Meta analysis and spontaneous reporting

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: [email protected]

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. F orm 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.NO 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