1. META -ANALYSIS
BY: Dr. VISHWAS A T L, PHARM.D , (Ph.D.)
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACY PRACTICE
BHARATHI COLLEGE OF PHARMACY
BHARATHINAGARA - 571422

2. CONTENTS
DEFINITION
AIM AND NEEDS
STEPS
QUALITY ASSESSMENT
ADVANTAGES
DISADVANTAGES
APPLICATIONS

3. DEFINITION
At first meta-analysis in the social science literature is defined as "The statistical
analysis of a large collection of analysis results from individual studies for the
purpose of integrating the findings".
Now Meta-analysis is defined as a quantitative, formal, epidemiological study
design used to systematically assess the results of previous research to derive
conclusions about that body of research. Typically, but not necessarily, the study is
based on randomized, controlled clinical trials.
Outcomes from a meta-analysis may include a more precise estimate of the effect of
treatment or risk factor for disease, or other outcomes, than any individual study
contributing to the pooled analysis.

4. AIM
Meta-analyses are conducted to assess the strength of evidence present on a
disease and treatment.
 One aim is to determine whether an effect exist.
Another aim is to determine whether the effect is positive or negative and,
ideally, to obtain a single summary estimate of the effect.
NEEDS
To establish statistical significance with studies that have conflicting
results.
To develop a more correct estimate of effect magnitude.
To provide a more complex analysis of harms, safety data, and benefits.
To examine subgroups with individual numbers that are not statistically
significant.

5. STEPS INVOLVED IN META - ANALYSIS
There are four basic steps involved in conducting meta-analysis:
1.Identification
2.Selection
3.Abstraction
4.Analysis

6. STEP1: IDENTIFICATION
The first step in a meta-analysis is to find all of the pertinent articles on topic.
Important sources of information for a meta-analysis include:
• MEDLINE
• EMBASE
• Cancer Lit, AIDS Line, and Tox Line
• Index Medicus
While MEDLINE, the database of the National Library of Medicine, is a good
starting point, it is not the only source of information. MEDLINE indexes
approximately 4100 journals, dating from 1966 to the present. It also has an
excellent feature called clinical queries.

7. There are also CD-ROM based search engines from BRS Colleague, Win SPIRS,
and others which offer different search options, but use essentially the same
underlying database.
The European version of MEDLINE is called EMBASE, and is a Dutch/English
collaboration. Depending on the topic, it may be appropriate to search the more
specialized National Library of Medicine databases, such as Cancer Lit, AIDS Line,
and Tox Line.
The Cochrane collaboration Controlled Trials Register, established in 1993, is an
important source of studies for a meta-analysis. The Register includes abstracts of
thousands of trials. It includes all controlled trials in the MEDLINE and EMBASE,
as well as the results of hand searches by Cochrane Collaboration volunteers of
thousands of journals not indexed by MEDLINE or EMBASE. MSU students,
faculty and staff can best access the Cochrane through the MSU Library.

8. STEP2: SELECTION
Once the author of a meta-analysis has assembled a large number of studies, it is
important to select the right ones. There are a variety of possible inclusion criteria:
•Whether the study include enough information for analysis (i.e. standard deviation or
standard error in addition to point estimate)
•The study design (i.e. controlled trials only vs randomized controlled trials only,
especially for studies of therapy)
•The year of study, if technology or typical dosing changes (for example, only include
studies since 1984 on dyspepsia if you're interested in helicobacter pylori)
•The dosage used in the study (to assure that an effective dose was used)
•The language of the article - you or a colleague have to be able to read it!
•The minimum sample size - very small studies may be unrepresentative and/or not
worth the effort
•The patient age (adults only, > 60 only, etc)
•The study setting (emergency department, outpatient, inpatient)

9. STEP3: ABSTRACTION
Once an appropriate group of studies has been identified, the author(s) have to abstract
the relevant data from each study. There are many sources of potential error in data
abstraction:
The article may be wrong due to typographical or copyediting errors.
Tables can be misinterpreted.
Errors can occur during you own data entry or abstraction process.
A good meta-analysis will take some or all of the following steps to minimize errors:
Use 2 independent reviewers.
Use a 3rd reviewer or consensus meeting to resolve conflicts.
Train reviewers by practicing with several articles to "calibrate“.
Use a standard form or database which constrains entries to the expected range.
Report the results of the data abstraction, including the percentage concordance or
even a kappa statistic.
Compare abstract and text to look for inconsistencies.
Bias can also creep into a meta-analysis.

10. STEP4: ANALYSIS
Homogeneity and heterogeneity describe the degree of between-study variability
in a group of studies. It is probably appropriate to combine the results from a
homogenous set of studies, but many would argue that results from heterogeneous
studies should not be combined. The Q statistic, interpreted using a chi-square
distribution, is often used as a test of homogeneity.
When there is significant heterogeneity, the between-study variance becomes
much larger than the within, and studies of different sample size receive relatively
similar weight. When there is homogeneity, sample size dominates, and both
models give similar results. Random effects models are therefore more
"conservative" and generate a wider confidence interval. Put another way, a
random effects model is less likely to show a significant treatment effect than
a fixed effects model.
In general, if the studies are homogenous, the researchers should use a fixed
effects model. If the studies are heterogeneous, the researcher should use a random
effects analysis.

11. QUALITY ASSESSMENT OF THE META - ANALYSIS
Assess for:
• Research questions clearly defined.
• Definition of inclusion criteria for studies.
• Adequacy of the search protocol.
• Assessment of methodological quality of the included studies.
• Calculation of a pooled estimate.
• Plot of the results (forest plot).
• Measurement of heterogeneity.
• Assessment of publication bias (funnel plot).

12. ADVANTAGES
Greater statistical power.
Confirmatory data analysis.
Meta-analyses are used by researchers to review large and sometimes complex
research.
Greater ability to extrapolate to general population affected.
Considered an evidence-based resource.
DISADVANTAGES
Difficult and time consuming to identify appropriate studies.
Not all studies provide adequate data for inclusion and analysis.
Requires advanced statistical techniques.
Heterogeneity of study populations.

13. APPLICATIONS
Pharmaceutical companies use meta-analysis to gain approval for new drugs, with
regulatory agencies sometimes requiring a meta-analysis as part of the approval
process.
Clinicians and applied researchers in medicine, education, psychology, criminal
justice, and a host of other fields use meta-analysis to determine which
interventions work, and which ones work best.
Meta analysis is also widely used in basic research to evaluate the evidence in
areas as diverse as sociology, social psychology, sex differences, finance and
economics, political science, marketing, ecology and genetics, among others.