RESEARCH

Drug-Related Morbidity
and Mortality: Updating
the Cost-of-Illness Model
Frank R. Ernst and Amy J. Grizzle

Objective: To update the 1995 estimate of $76.6 billion for the annual cost of drug-related morbidity and mortality resulting from drugrelated problems (DRPs) in the ambulatory setting in the United States to reflect current treatment patterns and costs. Design:
For this study, we employed the decision-analytic model developed by Johnson and Bootman. We used the models original design and
probability data, but used updated cost estimates derived from the current medical and pharmaceutical literature. Sensitivity anal-yses
were performed on cost data and on probability estimates. Setting: Ambulatory care environment in the United States in the year 2000.
Patients and Other Participants: A hypothetical cohort of ambulatory patients. Main Outcome Measures: Average cost of health care
resources needed to manage DRPs. Results: As estimated using the decision-tree model, the mean cost for a treat-ment failure was
$977. For a new medical problem, the mean cost was $1,105, and the cost of a combined treatment failure and result-ing new medical
problem was $1,488. Overall, the cost of drug-related morbidity and mortality exceeded $177.4 billion in 2000. Hospi-tal admissions
accounted for nearly 70% ($121.5 billion) of total costs, followed by long-term-care admissions, which accounted for 18% ($32.8 billion).
Conclusion: Since 1995, the costs associated with DRPs have more than doubled. Given the economic and medi-cal burdens associated
with DRPs, strategies for preventing drug-related morbidity and mortality are urgently needed.
J Am Pharm Assoc. 2001;41:1929.

Whenpeopleusemedications,anynumberofoutcomesare
possible. Most commonly, the patient benefits from pharma
cotherapeutic interventions; however, adverse events, ranging
fromminorsideeffectstodeath,mayoccur.Anydeviationfrom
theintendedbeneficialeffectofamedicationresultsinadrug
1

relatedproblem(DRP). OneormoreDRPsmaydevelopina
givenpatientaftertheinitialdrugtherapy.
Researchers have shown that costs associated with DRPs
exceedtheexpendituresforinitialdrugtherapy;thatis,thetotal
costofdrugrelatedmorbidityandmortalityexceedsthecostof
2,3

the medications themselves. DRPs are increasingly

recognizedasaseriousandurgentbutlargelypreventable
medicalproblem.
In1989Manasseproposedthat,becauseDRPsareofimmense

Received August 25, 2000, and in revised form January 8, 2001.

Accepted for publication January 19, 2001.
Frank R. Ernst, PharmD, is an Eli Lilly and Company Health Outcomes
Fellow; Amy J. Grizzle, PharmD, is assistant director, Center for Health
Outcomes and PharmacoEconomic Research, College of Pharmacy,
University of Arizona, Tucson.
Correspondence: Frank R. Ernst, PharmD, College of Pharmacy, Univer-sity
of Arizona, P.O. Box 210207, Tucson, AZ 85721-0207. Fax: 520-626-

3386. E-mail: Ernst@Pharmacy.Arizona.edu.

See related Viewpoint on page 156.

importance to the whole of

societyaswellastohealthcare
providers, administrators, and
patients, they should be
addressedasamatterofpublic
4,5

policy. In the following 6

years, research focused
primarily on documenting
increased rates of hospitaliza
tion resulting from
nonadherence to prescribed
medication regimens and/or
adversedrugeffects.

617

JohnsonandBootman, ina
widely cited study published
in 1995, detailed a costof
illness model they developed
to address drugrelated
morbidityandmortalityinthe
ambulatorycaresettinginthe
United States. Using a
structure originally developed
18,19
by Hepler and Strand,
Johnson and Bootman
developed a decisionanalytic
model for eight possible
negative outcomes of drug
therapy:
1
Untreatedindication

2
3
4
5
6

7
8

Improperdrugselection
Subtherapeuticdosage
Failuretoreceivedrugs
Overdosage
Adversedrugreactions

Druginteractions
Drug use without
indication
The model included
probabilities and costs

associated with the following

therapeuticoutcomes,anyone
ofwhichcouldresultfromthe
aboveeightpossibilities:

192

Journalofthe Association March/April2001Vol.41,No.2

AmericanPharmaceutical

valuesforthefollowingvariableshadchanged:

1
1
2
3
4
5
6
7

Notreatmentnecessary
Physicianvisit
Additionaltreatment
Emergencydepartmentvisit
Hospitaladmission
Longtermcarefacilityadmission
Death

Onthebasisofdataobtainedintheearly1990s,Johnsonand
Bootmanestimatedthat,onaverage,$76.6billion($30.1billionto
$136.8billion)isspentannuallyintheambulatorysettinginthe
UnitedStatestoresolveDRPs,withdrugrelatedhospitalizations
1

beingthelargestcomponentofthiscost. Atthetimeofthestudy,
their model seemed appropriate, based on an assessment of
20

previously published findings. The model did have some

acknowledgedweaknesses,however.Membersoftheexpertpan
el Johnson and Bootman consulted used their best estimates,
ratherthanactualempiricaldata,indeterminingtheprobabilities
oftherapeuticoutcomes;monetaryvalueswereextrapolatedfrom
previously published research reports and available statistical
reportsandusedtoestimatemeancosts.
Asrecenthistoryindicates,healthcaretrendschangequickly.
Therefore,someofthedatausedinthe1995study,andhencethe
estimatesdeveloped,areoutdated.Fortunately,empiricaldataare
availableforusewithcostofillnessmodels.Severalstudiespub
lishedsince1995have,forexample,investigatedthecostofdrug
21
relatedmorbidityandmortalityinspecificpatientpopulations.
24
Otheradditionstotheliteraturehaveexaminedtheincidence
25 31
andprobabilitiesofdrugmisadventures.

Objective
Ourpurposeforconductingthisstudywastoupdatethe1995
estimateof$76.6billionfortheannualcostofdrugrelatedmor
bidityandmortalityresultingfromDRPsintheambulatorysetting
intheUnitedStatestoreflectcurrenttreatmentpatternsandcosts.

Methods
Weduplicatedthe1995analysisusingJohnsonandBootmans
1

originaldecisionanalyticmodel andfulldataset(obtainedwith
thecooperationoftheoriginalauthors)onwhichthepublication
32

anditsprecedingreportwerebased. Wedidthistoensurewe
fullyunderstoodthemathematicalcalculationsanddecisionanal
yses performed during the previous study before we made any
attemptstoreassessthem.Weinvestigatedthepossibilitythatthe

Initialtreatmentcosts,suchasthoseforaphysician
visitanddrugs

Costsofnegativetherapeuticoutcomes,suchasadditional
physicianvisits,moredrugs,emergencydepartment(ED)visits,
hospitaladmissions,andlongtermcare(LTC)admissions

Updated Cost-of-Illness Model RESEARCH

Costs of nonnegativeoutcome treatment failures

(TFs)ornewmedicalproblems(NMPs)
2
Totalpathwaycosts
3
Outcome probability estimates for each of the
pathways.

Data Selection and Collection

Theoriginalstudyusedapanelofclinicalexpertstocollect
dataontherapeuticoutcomes,resourceuse,andprobabilities
18,19
associatedwiththeeightpotentialDRPs.
Theoriginalcost
datawerecollectedfromavarietyofnationallyrepresentative
datasources.Usingdatapublishedsincethe1995study,we
updatedthesevaluesforthepresentstudyandadjustedtoMay
33
2000 dollars using the Consumer Price Index. When we
could not find more recent data, we used the Johnson and
Bootmandata.
Between July 1999 and March 2000 we searched journal
articlespublishedsince1992usingMEDLINE,International
Pharmaceutical Abstracts, tertiary health statistic resources,
andothersearchenginesandelectronicandprinteddatabases
availablethroughtheArizonaHealthSciencesLibrary.Search
terms used in MEDLINE and IPA searches included drug
therapy,adverseeffect,morbidityandmortality,drugrelated,
druginduced,drugrelatedproblem,andcompliance.

Cost Calculations
Wedeterminedtheaveragecostsofphysicianvisits,prescrip
tionmedications,EDvisits,hospitaladmissions,andLTCadmis
sionsusingthemostrecentdataavailablebeforeMarch2000.To
minimizepotentialvariation,wereliedheavilyonthesamecost
ingsourcesusedforthe1995estimates.Thecostofaphysician
visitwasdeterminedusingaweightedaverageofthemeanphysi
34

cianfeesfornewandestablishedpatients, reportedfor1998.
Theaveragecostofaprescriptionwascalculatedbydividingthe
sumofreportedsalesforbothgenericandbrandprescription
drugsbythetotalnumberofgenericandbrandprescriptionsdis
35,36

pensedin1999.
TofactorinTF,anadjustedprescriptioncost
wasused;whenmakingthiscalculationweassumed,asJohnson
1,32
andBootmandid,that10%ofprescriptionsareneverfilled.
Thecostofhospitaladmissionswascalculatedbydividingthe
reportedhospitalrevenuefrominpatientadmissionsin1998bythe
37

numberofadmissionsforthatyear. LTCperadmissioncostwas
calculatedfromreporteddata,aswell,usingthe1996monthly
38

averagecostperLTCresident, adjustedforthe1996average
lengthofstay.AsintheJohnsonandBootmanstudy,pathway
costsinvolvingadditionalprescriptionsreflectedtheassumption
thatLTCadmissioncostsfollowedadditionalphysicianvisits,and
death cost pathways assumed that hospitalization preceded the
finaloutcome.Eachcomponentcostwasadjustedtoyear2000
dollars.Totalpathwaycosts,then,weresumsoftheupdatedcosts
ofindividualpathwaycomponents.
Vol.41,No.2March/April2001

193

JournaloftheAmericanPharmaceuticalAssociation

RESEARCH

Figure 1.
Drug-Related
Morbidity and
a
Mortality

Updated Cost-of-Illness Model

$
2
9
8
;
P
$151; P = .377

$147; P = .027

=
.
0
2
0

$256; P = .031

$298; P = .066

$
4
5
5
;
P
=

$455; P = .015

.
0
0
5

$12,793; P = .006

$9,636; P = .003

$12,793; P < .000

$151; P = .010

$260; P = .019

$302; P = .028

$459; P = .006
Health care
encounter
$12,797; P = .003

$1
2,
79
3;
P
=.
00
4

$
9,
6
3
6;
P
<
.
0
0
0

$1
2,
79
3;
P
<.
00
0

$9,640; P = .001

$12,797; P < .000

$
1
0
9
;
P

$147; P = .003

$256; P = .009

.
3
6
7

ED = emergency
department; LTC = longa
term-care. Derivation of

194
Journal
ofthe
America
n
Pharmac
eutical
Associati
on
March/A
pril2001
Vol.41,
No.2

aage outcome
vcosts is
eshown in
r Table 2.

Updated Cost-of-Illness Model

Table 1. Average Annual Costs of Health Care Resources to Manage Drug-Related Problems
Resource
Physician visit

Previous Cost Estimate

$64

RESEARCH

Recent Cost Estimate

$109

% Change
+70

New prescription

$25

$42

ED visit

$312

$308

Hospital admission

$5,415

$12,646

+134

LTC facility admission

$4,571

$9,489

+108

E
D
=
e
m
e
r
g
e
n
c
y
d
e
p
a
r
t
m
e
n
t
;
L
T
C
=
l
o
n
g
t
e
r
m
c
a
r
e
.
a

R
o
u
n
d
e
d
t
o
t
h
e
n
e
a
r
e
s
t
d
o
l
l
a
r
.
b
As detailed in Reference 1.

using
decision
analysis
Conditional
probabilities, costs, and software
sensitivities

were (TreeAge
calculated and analyzed DATA

Data Analysis

v3.5 for
Healthcare,
student
version:
TreeAge
Software,

+68

Inc., Boston, Mass.) and back

spreadsheet software technique
(MicrosoftEXCELv7.0: in which
Microsoft Corporation, we started
Redmond, Wash.). from the
Decisionanalysis
right side
modeling

usually of the
involvessixsteps:
decision
1. Identifying the tree (see
decision, including the Figure 1)
selectionofthedecision and
optionstobestudied. worked
2. Structuring the leftward,
decision and its or
consequences over backward
time.
in time.
3. Assessing the We
probability that each weighted
consequence will the cost of
occur.
each
4. Determining the possible
value of each outcome, outcomein
such as in dollars or a category
utilities.
(see Table
5. Selecting the option 2) by its
with the highest probability
expected outcome and added
value.
the
6. Determining the weighted
robustness of the
costs to
decision through
arrive at
sensitivity
analysis (i.e., variation the costs
of the probability and given at
outcome values over a the nodes.
39
To
likelyrange).
We performed each determine
of these steps and the total
examined the assump cost of ill
tions made by Johnson nessdueto
1
and Bootman by DRPs, we
reviewing articles pub multiplied
lishedsubsequently.We
theaverage
focused primarily on
steps 3 and 4, because cost of
the probabilities of each
certain outcomes and outcome
the costs associated bythetotal
with those outcomes number of
weremostlikelytohave
changed in the short occurrence
time period since the s of that
event (see
earlierstudy.
To determine the Table3).
estimatedprobabilitiesof
each category of
outcomes

(node Results
probabilities),

we
employed a folding In
assessing

needed
updates to
the event
probabiliti
es
previously
estimated
byJohnson
and
Bootmans
panel of
experts,we
found no
more
reliable
estimates
published
since the
earlierarti
cle.
Instead,
recent
studies

22,2

4,27

frequently
referred to
probabili
ties
reported in
the
Johnson
and
Bootman
model.

Additionally,theDRP$12,646.
categories developed inLTCper
1990 by Hepler andadmission
18
Strand and Strand etcost was
basedona
19
al. appear to remainmonthly
thestandardsdespitetheaverage of
timeelapsedsincetheir$3,135per
publication. Therefore,LTC
weretainedJohnsonand
38
BootmansoriginalDRPresident,
categories

andadjustedto
probabilities for ourthe 1996
average
1
decisiontree.
length of
New data definingstay of
costs associated with83.4 days.
drugrelated morbidityLength of
and mortality werestay was
readily available, anddetermine
theseformedthebasisofd by
new cost calculations.dividing
The costs used in thethe
updated model are5,224,710
presented alongside theLTC
1995 estimates in Tablepatient
37
1.Theaveragecost ofadays in
prescription

was1999 by
calculatedbydividingthethe years
sumofreportedsalesfor62,610
both generic and brandadmission
s. Hence,
prescription

drugs
this LTC
($111,101,894,000) by
admission
the total number of
was
generic and brand precalculated
scriptions dispensed into be
1999
$9,489per
35,36
stay when
(2,712,456,000).
Adjusted to year 2000adjustedto
year 2000
33
dollars, theaveragecostdollars.As
ofanewprescriptionwasin the
found to be $42. An1995
1
adjustedprescriptioncost
study,
of $38 was used topathway
calculate TF andcosts
TF/NMP

costsinvolving
attributable to the factadditional
that approximately 10%treatment
of prescriptions that areassumed
1,32
that LTC
neverfilled.
admission
We

calculatedcosts
hospital admission costfollowed
bydividingthereportedadditional
hospital revenue fromphysician
inpatient admissions invisits, and
1998
cost
($407,650,369,271) bypathways
the number ofinvolving
admissionsforthatyeardeath
37
(33,766,000).
assumed
Adjusting the result tothat
year 2000 dollars gavehospitaliza
us an averagetionwould
hospitalization cost ofprecede

the final
outcome.
Folding
back the
decision
tree
(Figure 1)
with
updated
terminal
node costs
revealed
that a TF
cost an
average of
$977; an
NMP,
$1,105;
and a
combined
TF and
resulting
NMP,
$1,488.
Further
more, the
average
costofany
drug
therapy
was shown
tobe$531,
and a
health care
encounter
(considere
d

a
physician
visit) was
expectedto
cost $376.
The latter
cost figure
has no
intrinsic
value and
is simply
the
weighted
mean cost
of the
entire
model(i.e.,
allpossible
outcomes),
asitwasin
1995.

Pathwa
ycost

totalswerebasedona
hypotheticalcohortof

Vol.41,No.2
March/April2001
Journalof
theAmerican
Pharmaceutical
Association195

$147
$256
$298
$455
$12,793
$9,636
$9,489

$151

Updated Cost-

$12,646

$308

$109
$109

$42

Physician visit
$109
$38
Additional prescription $109
$38
ED visit
$109
$38
Hospital admission
$109
$38
LTC admission
$109
$38

Treatmentfailure(TF)Notreatment$109$38

Optimal outcome

$109

$42

Drug
32

Physician
PathwayOutcomeVisit

InitialTreatment($)

Table 2. Drug-Related Morbidity and Mortality

33,34

Cost of Negative Therapeutic

Physician
Visit
Drug
ED Visit

Cost Definitions

22

Outcome
Hospital
Admission

35

LTC
Admission 35,36

Total
Pathway
Cost

RESEARCH
of-Illness Model

ambulatory
care patients
makingatotal
of
734,493,000
physician
officevisitsin
the United
Statesin1996,
asreportedby
theCentersfor
Disease
Control and
Prevention
(compared
withthe

40

669,689,000
visits in 1992,
as referenced
byJohnsonand
1,32
Bootman ).
Weestimat
ed the drug
related
morbidity and
mortality cost
ofillness to be
$177.4 billion
annually(Table
3), compared
with the $76.6
billion arrived
at by Johnson
and Bootman.
Of the updated
amount,
hospital
admissions
accounted for
$121.5 billion
(69%)peryear,
and LTC
admissions
represented
$32.8 billion
(18%).
Physicianvisits
accounted for
another $13.8
billion (8%),
whereas ED
visits and
additional
treatment cost
morethan$5.8
billion (3%)
and$3.5billion

(2%),respectively.
We evaluated the cost of
illness for its sensitivity to
changes in the component cost
estimates (e.g., hospital
admissioncost)aswellasforits
sensitivity to pathway proba
bilities. For the former, an
arbitrary10%waseitheradded
toorsubtractedfromthecostof
each component in turn, and
then all together. This analysis
alone revealed a range in the
costofillnessfrom$159.6bil
lionto$195.1billion.
When probability estimates
for the most highly probable
treatment event, additional
treatment (i.e., additional
prescription), were similarly
varied,thetotalcostofillness
ranged from $174.6 billion to
$180.2 billion. Varying these
probabilities resulted in little
change in the overall expected
costoftreatment(range,$373to
$380), but doing so expanded
the range of costs associated
withphysicianvisitstobetween
$11.8 billion (7%) and $15.9
billion (9%) while affecting
noneoftheothercategories.

Discussion
Duplicating the Johnson and
Bootman model in detailed
spreadsheets ensured that the
frameworkhadbeenaccurately
replicated, i.e., that using the
sameoutcomeprobabilitiesand
cost estimates from the 1995
studyproducedidenticalresults.
Additionally, duplicating the
JohnsonandBootmandecision
analytic model allowed for a
high

196
Journalofthe
American
Pharmaceutical
Association
March/April2001
Vol.41,No.2

Updated Cost-of-Illness Model

RESEARCH

Table 3. Summary of Cost of IllnessDrug-Related Morbidity and Mortality

Approximate
Total physician visits
Total hospital admissions

No. of Events
126,846,567

Cost/Event
$109

9,609,722

$12,646

18,703,833

$308

Total LTC facility admissions

3,454,460

$9,489

Total additional prescriptions

83,735,556

$42

Total ED visits

Total deaths
Total

E
D
=
e
m
e
r
g
e
n
c
y
d
e
p
a
r
t
m
e
n
t
;
L
T
C
=
l
o
n
g
t
e
r
m
c
a
r
e
.
a

R
o
u
n
d
e
d
t
o
t
h
e
n
e
a
r
e

218,113

% Increase
Total Cost (%)
$13,826,275,829 (7.8)

Since 1995
85.3

$121,524,547,854 (68.5)

156.1

$5,760,780,460 (3.2)

8.3

$32,779,372,199 (18.5)

127.7

$3,516,893,339 (2.0)

81.9

$177,407,869,681 (100)

131.7

s
t
d
o
l
l
a
r
.

change

degreeofconfidencethat(7%) in
confoundingfactorsweretotalcostof
not introduced by anyillness
structural changes to the(range,
tree. Replacing only the$159.6 bil
outcomespecific costlion to
estimates and resource$195.1
use values (number ofbillion).
annual physician visits)The same
produced results thatdegree of
were not confounded byvariance in
calculations performedLTCadmis
differentlyfromthe1995sion
study. Thus, neitherpathway
modelingnorcalculationscostcreated
should have contributeda 2%
tothedifferencesincostvariation in
estimates between theoverall cost
twostudies.
of illness,

The majority of costwhereasthe

increases appeared tovariance in
result from the estithecostofa
mates of hospital andphysician
LTCadmissionpathwayvisit
costs, which accordingresulted in
to estimates in theless than
literature were more1%
than twice the 1995variation in
estimates(Table1).Thethe total
data summarized incost.
Table3revealedthattheNevertheles
greatest increases ins, these
drugrelated morbiditythree com
andmortalitycostswereponent
in total hospitalcosts
admissions (2.6 times),contributed
total LTC admissionsthe most to
(2.3 times), and totalvariancesin
physician visits (1.9the $177.4
times). These eventsbillion cost
contributed the most toof illness
the total costofillnessattributable
estimate of $177.4to
billion.
sensitivity
Sensitivity analysis ofanalyses.
the

costofillnessThesesame
componentsshowedthatacomponent
10% variance in hospitalcosts were
admission pathway costresponsible
produced the greatestfor the

difference
betweenthe
$76.6
billion
figure from
1995 and
the $177.4
billionfrom
ourstudy.

Sensitiv
ity
analysis
was also
performed
for the
event with
thehighest
probability
of
occurrence
within
each arm:
additional
treatment
following
a DRP. A
10%
variance
in the
probability
of
additiona
l
treatment
resulted in
anaverage
cost of
illness
ranging
from
$174.6
billion to
$180.2
billion.
The
$308
average
cost of an
ED visit
was based
on the
1996 study
by

24
Dennehy et al. ($283;usedinthe
range, $65 to $501), at1995
the University ofstudy.This
CaliforniaSan Franciscostrategy
Medical Center, adjusted
was used
33
toyear2000dollars. Asto
theonlycostnotderived
41minimize
from the same source variation
referenced earlier by
in data
Johnson and Bootman,
this estimate was chosensources as
as a slightly morea
conservative one. Allconfoundin
other cost data wereg variable
based on updated
in the
information from the
update.
samesources
Because
the data
usedinthe
compariso
n study
spanned
approxi
mately 3
years
(1991
94)orwere
standardize
d to those
years, and
cost data
used here
spanned
about 4
years
(1996
2000), any
confoundin
g that
mighthave
been
introduced
by
different
spans of
time
should
have been
minimized.
Additionall
y, this
study
standardize
d data to
year 2000
dollars,
just as the
previous
study
standardize
d to 1992

dollars.
As
Johnson
and
Bootman
did, we
assumed
that 10%
of pre
scriptions
resultingin
TF were
never
presented
by patients
for
1,32

filling.
No
definitive
data
estimating
thenumber
of never
filled
prescriptio
nscouldbe
found in
the
literature.
However,
the
adjustment
of cost
estimates
for TF,
with or
without an
NMP,
clearly
represents
a problem
in
pharmacoe
conomics
studies.
Several
studies,
including
the Lipid
Research
Clinics
Coronary
Primary
Prevention
Trial
(LRC
CPPT) and
the
Helsinki
Heart
Study
(HHS),

remain

landmark
testamentstothecomplex
issue of adherence
because they revealed
that different levels of
adherence, especially in
cases where reported
intake misrepresents
actualadherence,canlead
to unexpected errors in
economic analyses of
42

outcomes. Moreover,
the 10% rate seemed
appropriate based on
recent data from Matsui
43

etal., whodocumented
neverfilled rates of 7%
for prescriptions for
pediatric patients, and
44

Watts et al., who

estimated a 30% never
filled rate among adult
patientswithasthma.
Because

DRPs
contributesignificantlyto
health care costs, the
1999 Institute of
45

Medicine (IOM) report

focused government and
public attention on the
issue and reinforced the
call to action issued by
investigatorsfortheheart
trials

previously
mentioned. In addition,
press releases from the
American Society of
HealthSystem
46

Pharmacists and other

discussions of DRPs and
the medication use
process are increasingly
working their way into
theawarenessofboththe
general public and the
4750

health professions.
The opportunity costs
(i.e., dollars unavailable
for other purposes)
resulting

from
medicationrelatederrors,
or DRPs, as the IOM
reportpointsout,willbe
paid by purchasers and
patients. The results of
this study have the
potential, therefore, to
help break the cycle of
inactionalludedtobythe
IOMcommittee.

Vol.41,No.2
March/April2001
Journalof
theAmerican
Pharmaceutical
Association197

RESEARCH
Updated Costof-Illness Model

Limitations
Thisstudyhadseveral
limitations. First, as in
theJohnsonandBootman
study, DRPs and related
costs were merely
estimates and included
only ambulatory care
settings in the United
States,

limiting
generalizability.
However, no decision
analysis model can
characterize all of the
dimensionsofhealthcare
that contribute to drug
related morbidity and
51

mortality.
Rather,
modeling may provide
insight into where the
processunderstudymay
beimproved.

The scant data

available to update
treatment patterns and
probabilitiesofevents
limited the current
analysis to cost data.
Sensitivity analysis
was used to minimize
the effects of using
estimates from the
originalexpertpanel.
Our

statistical
analysis was limited in
comparison with that
performed in 1995.
Johnson and Bootman
performed analyses
using mean values and
ranges for resource use
estimates determined
from the survey
responsesoftheirpanel
of clinical experts. In
the current study,
sensitivity analysis was
limited to (1) assessing
a10%changeineach
ofthecostcomponents,
such as hospital
admission cost and ED

visit cost, and (2) a

10% change in
additional treatment
andnotreatmentarms
of the model.
Nonetheless, estimates
from this study relied
heavily on data in the
literatureandontertiary
health

statistics
summaries, perhaps
enhancing the real
world precision of the
results.

The data used for

modeling

and
calculationscamefrom
published medical
literature, and our
search strategies may
have missed relevant
studies. However, we
recognized

this
potentially
confounding element
fromthebeginningand
madeeveryattemptto
discover all data
relevanttodrugrelated
morbidity and/or
mortality.
Our study did not
address several issues
studiedbyJohnsonand
Bootman, including the
impact

of
pharmaceutical care on
the results of modeling
analyses, comparisons
between the cost of
drugrelated illness and
other sources of
morbidityandmortality,
orsubgroupanalysesof
populations susceptible
tothedeleteriouseffects
of drugrelated illness.
Pharmaceutical care
may reduce DRPs, as
may

other
considerations.
Additionalresearchinto
the scope of and
solutions for the
problemofdrugrelated
morbidityandmortality
isneededandshouldbe

encouraged.

Conclusion
This study updated
Johnson

and
Bootmans 1995 cost
ofillness model
assessing

the
morbidity

and
mortality associated
with DRPs. Since
1995, the costs
associated with DRPs
have more than
doubled to an
estimated annual
average of $177.4
billion. Hospital
admissions and LTC
admissions remain the
primarycontributorsto
this total cost. Drug
related morbidity and
mortality continue to
poseaseriousmedical
andeconomicproblem
for society. More
attention should be
directed

toward
developing solutions
thatreducepreventable
morbidity, mortality,
and costs associated
withDRPs.

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trademarked
TheGreatAmerican
September3,1890,by
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MEDI CINE TAX STAMPS
Antikamniaasaprime
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exampleoftheneedfor
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Antikamnia
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firmfoolishlyadded
hadtobesealedwith
introducedintocodeine,heroin,
oneofthese19001901
medicineasan quinine,andsalolto
SpanishAmericanWar
theproductformulato
analgesicin1886,and
medicinetaxstamps
gainmoresales.This
4yearslaterwasincor
issuedbytheU.S.
ledSamuelHopkins
poratedasthemain
government.
ingredientofa Adams,inhisfamous
1906
proprietarycalled
GeorgeGriffenhagen,

seriesof
Antikamnia
Vienna,Virginia
articles
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titled
Theremedywas

Barrys
Tricoph
erous
YorkCity
wigmaker
Alexander
C.Barry
turnedhis
attentionto
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peoples
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1859,and
commenced
the
manufactur
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Tricophero
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No.2March/April theAmerican

Vol.41, 2001

Journalof

Pharmaceutical
Association199