might be
caries reversal, the models were rerun using questionable.
different probability values of reversal of caries.
Assumptions were also made about what items to The results of the one-way sensitivity analyses are
include in each of the interventions and sensitivity illustrated in Figures 1114 and presented in
analysis was performed using different codes to tabular form in Appendix 6 (Tables 2932).
determine the costs, namely the SDR codes used
in the industry submission. In Figure 11 the costs refer to those of current
management when the baseline cure rates of
HealOzone are used (0.074). The discounted NPV
Results for the cost of HealOzone was 40.49. The above
results indicate that the discounted NPV of the
The analysis, carried out over a 5-year period cost of the HealOzone comparator, using baseline
using the data reported in the trials, indicated that parameter values for HealOzone, was higher than
treatment using current management plus that of current management at any probability of
HealOzone cost more than current management cure with current management. This is mainly
alone for non-cavitated pit and fissure caries attributable to the fact that the baseline cure rate
(40.49 versus 24.78), but cost less for non- used in the model is less than 10%. The results
cavitated root caries (14.63 versus 21.45). For also indicate that as the probability of cure rate
non-cavitated pit and fissure caries 91.8% of the increases, the cost reduces and the number of
teeth treated using current management received teeth filled also reduces.
a filling and 8.2% of teeth were cured. For teeth
treated with current management plus In Figure 12 the costs refer to those of HealOzone
HealOzone, 89.2% received fillings and 10.8% plus current management when the baseline
were cured. This was different from the results of annual cure rate of current management is used
the Cochrane review by Ahovuo-Saloranta and (0.056). The discounted NPV for the cost of
colleagues,32 which reported that the reduction in current management was 24.78. Varying the
caries ranged from 86% at 12 months to 57% at probability of the cure rates of HealOzone plus
4854 months. This review focused, however, on current management, and using the baseline cure
the prevention (and not the treatment) of tooth rate probability for current management,
decay in children and adolescents who presented indicated that the HealOzone option was always
with no obvious caries. Based on the Holmes more expensive than current management when
study,54 1.5% of teeth were cured at 5 years in the the probability of cure using the HealOzone
non-cavitated root caries group treated with option was 70% or lower.
current management and 98.5% teeth were filled,
while 99.9% of teeth were cured by the In Figure 13 the costs of HealOzone reflect the
combination of current management and costs when the baseline probability of cure of 33

Queens Printer and Controller of HMSO 2006. All rights reserved.


Economic analysis

45.00

40.00

35.00
Current management
30.00
HealOzone
NPV ()

25.00

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of current management cure rate

FIGURE 11 One-way sensitivity analysis for non-cavitated pit and fissure caries: discounted NPV of each comparator at alternative
cure rates for current management, holding the baseline cure rate for HealOzone plus current management constant

45.00
Current management
40.00 HealOzone

35.00

30.00
NPV ()

25.00

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of HealOzone cure rate

FIGURE 12 One-way sensitivity analysis for non-cavitated pit and fissure caries: discounted NPV of each comparator at alternative
cure rates for HealOzone plus current management, holding the baseline cure rate for current management constant

current management (0.01) was used and the In Figure 14 the costs of current management reflect
probability of cure of HealOzone management was the costs when the baseline probability of cure of
varied accordingly. The one-way sensitivity analysis HealOzone (0.98) was used and the probability of
results show that discounted NPVs for the costs of cure of current management was varied accordingly.
current management plus HealOzone were lower The discounted NPVs for the costs of current
than those of current management only when cure management were higher than those of current
rates from current management plus HealOzone management plus HealOzone when the cure rate
34 were at least 80% and above. for current management was 40% or lower.
Health Technology Assessment 2006; Vol. 10: No. 16

45.00
Current management
40.00
HealOzone
35.00

30.00

25.00
NPV ()

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of HealOzone cure rate

FIGURE 13 One-way sensitivity analysis for non-cavitated root caries: discounted NPV of each comparator at alternative cure rates
for HealOzone plus current management, holding the baseline cure rate for current management constant

25.00

Current management

20.00 HealOzone

15.00
NPV ()

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of current management cure rate

FIGURE 14 One-way sensitivity analysis for non-cavitated root caries: discounted NPV of each comparator at alternative cure rates
for current management, holding the baseline cure rate for HealOzone plus current management constant 35

Queens Printer and Controller of HMSO 2006. All rights reserved.


Economic analysis

TABLE 18 Industry submission model inputs for annual treatment items and cost for patients under 18 years of agea

Procedure SDR code Unit cost ()

Non-cavitated pit and fissure caries


Fissure sealant: sealant only 1441 6.50
Fissure sealant: composite resin 1442 9.15
Fissure sealant: composite resin and glass ionomer 1444 13.71
Root caries
Composite/synthetic: one filling 1421 13.22
Composite/synthetic: two or more fillings 1421 10.32
Glass ionomer: one filling 1426 12.08
Glass ionomer: two or more fillings 1426 8.22
a
The current costs of treatment were estimated using the GDS treatment items reported for the year ending March 2003
(KaVo Dental Ltd, industry submission, 2004, p. 62).

One-way sensitivity analysis was also carried out therefore, the results should be regarded mainly as
using similar SDR codes to those used in the illustrations of the key variables and hence
industry submission. Table 18 shows the SDR codes interpreted cautiously as they reflect the
used by the industry for patients under 18 years of parameter values and assumptions used in the
age. The figures for those over 18 years were model. A further constraint was the lack of long-
similar. This did not alter the results for non- term data on the effectiveness of HealOzone (it is
cavitated pit fissure caries as the discounted NPV not known whether caries that is reversed will
of current management remained lower than that always stay in the inactive/arrested state or
of the HealOzone comparator (22.65 versus whether future treatments will be required). To
33.39). These results could be attributed to the attempt to model longer term effects the available
fact that it was assumed that patients received the 12-month data were extrapolated to 5 years. It is
same treatment as the initial one and the cost of not known at this stage whether this assumption is
current management plus HealOzone is much valid. Another possible area of uncertainty was
higher than that of current management alone, related to whether the response to HealOzone
given that HealOzone is an additional treatment treatment would increase with increasing dose
rather than an alternative treatment. Results using levels.
the SDR codes used for non-cavitated root caries
in the industry model gave similar results to those It was not possible to model the treatment of
in the base-case analysis. HealOzone cost less than cavitated caries since no effectiveness data on
current management (17.66 versus 30.41). direct comparisons were available. The analysis
was carried out on a hypothetical cohort of teeth
with carious lesions and did into take into account
Discussion the proportion of teeth that are unsuitable for
HealOzone treatment. Further research is
The economic analysis was greatly constrained by therefore necessary to support a complete
the uncertainty over clinical effectiveness; economic evaluation.

36
Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 6
Implications for the NHS
National Service Framework was estimated that there were 294 HealOzone
units in the UK (at June 2004). Were ozone
The majority of general dental practitioners in the therapy to be made available, provision of
UK are contracted to the NHS through GDS, HealOzone units would have to be increased much
although, as independent contractors, dentists beyond this to allow all suitable patients fair access
who offer NHS treatment may also offer certain to the treatment.
treatments on a private basis. Dentists receive
fixed fees per item of treatment for adults, while
for children they receive a combination of fixed
fees per item and capitation fees. Under this NHS
Equity issues
system patients can pay up to 80% of the cost of The availability of HealOzone treatment is
their treatment up to a maximum cost of around currently limited to those people who are able
366. Some patients are entitled to free NHS and willing to pay for the treatment privately.
dental treatment, including children, young However, in the present state of knowledge, it
people in full-time education, pregnant women cannot be said that people suffer by being unable
and those with a child under 1 year old, and to afford it.
people on low incomes. The costs of running a
dental practice, including capital costs of
equipment, are met by the dental practice rather
than the NHS, and recovered from the fee for
Budget implications to the NHS
service charges paid by the patients and the NHS. At present, HealOzone is only available to patients
In addition to dentists contracted to provide NHS through private dental care. The aim of this
treatment, some of whom also offer private section is to estimate what the implications would
treatment, there are many dentists in the UK who be to the NHS if HealOzone were made available
only provide treatment on a private basis. as an NHS dental service.
Currently, HealOzone treatment is only available
as a private treatment from a limited number of The models used in the economic evaluation
dentists. described in Chapter 5 considered the costs and
effectiveness of current treatment with and without
the addition of HealOzone for arresting the
Health targets progression of dental caries (further details of
these cost calculations are presented in Appendix
There are no specific health targets, although in 6). The evaluation does not consider those teeth
England the Department of Health set a target to with carious lesions, which would be unsuitable for
reduce tooth decay in 5-year-olds to low levels by HealOzone therapy. These could be considered in
2003, while in Wales the official target was to the estimated implications to the NHS for the
achieve no more than 48% of 5-year-olds having total population of teeth with carious lesions if
tooth decay by 2002.80 estimated numbers of such teeth were available. To
achieve this it is necessary to make assumptions
The new Base Dental Contract (based on the about the proportion of teeth currently treated for
personal dental services model) will be introduced caries that would be suitable for alternative
for all practices in April 2006. The new contract HealOzone treatment. This proportion would be
will be more likely to have a greater preventive used to calculate the total annual number of
and capitation element.81 treated teeth.

Data from GDS provide statistics for the numbers


Fair access of teeth treated by SDR code in a year for adults
and children in England and Wales. At the time of
At the time of writing HealOzone treatment was writing the latest available GDS data were those
only available through private dental care and it pertaining to the year ending March 2003. 37

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Implications for the NHS

TABLE 19 NHS annual cost for treatment of non-cavitated pit and fissure caries

NPV of treatment cost over 5 years ()

Current management 8,565,765


HealOzone plus current management 13,996,280
Net difference in cost 5,430,515
Net difference in cost per tooth treated initially 15.71

TABLE 20 NHS annual cost for treatment of non-cavitated root caries

NPV of treatment cost over 5 years ()

Current management 7,371,882


HealOzone plus current management 5,876,885
Net difference in cost 1,494,997
Net difference in cost per tooth treated initially 4.35

The following results were calculated by difference in numbers of teeth filled at 5 years for
combining the GDS data with assumptions about the HealOzone comparator and current
the SDR codes relevant to each caries type to management (308,340317,327). The incremental
estimate annual numbers of teeth treated for non- cost per filling avoided, using these assumptions,
cavitated pit and fissure caries and non-cavitated would be estimated at 604.23.
root caries. Again, teeth with cavitated caries were
not considered given the absence of evidence on The industry submission estimates for the
the effectiveness of HealOzone as a comparator percentage of teeth currently treated that would
treatment for cavitated caries. be suitable for HealOzone, obtained from the
opinion of current users of HealOzone, were 92%
Non-cavitated pit and fissure caries for non-cavitated pit and fissure caries, 76% for
The discounted NPV for the cost over 5 years of cavitated pit and fissure caries, and 76% for root
teeth treated initially with current management or caries. These figures were derived from Table 15 in
HealOzone plus current management was the industry submission.
reported in Chapter 5. These figures were
combined with the numbers of teeth treated Non-cavitated root caries
initially using annual GDS data for the SDR codes The total discounted NPV over 5 years for treating
in the present treatment definitions. The results non-cavitated root caries, using the best case for
should, however, be interpreted with extreme HealOzone again, would be estimated at
caution given that they are based on the limited 7,371,882 for current management and
effectiveness data available for the economic 5,876,885 for HealOzone therapy. The net
analysis, as reported in Chapters 3 and 5 of this difference in these two costs shows that
report. HealOzone therapy would save the NHS 4.35 per
tooth treated initially with HealOzone in addition
The total discounted NPV over 5 years for treating to current management for root caries, a total cost
non-cavitated primary fissure caries was estimated saving over 5 years of 1,494,997 (Table 20).
at 8,565,765 for current management and
13,996,280 for HealOzone therapy (Table 19). These figures are estimated using base-case values
The base-case results showed that by 5 years for caries reversal rates. Limited suitable
fillings were present in 91.8% of teeth treated with effectiveness data were available for reversal rates
current management compared with 89.2% of of root caries, apart from a single study reporting
teeth treated with HealOzone plus current reversal rates of 1% for current management and
management. Using these figures the incremental 98% for HealOzone treatment. Given the extreme
cost per tooth treated would be 15.71, at an values of reversal rates for the comparators, based
initial total cost to the NHS of 5,430,515. The on the limited effectiveness data available at the
incremental cost over 5 years for the HealOzone time of analysis, these results need to be
comparator compared with current management interpreted with caution. It was only possible to
38 (13,996,2808,565,765 ) was divided by the carry out limited one-way sensitivity analyses,
Health Technology Assessment 2006; Vol. 10: No. 16

varying cure rates separately for the HealOzone on the tooth population. For example, it is
and current management comparators (see unknown how long an arrested carious lesion
Chapter 5). From the results of the sensitivity remains inactive. Any prospective trial should have
analyses it can be seen that the net difference in sufficient follow-up to allow for this.
cost per tooth treated initially was higher for
current management unless the probability of cure Importantly, the above results are based on the
for the HealOzone comparator was lower than authors assumptions for the management of the
approximately 80%. different types of caries.

It is advisable that the reader interprets all such In addition, it is difficult to estimate the actual
results merely as an illustration of possible cost of HealOzone to the NHS. Assuming that
scenarios. In the light of limited evidence on patients who pay some of their dental treatment
effectiveness, a more detailed analysis of budget fees are willing to pay no more than current
implications was not considered likely to add any treatment for the same condition initially, what
useful information to the evaluation. would the cost-effectiveness ratio be? Would
patients opt for this treatment if it was more
The cost implications over time are difficult to expensive?
ascertain since there are many uncertain factors to
take into account. Further research is required to Finally, would patients be given a choice for caries
model the cost implications over time, taking into management or would dentists have to follow
account the cost of rerestorations beyond the some guidelines about the best treatment? This
lifetime of first fillings and their effects over time has implications on the numbers of teeth treated.

39

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Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 7
Discussion
Main results removal of plaque by a dentist or hygienist), which
has been used effectively in the management of
Clinical effectiveness dental caries in adults. A recent study assessing the
The literature on ozone treatment is still at a outcomes of a 30-year preventive programme
relatively early stage, in the sense that only one based on professional and self-performed plaque
paper has been published in full in a refereed control has shown how high standards of oral
journal. Most of the reports are available only in hygiene are associated with a very low incidence of
abstract form, as conference proceedings, and dental caries and periodontal disease in adults.82
inevitably give few details. Many trials are still very
short term and none of the studies has followed Cost-effectiveness
up the patients after they have stopped ozone If HealOzone led to a reduction in future fillings,
treatment for a reasonable length of time. It is also then the extra cost might be justified. The authors
worthwhile remembering that caries is a dynamic do not believe that the evidence base yet supports
process: a lesion can remineralise without the that.
need for any intervention, and the rate of caries
progression can be very slow.
Need for further research
HealOzone is supposed to kill the microorganisms
(bacteria) responsible for dental plaque formation. Nearly all the research to date comes from the
However, unless patients have improved their same group who developed and pioneered the
plaque control and eliminated the causes of the procedure, and have the greatest experience in its
increased numbers of microorganisms, the plaque use. There is a need for large, well-conducted
will re-form and the lesion will progress again. RCTs to assess the effectiveness and cost-
This raises the question of whether HealOzone is effectiveness of HealOzone for the management of
a reasonable preventive technology. Furthermore, both occlusal and root caries. In particular, future
treatments based on HealOzone would need to be trials:
repeated for an indeterminate numbers of years to
be beneficial, with obvious cost implications. should be conducted by independent research
teams
The available evidence is conflicting, with the root should be properly randomised so that an equal
caries treatment showing much better results than number of lesions, or paired lesions, per mouth
treatment for pit and fissure caries. However, the are allocated to intervention groups
results are surprising, partly because the ozone should apply appropriate statistical methods for
group did so well, with 99% cure or improvement, the analysis of paired-data on a patient basis;
but mainly because the control group performed should use validated and reproducible criteria
very badly, despite receiving the same care for the assessment of caries
package (oral hygiene, topical fluoride, etc.) but should measure relevant outcomes such as
without the application of ozone. Compliance of reduction in caries incidence over a reasonable
patients with treatment, however, was not assessed period (at least 2 years, but realistically much
in the included studies. longer)
should mask participants and outcome assessors
In particular, it proved difficult to identify the should provide both a statistical and a clinical
additional role of ozone gas from the patient kit interpretation of their findings
or the synergistic effect between ozone and the should conform to the CONSORT guidelines
patient kit, which contained, among other for the reporting of RCTs.83
elements, fluoride and xyliton. It would have been
useful, for example, to know the effects of ozone Owing to the natural history of the caries process,
alone, namely ozone gas, together with the any future trial would need to include a very long
patients normal brushing or how HealOzone follow-up, which would have a significant impact
compares to professional plaque control (the on trial costs. 41

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Discussion

There also appears to be a need for evaluation of It should be based on data from properly
the different methods of assessing caries severity. conducted RCTs of HealOzone versus
The base case could be clinical examination, with appropriate comparators (e.g. no treatment or
the marginal benefits and costs of more current management).
sophisticated techniques assessed. Although the Follow-up of patients should be long enough to
economic evaluation was not able to provide allow identification of both short-term and
results that could be used by decision-makers, it long-term resource use and effectiveness.
was a valuable exercise in highlighting the paucity Outcome data must include both short-term
of good quality data on key parameters. In and long-term rates of caries reversal, caries
particular, the paucity of suitable data from progression, retreatment and/or rerestoration.
published clinical trials comparing the Separate consideration is needed for cavitated
effectiveness of HealOzone with appropriate and non-cavitated caries.
comparators restricted the scope of the economic Sufficient power is needed to allow for robust
model. No comparable quality of life data were subgroup analyses for deciduous and
available for the comparators, thus limiting the permanent teeth, and for variation in caries
range of outcomes available for an evaluation. severity.
These gaps in the data needed to undertake an An estimate of the unit cost of HealOzone to
informative economic evaluation of HealOzone the NHS should be based on calculations
can only be filled through further research in the similar to those underlying the SDR figures for
form of prospective RCTs. current dental treatments provided by the NHS.
Factors affecting patients quality of life should
To provide adequate information to assess the be considered, both at the point of treatment
cost-effectiveness of HealOzone, any future and during follow-up (e.g. the effect on quality
economic evaluation of HealOzone should feature of life due to pain from toothache).
the following characteristics:

42
Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 8
Conclusion
ny treatment that preserves teeth and avoids conclude that it is a cost-effective addition to the
A fillings is welcome. However, the current
evidence base for HealOzone is insufficient to
management and treatment of occlusal and root
caries.

43

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Health Technology Assessment 2006; Vol. 10: No. 16

Acknowledgements
rateful thanks to Heather Mackintosh for her joint venture between the Health Services
G secretarial support. Research Unit at Aberdeen and the Medical Care
Research Unit at Sheffield University forms the
The views and opinions expressed are those of the Review Body for Interventional Procedures
authors and do not necessarily reflect those of the (ReBIP) Programme within NICE. ReBIP
funding bodies. undertakes systematic reviews and, where
appropriate, establishes UK registries to collect
Publication information and analyse data on the efficacy and safety of
The Aberdeen Health Technology Assessment selected procedures.
Group is part of the Institute of Applied Health
Sciences (IAHS). The Institute of Applied Health Contribution of authors
Sciences within the College of Medicine and Life Miriam Brazzelli (Research Fellow) and Shona
Sciences of the University of Aberdeen is made up Fielding (Medical Statistician) completed the
of discrete but methodologically related research review of effectiveness. Lynda McKenzie (Research
groups. The HTA Group is drawn mainly from the Fellow) conducted the review of economic
Health Services Research Unit, the Department of evaluations. Lynda McKenzie and Mary Kilonzo
Public Health and the Health Economics (Research Fellow) conducted the economic
Research Unit. evaluation. Cynthia Fraser (Information Scientist)
developed and ran the search strategies. Norman
The HTA Group carries out independent health Waugh (Professor of Public Health) provided
technology assessment reports (TARs) for the UK oversight and contributed to drafting the review.
HTA Programme, which commissions TARs for Jan Clarkson (Honary Consultant in Paediatric
the National Institute for Health and Clinical Dentistry) provided clinical advice and
Excellence (NICE) and other bodies, such as the commented on the draft review.
National Screening Committee. In addition, a

45

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Health Technology Assessment 2006; Vol. 10: No. 16

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URL: http://iadr.confex.com/iadr/2004Hawaii/
Rev 2004; Issue 3. Art. No. CD001830. DOI
techprogram/abstract_47326.htm.
10.1002/14651858.CD001830.pub2.
45. Abu-Nabaa LA, Al Shorman HM, Stevenson M,
33. Dental Practice Board. Dental review of the general
Lynch E. Ozone treatment of pit and fissure caries:
and personal dental services of the NHS. 20022003
6-month results. 32nd Annual Meeting of AADR,
[monograph on the Internet]. URL:
San Antonio, Texas, March 2003 [conference
http://www.dpb.nhs.uk/. Accessed July 2004.
proceedings on the Internet].
34. Verhagen AP. The Delphi list: a criteria list for URL: http://iadr.confex.com/iadr/2003SanAnton/
quality assessment of randomized clinical trials for techprogram/abstract_27269.htm.
conducting systematic reviews developed by the
46. Abu-Nabaa LA, Al Shorman HM, Lynch E. Ozone
Delphi consensus. J Clin Epidemiol 1998;
treatment of primary occlusal pit and fissure caries:
51:123541.
12 month clinical severity changes. Caries Res 2003;
35. Holmes J. Clinical reversal of root caries using 37:272.
ozone, double-blind, randomised, controlled
47. Abu-Nabaa LA, Al Shorman HM, Lynch E. Ozone
18-month trial. Gerodontology 2003;20:10614.
treatment of primary occlusal pit and fissure caries:
36. Baysan A, Lynch E. Management of root caries 12 month electrical impedance results and clinical
48 using ozone. KaVo Dental Ltd website. implications. Caries Res 2003;37:272.
Health Technology Assessment 2006; Vol. 10: No. 16

48. Abu-Nabaa LA, Al Shorman HM. 6-months fissure DIAGNOdent measurements. J Oral Rehabil 2004;
sealant retention over ozone-treated occlusal caries. 31:8959.
IADR/AADR/CADR 82nd Annual Conference,
59. Macfarlane TV, Worthington HV. Some aspects of
Honolulu, Hawaii, March 2004 [conference
data analysis in dentistry. Community Dent Health
proceedings on the Internet].
1999;16:21619.
URL: http://iadr.confex.com/iadr/2004Hawaii/
techprogram/abstract_45125.htm. 60. Rickard GD, Richardson R, Johnson T, McColl D,
Hooper L. Ozone therapy for the treatment of
49. Abu-Nabaa LA, Al Shorman HM, Lynch E. Ozone
dental caries. Cochrane Database Syst Rev 2004;
management of occlusal pit & fissure caries (PFC): 12
Issue 3. Art. No. CD004153. DOI
month review. DentalOzone website. London: Dental
10.1002/14651858.CD004153.pub2.
Clinique. URL: http://www.dentalozone.co.uk/
research4.html. 61. Drummond M, OBrien B, Stoddard G, Torrance
G. Critical assessment of economic evaluation. Methods
50. Abu-Nabaa LA, Al Shorman HM, Lynch E. Ozone
for the economic evaluation of health care programmes.
efficacy in the treatment of pit and fissure caries.
Oxford: Oxford University Press; 1997.
J Dent Res 2003;82(Special Issue C):C-535.
pp. 2751.
51. Abu-Nabaa LA, Al Shorman HM, Lynch E. Clinical
62. Johnson N, Johnson J, Lynch E. Cost benefit
indices changes in ozone treatment of pit and
assessment of a novel ozone delivery system vs
fissure caries. 32nd Annual Meeting of AADR, San
conventional treatment. 32nd Annual Meeting of
Antonio, Texas, March 2003 [conference
AADR, San Antonio, Texas, March 2003
proceedings on the Internet].
[conference proceedings on the Internet].
URL: http://iadr.confex.com/iadr/2003SanAnton/
URL: http://iadr.confex.com/iadr/2003SanAnton/
techprogram/abstract_27273.htm.
techprogram/abstract_27588.htm.
52. Abu-Nabaa LA, Al Shorman HM, Lynch E.
63. Domingo H, Holmes J, Abu-Nabaa LA,
6-month clinical indices changes after ozone
Al Shorman HM, Baysan A, Freeman R.
treatment of pit and fissure caries (PFC). 81st
Economic savings treating root caries with ozone.
Annual Conference of IADR, Goteberg, Sweden,
DentalOzone website. URL:
June 2003 [conference proceedings on the
www.dentalozone.co.uk/research6.html. Accessed
Internet]. URL: http://iadr.confex.com/iadr/
August 2004.
2003Goteborg/techprogram/abstract_35236.htm.
64. Amendment 92 to the Statement of Dental Remuneration
53. Holmes J, Lynch E. Reversal of occlusal caries using
[document on the Internet]. UK Department of
air abrasion, ozone and sealing. IADR/AADR/CADR
Health. URL: http://www.dh.gov.uk/assetRoot/
82nd Annual Conference, Honolulu, Hawaii, March
04/08/11/28/04081128.pdf. Accessed July 2004.
2004 [conference proceedings on the Internet].
URL: http://iadr.confex.com/iadr/2004Hawaii/ 65. General dental services statistics. Dental Practice
techprogram/abstract_47218.htm. Board website. URL: http://www.dpb.nhs.uk/gds/
index.shtml. Assessed July 2004.
54. Holmes J. Clinical reversal of occlusal pit and
fissure caries using ozone. 81st Annual Conference 66. NHS Centre for Reviews and Dissemination. Dental
of the International Association for Dental restorations: what type of filling? Effective Health
Research, Goteberg, Sweden, June 2003. Care 1999;5(2):112.
55. Hamid A. Clinical reversal of occlusal pit and 67. Florio FM, Pereira AC, Meneghim MC, Ramacciato
fissure caries using ozone. IADR/AADR/CADR 82nd JC. Evaluation of non-invasive treatment applied to
Annual Conference, Honolulu, Hawaii, March 2004 occlusal surfaces. Journal of Dentistry for Children
[conference proceedings on the Internet]. URL: 2001;68:32631.
from: http://iadr.confex.com/iadr/2004Hawaii/
68. Qvist V, Laurberg L, Poulsen A, Teglers PT.
techprogram/abstract_47414.htm.
Eight-year study on conventional glass ionomer and
56. Megighian GD, Bertolini L. In-vivo reversal of amalgam restorations in primary teeth. Acta Odontol
occlusal caries with ozone after six months. Scand 2004;62:3745.
DentalOzone website. London: Dental Clinique.
69. Vilkinis V, Horsted-Bindslev P, Baelum V. Two-year
URL: http://www.dentalozone.co.uk/research8.html.
evaluation of class II resin-modified glass ionomer
Accessed August 2004.
cement/composite open sandwich and composite
57. Lynch E, Johnson J, Johnson J. Clinical reversal of restorations. Clinical Oral Investigation
root caries using ozone. DentalOzone website. London: 2000;4:1339.
Dental Clinique.
70. Qvist V, Laurberg L, Poulsen A, Teglers PT.
URL: http://www.dentalozone.co.uk/research7.html.
Longevity and cariostatic effects of everyday
Assessed August 2004.
conventional glass-ionomer and amalgam
58. Kuhnisch J, Ziehe A, Brandstadt A, Heinrich- restorations in primary teeth: three-year results.
Weltzien R. An in vitro study of the reliability of J Dent Res 1997;76:138796. 49

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References

71. Baysan A, Lynch E. Effect of ozone on the oral 77. Megighian GD, Bertolini L, De Pieri A, Lynch E.
microbiota and clinical severity of primary root In-vivo treatment of occlusal caries with ozone:
caries. American Journal Dentistry 2004;17:5660. one and two months effect with light induced
fluorescence (QLF) as diagnostic methods. 81st
72. Morrison R, Lynch E. Remineralization of occlusal
Annual Conference of the International Association
pit and fissure caries after using ozone. 32nd
for Dental Research, Goteberg, Sweden, June 2003
Annual Meeting of AADR, San Antonio, Texas,
[conference proceedings on the Internet]. URL:
March 2003 [conference proceedings on the
http://iadr.confex.com/iadr/2003Goteborg/
Internet]. URL: from:http://iadr.confex.com/iadr/
techprogram/abstract_36918.htm.
2003SanAnton/techprogram/abstract_27482.htm.
73. Stinson P, Al Shorman HM, Abu-Nabaa LA. 78. Healozone Users Congresses. July 2003 [document
Lynch E. Clinical reversal of occlusal pit and fissure on the Internet]. HealOzone website.
caries after using ozone. 32nd Annual Meeting of URL: http://www.the-o-zone.cc/O3cong.doc.
AADR, San Antonio, Texas, March 2003 Accessed April 2004.
[conference proceedings on the Internet].
79. National Institute for Clinical Excellence. Guide to
URL: http://iadr.confex.com/iadr/2003SanAnton/
the methods of technology appraisal (reference N0515).
techprogram/abstract_27499.htm.
London: NICE, 2004.
74. Cronshaw MA. Treatment of primary occlusal pit
and fissure caries with ozone: six-month results. 80. Primary dental care services in England & Wales
81st Annual Conference of the International [document on the Internet]. London: Audit
Association for Dental Research, Goteberg, Sweden, Commission; 2002. URL: http://www.audit-
June 2003 [conference proceedings on the commission.gov.uk/. Assessed August 2004.
Internet]. URL: http://iadr.confex.com/iadr/
81. NHS Dentistry: next steps in local commissioning
2003Goteborg/techprogram/abstract_34889.htm.
[document on the Internet]. London: UK
75. Domingo H, Abu-Nabaa LA, Al Shorman HM, Department of Health; 2004.
Holmes J, Marashdeh M, Abu-Salem O, et al. URL: http://www.dh.gov.uk/assetRoot/
Reducing barriers to care in patients managed with 04/08/68/59/04086859.pdf. Accessed
ozone. 32nd Annual Meeting of AADR, San August 2004.
Antonio, Texas, March 2003 [conference
proceedings on the Internet]. 82. Axelsson P, Nystrom B, Lindhe J. The long-term
URL: http://iadr.confex.com/iadr/2003SanAnton/ effect of a plaque control program on tooth
techprogram/abstract_27392.htm. mortality, caries and periodontal disease in adults.
Results after 30 years of maintenance. J Clin
76. Holmes J, Lynch E. Clinical reversal of occlusal Periodontol 2004;31:74957.
fissure caries using ozone. 81st Annual Conference
of the International Association for Dental 83. Moher D, Schulz KF, Altman D, for the CONSORT
Research, Goteberg, Sweden, June 2003 Group. The CONSORT statement: revised
[conference proceedings on the Internet]. recommendations for improving the quality of
URL: http://iadr.confex.com/iadr/2003Goteborg/ reports of parallel-group randomized trials. JAMA
techprogram/abstract_36308.htm. 2001;285:198791.

50
Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 1
Literature search strategies
Sources searched for systematic Search strategies used to identify
reviews, other evidence-based reports assessing ozone therapy
reports and background for dental caries
information MEDLINE (1966 to week 1 2004),
Databases EMBASE (1980 to week 20 2004),
Cochrane Database of Systematic Reviews (CDSR). (MEDLINE Extra 17 May 2004)
The Cochrane Library (Issue 2, 2004). Ovid Multifile Search.
Database of Abstracts of Reviews of Effectiveness URL: http://gateway.ovid.com/athens
(NHS Centre for Reviews and Dissemination), 1 (healozone or curazone).tw.
April 2004. 2 ozone/ (14334)
HTA Database (NHS Centre for Reviews and 3 (ozone or o3).tw.
Dissemination), April 2004. 4 (oxidat$ or oxidis$).tw.
Trip database. URL: http://www.tripdatabase.com/. 5 or/2-4
Accessed May 2004. 6 exp tooth demineralization/ use mesz
7 dental caries/ use emez
Websites 8 demineralization/ use emez
The Dental, Oral and Craniofacial Data Resource 9 Dental Caries Susceptibility/ use mesz
Center (DRC). URL: http://drc.nidcr.nih.gov/ 10 Dental Enamel Solubility/
default.htm. Accessed July 2004. 11 (caries or carious).tw.
National Center for Health Statistics. 12 ((tooth or teeth or dental or dentine or enamel
URL: http://www.cdc.gov/nchs/nhanes.htm. or root? or occlusal) adj5 decay$).tw.
Accessed July 2004. 13 ((tooth or teeth or dental or dentine or enamel
British Association for the Study of Community or root? or occlusal) adj5 cavit$).tw.
Dentistry. URL: http://www.bascd.org/ Accessed 14 ((tooth or teeth or dental or root? or dentine or
July 2004. occlusal or enamel or cavitated) adj5
KaVo Dental Ltd. URL: http://www.kavo.com/En/ lesion?).tw.
default.asp. Accessed April 2004. 15 ((tooth or teeth or dental or dentine or
CurOzone USA Inc. enamel) adj5 (minerali$ or deminerali$ or
URL: http://www.curozone.com/. Accessed April reminerali$)).tw.
2004. 16 or/6-15
DentalOzone. London: Dental Clinique. 17 1 or (5 and 16)
URL: http://www.dentalozone.co.uk/. Accessed 18 human/
April 2004. 19 animal/ use mesz
HealOzone. Dr Julian Holmes. URL: 20 nonhuman/ use emez
http://www.the-o-zone.cc/. Accessed April 2004. 21 (19 or 20) not 18
NHS Dental Practice Board. 22 17 not 21
URL: http://www.dpb.nhs.uk/gds/index.shtml. 23 remove duplicates from 22
Accessed July 2004.
Department of Health.
URL: http://www.dh.gov.uk/Home/fs/en.
Accessed April 2004.

51

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Appendix 1

Science Citation Index 1981 to 16 May AMED (1985 to May 2004)


2004) Ovid. URL: http://gateway.ovid.com/
Web of Science Proceedings 1990 to athens
15 May 2004) 1 (healozone or curazone).tw
Web of Knowledge. 2 (ozone or o3).tw.
URL: http://wok.mimas.ac.uk/ 3 (oxidat$ or oxidis$).tw.
#1 TS= (Healozone or curazone) 4 or/2-3
#2 TS= (ozone or o3) 5 (caries or carious).tw
#3 TS=(oxidat* or oxidis*) 6 ((tooth or teeth or dental or dentine or enamel
#4 #2 or #3 or root? or occlusal) adj5 decay$).tw
#5 TS=(caries or carious) 7 ((tooth or teeth or dental or dentine or enamel
#6 TS=((tooth or teeth or dental or dentine or or root? or occlusal) adj5 cavit$).tw
enamel or root* or occlusal) SAME decay*) 8 ((tooth or teeth or dental or root? or dentine or
#7 TS=((tooth or teeth or dental or root* or occlusal or enamel or cavitated) adj5 lesion?).tw
dentine or occlusal or enamel or cavitated) 9 ((tooth or teeth or dental or dentine or
SAME lesion*) enamel) adj5 (minerali$ or deminerali$ or
#8 TS=((tooth or teeth or dental or dentine or reminerali$)).tw
enamel or root* or occlusal) SAME cavit*) 10 or/5-9
#9 TS=(( tooth or teeth or dental or dentine or 11 1 or (4 and 10)
enamel) SAME (minerali* OR deminerali* 12
OR reminerali*))
#10 #5 OR #6 OR #7 OR #8 OR #9 Cochrane Library Issue 2, 2004
#11 #4 AND #10 URL: http://www.update-software.com/
#12 #1 OR #11 clibng/cliblogon.htm
National Research Register
BIOSIS (1985 to 12 May 2004) (Issue 2, 2004)
Edina. URL: http://edina.ac.uk/biosis/ URL: http://www.update-
(tn: (humans)) and (((al: (healozone)) or al: software.com/National/
(curazone)) or ((((al: (oxidat*)) or al: (oxidis*)) or #1. (healozone or curazone)
((al: (ozone)) or al: (o3))) and ((((((al: (caries)) or #2. OZONE single term (MeSH)
al: (carious)) or ((((al: (root n5 decay*)) or al: #3. (ozone or o3)
(roots n5 decay*)) or (((al: (dentine n5 decay*)) or #4. (oxidat* or oxidis*)
al: (enamel n5 decay*)) or al: (occlusal n5 #5. (#2 or #3 or #4)
decay*))) or (((al: (tooth n5 decay*)) or al: (teeth #6. TOOTH DEMINERALIZATION explode
n5 decay*)) or al: (dental n5 decay*)))) or ((((al: tree 1 (MeSH)
(root n5 cavit*)) or al: (roots n5 cavit*)) or (((al: #7. DENTAL CARIES SUSCEPTIBILITY single
(dentine n5 cavit*)) or al: (occlusal n5 cavit*)) or term (MeSH)
al: (enamel n5 cavit*))) or (((al: (tooth n5 cavi*)) #8. DENTAL ENAMEL SOLUBILITY single
or al: (teeth n5 cavit*)) or al: (dental n5 cavit*)))) term (MeSH)
or (((((al: (root n5 lesion*)) or al: (roots n5 #9. (caries or carious)
lesion*)) or (((al: (dentine n5 lesion*)) or al: #10. ((tooth or teeth or dental or dentine or
(enamel n5 lesion*)) or al: (occlusal n5 lesion*))) enamel or root* or occlusal) and decay*)
or (((al: (tooth n5 lesion*)) or al: (teeth n5 #11. ((tooth or teeth or dental or dentine or
lesion*)) or al: (dental n5 lesion*))) or (al: enamel or root* or occlusal) and cavit*)
(cavitated n5 lesion*)))) or ((((((al: (tooth n5 #12. ((tooth or teeth or dental or dentine or
minerali*)) or al: (tooth n5 reminerali*)) or al: enamel or root* or occlusal or cavitated) and
(tooth n5 deminerali*)) or (((al: (teeth n5 lesion*)
mineral*)) or al: (teeth n5 reminerali*)) or al: #13. ((tooth or teeth or dental or dentine or
(teeth n5 deminerali*))) or (((al: (dent* n5 enamel) and (mineralis* or demineralis* or
minerali*)) or al: (dent* n5 reminerali*)) or al: remineralis*))
(dent* n5 deminerali*))) or (((al: (enamel n5 #14. ((tooth or teeth or dental or dentine or
minerali*)) or al: (enamel n5 reminerali*)) or al: enamel) and (mineraliz* or demineraliz* or
(enamel n5 deminerali*)))))) remineraliz*))
#15. (#6 or #7 or #8 or #9 or #10 or #11 or
#12 or #13 or #14)
#16. (#5 and #15)
52 #17. (#1 or #16)
Health Technology Assessment 2006; Vol. 10: No. 16

DARE, NHS Economic Evaluation IARD/AADR/CADR 82nd General Session,


Database and HTA Databases Honolulu, March2004
(April 2004) AADR 32nd Annual Meeting and Exhibition, San
NHS Centre for Reviews and Antonio, March 2003
Dissemination IADR 81st General Session, Goteberg 2003
URL: http://nhscrd.york.ac.uk/ IADR, Irish Division Annual Meeting, Belfast,
welcome.htm 2004
Ozone or healozone or oxid* - all fields BSDR Ann Scientific Meeting, Birmingham, April
Dental or caries or carious all fields 2004

Clinical Trials (18 May 2004) ozone or healozone or oxid*


URL: http://clinicaltrials.gov/ct/gui/c/r
Current Controlled Trials (18 May Handsearching
2004)
URL: http://www.controlled-trials.com/ Journal of Dental Research
Ozone or healozone or oxid* all fields Vol. 79 (Special Issue 2000): 78th General Session
of IADR, Washington, USA, April 2000.
Health Management Information Vol. 79(5) 2000: British Section: Annual Scientific
Consortium (May 2004) Session, Lancaster, UK, April 2000; Irish Section:
1 (healozone or curazone).tw. Annual Scientific Meeting, Newcastle, Ireland,
2 dental caries/ January 1999.
3 (caries or carious).tw. Vol. 80 (Special Issue, AADR Abstracts, January
4 ((tooth or teeth or dental or dentine or enamel 2001): 30th Annual Meeting AADR/25th Annual
or root? or occlusal) adj1 decay$).tw. Meeting CADR, Chicago, USA, March 2001.
5 ((tooth or teeth or dental or dentine or enamel Vol. 80(4) (April 2001): British Society for Dental
or root? or occlusal) adj1 cavit$).tw. Research and Irish Division, Continental
6 ((tooth or teeth or dental or dentine or enamel European (1999 and 2000).
or cavitated) adj1 lesion?).tw.
7 ((tooth or teeth or dental or dentine or Caries Research
enamel) adj1 (minerali$ or deminerali$ or Vol. 37(4): 50th Annual ORCA Congress, Konstanz
reminerali$)).tw. Germany, July 2003.
8 or/1-7 Vol. 36(3): 49th Annual ORCA Congress, Naantali
9 limit 8 to yr=1995 2004 Finland, July 2002.
Vol. 35(4): 48th Annual ORCA Congress, Graz,
Conference Papers Index (1982 to Austria, July 2001.
May 2002) Vol 34(4): 47th Annual ORCA Congress, Alghero,
Cambridge Scientific Abstracts Sardinia, July 2000.
URL: http://www.csa1.co.uk/
KW=(healozone or curazone) or (KW=(ozone or
oxidat* or oxidis*) and KW=(caries or carious or Websites
dental)) or (KW=(ozone or oxidat* or oxidis*)
and KW=(teeth or tooth or cavit*)) or KaVo Dental Ltd. URL: http://www.kavo.com/En/
(KW=(ozone or oxidat* or oxidis*) and default.asp. Accessed April 2004.
KW=(occlusal or decay* or lesion*)) CurOzone USA Inc.
URL: http://www.curozone.com/. Accessed April
Zetoc Conference Search (1993 to 2004.
May 2004) DentalOzone. London: Dental Clinique.
MIMAS URL: http://zetoc.mimas.ac.uk/ URL: http://www.dentalozone.co.uk/. Accessed
Ozone or healoaone or oxid* and (conference: April 2004.
dental or dentist or caries) HealOzone. Dr Julian Holmes.
URL: http://www.the-o-zone.cc. Accessed April
IADR Meeting abstracts 2004.
URL: http://www.iadr.com/Meetings/
index.html
IARD/AADR/CADR 80th General Session, San
Diego, March 2002 53

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Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 2
Data extraction form
HEALOZONE TECHNOLOGY ASSESSMENT REVIEW

DATA EXTRACTION FORM

Reviewer ID: Date information extracted:

Study Details

Study ID: _____________________________________________

Study identifier: _______________________________________


(Surname of first author + year of publication)

Study origin: _________________________________________

Language: ____________________________________________

Published Unpublished

Full text Abstract only

Study Design

RCT Other __________________________________________

Quasi RCT

Observational Study

For RCTs only: What is the unit of randomisation?

Patient

Tooth/lesion

Tooth/lesion pair

55

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Appendix 2

Participants

Number of eligible patients: Number of patients randomised:

Inclusion criteria: Exclusion criteria:

Interventions

Type of intervention Number of participants

Group 1:

Group 2:

Group 3:

Patient Characteristics

Intervention 1 Intervention 2 Intervention 3 Total


Age (mean, range)
Sex (M/F)
Permanent/Deciduous teeth
Primary or Secondary caries
Comparability at baseline

Characteristics of the intervention

Location of trial centre(s):

Source of participants:

Method of recruitment:

56
Health Technology Assessment 2006; Vol. 10: No. 16

Method of randomisation:

Dosage of HealOzone application:

Repeated applications:

Was a reductant applied? If yes, what was its formulation?

Did patient receive the aftercare kit (e.g. toothpaste, mouth rinse and spray)?

Length of follow-up:

Compliance with the treatment:

Number lost to follow-up:

Caries Information

Method of caries examination:

Tooth location, lesion location, and type of lesion:

Severity of caries:

Outcomes

Intervention 1 Intervention 2 Intervention 3


Non-cavitated caries

Reversal of caries

Progression of caries

Utilisation of dental resources

57

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Appendix 2

Adverse reactions

Patientcentred measures (e.g. patient


satisfaction and preference, relief of
pain/discomfort)

Quality of life

Cavitated caries

Time to restorative interventions

Need for further restorative


interventions

Symptoms of pulpal pathology

Other comments

58
Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 3
Checklist for the quality assessment of randomised
controlled trials
(adapted from Verhagen, 199834)

Criteria Yes No Unclear Comments

1. Was the assignment to the treatment groups really random?


Adequate approaches to sequence generation
computer-generated random tables

random number tables

Inadequate approaches to sequence generation


use of alternation, case record numbers, birth dates or week days

2. Was the unit of randomisation clear?


3. Was the treatment allocation concealed?
Adequate approaches to concealment of randomisation
centralised or pharmacy-controlled randomisation

serially-numbered identical containers

on-site computer based system with a randomisation sequence that is

not readable until allocation


other approaches with robust methods to prevent foreknowledge of

the allocation sequence to clinicians and patients


Inadequate approaches to concealment of randomisation
use of alternation, case record numbers, birth dates or week days

open random numbers lists

serially numbered envelopes (even sealed opaque envelopes can be

subject to manipulation)
4. Were the groups similar at baseline in terms of prognostic factors?
5. Were the eligibility criteria specified?
6. Were the groups treated in the same way apart from the
intervention received?
7. Was the outcome assessor blinded to the treatment allocation?
8. Was the care provider blinded?
9. Were the patients blinded?
10. Were the point estimates and measures of variability presented
for the primary outcome measures?
11. Was the withdrawal/dropout rate likely to cause bias?
12. Did the analyses include an intention-to-treat analysis?

59

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Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 4
Characteristics of included studies:
full-text reports

61

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62
TABLE 21 Characteristics of full-text reports

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
Appendix 4

of participants and criteria


carious lesions

Root caries: permanent dentition


Baysan and Lynch, n =79 (220 primary Design: RCT Two or four Group 1: cleaning of the Reversal of caries, groups 1 and 2: The number of lesions in
200436,4144 cavitated and non- (unpublished) primary non- tooth surface, application of at 12 months 47% of PRCLs each intervention group was
(Belfast, UK) cavitated root carious cavitated and O3 + reductant reversed from severity index 1 to not clearly reported
Unit of
lesions) cavitated root The procedure was 0 (hard) in the ozone group,
randomisation: All subjects enrolled in the
carious lesions repeated after 1 month while none became hard in the
Age, mean SD (range): lesion study received preventive
with severity without ozone and at control group (p < 0.001). 52%
65 14.76 (3072) years advice, including oral
Method of index II 3 months with ozone of lesions reversed from 2 to 1 in
hygiene and dietary advice,
Gender (M/F): 49/30 randomisation: (leathery the ozone group compared with
Group 2: reductant only. and were given a toothbrush
NS lesions) 11.6% in the control group
Tooth and lesion location: The procedure was and toothpaste (Natural
root surface lesions. (p < 0.001)
Concealment of repeated after 1 month and White, Natural White Inc.,
allocation: NS at the 3-month follow-up Cavitated lesions in the ozone USA, 1100 ppm F)
Caries risk assessment:
NS group did not show the same
Blinding: unclear Group 3: O3 + sealant (Seal Unclear whether cleaning of
& Protect, Dentsply, trend of improvement of non-
the root surface was
ITT: no cavitated lesions. Percentage of
Germany) performed before treatment
Length of follow- lesions that became hard
The procedure was in groups 2, 3 and 4
up: 12 months decreased from 9.1 at 1 month to
repeated at 3 months. 1.4 at 9 months, suggesting It was reported that subjects
Lost at follow-up: Sealants were reapplied only worsening of cavitated carious who presented with any
five subjects if a partial or complete loss lesions. Data for the control form of discomfort were
of the sealant was suspected group were not given immediately treated with
Comparability of
groups at Group 4: sealant only (Seal conventional drilling and
Marginal adaptation of the root
baseline: unclear & Protect, Dentsply, filling procedures, but no
sealant (modified USPHS criteria):
Germany) further information was
Setting: general 61% intact sealants in the
Sealants were reapplied provided
dental practices O3 + sealant group compared
after 1 and 3 months only if with 26.1% in the sealant-only Methods for statistical
a partial or complete loss of group (p < 0.001) analyses not clearly
the sealant was suspected reported. Unclear whether
Significant differences in the
Reductant formulation: the results were adjusted
changes in both the ECM readings
Sodium fluoride (1100 ppm for covariates/risk factors
and DIAGNOdent readings in the
F), xylitol, sodium benzoate, ozone and control groups Emphasis on non-cavitated
among other active (p < 0.001) lesions
ingredients
Ozone dosage: 10 seconds Adverse events: none observed

continued
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Caries assessment: ECM III


(Lode Diagnostics BV, The
Netherlands), DIAGNodent
(KaVo, Germany) and
clinical criteria. The severity
of lesions was assessed on a
four-point scale (0 = hard
lesions; 4 = soft lesions). In
addition, modified USPHS
criteria were used for
assessing groups 3 and 4
Assessors/operators: single
operator (A. Baysan)
Ozone device output: NS

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continued
Health Technology Assessment 2006; Vol. 10: No. 16

63
64
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
Appendix 4

carious lesions

Holmes, 200335,39,40 n = 89 (178 primary non- Design: RCT Adults with Group 1: application of O3 18 months follow-up. All subjects enrolled in the
(Berkshire, UK) cavitated root carious two leathery + reductant + patient care study received information
Unit of Reversal of caries: 87/87 lesions in
lesions, 89 lesions in each non-cavitated kit on oral hygiene, brushing
randomisation: the ozone group reversed
group) PRCLs techniques and diet. In
lesion Group 2: air treatment + (became hard) compared with
particular, all subjects
Age, mean SD (range): reductant only + patient 1/87 in the control group
Method of received instructions on
70.8 6 (6082) care kit (p < 0.01)
randomisation: how to use the
Tooth and lesion computer- Repeated applications of O3 Progression of caries: 32/87 remineralising toothpaste
location: leathery roof generated + reductant at 3, 6, 12 and lesions in the control group twice a day, the mineral
surface lesions (severity random tables 18 months worsened from leathery to soft mouthwash twice a day and
index II) and 54/87 did not change the remineralising spray four
Concealment of Reductant formulation:
Caries risk assessment: xylitol, fluoride, calcium, Adverse events: none observed times a day
allocation: NS
NS phosphate and zinc (no All subjects were offered a
Blinding: double
concentrations provided) pharmacological treatment,
blind
Ozone dosage: 40 seconds which they all accepted as
ITT: no an alternative to the
Caries assessment: ECM traditional drilling and filling.
Length of follow-
(Lode Diagnostics BV, The No details of the
up: 3, 6, 12, 18
Netherlands), DIAGNodent pharmacological treatment
and 21 months
(KaVo, Germany) and were provided
Lost at follow-up: visual/tactile examination
two at 18 months method The two dentists who
allocated subjects to
Comparability of Assessors/operators: the intervention groups and
groups at ozone treatment was assessed severity of lesions,
baseline: unclear applied by a different and the third dentist who
operator to the one assessed reproducibility of
Setting: general
recording the severity of data, were not
dental practice
lesions. Unclear whether acknowledged in the paper
the operator who assessed
outcomes was the same one The 21-month findings
who did allocated subjects published in abstract format
to intervention groups. A (Holmes, 200440 seem to
contradict those reported in
sample of 15 subjects (30
the full text
lesions) was examined by a
third dentist to test
reproducibility of results
continued
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Ozone device output: it was


reported that the
HealOzone unit was fitted
with a modified control
integrated electronic chip.
Unclear whether this
modified chip could allow
better calibration and
monitoring of ozone doses

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continued
Health Technology Assessment 2006; Vol. 10: No. 16

65
66
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
Appendix 4

carious lesions

Pit and fissure caries: permanent dentition


Abu-Nabaa, 2003, n = 90 Design: RCT Males and Before treatment all lesions Groups 1 and 2 All subjects enrolled in the
main study37,4550 (258 primary occlusal pit (unpublished) females were disclosed and cleaned study received preventive
Reversal of caries: no significant
(Belfast, UK) and fissure carious >12 years old with an air-abrasive system advice and were given a
Unit of differences between groups in the
lesions) with primary (PROPHYflex 2, KaVo, toothbrush and toothpaste
randomisation: mean change from baseline:
occlusal pit Germany) (Natural White; Natural
Age: 79 subjects between lesion Group 1: 0.283 (0.64)
and fissure White Inc., UK, 1100 ppm F)
12 and 31 years, 8 Group 1: application of O3 Group 2: 0.443 (0.74);
Method of carious lesions
subjects between 32 and + reductant (p = 0.112) Sealant was reapplied if
randomisation: in at least two
41 years, and 3 subjects necessary and O3 application
random sampling teeth of the Group 2: reductant ECM values: no significant
>41 years repeated
digit tables permanent only/control differences in the mean change
Gender (M/F): 35/55 posterior from baseline values between Subjects attendance to
Concealment of Group 3: O3 + reductant +
dentition, groups: follow-up visits varied. The
Tooth and lesion location: allocation: NS fissure sealant (Guardian,
which were Group 1 (109 lesions): mean loge number of subjects assessed
all posterior teeth in the Kerr)
Blinding: unclear accessible for change 0.020 (1.4) by ECM differed from the
upper and lower jaws.
the diagnostic Group 4: reductant + Group 2 (109 lesions): 0.073 number of subjects assessed
Central grooves and pits ITT: no
procedures sealant (1.61) (p = 0.75) by DIAGNOdent at follow-
were the most commonly
Length of follow- up visits
observed lesions Reductant formulation: Excluding teeth with baseline
up: 1, 3, 6, 9 and
Sodium fluoride (1100 ppm ECM score 0:
Caries risk assessment: 12 months
F), xylitol and zinc chloride Group 1 (77 lesions): 0.327 (1.32)
NS
Lost at follow-up: among other active Group 2 (69 lesions): 0.073
32 subjects ingredients (1.37); p = 0.54
Comparability of Ozone dosage: 10 seconds DIAGNOdent values: no
groups at baseline: significant differences between
Caries assessment: ECM
more severe groups (p > 0.05) at any follow-
(Lode Diagnostics BV, The
lesions (index
Netherlands), DIAGNodent up visits
scores of 2 and 3)
(KaVo, Germany) and Groups 3 and 4
in the treatment
clinical severity (Ekstrand,
group (p = 0.055). Secondary caries: no significant
1998).9 In addition, modified
More molars in the differences between groups (two
USPHS criteria +
treatment group secondary caries in the ozone
radiographic assessments
than in the control group and two secondary caries
were used for assessing
group. in the control group)
groups 3 and 4
Setting: general
dental practice
continued
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Assessors/operators: three Sealant retention: partial loss in


operators were reported to the margins of the sealants in
assess radiographs. A single 32.7% in the O3 + sealant group
operator assessed the compared with 29.8% in the
lesions and interpreted ECM sealant-only group (p > 0.05)
and DIAGNOdent findings
(L. Abu-Nabaa) No significant differences in terms
of fissure sealant colour and
Ozone device output: NS
radiographic depth of
radiolucency between groups

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continued
Health Technology Assessment 2006; Vol. 10: No. 16

67
68
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
Appendix 4

carious lesions

Abu-Nabaa, 2003, n=8 Design: RCT Males and Before treatment all lesions Clinical severity scores: not All subjects enrolled in the
pilot study37,51,52 (38 occlusal pit and fissure (unpublished) females were disclosed and cleaned significant differences between study received preventive
(Belfast, UK) lesions, 19 in each group) >12 years old with an air-abrasive system groups at any follow-up visits advice and were given a
Unit of
with primary (PROPHYflex 2, KaVo, (p > 0.05) toothbrush and toothpaste
randomisation:
occlusal pit Germany) (1100 ppm F)
lesion ECM and DIAGNOdent readings:
and fissure
Group 1: application of O3 no significant differences between
Method of carious lesions
+ reductant groups (p > 0.05)
randomisation: in at least two
random sampling teeth of the Group 2: reductant only Clinical indices
digit tables permanent Hardness index score: 11 lesions
At 3 months group 1
posterior in the ozone group became
Concealment of received another application
dentition, harder compared with four in the
allocation: NS of O3
which were control group (p < 0.05)
Blinding: unclear accessible for Reductant formulation: Two lesions in the control group
the diagnostic sodium fluoride became softer
ITT: no
procedures (1100 ppm F), xylitol and
Change in the visual index score:
Length of follow- zinc chloride among other
eight teeth in the treatment
up: 1, 3 and active ingredients
group changed positively at the
6 months
Ozone dosage: 40 seconds 6-month follow-up compared
Lost at follow-up: with one tooth in the control
Caries assessment: ECM
unclear group (p < 0.05)
(Lode Diagnostics BV, The
Comparability of Netherlands), DIAGNOdent Change in the cavitation score:
groups at baseline: (KaVo, Germany), and six teeth had a decreased cavity
more severe clinical criteria (Ekstrand,score in the ozone group
lesions (index 1998)9 compared with five teeth in the
score of 3) in the control group. The difference
Assessors/operators:
control group
Unclear. It would seem that between intervention groups was
Setting: general a single operator assessed not significant (p > 0.05)
dental practice the lesions and interpreted Change in colour: no significant
ECM and DIAGNOdent differences between groups
findings (L. Abu-Nabaa) (p > 0.05)
Ozone device output: 33% Change in frosted enamel and
of the outcome expected undermined enamel: no significant
differences between groups
(p > 0.05)
continued
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Pit and fissure caries: primary dentition

Abu-Salem, 200438 n = 21 Design: RCT (unpublished) Children Before treatment, teeth 12-month follow-up All subjects received
(Belfast, UK) (74 non-cavitated occlusal 79 years old were cleaned using the preventive advice and
Unit of randomisation: Clinical severity scores:
carious lesions in primary with at least PROPHYflex-2 system for were given a
lesion overall there was a little
molars) two carious 5 seconds toothbrush (Brilliant,
reduction in clinical
Method of randomisation: lesions in the soft toothbrush;
Age range: 79 years Group 1: O3 + reductant severity scores in the
computer-generated posterior Brilliant Products, UK)
(7 years 28%, 8 years ozone group and an
random tables primary teeth Group 2: reductant only and toothpaste
48%, 9 years 24%) increase in scores in the
and absence Reductant formulation: (Natural White, Natural
Concealment of allocation: control group. There was
Gender (M/F): 9/21 of occlusal White Inc., UK
NS sodium benzoate a significant effect of
Caries risk assessment: restoration, (1100 ppm F), xylitol, zinc 1100 ppm F) at each
treatment on clinical
Blinding: examiner blinded fissure recall to be used
NS chloride and sodium citrate severity scores over time
to results of previous tests sealants, throughout the study
among other active (mixed models ANOVA
and outcomes of previous hypoplastic ingredients p < 0.01) The mean loge ECM
records pits and
readings, mean
fractures Ozone dosage: 10 seconds Log ECM and
ITT: no DIAGNOdent readings,

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extending into DIAGNOdent readings:
Caries assessment: ECM ECM scores,
Length of follow-up: 3, 6, 9 dentine or there was a significant
(Lode Diagnostics BV, The DIAGNOdent scores
and 12 months cavitations effect of time and
Netherlands), DIAGNOdent and clinical severity
Lost at follow-up: four resulting from treatment on the mean
(KaVo, Germany) and index were analysed
subjects (16 lesions) carious attack clinical criteria (Ekstrand,
loge ECM readings
using ANOVA (mixed
on the (p < 0.001) and the mean
1998)9 effect model)
Comparability of groups at occlusal DIAGNOdent readings
baseline: there was a surface (p < 0.001). There was Results reported in a
significant difference in also an overall significant format that did not
mean DIAGNOdent scores effect of time and allow any further
at baseline (p < 0.01). treatment on ECM scores analysis
Lesions in ozone group (p < 0.001) and an overall
appeared to be more increase in the
severe than those in the DIAGNOdent scores in
control group. the control group
Setting: general dental compared with the ozone
practice group (p < 0.05)

NS, not stated; ITT, intention-to-treat, O3, ozone gas.


Health Technology Assessment 2006; Vol. 10: No. 16

69
Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 5
Characteristics of included studies:
abstracts

71

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72
TABLE 22 Characteristics of abstracts

Author(s) No. of participants Design Inclusion Interventions Results Notes


(no. and type of criteria
Appendix 5

lesions)

Root caries
Lynch et al., 260 (two PRCLs: 60 Design: RCT Two primary Group 1: O3 (260 lesions) Reversal of caries:
200457 (Belfast, subjects with two soft root carious Soft lesions: at 6 months, 48/60 of
Unit of Group 2: no treatment
UK) PRCLs and 200 with lesions ozone-treated soft PRCLs had
randomisation: lesion (260 lesions)
two leathery non- reversed (from index 4 to 3), no
cavitated PRCLs, least Concealment of Ozone dosage: NS significant changes in control soft
severe category) allocation: NS lesions (p < 0.01)
Caries assessment: clinical
Blinding: blinded assessment Leathery lesions: 189/200 of
outcome assessor ozone-treated PRCLs had
reversed from index 1 to 0 (hard
ITT: no
to arrested), no significant
Length of follow-up: changes for control lesions
6 months (p < 0.01)
Lost at follow-up: NS Adverse events: none observed
Setting: NS

Pit and fissure caries


Holmes and Lynch, 38 (76 non-cavitated Design: RCT Two non- Group 1: air abrasion + O3 No post-operative sensitivity was Progression of caries in the
200453 (Belfast, occlusal caries lesions) cavitated early + mineral wash + glass associated with ozone treatment, conventional treatment
Unit of
UK) occlusal ionomer sealant. After 3 while 6/35 subjects in the group not reported
randomisation: lesion
carious lesions months the glass ionomer conventional treatment group
Sensitivity is a measure
Concealment of with sealant was dissected and complained of some post-
used to assess large necrotic
allocation: NS radiographic replaced with a posterior operative sensitivity
lesions and it is considered
radiolucencies composite
Blinding: NS Reversal of caries: at 3 months all inappropriate for assessing
extending
Group 2: conventional ozone dentine caries was hard early carious lesions
ITT: no 24 mm into
drilling and filling using and required no additional
Length of follow-up: dentine posterior composite removal
6 months
Ozone dosage: 40 seconds Adverse events: none observed
Lost at follow-up:
Caries assessment:
three subjects
radiographic and clinical
Setting: general dental assessment
practice

continued
TABLE 22 Characteristics of abstracts (contd)

Author(s) No. of participants Design Inclusion Interventions Results Notes


(no. and type of criteria
lesions)

Holmes, 200354 376 (2364 primary non- Design: RCT Primary Group 1: O3 treatment Reversal of caries: 99% in the A total of 1937/2364
(Berkshire, UK) cavitated occlusal fissure occlusal ozone group (1918 lesions); the received ozone application.
Unit of Group 2: no treatment
lesions) fissure lesions control lesions did not change Unclear how many lesions
randomisation: lesion
with caries Ozone dosage: 10, 20, 30 or significantly were randomly allocated to
Concealment of judged to 40 seconds depending on each group (unbalanced
The DIAGNOdent values
allocation: NS extend 2 mm the clinical severity. randomisation?)
correlated with the clinical
into dentine Applications were repeated
Blinding: NS findings (p < 0.01)
(1170 teeth) every 3 months if reversal
ITT: no had not occurred Adverse events: none observed
Length of follow-up: Caries assessment:
12 months DIAGNOdent (KaVo,
Germany) and clinical
Lost at follow-up: 61
assessment
Setting: general dental
practice

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Hamid, 200355 184 (184 non-cavitated Design: RCT Primary early Group 1: O3 treatment Reversal of caries: 86.6% in the
(London, UK) pit and fissure carious occlusal (92 lesions) ozone group; the control lesions
Unit of
lesions) pit/fissure did not change significantly
randomisation: patient Group 2: no treatment
lesions with (p < 0.05)
(92 lesions)
Concealment of caries
The DIAGNOdent values
allocation: NS extending up Ozone dosage: 40 seconds
correlated with the clinical
to 1 mm into at baseline and at 3 months
Blinding: NS findings
dentine Caries assessment: clinical
ITT: unclear Adverse events: none observed
assessment and
Length of follow-up: DIAGNOdent (KaVo,
6 months Germany)
Lost at follow-up:
unclear
Setting: NS

continued
Health Technology Assessment 2006; Vol. 10: No. 16

73
74
TABLE 22 Characteristics of abstracts (contd)

Author(s) No. of participants Design Inclusion Interventions Results Notes


(no. and type of criteria
Appendix 5

lesions)

Megighian and 80 (300 pit and fissure Design: randomised Pit and fissure Group 1: O3 (220 lesions) Reversal of caries: ozone-treated Unclear whether the
Bertolini, 200456 carious lesions) clinical trial carious lesions lesions clinically reversed proportion of lesions that
Group 2: no treatment (80
(Verona, Italy) (p < 0.05), while control lesions clinically reversed or
Unit of lesions)
did not showed a reduction in
randomisation: lesion
Ozone dosage: 20, 30 or 40 DIAGNOdent readings
DIAGNOdent: significant overall
Concealment of seconds according to clinical were all ozone-treated
reduction in readings for ozone-
allocation: NS severity lesions or included some
treated lesions, while control
Caries assessment: clinical control lesions
Blinding: double blind lesions showed an increase in
assessment and DIAGNOdent readings
ITT: no
DIAGNOdent (KaVo,
85% of teeth clinically reversed
Length of follow-up: Germany)
and showed a DIAGNOdent
6 months
reduction
Lost at follow-up: NS
Setting: private
practice, Italy
Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 6
Structure of the economic model
Decision models to assess costs consequences that occur over a series of years (in
this study up to 5 years). At the beginning of the
and benefits of HealOzone first year each patient receives current
The four models depicted in Figures 1518 have a management plus HealOzone and hence a
similar structure; therefore, only current probability of 1 is attached. At the end of the first
management plus HealOzone is described here. year there is a chance that the patients are cured
Markov models can be used to estimate costs and (caries are reversed) or they have progressed. If

Cure
Current management Cured post current management plus HealOzone
probcurel
plus HealOzone
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current
management plus HealOzone
Current management
plus HealOzone 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcurel
Cured post retreatment
0
Filled tooth
0

FIGURE 15 Decision model to assess the cost and benefits of current management plus HealOzone of non-cavitated root caries
(Markov model)

Cure
Cured post current management
probcure
Current management
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current management

Current management 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcure
Cured post retreatment
0
Filled tooth
0

FIGURE 16 Decision model to assess the costs and benefits of current management of non-cavitated root caries 75

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Appendix 6

Cure
Cured post current management
probcure
Current management
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current management

Current management 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcure
Cured post retreatment
0
Filled tooth
0

FIGURE 17 Decision model to assess the costs and benefits of current management of non-cavitated pit and fissure caries

Cure
Current management Cured post current management plus HealOzone
probcurel
plus HealOzone
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current
management plus HealOzone
Current management
plus HealOzone 0
M Cured
Cured post retreatment
Retreatment probcurel
0 Progress
Filled tooth
1-probcurel
Cured post retreatment
0
Filled tooth
0

FIGURE 18 Decision model to assess the costs and benefits of current management plus HealOzone of non-cavitated pit and fissure
caries

they have progressed there is a chance that they of cure does not change in the third branch and
receive the same treatment or a new treatment those who go into the third branch are either
(filling). The chance of a patient being cured is cured or filled. The filled tooth state is a terminal
pbcure1 and not being cured is 1-pbcure1. The state and patients do not leave it. The model also
chance that a patient will receive the same assumes that when a patient is cured they remain
treatment is probretreat. In the model it is cured for as long as the model runs.
assumed that the patient has a 50% chance of
receiving the same treatment or having a filling. If Details of cost calculations are shown in
the first treatment fails the patient moves to the Tables 2330.
76 third branch or the fifth branch. The probability
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 23 Annual treatment numbers for non-cavitated caries based on each relevant SDR code by age group for year ending March
200365

Treatment No. of Total teeth


SDR code numbers caries types No. of teeth treated

Age <18 years


Non-cavitated pit and fissure caries 601 3,930 2 1 1,965
3631 2,393 2 1 1,196.5
701 73 1 1 73
Total 3,234.5
Non-cavitated root caries 601 3,930 2 1 1,965
3631 2,393 2 1 1,196.5
Total 3,161.5

Age 18 years
Non-cavitated pit and fissure caries 601 11,728 2 1 5,864
3631 669,304 2 1 334,652
701 1,922 1 1 1,922
Total 342,438
Non-cavitated root caries 601 11,728 2 1 5,864
3631 669,304 2 1 334,652
Total 340,516

Where one SDR code was relevant to more than one type of caries the published treatment numbers were divided by the
number of relevant types of caries. Similar adjustments were provided for the numbers of teeth to which any one SDR code
applied.

TABLE 24 Percentage teeth treated by age group of patient, based on numbers in Table 23

SDR code <18 years (%) 18 years (%)

Non-cavitated pit and fissure caries 601 25.1 74.9


3631 0.4 99.6
701 3.7 96.3
Non-cavitated root caries 601 25.1 74.9
3631 0.4 99.6

TABLE 25 Calculation for cost to NHS based on 100% treatment items paid for those <18 years and 40% all treatment items paid
for those 18 years

NHS cost ()

SDR code <18 years 18 years Unit cost <18 years 18 years Weighted
() average NHS
fee across all
age ()

Non-cavitated pit and 601 25.1% 74.9% 7.70 7.70 3.08 4.24
fissure caries 3631 0.4% 99.6% 4.60 4.60 1.84 1.85
701 3.7% 96.3% 6.95 6.95 2.78 2.93
Total 19.25 7.70 9.02
Non-cavitated root caries 601 25.1% 74.9% 7.70 7.70 3.08 4.24
3631 0.4% 99.6% 4.60 4.60 1.84 1.85
Total 12.30 4.92 6.09

77

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Appendix 6

TABLE 26 Cost calculations for treatment of cavitated caries

SDR code Total annual Annual No. of No. of Total teeth


treatment treatment caries teeth treated
numbers numbers types

Age <18 years


Cavitated pit and fissure caries 1441 1,025,404 1 1
1442 201,308 1 1 201,308
1443 163,379 1 1 163,379
Anterior teeth 1401a 557,753 278,876.5 1 1 278,876.5
Posterior teeth 1421a 386,061 193,030.5 1 1 193,030.5
1421a 35,681 17,840.5 1 2 35,681
Age 18 years
Cavitated pit and fissure caries 1441 147,980 1 1 147,980
1442 86,667 1 1 86,667
1443 68,353 1 1 68,353
1401a 1,671,224 835,612 1 1 835,612
1421a 4,141,954 2,070,977 1 1 2,070,977
1421a 346,816 173,408 1 2 346,816

Figures assume a treatment mix of SDR codes 1441, 1442 and 1443 plus either 1401 or 1421. All patients also receive SDR
code 0101 (initial dental assessment).
It is also assumed that 50% of treatments are for anterior and 50% for posterior teeth.
a
50% mix assumed.

TABLE 27 Steps used to calculate the mean cost of a filling when different proportions of children and adults receive different
treatment mixes by SDR code

% treatment for NHS cost ()


cavitated caries (fillings)

SDR <18 years 18 years Unit cost <18 years 18 years Weighted
code () average NHS
fee across all
age ()

1441 87.4 12.6 6.95 6.95 2.78 6.42


1442 69.9 30.1 9.80 9.80 3.92 8.03
1443 70.5 29.5 10.55 10.55 4.22 8.68
1401a 25.0 75.0 7.50 7.50 3.00 4.13
1421a 8.5 91.5 14.15 14.15 5.66 6.38
1421a 9.3 90.6 14.15 14.15 5.66 6.45
63.10 63.10 25.24 40.10
Overall % mix children/adults
for fillings and mean cost per filling 45.1 54.9 12.62 12.62 5.05 8.02
Initial dental assessment 101 100 100 7.05 7.05 2.82 4.73
Total average cost per filling visit 19.67 7.87 12.75
a
50% mix assumed.

78
Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 28 HealOzone cost calculations

% who have caries


treatmenta
Cost to NHS ()
1st year initial treatment Unit cost <18 years 18 years <18 years 18 years Weighted
option () average cost
to NHS ()

Non-cavitated pit and fissure caries


Currentb 19.25 19.25 7.70 9.02
HealOzone 20.00 20.00 8.00 25.1 74.9 11.01
Current + HealOzone 39.25 15.70 20.03
Non-cavitated root caries
Currentb 12.30 12.30 4.92 6.09
HealOzone 20.00 20.00 8.00 25.1 74.9 11.01
Current + HealOzone 32.30 12.92 17.10
a
Non-cavitated pit and fissure caries treatment or non-cavitated root caries treatment (see Table 25).
b
See Tables 24 and 25.

Non-cavitated pit and fissure caries


The combined cost of HealOzone and current management is 40.49 and the cost of current
management alone is 24.78.

TABLE 29 Results of one-way sensitivity analysis for non-cavitated pit fissure caries (current management versus current management
and HealOzone) holding current management plus HealOzone cost constant

Current Additional cost of


Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 26.06 40.49 14.43


0.1 0.015 0.985 23.81 40.49 16.68
0.2 0.145 0.855 21.67 40.49 18.82
0.3 0.28 0.72 19.66 40.49 20.83
0.4 0.405 0.595 17.77 40.49 22.72
0.5 0.52 0.48 16.00 40.49 24.49
0.6 0.625 0.375 14.36 40.49 26.13
0.7 0.72 0.28 12.84 40.49 27.65
0.8 0.805 0.195 11.44 40.49 29.05
0.9 0.88 0.12 10.17 40.49 30.32
1 1 0 9.02 40.49 31.47

TABLE 30 Results of one-way sensitivity analysis for non-cavitated pit fissure caries (current management versus current management
and HealOzone) holding current management cost constant

Current Additional cost of


Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 24.78 42.58 17.80


0.1 0.015 0.985 24.78 39.77 14.99
0.2 0.145 0.855 24.78 37.08 12.30
0.3 0.28 0.72 24.78 34.52 9.74
0.4 0.405 0.595 24.78 32.08 7.30
0.5 0.52 0.48 24.78 29.76 4.98
0.6 0.625 0.375 24.78 27.57 2.79
0.7 0.72 0.28 24.78 25.50 0.72
0.8 0.805 0.195 24.78 23.55 1.23
0.9 0.88 0.12 24.78 21.73 3.05
1 1 0 24.78 20.03 4.75
79

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Appendix 6

Non-cavitated root caries


The combined cost of HealOzone and current management is 14.63 and the cost of current
management alone is 21.45 (Tables 31 and 32).

TABLE 31 Results of one-way sensitivity analysis for non-cavitated root caries (current management versus current management and
HealOzone) holding current management cost constant

Current Additional cost of


Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 21.45 38.18 16.73


0.1 0.145 0.855 21.45 35.52 14.07
0.2 0.28 0.72 21.45 32.98 11.53
0.3 0.405 0.595 21.45 30.57 9.12
0.4 0.52 0.48 21.45 28.27 6.82
0.5 0.625 0.375 21.45 26.10 4.65
0.6 0.72 0.28 21.45 24.06 2.61
0.7 0.805 0.195 21.45 22.13 0.68
0.8 0.88 0.12 21.45 20.33 1.12
0.9 0.945 0.055 21.45 18.65 2.80
1 1 0 21.45 17.10 4.35

TABLE 32 Results of one-way sensitivity analysis for non-cavitated root caries (current management versus current management and
HealOzone) holding current management plus HealOzone cost constant

Current Additional cost of


Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 21.67 14.63 7.04


0.1 0.145 0.855 19.56 14.63 4.93
0.2 0.28 0.72 17.57 14.63 2.94
0.3 0.405 0.595 15.70 14.63 1.07
0.4 0.52 0.48 13.96 14.63 0.67
0.5 0.625 0.375 12.34 14.63 2.29
0.6 0.72 0.28 10.84 14.63 3.79
0.7 0.805 0.195 9.47 14.63 5.16
0.8 0.88 0.12 8.22 14.63 6.41
0.9 0.945 0.055 7.09 14.63 7.54
1 1 0 6.09 14.63 8.54

80
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Health Technology Assessment reports


published to date
Volume 1, 1997 No. 11 No. 6
Newborn screening for inborn errors of Effectiveness of hip prostheses in
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The diagnosis, management, treatment of laxatives in the elderly.
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and costs of prostate cancer in England
Bone marrow and peripheral blood
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When and how to assess fast-changing A review by Johnson PWM, Simnett SJ,
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No. 15 No. 5 No. 17 (Pt 1)


Ethical issues in the design and conduct Methods for evaluating area-wide and The debridement of chronic wounds:
of randomised controlled trials. organisation-based interventions in a systematic review.
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technology assessment: a review of the Assessing the costs of healthcare wounds.
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The costs and benefits of paramedic Cooperatives and their primary care and electron beam computed
skills in pre-hospital trauma care. emergency centres: organisation and
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A systematic review of comparisons of Eliciting public preferences for Home treatment for mental health
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Bayesian methods in health technology (7) laser therapy, therapeutic By Chilcott J, Wight J, Lloyd Jones
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No. 1 A, Burls A. (3) Day hospital versus outpatient
Clinical and cost-effectiveness of care.
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clinical effectiveness and cost- A rapid and systematic review of the
By Sassi F, Archard L, Le Grand J.
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No. 4 treating surgical wounds healing by effectiveness of gemcitabine for the
Quality-of-life measures in chronic secondary intention. treatment of pancreatic cancer.
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No. 25 No. 35 No. 9


A rapid and systematic review of the A systematic review of controlled trials Zanamivir for the treatment of influenza
evidence for the clinical effectiveness of the effectiveness and cost- in adults: a systematic review and
and cost-effectiveness of irinotecan, effectiveness of brief psychological economic evaluation.
oxaliplatin and raltitrexed for the treatments for depression. By Burls A, Clark W, Stewart T,
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No. 36 A review of the natural history and
No. 26 Cost analysis of child health epidemiology of multiple sclerosis:
Comparison of the effectiveness of surveillance. implications for resource allocation and
inhaler devices in asthma and chronic By Sanderson D, Wright D, Acton C, health economic models.
obstructive airways disease: a systematic Duree D. By Richards RG, Sampson FC,
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H, Hatrick C, Salas C, Parry D, et al. No. 2 The clinical effectiveness and cost-
Fludarabine as second-line therapy for effectiveness of surgery for people with
No. 28 B cell chronic lymphocytic leukaemia:
A rapid and systematic review of the morbid obesity: a systematic review and
a technology assessment. economic evaluation.
clinical effectiveness and cost-
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(unblinded) controlled trial. arrangements for older people. By Lewis R, Bagnall A-M, King S,
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Miller P, Kerslake R, Pringle M. Cannaby AM, Baker R, Wilson A, et al.
No. 15
No. 31 No. 5 A systematic review of the effectiveness
Design and use of questionnaires: a The clinical effectiveness and cost- and cost-effectiveness of metal-on-metal
review of best practice applicable to effectiveness of inhaler devices used in hip resurfacing arthroplasty for
surveys of health service staff and the routine management of chronic treatment of hip disease.
patients. asthma in older children: a systematic By Vale L, Wyness L, McCormack K,
By McColl E, Jacoby A, Thomas L, review and economic evaluation. McKenzie L, Brazzelli M, Stearns SC.
Soutter J, Bamford C, Steen N, et al. By Peters J, Stevenson M, Beverley C,
Lim J, Smith S. No. 16
No. 32 The clinical effectiveness and cost-
A rapid and systematic review of the No. 6 effectiveness of bupropion and nicotine
clinical effectiveness and cost- The clinical effectiveness and cost- replacement therapy for smoking
effectiveness of paclitaxel, docetaxel, effectiveness of sibutramine in the cessation: a systematic review and
gemcitabine and vinorelbine in non- management of obesity: a technology economic evaluation.
small-cell lung cancer. assessment. By Woolacott NF, Jones L, Forbes CA,
By Clegg A, Scott DA, Sidhu M, By OMeara S, Riemsma R, Shirran Mather LC, Sowden AJ, Song FJ, et al.
Hewitson P, Waugh N. L, Mather L, ter Riet G.
No. 17
No. 33 No. 7 A systematic review of effectiveness and
Subgroup analyses in randomised The cost-effectiveness of magnetic economic evaluation of new drug
controlled trials: quantifying the risks of resonance angiography for carotid treatments for juvenile idiopathic
false-positives and false-negatives. artery stenosis and peripheral vascular arthritis: etanercept.
By Brookes ST, Whitley E, disease: a systematic review. By Cummins C, Connock M,
Peters TJ, Mulheran PA, Egger M, By Berry E, Kelly S, Westwood ME, Fry-Smith A, Burls A.
Davey Smith G. Davies LM, Gough MJ, Bamford JM,
et al. No. 18
No. 34 Clinical effectiveness and cost-
Depot antipsychotic medication in the No. 8 effectiveness of growth hormone in
treatment of patients with schizophrenia: Promoting physical activity in South children: a systematic review and
(1) Meta-review; (2) Patient and nurse Asian Muslim women through exercise economic evaluation.
attitudes. on prescription. By Bryant J, Cave C, Mihaylova B,
By David AS, Adams C. By Carroll B, Ali N, Azam N. Chase D, McIntyre L, Gerard K, et al. 85

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No. 19 No. 28 No. 2


Clinical effectiveness and cost- Clinical effectiveness and cost Systematic review of the effectiveness
effectiveness of growth hormone in consequences of selective serotonin and cost-effectiveness, and economic
adults in relation to impact on quality of reuptake inhibitors in the treatment of evaluation, of home versus hospital or
life: a systematic review and economic sex offenders. satellite unit haemodialysis for people
evaluation. By Adi Y, Ashcroft D, Browne K, with end-stage renal failure.
By Bryant J, Loveman E, Chase D, Beech A, Fry-Smith A, Hyde C. By Mowatt G, Vale L, Perez J, Wyness
Mihaylova B, Cave C, Gerard K, et al. L, Fraser C, MacLeod A, et al.
No. 29
No. 20 Treatment of established osteoporosis: No. 3
Clinical medication review by a a systematic review and costutility Systematic review and economic
pharmacist of patients on repeat analysis. evaluation of the effectiveness of
prescriptions in general practice: a By Kanis JA, Brazier JE, Stevenson M, infliximab for the treatment of Crohns
randomised controlled trial. Calvert NW, Lloyd Jones M. disease.
By Zermansky AG, Petty DR, Raynor By Clark W, Raftery J, Barton P,
DK, Lowe CJ, Freementle N, Vail A. No. 30 Song F, Fry-Smith A, Burls A.
Which anaesthetic agents are cost-
No. 4
No. 21 effective in day surgery? Literature
A review of the clinical effectiveness and
The effectiveness of infliximab and review, national survey of practice and
cost-effectiveness of routine anti-D
etanercept for the treatment of randomised controlled trial.
prophylaxis for pregnant women who
rheumatoid arthritis: a systematic review By Elliott RA Payne K, Moore JK,
are rhesus negative.
and economic evaluation. Davies LM, Harper NJN, St Leger AS,
By Chilcott J, Lloyd Jones M, Wight
By Jobanputra P, Barton P, Bryan S, et al.
J, Forman K, Wray J, Beverley C, et al.
Burls A.
No. 31 No. 5
No. 22 Screening for hepatitis C among Systematic review and evaluation of the
A systematic review and economic injecting drug users and in use of tumour markers in paediatric
evaluation of computerised cognitive genitourinary medicine clinics: oncology: Ewings sarcoma and
behaviour therapy for depression and systematic reviews of effectiveness, neuroblastoma.
anxiety. modelling study and national survey of By Riley RD, Burchill SA, Abrams KR,
By Kaltenthaler E, Shackley P, Stevens current practice. Heney D, Lambert PC, Jones DR, et al.
K, Beverley C, Parry G, Chilcott J. By Stein K, Dalziel K, Walker A,
McIntyre L, Jenkins B, Horne J, et al. No. 6
No. 23 The cost-effectiveness of screening for
A systematic review and economic No. 32 Helicobacter pylori to reduce mortality
evaluation of pegylated liposomal The measurement of satisfaction with and morbidity from gastric cancer and
doxorubicin hydrochloride for ovarian healthcare: implications for practice peptic ulcer disease: a discrete-event
cancer. from a systematic review of the simulation model.
By Forbes C, Wilby J, Richardson G, literature. By Roderick P, Davies R, Raftery J,
Sculpher M, Mather L, Reimsma R. By Crow R, Gage H, Hampson S, Crabbe D, Pearce R, Bhandari P, et al.
Hart J, Kimber A, Storey L, et al. No. 7
No. 24
A systematic review of the effectiveness No. 33 The clinical effectiveness and cost-
of interventions based on a stages-of- The effectiveness and cost-effectiveness effectiveness of routine dental checks: a
change approach to promote individual of imatinib in chronic myeloid systematic review and economic
behaviour change. leukaemia: a systematic review. evaluation.
By Riemsma RP, Pattenden J, Bridle C, By Garside R, Round A, Dalziel K, By Davenport C, Elley K, Salas C,
Sowden AJ, Mather L, Watt IS, et al. Stein K, Royle R. Taylor-Weetman CL, Fry-Smith A,
Bryan S, et al.
No. 25 No. 34
No. 8
A systematic review update of the A comparative study of hypertonic
A multicentre randomised controlled
clinical effectiveness and cost- saline, daily and alternate-day
trial assessing the costs and benefits of
effectiveness of glycoprotein IIb/IIIa rhDNase in children with cystic
using structured information and
antagonists. fibrosis.
analysis of womens preferences in the
By Robinson M, Ginnelly L, Sculpher By Suri R, Wallis C, Bush A,
management of menorrhagia.
M, Jones L, Riemsma R, Palmer S, et al. Thompson S, Normand C, Flather M,
By Kennedy ADM, Sculpher MJ,
et al.
No. 26 Coulter A, Dwyer N, Rees M,
A systematic review of the effectiveness, No. 35 Horsley S, et al.
cost-effectiveness and barriers to A systematic review of the costs and No. 9
implementation of thrombolytic and effectiveness of different models of Clinical effectiveness and costutility of
neuroprotective therapy for acute paediatric home care. photodynamic therapy for wet age-related
ischaemic stroke in the NHS. By Parker G, Bhakta P, Lovett CA, macular degeneration: a systematic review
By Sandercock P, Berge E, Dennis M, Paisley S, Olsen R, Turner D, et al. and economic evaluation.
Forbes J, Hand P, Kwan J, et al. By Meads C, Salas C, Roberts T,
Volume 7, 2003 Moore D, Fry-Smith A, Hyde C.
No. 27
A randomised controlled crossover No. 1 No. 10
trial of nurse practitioner versus How important are comprehensive Evaluation of molecular tests for
doctor-led outpatient care in a literature searches and the assessment of prenatal diagnosis of chromosome
bronchiectasis clinic. trial quality in systematic reviews? abnormalities.
By Caine N, Sharples LD, Empirical study. By Grimshaw GM, Szczepura A,
Hollingworth W, French J, Keogan M, By Egger M, Jni P, Bartlett C, Hultn M, MacDonald F, Nevin NC,
86 Exley A, et al. Holenstein F, Sterne J. Sutton F, et al.
Health Technology Assessment 2006; Vol. 10: No. 16

No. 11 No. 21 No. 30


First and second trimester antenatal Systematic review of the clinical The value of digital imaging in diabetic
screening for Downs syndrome: the effectiveness and cost-effectiveness retinopathy.
results of the Serum, Urine and of tension-free vaginal tape for By Sharp PF, Olson J, Strachan F,
Ultrasound Screening Study treatment of urinary stress Hipwell J, Ludbrook A, ODonnell M,
(SURUSS). incontinence. et al.
By Wald NJ, Rodeck C, By Cody J, Wyness L, Wallace S,
Hackshaw AK, Walters J, Chitty L, Glazener C, Kilonzo M, Stearns S, No. 31
Mackinson AM. et al. Lowering blood pressure to prevent
myocardial infarction and stroke:
No. 12 No. 22 a new preventive strategy.
The effectiveness and cost-effectiveness The clinical and cost-effectiveness of By Law M, Wald N, Morris J.
of ultrasound locating devices for patient education models for diabetes:
central venous access: a systematic a systematic review and economic No. 32
review and economic evaluation. evaluation. Clinical and cost-effectiveness of
By Calvert N, Hind D, McWilliams By Loveman E, Cave C, Green C, capecitabine and tegafur with uracil for
RG, Thomas SM, Beverley C, Royle P, Dunn N, Waugh N. the treatment of metastatic colorectal
Davidson A. cancer: systematic review and economic
No. 23 evaluation.
No. 13
The role of modelling in prioritising By Ward S, Kaltenthaler E, Cowan J,
A systematic review of atypical
and planning clinical trials. Brewer N.
antipsychotics in schizophrenia.
By Chilcott J, Brennan A, Booth A,
By Bagnall A-M, Jones L, Lewis R, No. 33
Karnon J, Tappenden P.
Ginnelly L, Glanville J, Torgerson D, Clinical and cost-effectiveness of new
et al. No. 24 and emerging technologies for early
Costbenefit evaluation of routine localised prostate cancer: a systematic
No. 14
Prostate Testing for Cancer and influenza immunisation in people 6574 review.
Treatment (ProtecT) feasibility years of age. By Hummel S, Paisley S, Morgan A,
study. By Allsup S, Gosney M, Haycox A, Currie E, Brewer N.
By Donovan J, Hamdy F, Neal D, Regan M.
No. 34
Peters T, Oliver S, Brindle L, et al. No. 25 Literature searching for clinical and
No. 15 The clinical and cost-effectiveness of cost-effectiveness studies used in health
Early thrombolysis for the treatment pulsatile machine perfusion versus cold technology assessment reports carried
of acute myocardial infarction: a storage of kidneys for transplantation out for the National Institute for
systematic review and economic retrieved from heart-beating and non- Clinical Excellence appraisal
evaluation. heart-beating donors. system.
By Boland A, Dundar Y, Bagust A, By Wight J, Chilcott J, Holmes M, By Royle P, Waugh N.
Haycox A, Hill R, Mujica Mota R, Brewer N.
No. 35
et al.
No. 26 Systematic review and economic
No. 16 Can randomised trials rely on existing decision modelling for the prevention
Screening for fragile X syndrome: electronic data? A feasibility study to and treatment of influenza
a literature review and modelling. explore the value of routine data in A and B.
By Song FJ, Barton P, Sleightholme V, health technology assessment. By Turner D, Wailoo A, Nicholson K,
Yao GL, Fry-Smith A. By Williams JG, Cheung WY, Cooper N, Sutton A, Abrams K.
Cohen DR, Hutchings HA, Longo MF,
No. 17 No. 36
Russell IT.
Systematic review of endoscopic sinus A randomised controlled trial to
surgery for nasal polyps. No. 27 evaluate the clinical and cost-
By Dalziel K, Stein K, Round A, Evaluating non-randomised intervention effectiveness of Hickman line
Garside R, Royle P. studies. insertions in adult cancer patients by
By Deeks JJ, Dinnes J, DAmico R, nurses.
No. 18
Sowden AJ, Sakarovitch C, Song F, et al. By Boland A, Haycox A, Bagust A,
Towards efficient guidelines: how to
monitor guideline use in primary Fitzsimmons L.
No. 28
care. A randomised controlled trial to assess No. 37
By Hutchinson A, McIntosh A, Cox S, the impact of a package comprising a Redesigning postnatal care: a
Gilbert C. patient-orientated, evidence-based self- randomised controlled trial of
No. 19 help guidebook and patient-centred protocol-based midwifery-led care
Effectiveness and cost-effectiveness of consultations on disease management focused on individual womens
acute hospital-based spinal cord injuries and satisfaction in inflammatory bowel physical and psychological health
services: systematic review. disease. needs.
By Bagnall A-M, Jones L, By Kennedy A, Nelson E, Reeves D, By MacArthur C, Winter HR,
Richardson G, Duffy S, Richardson G, Roberts C, Robinson A, Bick DE, Lilford RJ, Lancashire RJ,
Riemsma R. et al. Knowles H, et al.

No. 20 No. 29 No. 38


Prioritisation of health technology The effectiveness of diagnostic tests for Estimating implied rates of discount in
assessment. The PATHS model: the assessment of shoulder pain due to healthcare decision-making.
methods and case studies. soft tissue disorders: a systematic review. By West RR, McNabb R,
By Townsend J, Buxton M, By Dinnes J, Loveman E, McIntyre L, Thompson AGH, Sheldon TA,
Harper G. Waugh N. Grimley Evans J. 87

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Health Technology Assessment reports published to date

No. 39 No. 7 No. 15


Systematic review of isolation policies in Clinical effectiveness and costs of the Involving consumers in research and
the hospital management of methicillin- Sugarbaker procedure for the treatment development agenda setting for the
resistant Staphylococcus aureus: a review of of pseudomyxoma peritonei. NHS: developing an evidence-based
the literature with epidemiological and By Bryant J, Clegg AJ, Sidhu MK, approach.
economic modelling. Brodin H, Royle P, Davidson P. By Oliver S, Clarke-Jones L,
By Cooper BS, Stone SP, Kibbler CC, Rees R, Milne R, Buchanan P,
Cookson BD, Roberts JA, Medley GF, No. 8
Gabbay J, et al.
et al. Psychological treatment for insomnia in
the regulation of long-term hypnotic No. 16
No. 40
drug use. A multi-centre randomised controlled
Treatments for spasticity and pain in
By Morgan K, Dixon S, Mathers N, trial of minimally invasive direct
multiple sclerosis: a systematic review.
Thompson J, Tomeny M. coronary bypass grafting versus
By Beard S, Hunn A, Wight J.
percutaneous transluminal coronary
No. 41 No. 9
Improving the evaluation of therapeutic angioplasty with stenting for proximal
The inclusion of reports of randomised stenosis of the left anterior descending
trials published in languages other than interventions in multiple sclerosis:
development of a patient-based measure coronary artery.
English in systematic reviews.
of outcome. By Reeves BC, Angelini GD, Bryan
By Moher D, Pham B, Lawson ML,
By Hobart JC, Riazi A, Lamping DL, AJ, Taylor FC, Cripps T, Spyt TJ, et al.
Klassen TP.
Fitzpatrick R, Thompson AJ. No. 17
No. 42
The impact of screening on future No. 10 Does early magnetic resonance imaging
health-promoting behaviours and health A systematic review and economic influence management or improve
beliefs: a systematic review. evaluation of magnetic resonance outcome in patients referred to
By Bankhead CR, Brett J, Bukach C, cholangiopancreatography compared secondary care with low back pain?
Webster P, Stewart-Brown S, Munafo M, with diagnostic endoscopic retrograde A pragmatic randomised controlled
et al. cholangiopancreatography. trial.
By Kaltenthaler E, Bravo Vergel Y, By Gilbert FJ, Grant AM, Gillan
Volume 8, 2004 Chilcott J, Thomas S, Blakeborough T, MGC, Vale L, Scott NW, Campbell MK,
Walters SJ, et al. et al.
No. 1
What is the best imaging strategy for No. 11 No. 18
acute stroke? The clinical and cost-effectiveness of
The use of modelling to evaluate new
By Wardlaw JM, Keir SL, Seymour J, anakinra for the treatment of
drugs for patients with a chronic
Lewis S, Sandercock PAG, Dennis MS, rheumatoid arthritis in adults: a
condition: the case of antibodies against
et al.
tumour necrosis factor in rheumatoid systematic review and economic analysis.
No. 2 arthritis. By Clark W, Jobanputra P, Barton P,
Systematic review and modelling of the By Barton P, Jobanputra P, Wilson J, Burls A.
investigation of acute and chronic chest Bryan S, Burls A.
pain presenting in primary care. No. 19
By Mant J, McManus RJ, Oakes RAL, No. 12 A rapid and systematic review and
Delaney BC, Barton PM, Deeks JJ, et al. Clinical effectiveness and cost- economic evaluation of the clinical and
effectiveness of neonatal screening for cost-effectiveness of newer drugs for
No. 3 inborn errors of metabolism using treatment of mania associated with
The effectiveness and cost-effectiveness tandem mass spectrometry: a systematic bipolar affective disorder.
of microwave and thermal balloon
review. By Bridle C, Palmer S, Bagnall A-M,
endometrial ablation for heavy
By Pandor A, Eastham J, Beverley C, Darba J, Duffy S, Sculpher M, et al.
menstrual bleeding: a systematic review
Chilcott J, Paisley S.
and economic modelling. No. 20
By Garside R, Stein K, Wyatt K, No. 13 Liquid-based cytology in cervical
Round A, Price A. Clinical effectiveness and cost- screening: an updated rapid and
No. 4 effectiveness of pioglitazone and systematic review and economic
A systematic review of the role of rosiglitazone in the treatment of analysis.
bisphosphonates in metastatic disease. type 2 diabetes: a systematic By Karnon J, Peters J, Platt J,
By Ross JR, Saunders Y, Edmonds PM, review and economic Chilcott J, McGoogan E, Brewer N.
Patel S, Wonderling D, Normand C, et al. evaluation.
By Czoski-Murray C, Warren E, No. 21
No. 5 Systematic review of the long-term
Chilcott J, Beverley C, Psyllaki MA,
Systematic review of the clinical effects and economic consequences of
Cowan J.
effectiveness and cost-effectiveness of treatments for obesity and implications
capecitabine (Xeloda ) for locally No. 14 for health improvement.
advanced and/or metastatic breast cancer. Routine examination of the newborn: By Avenell A, Broom J, Brown TJ,
By Jones L, Hawkins N, Westwood M, the EMREN study. Evaluation of an Poobalan A, Aucott L, Stearns SC, et al.
Wright K, Richardson G, Riemsma R. extension of the midwife role
No. 6 including a randomised controlled No. 22
Effectiveness and efficiency of guideline trial of appropriately trained midwives Autoantibody testing in children with
dissemination and implementation and paediatric senior house newly diagnosed type 1 diabetes
strategies. officers. mellitus.
By Grimshaw JM, Thomas RE, By Townsend J, Wolke D, Hayes J, By Dretzke J, Cummins C,
MacLennan G, Fraser C, Ramsay CR, Dav S, Rogers C, Bloomfield L, Sandercock J, Fry-Smith A, Barrett T,
88 Vale L, et al. et al. Burls A.
Health Technology Assessment 2006; Vol. 10: No. 16

No. 23 No. 32 No. 41


Clinical effectiveness and cost- The Social Support and Family Health Provision, uptake and cost of cardiac
effectiveness of prehospital intravenous Study: a randomised controlled trial and rehabilitation programmes: improving
fluids in trauma patients. economic evaluation of two alternative services to under-represented groups.
By Dretzke J, Sandercock J, Bayliss S, forms of postnatal support for mothers By Beswick AD, Rees K, Griebsch I,
Burls A. living in disadvantaged inner-city areas. Taylor FC, Burke M, West RR, et al.
By Wiggins M, Oakley A, Roberts I, No. 42
No. 24
Newer hypnotic drugs for the short- Turner H, Rajan L, Austerberry H, et al. Involving South Asian patients in
term management of insomnia: a No. 33 clinical trials.
systematic review and economic Psychosocial aspects of genetic screening By Hussain-Gambles M, Leese B,
evaluation. of pregnant women and newborns: Atkin K, Brown J, Mason S, Tovey P.
By Dndar Y, Boland A, Strobl J, a systematic review. No. 43
Dodd S, Haycox A, Bagust A, By Green JM, Hewison J, Bekker HL, Clinical and cost-effectiveness of
et al. Bryant, Cuckle HS. continuous subcutaneous insulin
No. 25 infusion for diabetes.
No. 34
Development and validation of methods By Colquitt JL, Green C, Sidhu MK,
Evaluation of abnormal uterine Hartwell D, Waugh N.
for assessing the quality of diagnostic
bleeding: comparison of three
accuracy studies. No. 44
outpatient procedures within cohorts
By Whiting P, Rutjes AWS, Dinnes J, Identification and assessment of
defined by age and menopausal status.
Reitsma JB, Bossuyt PMM, Kleijnen J. ongoing trials in health technology
By Critchley HOD, Warner P,
No. 26 Lee AJ, Brechin S, Guise J, Graham B. assessment reviews.
EVALUATE hysterectomy trial: a By Song FJ, Fry-Smith A, Davenport
multicentre randomised trial comparing No. 35 C, Bayliss S, Adi Y, Wilson JS, et al.
abdominal, vaginal and laparoscopic Coronary artery stents: a rapid systematic
review and economic evaluation. No. 45
methods of hysterectomy. Systematic review and economic
By Garry R, Fountain J, Brown J, By Hill R, Bagust A, Bakhai A,
evaluation of a long-acting insulin
Manca A, Mason S, Sculpher M, et al. Dickson R, Dndar Y, Haycox A, et al.
analogue, insulin glargine
No. 27 No. 36 By Warren E, Weatherley-Jones E,
Methods for expected value of Review of guidelines for good practice Chilcott J, Beverley C.
information analysis in complex health in decision-analytic modelling in health No. 46
economic models: developments on the technology assessment. Supplementation of a home-based
health economics of interferon- and By Philips Z, Ginnelly L, Sculpher M, exercise programme with a class-based
glatiramer acetate for multiple sclerosis. Claxton K, Golder S, Riemsma R, et al. programme for people with osteoarthritis
By Tappenden P, Chilcott JB, of the knees: a randomised controlled
Eggington S, Oakley J, McCabe C. No. 37
Rituximab (MabThera) for aggressive trial and health economic analysis.
No. 28 By McCarthy CJ, Mills PM,
non-Hodgkins lymphoma: systematic
Effectiveness and cost-effectiveness of Pullen R, Richardson G, Hawkins N,
review and economic evaluation.
imatinib for first-line treatment of Roberts CR, et al.
By Knight C, Hind D, Brewer N,
chronic myeloid leukaemia in chronic Abbott V. No. 47
phase: a systematic review and economic Clinical and cost-effectiveness of once-
analysis. No. 38 daily versus more frequent use of same
By Dalziel K, Round A, Stein K, Clinical effectiveness and cost- potency topical corticosteroids for atopic
Garside R, Price A. effectiveness of clopidogrel and eczema: a systematic review and
modified-release dipyridamole in the economic evaluation.
No. 29 secondary prevention of occlusive
VenUS I: a randomised controlled trial By Green C, Colquitt JL, Kirby J,
vascular events: a systematic review and Davidson P, Payne E.
of two types of bandage for treating economic evaluation.
venous leg ulcers. No. 48
By Jones L, Griffin S, Palmer S, Main
By Iglesias C, Nelson EA, Cullum NA, Acupuncture of chronic headache
C, Orton V, Sculpher M, et al.
Torgerson DJ on behalf of the VenUS disorders in primary care: randomised
Team. No. 39 controlled trial and economic analysis.
Pegylated interferon -2a and -2b in By Vickers AJ, Rees RW, Zollman CE,
No. 30
combination with ribavirin in the McCarney R, Smith CM, Ellis N, et al.
Systematic review of the effectiveness
and cost-effectiveness, and economic treatment of chronic hepatitis C: a
No. 49
evaluation, of myocardial perfusion systematic review and economic
Generalisability in economic evaluation
scintigraphy for the diagnosis and evaluation. studies in healthcare: a review and case
management of angina and myocardial By Shepherd J, Brodin H, Cave C, studies.
infarction. Waugh N, Price A, Gabbay J. By Sculpher MJ, Pang FS, Manca A,
By Mowatt G, Vale L, Brazzelli M, No. 40 Drummond MF, Golder S, Urdahl H,
Hernandez R, Murray A, Scott N, et al. Clopidogrel used in combination with et al.
No. 31 aspirin compared with aspirin alone in No. 50
A pilot study on the use of decision the treatment of non-ST-segment- Virtual outreach: a randomised
theory and value of information analysis elevation acute coronary syndromes: a controlled trial and economic evaluation
as part of the NHS Health Technology systematic review and economic of joint teleconferenced medical
Assessment programme. evaluation. consultations.
By Claxton
on K,
K Ginnelly L, Sculpher By Main C, Palmer S, Griffin S, By Wallace P, Barber J, Clayton W,
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Health Technology Assessment reports published to date

Volume 9, 2005 No. 10 No. 18


Measurement of health-related quality A randomised controlled comparison of
No. 1
of life for people with dementia: alternative strategies in stroke care.
Randomised controlled multiple
development of a new instrument By Kalra L, Evans A, Perez I,
treatment comparison to provide a
(DEMQOL) and an evaluation of Knapp M, Swift C, Donaldson N.
cost-effectiveness rationale for the
current methodology.
selection of antimicrobial therapy in No. 19
By Smith SC, Lamping DL,
acne. The investigation and analysis of critical
Banerjee S, Harwood R, Foley B,
By Ozolins M, Eady EA, Avery A, incidents and adverse events in
Smith P, et al.
Cunliffe WJ, ONeill C, Simpson NB, healthcare.
et al. By Woloshynowych M, Rogers S,
No. 11 Taylor-Adams S, Vincent C.
No. 2 Clinical effectiveness and cost-
Do the findings of case series studies effectiveness of drotrecogin alfa No. 20
vary significantly according to (activated) (Xigris) for the treatment of Potential use of routine databases in
methodological characteristics? severe sepsis in adults: a systematic health technology assessment.
By Dalziel K, Round A, Stein K, review and economic evaluation. By Raftery J, Roderick P, Stevens A.
Garside R, Castelnuovo E, Payne L. By Green C, Dinnes J, Takeda A,
No. 21
Shepherd J, Hartwell D, Cave C,
Clinical and cost-effectiveness of newer
No. 3 et al.
immunosuppressive regimens in renal
Improving the referral process for
transplantation: a systematic review and
familial breast cancer genetic No. 12 modelling study.
counselling: findings of three A methodological review of how By Woodroffe R, Yao GL, Meads C,
randomised controlled trials of two heterogeneity has been examined in Bayliss S, Ready A, Raftery J, et al.
interventions. systematic reviews of diagnostic test
By Wilson BJ, Torrance N, Mollison J, accuracy. No. 22
Wordsworth S, Gray JR, Haites NE, et al. By Dinnes J, Deeks J, Kirby J, A systematic review and economic
Roderick P. evaluation of alendronate, etidronate,
No. 4 risedronate, raloxifene and teriparatide
Randomised evaluation of alternative for the prevention and treatment of
No. 13
electrosurgical modalities to treat postmenopausal osteoporosis.
Cervical screening programmes: can
bladder outflow obstruction in men with By Stevenson M, Lloyd Jones M,
automation help? Evidence from
benign prostatic hyperplasia. De Nigris E, Brewer N, Davis S,
systematic reviews, an economic analysis
By Fowler C, McAllister W, Plail R, Oakley J.
and a simulation modelling exercise
Karim O, Yang Q.
applied to the UK. No. 23
No. 5 By Willis BH, Barton P, Pearmain P, A systematic review to examine the
A pragmatic randomised controlled trial Bryan S, Hyde C. impact of psycho-educational
of the cost-effectiveness of palliative interventions on health outcomes and
therapies for patients with inoperable No. 14 costs in adults and children with difficult
oesophageal cancer. Laparoscopic surgery for inguinal asthma.
By Shenfine J, McNamee P, Steen N, hernia repair: systematic review of By Smith JR, Mugford M, Holland R,
Bond J, Griffin SM. effectiveness and economic evaluation. Candy B, Noble MJ, Harrison BDW, et al.
By McCormack K, Wake B, Perez J,
No. 6 Fraser C, Cook J, McIntosh E, et al. No. 24
Impact of computer-aided detection An evaluation of the costs, effectiveness
prompts on the sensitivity and specificity No. 15 and quality of renal replacement
of screening mammography. Clinical effectiveness, tolerability and therapy provision in renal satellite units
By Taylor P, Champness J, Given- cost-effectiveness of newer drugs for in England and Wales.
Wilson R, Johnston K, Potts H. epilepsy in adults: a systematic review By Roderick P, Nicholson T, Armitage
and economic evaluation. A, Mehta R, Mullee M, Gerard K, et al.
No. 7 By Wilby J, Kainth A, Hawkins N, No. 25
Issues in data monitoring and interim Epstein D, McIntosh H, McDaid C, et al. Imatinib for the treatment of patients
analysis of trials.
with unresectable and/or metastatic
By Grant AM, Altman DG, Babiker
No. 16 gastrointestinal stromal tumours:
AB, Campbell MK, Clemens FJ,
A randomised controlled trial to systematic review and economic
Darbyshire JH, et al.
compare the cost-effectiveness of evaluation.
No. 8 tricyclic antidepressants, selective By Wilson J, Connock M, Song F, Yao
Lay publics understanding of equipoise serotonin reuptake inhibitors and G, Fry-Smith A, Raftery J, et al.
and randomisation in randomised lofepramine.
By Peveler R, Kendrick T, Buxton M, No. 26
controlled trials. Indirect comparisons of competing
By Robinson EJ, Kerr CEP, Stevens Longworth L, Baldwin D, Moore M,
et al. interventions.
AJ, Lilford RJ, Braunholtz DA, Edwards By Glenny AM, Altman DG, Song F,
SJ, et al. Sakarovitch C, Deeks JJ, DAmico R, et al.
No. 17
No. 9 Clinical effectiveness and cost- No. 27
Clinical and cost-effectiveness of effectiveness of immediate angioplasty Cost-effectiveness of alternative
electroconvulsive therapy for depressive for acute myocardial infarction: strategies for the initial medical
illness, schizophrenia, catatonia and systematic review and economic management of non-ST elevation acute
mania: systematic reviews and economic evaluation. coronary syndrome: systematic review
modelling studies. By Hartwell D, Colquitt J, Loveman and decision-analytical modelling.
By Greenhalgh J, Knight C, Hind D, E, Clegg AJ, Brodin H, Waugh N, By Robinson M, Palmer S, Sculpher
90 Beverley C, Walters S. et al. M, Philips Z, Ginnelly L, Bowens A, et al.
Health Technology Assessment 2006; Vol. 10: No. 16

No. 28 No. 38 No. 46


Outcomes of electrically stimulated The causes and effects of socio- The effectiveness of the Heidelberg
gracilis neosphincter surgery. demographic exclusions from clinical Retina Tomograph and laser diagnostic
By Tillin T, Chambers M, Feldman R. trials. glaucoma scanning system (GDx) in
By Bartlett C, Doyal L, Ebrahim S, detecting and monitoring glaucoma.
No. 29 Davey P, Bachmann M, Egger M, By Kwartz AJ, Henson DB,
The effectiveness and cost-effectiveness et al. Harper RA, Spencer AF,
of pimecrolimus and tacrolimus for McLeod D.
atopic eczema: a systematic review and No. 39
economic evaluation. Is hydrotherapy cost-effective? A No. 47
By Garside R, Stein K, Castelnuovo E, randomised controlled trial of combined Clinical and cost-effectiveness of
Pitt M, Ashcroft D, Dimmock P, et al. hydrotherapy programmes compared autologous chondrocyte implantation
with physiotherapy land techniques in for cartilage defects in knee joints:
No. 30 children with juvenile idiopathic systematic review and economic
Systematic review on urine albumin arthritis. evaluation.
testing for early detection of diabetic By Epps H, Ginnelly L, Utley M, By Clar C, Cummins E, McIntyre L,
complications. Southwood T, Gallivan S, Sculpher M, Thomas S, Lamb J, Bain L, et al.
By Newman DJ, Mattock MB, Dawnay et al.
ABS, Kerry S, McGuire A, Yaqoob M, et al. No. 48
No. 40 Systematic review of effectiveness of
No. 31 different treatments for childhood
A randomised controlled trial and cost-
Randomised controlled trial of the cost- retinoblastoma.
effectiveness study of systematic
effectiveness of water-based therapy for By McDaid C, Hartley S,
screening (targeted and total population
lower limb osteoarthritis. Bagnall A-M, Ritchie G, Light K,
screening) versus routine practice for
By Cochrane T, Davey RC, Riemsma R.
the detection of atrial fibrillation in
Matthes Edwards SM.
people aged 65 and over. The SAFE
study. No. 49
No. 32
By Hobbs FDR, Fitzmaurice DA, Towards evidence-based guidelines
Longer term clinical and economic
Mant J, Murray E, Jowett S, Bryan S, for the prevention of venous
benefits of offering acupuncture care to
et al. thromboembolism: systematic
patients with chronic low back pain.
reviews of mechanical methods, oral
By Thomas KJ, MacPherson H,
No. 41 anticoagulation, dextran and regional
Ratcliffe J, Thorpe L, Brazier J,
Displaced intracapsular hip fractures anaesthesia as thromboprophylaxis.
Campbell M, et al.
in fit, older people: a randomised By Roderick P, Ferris G, Wilson K,
No. 33 comparison of reduction and fixation, Halls H, Jackson D, Collins R,
Cost-effectiveness and safety of epidural bipolar hemiarthroplasty and total hip et al.
steroids in the management of sciatica. arthroplasty.
By Keating JF, Grant A, Masson M, No. 50
By Price C, Arden N, Coglan L,
Scott NW, Forbes JF. The effectiveness and cost-effectiveness
Rogers P.
of parent training/education
No. 34 No. 42 programmes for the treatment of
The British Rheumatoid Outcome Study Long-term outcome of cognitive conduct disorder, including oppositional
Group (BROSG) randomised controlled behaviour therapy clinical trials in defiant disorder, in children.
trial to compare the effectiveness and central Scotland. By Dretzke J, Frew E, Davenport C,
cost-effectiveness of aggressive versus By Durham RC, Chambers JA, Barlow J, Stewart-Brown S,
symptomatic therapy in established Power KG, Sharp DM, Macdonald RR, Sandercock J, et al.
rheumatoid arthritis. Major KA, et al.
By Symmons D, Tricker K, Roberts C, Volume 10, 2006
No. 43
Davies L, Dawes P, Scott DL.
The effectiveness and cost-effectiveness No. 1
No. 35 of dual-chamber pacemakers compared The clinical and cost-effectiveness of
Conceptual framework and systematic with single-chamber pacemakers for donepezil, rivastigmine, galantamine
review of the effects of participants and bradycardia due to atrioventricular and memantine for Alzheimers
professionals preferences in randomised block or sick sinus syndrome: disease.
controlled trials. systematic review and economic By Loveman E, Green C, Kirby J,
By King M, Nazareth I, Lampe F, evaluation. Takeda A, Picot J, Payne E,
Bower P, Chandler M, Morou M, et al. By Castelnuovo E, Stein K, Pitt M, et al.
Garside R, Payne E.
No. 36 No. 2
The clinical and cost-effectiveness of No. 44 FOOD: a multicentre randomised trial
implantable cardioverter defibrillators: Newborn screening for congenital heart evaluating feeding policies in patients
a systematic review. defects: a systematic review and admitted to hospital with a recent
By Bryant J, Brodin H, Loveman E, cost-effectiveness analysis. stroke.
Payne E, Clegg A. By Knowles R, Griebsch I, Dezateux By Dennis M, Lewis S, Cranswick G,
C, Brown J, Bull C, Wren C. Forbes J.
No. 37
A trial of problem-solving by community No. 45 No. 3
mental health nurses for anxiety, The clinical and cost-effectiveness of left The clinical effectiveness and cost-
depression and life difficulties among ventricular assist devices for end-stage effectiveness of computed tomography
general practice patients. The CPN-GP heart failure: a systematic review and screening for lung cancer: systematic
study. economic evaluation. reviews.
By Kendrick T, Simons L, By Clegg AJ, Scott DA, Loveman E, By Black C, Bagust A, Boland A,
Mynors-Wallis L, Gray A, Lathlean J, Colquitt J, Hutchinson J, Royle P, Walker S, McLeod C, De Verteuil R,
Pickering R, et al. et al. et al. 91

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Health Technology Assessment reports published to date

No. 4 No. 8 No. 12


A systematic review of the effectiveness Surveillance of Barretts oesophagus: A series of systematic reviews to inform
and cost-effectiveness of neuroimaging exploring the uncertainty through a decision analysis for sampling and
assessments used to visualise the systematic review, expert workshop and treating infected diabetic foot ulcers.
seizure focus in people with refractory economic modelling. By Nelson EA, OMeara S, Craig D,
epilepsy being considered for By Garside R, Pitt M, Somerville M, Iglesias C, Golder S, Dalton J, et al.
surgery. Stein K, Price A, Gilbert N. No. 13
By Whiting P, Gupta R, Burch J, Randomised clinical trial, observational
No. 9
Mujica Mota RE, Wright K, Marson A, study and assessment of cost-effectiveness
Topotecan, pegylated liposomal
et al. of the treatment of varicose veins
doxorubicin hydrochloride and
paclitaxel for second-line or subsequent (REACTIV trial).
No. 5
treatment of advanced ovarian cancer: a By Michaels JA, Campbell WB,
Comparison of conference abstracts
systematic review and economic Brazier JE, MacIntyre JB, Palfreyman SJ,
and presentations with full-text
evaluation. Ratcliffe J, et al.
articles in the health technology
assessments of rapidly evolving By Main C, Bojke L, Griffin S, No. 14
technologies. Norman G, Barbieri M, Mather L, The cost-effectiveness of screening for
By Dundar Y, Dodd S, Dickson R, et al. oral cancer in primary care.
Walley T, Haycox A, Williamson PR. No. 10 By Speight PM, Palmer S, Moles DR,
Evaluation of molecular techniques in Downer MC, Smith DH,
No. 6 prediction and diagnosis of Henriksson M et al.
Systematic review and evaluation of cytomegalovirus disease in No. 15
methods of assessing urinary immunocompromised patients. Measurement of the clinical and cost-
incontinence. By Szczepura A, Westmoreland D, effectiveness of non-invasive diagnostic
By Martin JL, Williams KS, Abrams Vinogradova Y, Fox J, Clark M. testing strategies for deep vein
KR, Turner DA, Sutton AJ, Chapple C,
No. 11 thrombosis.
et al.
Screening for thrombophilia in high-risk By Goodacre S, Sampson F, Stevenson
situations: systematic review and cost- M, Wailoo A, Sutton A, Thomas S, et al.
No. 7
The clinical effectiveness and effectiveness analysis. The Thrombosis: No. 16
cost-effectiveness of newer drugs for Risk and Economic Assessment of Systematic review of the effectiveness
children with epilepsy. A systematic Thrombophilia Screening (TREATS) and cost-effectiveness of HealOzone
review. study. for the treatment of occlusal pit/fissure
By Connock M, Frew E, Evans B-W, By Wu O, Robertson L, Twaddle S, caries and root caries.
Bryan S, Cummins C, Fry-Smith A, Lowe GDO, Clark P, Greaves M, By Brazzelli M, McKenzie L, Fielding
et al. et al. S, Fraser C, Clarkson J, Kilonzo M, et al.

92
Health Technology Assessment 2006; Vol. 10: No. 16

Health Technology Assessment


Programme
Director, Deputy Director,
Professor Tom Walley, Professor Jon Nicholl,
Director, NHS HTA Programme, Director, Medical Care Research
Department of Pharmacology & Unit, University of Sheffield,
Therapeutics, School of Health and Related
University of Liverpool Research

Prioritisation Strategy Group


Members

Chair, Professor Bruce Campbell, Professor Jon Nicholl, Director, Dr Ron Zimmern, Director,
Professor Tom Walley, Consultant Vascular & General Medical Care Research Unit, Public Health Genetics Unit,
Director, NHS HTA Programme, Surgeon, Royal Devon & Exeter University of Sheffield, School Strangeways Research
Department of Pharmacology & Hospital of Health and Related Research Laboratories, Cambridge
Therapeutics,
Dr Edmund Jessop, Medical Dr John Reynolds, Clinical
University of Liverpool
Advisor, National Specialist, Director, Acute General
Commissioning Advisory Group Medicine SDU, Radcliffe
(NSCAG), Department of Hospital, Oxford
Health, London

HTA Commissioning Board


Members

Programme Director, Professor Ann Bowling, Professor Fiona J Gilbert, Dr Linda Patterson,
Professor Tom Walley, Professor of Health Services Professor of Radiology, Consultant Physician,
Director, NHS HTA Programme, Research, Primary Care and Department of Radiology, Department of Medicine,
Department of Pharmacology & Population Studies, University of Aberdeen Burnley General Hospital
Therapeutics, University College London
University of Liverpool Professor Adrian Grant, Professor Ian Roberts, Professor
Dr Andrew Briggs, Public Director, Health Services of Epidemiology & Public
Chair,
Health Career Scientist, Health Research Unit, University of Health, Intervention Research
Professor Jon Nicholl,
Economics Research Centre, Aberdeen Unit, London School of
Director, Medical Care Research
University of Oxford Hygiene and Tropical Medicine
Unit, University of Sheffield,
Professor F D Richard Hobbs,
School of Health and Related
Professor John Cairns, Professor Professor of Primary Care & Professor Mark Sculpher,
Research
of Health Economics, Public General Practice, Department of Professor of Health Economics,
Deputy Chair, Health Policy, London School of Primary Care & General Centre for Health Economics,
Professor Jenny Hewison, Hygiene and Tropical Medicine, Practice, University of Institute for Research in the
Professor of Health Care London Birmingham Social Services, University of York
Psychology, Academic Unit of
Psychiatry and Behavioural Professor Nicky Cullum, Professor Peter Jones, Head of
Sciences, University of Leeds Dr Jonathan Shapiro, Senior
Director of Centre for Evidence Department, University
School of Medicine Fellow, Health Services
Based Nursing, Department of Department of Psychiatry,
Management Centre,
Health Sciences, University of University of Cambridge
Birmingham
York
Dr Jeffrey Aronson
Professor Sallie Lamb,
Reader in Clinical Ms Kate Thomas,
Mr Jonathan Deeks, Professor of Rehabilitation,
Pharmacology, Department of Deputy Director,
Senior Medical Statistician, Centre for Primary Health Care,
Clinical Pharmacology, Medical Care Research Unit,
Centre for Statistics in University of Warwick
Radcliffe Infirmary, Oxford University of Sheffield
Medicine, University of Oxford
Professor Deborah Ashby, Professor Stuart Logan,
Professor of Medical Statistics, Dr Andrew Farmer, Senior Director of Health & Social Ms Sue Ziebland,
Department of Environmental Lecturer in General Practice, Care Research, The Research Director, DIPEx,
and Preventative Medicine, Department of Primary Peninsula Medical School, Department of Primary Health
Queen Mary University of Health Care, Universities of Exeter & Care, University of Oxford,
London University of Oxford Plymouth Institute of Health Sciences

93
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Queens Printer and Controller of HMSO 2006. All rights reserved.


Health Technology Assessment Programme

Diagnostic Technologies & Screening Panel


Members

Chair, Professor Adrian K Dixon, Dr Susanne M Ludgate, Medical Professor Lindsay Wilson
Dr Ron Zimmern, Director of Professor of Radiology, Director, Medicines & Turnbull, Scientific Director,
the Public Health Genetics Unit, University Department of Healthcare Products Regulatory Centre for MR Investigations &
Strangeways Research Radiology, University of Agency, London YCR Professor of Radiology,
Laboratories, Cambridge Cambridge Clinical School University of Hull
Professor William Rosenberg,
Professor of Hepatology, Liver Professor Martin J Whittle,
Dr David Elliman, Research Group, University of
Ms Norma Armston, Consultant Paediatrician/ Associate Dean for Education,
Southampton Head of Department of
Lay Member, Bolton Hon. Senior Lecturer,
Population Health Unit, Obstetrics and Gynaecology,
Dr Susan Schonfield, Consultant
Professor Max Bachmann Great Ormond St. Hospital, University of Birmingham
in Public Health, Specialised
Professor of Health London Services Commissioning North
Care Interfaces, Dr Dennis Wright,
West London, Hillingdon
Department of Health Consultant Biochemist &
Professor Glyn Elwyn, Primary Care Trust
Policy and Practice, Clinical Director,
University of East Anglia Primary Medical Care Dr Phil Shackley, Senior Pathology & The Kennedy
Research Group, Lecturer in Health Economics, Galton Centre,
Professor Rudy Bilous Swansea Clinical School, School of Population and Northwick Park & St Marks
Professor of Clinical Medicine & University of Wales Swansea Health Sciences, University of Hospitals, Harrow
Consultant Physician, Newcastle upon Tyne
The Academic Centre, Mr Tam Fry, Honorary
South Tees Hospitals NHS Trust Chairman, Child Growth Dr Margaret Somerville, PMS
Foundation, London Public Health Lead, Peninsula
Dr Paul Cockcroft, Medical School, University of
Consultant Medical Plymouth
Microbiologist and Clinical Dr Jennifer J Kurinczuk,
Director of Pathology, Consultant Clinical Dr Graham Taylor, Scientific
Department of Clinical Epidemiologist, Director & Senior Lecturer,
Microbiology, St Mary's National Perinatal Regional DNA Laboratory, The
Hospital, Portsmouth Epidemiology Unit, Oxford Leeds Teaching Hospitals

Pharmaceuticals Panel
Members

Chair, Mr Peter Cardy, Chief Dr Christine Hine, Consultant in Professor Jan Scott, Professor
Dr John Reynolds, Chair Executive, Macmillan Cancer Public Health Medicine, South of Psychological Treatments,
Division A, The John Radcliffe Relief, London Gloucestershire Primary Care Institute of Psychiatry,
Hospital, Oxford Radcliffe Trust University of London
Hospitals NHS Trust Professor Imti Choonara,
Professor in Child Health, Professor Stan Kaye, Mrs Katrina Simister, Assistant
Academic Division of Child Cancer Research UK Director New Medicines,
Health, University of Professor of Medical Oncology, National Prescribing Centre,
Professor Tony Avery,
Nottingham Section of Medicine, Liverpool
Head of Division of Primary
The Royal Marsden Hospital,
Care, School of Community
Dr Robin Ferner, Consultant Sutton Dr Richard Tiner, Medical
Health Services, Division of
General Practice, University of Physician and Director, West Director, Medical Department,
Ms Barbara Meredith,
Nottingham Midlands Centre for Adverse Association of the British
Lay Member, Epsom
Drug Reactions, City Hospital Pharmaceutical Industry,
Ms Anne Baileff, Consultant NHS Trust, Birmingham Dr Andrew Prentice, Senior London
Nurse in First Contact Care, Lecturer and Consultant
Southampton City Primary Care Dr Karen A Fitzgerald, Obstetrician & Gynaecologist, Dr Helen Williams,
Trust, University of Consultant in Pharmaceutical Department of Obstetrics & Consultant Microbiologist,
Southampton Public Health, National Public Gynaecology, University of Norfolk & Norwich University
Health Service for Wales, Cambridge Hospital NHS Trust
Professor Stirling Bryan, Cardiff
Professor of Health Economics, Dr Frances Rotblat, CPMP
Health Services Mrs Sharon Hart, Head of Delegate, Medicines &
Management Centre, DTB Publications, Drug & Healthcare Products Regulatory
University of Birmingham Therapeutics Bulletin, London Agency, London

94
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
Health Technology Assessment 2006; Vol. 10: No. 16

Therapeutic Procedures Panel


Members
Chair, Dr Carl E Counsell, Clinical Ms Maryann L Hardy, Professor James Neilson,
Professor Bruce Campbell, Senior Lecturer in Neurology, Lecturer, Division of Professor of Obstetrics and
Consultant Vascular and Department of Medicine and Radiography, University of Gynaecology, Department of
General Surgeon, Department Therapeutics, University of Bradford Obstetrics and Gynaecology,
of Surgery, Royal Devon & Aberdeen University of Liverpool
Exeter Hospital Professor Alan Horwich,
Ms Amelia Curwen, Executive Dr John C Pounsford,
Director of Clinical R&D, Consultant Physician,
Director of Policy, Services and
Academic Department of Directorate of Medical Services,
Research, Asthma UK, London
Radiology, The Institute of North Bristol NHS Trust
Professor Gene Feder, Professor Cancer Research,
of Primary Care R&D, London Karen Roberts, Nurse
Department of General Practice Consultant, Queen Elizabeth
and Primary Care, Barts & the Hospital, Gateshead
Dr Simon de Lusignan,
London, Queen Marys School Senior Lecturer, Dr Vimal Sharma, Consultant
Dr Aileen Clarke, of Medicine and Dentistry, Primary Care Informatics, Psychiatrist/Hon. Senior Lecturer,
Reader in Health Services London Department of Community Mental Health Resource Centre,
Research, Public Health & Health Sciences, Cheshire and Wirral Partnership
Policy Research Unit, Barts & Professor Paul Gregg, St Georges Hospital Medical NHS Trust, Wallasey
the London School of Medicine Professor of Orthopaedic School, London
& Dentistry, London Surgical Science, Department of Dr L David Smith, Consultant
General Practice and Primary Cardiologist, Royal Devon &
Dr Matthew Cooke, Reader in Care, South Tees Hospital NHS Professor Neil McIntosh, Exeter Hospital
A&E/Department of Health Trust, Middlesbrough Edward Clark Professor of
Advisor in A&E, Warwick Child Life & Health, Professor Norman Waugh,
Emergency Care and Ms Bec Hanley, Co-Director, Department of Child Life & Professor of Public Health,
Rehabilitation, University of TwoCan Associates, Health, University of Department of Public Health,
Warwick Hurstpierpoint Edinburgh University of Aberdeen

95
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
Health Technology Assessment Programme

Expert Advisory Network


Members

Professor Douglas Altman, Mr John Dunning, Dr Duncan Keeley, Professor Chris Price,
Director of CSM & Cancer Consultant Cardiothoracic General Practitioner (Dr Burch Visiting Chair Oxford, Clinical
Research UK Med Stat Gp, Surgeon, Cardiothoracic & Ptnrs), The Health Centre, Research, Bayer Diagnostics
Centre for Statistics in Surgical Unit, Papworth Thame Europe, Cirencester
Medicine, University of Oxford, Hospital NHS Trust, Cambridge
Institute of Health Sciences, Dr Donna Lamping, Professor Peter Sandercock,
Headington, Oxford Mr Jonothan Earnshaw, Research Degrees Programme Professor of Medical Neurology,
Consultant Vascular Surgeon, Director & Reader in Psychology, Department of Clinical
Professor John Bond, Gloucestershire Royal Hospital, Health Services Research Unit, Neurosciences, University of
Director, Centre for Health Gloucester London School of Hygiene and Edinburgh
Services Research, University of Tropical Medicine, London
Newcastle upon Tyne, School of Professor Martin Eccles, Dr Eamonn Sheridan,
Population & Health Sciences, Professor of Clinical Mr George Levvy, Consultant in Clinical Genetics,
Newcastle upon Tyne Effectiveness, Centre for Health Chief Executive, Motor Genetics Department,
Services Research, University of Neurone Disease Association, St Jamess University Hospital,
Mr Shaun Brogan, Newcastle upon Tyne Northampton Leeds
Chief Executive, Ridgeway
Professor Pam Enderby, Professor James Lindesay, Dr Ken Stein,
Primary Care Group, Aylesbury
Professor of Community Professor of Psychiatry for the Senior Clinical Lecturer in
Rehabilitation, Institute of Elderly, University of Leicester, Public Health, Director,
Mrs Stella Burnside OBE,
General Practice and Primary Leicester General Hospital Peninsula Technology
Chief Executive, Office of the
Care, University of Sheffield Assessment Group,
Chief Executive. Trust Professor Julian Little, University of Exeter
Headquarters, Altnagelvin Professor of Human Genome
Hospitals Health & Social Mr Leonard R Fenwick,
Chief Executive, Newcastle Epidemiology, Department of Professor Sarah Stewart-Brown,
Services Trust, Altnagelvin Area Epidemiology & Community Professor of Public Health,
Hospital, Londonderry upon Tyne Hospitals NHS Trust
Medicine, University of Ottawa University of Warwick,
Professor David Field, Division of Health in the
Ms Tracy Bury, Professor Rajan Madhok, Community Warwick Medical
Professor of Neonatal Medicine,
Project Manager, World Medical Director & Director of School, LWMS, Coventry
Child Health, The Leicester
Confederation for Physical Public Health, Directorate of
Royal Infirmary NHS Trust
Therapy, London Clinical Strategy & Public Professor Ala Szczepura,
Mrs Gillian Fletcher, Health, North & East Yorkshire Professor of Health Service
Professor Iain T Cameron, & Northern Lincolnshire Health Research, Centre for Health
Antenatal Teacher & Tutor and
Professor of Obstetrics and Authority, York Services Studies, University of
President, National Childbirth
Gynaecology and Head of the Warwick
Trust, Henfield
School of Medicine, Professor David Mant,
University of Southampton Professor Jayne Franklyn, Professor of General Practice, Dr Ross Taylor,
Professor of Medicine, Department of Primary Care, Senior Lecturer, Department of
Dr Christine Clark, Department of Medicine, University of Oxford General Practice and Primary
Medical Writer & Consultant University of Birmingham, Care, University of Aberdeen
Pharmacist, Rossendale Professor Alexander Markham,
Queen Elizabeth Hospital,
Director, Molecular Medicine Mrs Joan Webster,
Edgbaston, Birmingham
Professor Collette Clifford, Unit, St Jamess University Consumer member, HTA
Professor of Nursing & Head of Ms Grace Gibbs, Hospital, Leeds Expert Advisory Network
Research, School of Health Deputy Chief Executive,
Sciences, University of Dr Chris McCall,
Director for Nursing, Midwifery
Birmingham, Edgbaston, General Practitioner, The
& Clinical Support Services,
Birmingham Hadleigh Practice, Castle Mullen
West Middlesex University
Hospital, Isleworth Professor Alistair McGuire,
Professor Barry Cookson,
Director, Laboratory of Professor of Health Economics,
Dr Neville Goodman, London School of Economics
Healthcare Associated Infection, Consultant Anaesthetist,
Health Protection Agency, Southmead Hospital, Bristol Dr Peter Moore,
London Freelance Science Writer, Ashtead
Professor Alastair Gray,
Professor Howard Cuckle, Professor of Health Economics, Dr Sue Moss, Associate Director,
Professor of Reproductive Department of Public Health, Cancer Screening Evaluation
Epidemiology, Department of University of Oxford Unit, Institute of Cancer
Paediatrics, Obstetrics & Research, Sutton
Gynaecology, University of Professor Robert E Hawkins,
Leeds CRC Professor and Director of Mrs Julietta Patnick,
Medical Oncology, Christie CRC Director, NHS Cancer Screening
Dr Katherine Darton, Research Centre, Christie Programmes, Sheffield
Information Unit, MIND Hospital NHS Trust, Manchester
The Mental Health Charity, Professor Tim Peters,
London Professor Allen Hutchinson, Professor of Primary Care
Director of Public Health & Health Services Research,
Professor Carol Dezateux, Deputy Dean of ScHARR, Academic Unit of Primary
Professor of Paediatric Department of Public Health, Health Care, University of
Epidemiology, London University of Sheffield Bristol

96
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
HTA

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Health Technology Assessment 2006; Vol. 10: No. 16
Health Technology Assessment 2006; Vol. 10: No. 16

Systematic review of the effectiveness


and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

HealOzone for the treatment of occlusal pit/fissure caries and root caries
M Brazzelli, L McKenzie, S Fielding, C Fraser,
J Clarkson, M Kilonzo and N Waugh
Feedback
The HTA Programme and the authors would like to know
your views about this report.
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your comments. If you prefer, you can send your comments
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We look forward to hearing from you.

May 2006

The National Coordinating Centre for Health Technology Assessment,


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Fax: +44 (0) 23 8059 5639 Email: hta@hta.ac.uk
Health Technology Assessment
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http://www.hta.ac.uk ISSN 1366-5278