meta analysis and spontaneous reporting of ADR's

1. NIZAMUDDIN
PHARM.D
META-ANALYSIS

2.  DEFINITION:-
Definition :-
Meta-analysis has been defined as the statistical analysis of a
collection of analytical results for the purpose of integrating the
findings.
Meta analysis may be regarded as a state of the art literature review,
employing statistical methods in conjuction with a thourough and
systematic qualitative review.
One of the potential benefits of meta analysis is the potential to
shorten the time between a medical research finding and the clinical
implementation of the new therapy. this is a concernnot only for the
development of new drugs,but for the exploration of new indications
for existing therapies.

3. •meta analysis is a statistical technique for combining the results of
independent but similar studies to obtain an overall estimate of
treatment effect.
Meta-analysis is currently the most common approach for quantitatively combining
the results of the same out-come from different studies.
Quantitative approach for systematically combining results of previous
research to arrive at conclusions about the body of research.

4.  PROTOCOLS
PROTOCOLS FOR REPORTRING OF META
ANALYSES by QUOROM & MOOSE
The purpose of QUOROM & MOOSE guidelines is to provide proper
procedures for conducting a meta analysis and to standardize the methods of
reporting a meta analysis.
QUORUM STATEMENT
Quality of reporting of meta analyses - for clinicals randomized controlled
trials.
MOOSE GUIDELINES
Meta analysis of observational studies in Epidemiology.

5.  FUNCTIONS OF META-ANALYSIS:-
 Indentifies heterogeneity in effects among multiple studies
and, where appropriate, provide summary measure.
 Increase statistical power and precision to detect an effect.

 Develops, refines and tests hypothesis.

 Identifies the data gap in the knowledge base and suggest
direction for future research.

6. •1.Define the purpose.
2. perform the literature search.
3. establish the inclusion/exclusion criteria.
4.collect the data.
5.perform statistical analysis.
6.formulate conclusions.
 STEPS INVOLVED IN
CONDUCTING A META ANALYSIS

7.  Define the purpose
•Common purposes addressed in meta analysis are wether
one treatment is more effective than another or if exposure to
certain agent will result in disease.
•The literature search is a critical step in the meta
analysis and often the most difficult part.
 Perform literature search

8.  Establish Inclusion/Exclusion criteria
•the inclusion and exclusion criteria for studies needs to be defined at the
begining during the design stage of the meta analysis.
•factors determining inclusion in the analysis are :-
•study design, population characteristics,
•types of treatment or exposures and outcome measures.
•meta analysis eeds to be documented :-
one should keep track of the studies includes and excludes at each step
of the selection process to document the selection process.
•the type of the data to be extracted from each study should be
determinesd in the desin phase and a standardized form is constructed to
record the data.
 Collect the Data

9.  Perform Statistical Analyses
There are 2 stages for statistical process of Meta analysis
probability value (p value)
P >0.05 statistically Insignificant
P< 0.05 statistically significant
Relative risk (RR) or Odds Ratio (OR)
Risk= a/a+b Odds = a/b
Confidence Intervals (CI)
Calculated as weighted average of individual statistics.
1.Treatment effect for each study.
2. Overall Treatment effect.

10.  Formulate Conclusions
Formulate the overall conclusion for the meta
analysis done for the study data.

11.  FOREST PLOT:-
•The graphical display of results from individual studies on a
common scale is a forest plot.
•The typical graph for displaying results of a meta analysis is
called a “forest plot”
•In the forest plot each study is represented by a black square
and a horizontal line. The area of the black square reflects
theweight of the study in meta analysis.

12.  TYPES OF META ANALYSIS MODELS
1.FIXED EFFECT MODEL
2. RANDOM EFFECT MODEL

13.  FIXED EFFECT MODEL
 Fixed-effect model
 we assume that all studies in the meta-analysis share a common
(true) effect size.
 All factors that could influence the effect size are the same in all
the studies, and therefore the true effect size is the same in all
the studies.
 The fixed effects model assumes that all included studies
investigate the same population, use the same variables,
outcome definitions etc.,
 The fixed effect model provides a weighted average of a series
of study estimates.

14.  RANDOM EFFECT MODEL
 Random effects model
 In random effects model, we assume two components of
variation :
 1. Sampling variation
 2. Random variation
 In random effects models effect sizes will differ because
they are sampled from an unknown distribution.
 The random effect model provides a weighted average of a
group of study estimates.

15. ADVANATGES OF META ANALYSIS
Results can be generalized to a larger population
The precision and accuracy of estimates can be improved as more data is
used. This, in turn, may increase the statistical power to detect an effect.
Inconsistency of results across studies can be quantified and analyzed. For
instance, inconsistency may arise from sampling error, or study results
(partially) influenced by differences between study protocols
Hypothesis testing can be applied on summary estimates
Moderators can be included to explain variation between studies
The presence of publication bias can be investigated

16.  META ANALYSIS SOFTWARES
•FREE SOFTWARES
•RevMan
•Meta-Analyst
•Meta-Stat
•commercial
•Meta-Win
•WEasy MA

17. SPONTANEOUS
REPORTING

18. THE SPONTANEOUS REPORTING SYSTEM
It is a Passive survillance system
Health professionals are encouraged to report
adverse reactions which they believe to be drug
related directly to the
 The Regulatory authority
 The marketing company of the suspected product on a
 voluntary basis.

19. The Spontaneus reporting system
has three stages :-
1. Data Acquisitiuon:- which depends largely on the input of
information derived from reports submitted by the health
professionals who have encountered what they suspecyt is an
ADR
2. Data Assessment : which involves the assessment of
individual case reports and assessment of pooled data obtained
from various sources such as the international datasbase of
WHO.
3. Data Interpretation :- Based upon the available data and
assessments made, a signal related to the adverse drug reaction
may be generated.

20. FORMS for ADR’sReporting
For the collection of data on ADR's reporting, different
forms are used by different countries.
INDIA :- Suspected adverse reaction report form
UK :- yellow card since 1964
AUSTRALIA :- blue card since 1964
US :- MedWatch
 form FDA 3500 - voluntary reporting
 form FDA 3500 A- Mandat0ry reporting

21. INDIA :- Suspected ADR report form :-
 Indian Pharmacopoeia Commision (IPC),Ghaziabad is functioning as a National
Coordination Centre (NCC) for Pharmacovigilance Programme of India (PvPI).
150 ADR Monitoring centres (AMCs) were established in various medical institutions
across India to monitor and collect ADR reports under NCC-PvPI
What to Report
PvPI encourages all types of suspected ADR's reporting whether they are known,
Unknown, Serious,or nonserious,frequent.
Where to Report
All healthcare professionals and patients can report ADRs to NCC or AMCs.
How to Report
Suspected ADR reporting forms are available on the website of IPC.
( Available in 10 vernacular languages)

22. Suspected adverse reaction report form

23. UK :- yellow card since 1964
The yellow card scheme is the UK system for collecting information
on suspected adverse drug reactions to medicines. The scheme allows
the safety of the medicines and vaccines that are on the marketto be
monitored.
It is run by the Medicines and health care products regulatory
agency (MHRA) and the commission on human medicines (CHM).
Suspected ADRs are collected on all licensed medicines and
vaccines,from those on prescription to medicines bought over the
counter from a pharmacist or supermarket.
Yellow cards are available from pharmacies and hospitals.

24. UK :- yellow card

25. AUSTRALIA :- blue card since 1964
 Blue Card is a Form to report suspected adverse
reactions to vaccines and prescription, over the counter and
complimentary medicines in australia.
Send completed blue cards to (Therapeutic Goods
Administration, Department of Health )TGA.
By mail to : pharmacovigillance and special access branch,
reply paid 100,Woden ACT 2606.
By fax to: 02 6232 8392
By email to: adr.reports@tga.gov.au

26. AUSTRALIA :- blue card

27. UNITED STATES :- MEDWATCH

28. Form FDA 3500 - voluntary reporting
For use by health care professionals, Consumers, and
Patients.
Submit the completed form by using built-in postage-
paid mailer, or fax.

29. Form FDA 3500

30. Form FDA 3500 A- Mandatory reporting
For use by IND reporters,manufacturers,
distributors, importers user facilities personel.
Submit the completed form form by using
built-in postage-paid mailer, or fax.

31. Form FDA 3500A

32. Advantages & Disadavantages of spontaneous reporting
SL.N
O
ADVANATGES DISADVANATGES
1 - Large Population Under Reporting.
2 - All medicines Poor quality of reports.
3. Long Perspective No denominator data.
4. -Hospital and out patient care Reporting varies with
-severity of reaction
- time from market introduction.
- promotional claims
- promotion of reporting systems.
- publicity of specific assosiation.
5. patient analysis possible
6. Inexpensive