Faculty of Medicine Ain Shams University

Template Protocol Systematic Review/ Meta-analysis

TITLE:

Example 1: Vitamins C and E for asthma and exercise-induced

Bronchoconstriction: a met-analysis

Example 2: Breast cancer and deodorants/antiperspirants: a systematic review.

Example 3: Urinary bladder cancer and the petroleum industry: a quantitative

review.

BACKGROUND/ INTRODUCTION/ REVIEW:

Example 1: Selenium deficiency may be important in chronic asthma.

Observational studies have demonstrated that patients with chronic asthma
may have lower levels of selenium than their control. Nevertheless, selenium
supplementation has not been recommended with drug therapy for asthma.
This review systematically examines RCTs that evaluated the role of selenium
supplementation in chronic asthma.

Example 2: Over the last decade, the possible association between underarm
deodorants/antiperspirants use and breast cancer risk has raised important
interest in the scientific community.

OBJECTIVE:

Example 1: To assess the effects of supplementation of vitamins C and E

versus placebo (or no vitamin C and E supplementation) on exacerbations and
health-related quality of life (HRQL) in adults and children with chronic asthma.
To also examine the potential effects of vitamins C and E on exercise-induced
bronchoconstriction in people with asthma and in people without a diagnosis of
asthma who experience symptoms only on exercise.

Example 2: The objective of our systematic review is to estimate the pooled risk
of deodorants/ antiperspirants use for breast cancer.

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METHODOLOGY:

Criteria for considering studies for this review

- Types of studies

Example 1: The review will be restricted to randomised controlled trials (RCT),

which studied the efficiency of .for of chronic asthma.

Example 2: Published observational studies on breast cancer risk and deo-

dorants use were identified through a comprehensive MEDLINE/ PubMed
search (from 1966 to August 2016) and PsycLIT (from 1887 to August 2016)
using a variety of Medical Subjects Headings and free text words (Deodorants
or Parabens or Antiperspirants) and (Breast) and (Case-Control or Case-
Referent or Retrospective or Cohort or Follow-up or Incident or Prospective or
Epidemiology).

- Types of participants

Example: Participants will be adults or children (over the age of 2 years) with a
diagnosis of asthma.

- Types of interventions

Example: X drug administered as a supplementary treatment for at least 2

weeks, versus placebo.

- Types of outcome measures

Example 1: At least one of these outcome measures will be considered:

1) Lung function (FEV1, % predicted FEV1, diary and clinic PEFR and PEFR
variability).

2) Asthmatic symptoms (including symptom scores).

3) If level improved after the intervention or not (if available).

4) If selenium-dependent enzyme glutathione peroxidase function improved

after the intervention or not (if available).

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Search strategy for identification of studies

Example 1: An initial search will be carried out using the Cochrane Airways
Group Asthma RCT register. Additional and separate searches will be carried
out on MEDLINE (1966-2017), EMBASE (1980-2017), PUBMED and also on all
relevant respiratory journals that are available as electronic data bases.

Randomised controlled trials will be identified using the following search

strategy: placebo* OR trial* OR random* OR double-blind OR double blind OR
single-blind OR single blind OR controlled study OR comparative study.

Review articles and bibliographies of each RCT identified will be searched for
additional references that may contain further RCTs. Personal contact with
colleagues, collaborators and other trialists working in the field of asthma will be
made to identify other published and unpublished relevant studies.

OR

Example 2: Published observational studies on breast cancer risk and

deodorants use were identified through a comprehensive MEDLINE/PubMed
search (from 1966 to August 2016) and PsycLIT (from 1887 to August 2016)
using a variety of Medical Subjects Headings and free text words: ((Deodorants
OR Parabens OR antiperspirants) AND (Breast) AND (CASE-CONTROL OR
CASE-REFERENT OR RETROSPECTIVE OR COHORT OR FOLLOW-UP OR
INCIDENT OR PROSPECTIVE OR EPIDEMIOLOGY). We conducted
additional searches of Current Contents, Best Evidence, previous reviews,
examination of cited reference sources and personal contact and discussion
with several investigators expert in the field. Published case reports, or studies
evaluating deodorants use but as exposed and no exposed women were
excluded.

When two or more papers were based on an identical study, the paper that
principally investigated the relationship between breast cancer and deodorants
use was used.

No restrictions on the language of publications will be employed.

OR

Our review will include studies published in Arabic, English and French.

OR

We will consider studies in English, French and Spanish and no attempts were
made to locate any unpublished studies.

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Methods of the review

- Locating and selecting studies

Abstracts of articles identified using the search strategy above will be viewed,
and articles that appear to fulfil the inclusion criteria will be retrieved in full. Data
on at least one of the outcome measures must be included in the study.

Each article identified will be reviewed and categorised into one of the following
groups:

-included: RCT or CCT that meets the described inclusion criteria and those
where it is impossible to tell from the abstract, title or MESH headings;

- excluded: non RCT or CCT.

When there will be a doubt, a second reviewer will assess the article and a
consensus will be reached.

- Data extraction

Data will be independently extracted by two reviewers and cross-checked.

OR

A copy of each paper identified will be obtained, and relevant data will be
abstracted by the first reviewer (M.K.M.E.) for a quantitative overview. The odds
ratio and the country where the study was carried out will also be ascertained.
In case of discrepancies or when the information presented in a study is
unclear, abstraction by a second reviewer (F.M.F.I.) will be sought to resolve
the discrepancy.

- Statistical considerations

Outcomes from included trials will be combined using the Review Manager
software.

Reasons for heterogeneity for studies will be explored and, if necessary,

sensitivity analysis will be performed on the basis of methodological quality and
random effects versus fixed effects modelling. Subgroup analyses are planned
based on:

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a) Age (children or adults)

b) Asthma severity

c) Length of supplementary treatment

OR

Data will be abstracted from every study in the form of a risk estimate and its
95% confidence interval (CI). Pooled risk estimate will be obtained by weighing
each study by the inverse variance of the effect measure on a logarithmic scale.

When a risk estimate and its 95% confidence interval were not available from
the article, we calculated unadjusted values from the published data of the
article, using the Epi Info 6 computer program version 6.04d.

This approach to pooling the results assumes that the study populations being
compared are similar and hence corresponds to a fixed effect analysis. The
validity of pooling the risk estimates will be tested (test of homogeneity) using a
chi-square test (Fleiss, 1993). A violation of this test implies that the studies
being grouped differ from one another. In the presence of significant
heterogeneity of the effect measure among studies being compared, we will
perform a random effect analysis that is based on the method described by
DerSimonian and Laird (1986). The random effect analysis accounts for the
interstudy variation. Because the test of homogeneity has low power, we will
report the figures of the random effect analysis even with the absence of
significant heterogeneity.

All statistical analysis for pooling the studies will be performed on the STATA
statistical Software, release 14.0 (Stata Crop. 2015, College Station, Texas,
USA).

. Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res
1993;2(2):121-45.

. DerSimonian R, Laird N. Meta-analysis in clinical trials. Contr Clin Trials

1986;7:177-88.

- Evidence of publication bias will be sought using the funnel plot

method.

A funnel plot is a simple scatter plot of the intervention effect estimates from
individual studies against some measure of each studys size or precision.

REFERENCES:

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