1 BETTER APPROACHES TO MONITORING MEDICAL PRODUCT SAFETY ARE NEEDED

2 EVALUATING THE SAFETY OF MARKETED MEDICAL PRODUCTS IS AN “ORPHAN” RESEARCH AREA FDA has responsibility, but –internal resources have been primarily directed to evaluation of new products –has minimal funds for extramural research Pharmaceutical industry has responsibility, but –internal resources are primarily directed to evaluation of new products –“Best practices” not established; FDA has little basis to mandate much besides reporting and case follow-up

3 ROLE OF ACADEMIA Research of academic scientists primarily supported by grants NIH can stimulate research in certain areas by requesting targeted applications Development of statistical methodology in medical research has focused on areas of greatest interest to NIH: clinical trials, epidemiological research Little or no grant support for methods in post-marketing safety surveillance

4 EVALUATING PRODUCT SAFETY IS OF INCREASING IMPORTANCE Availability of new products is rapidly increasing; many treat previously untreatable chronic conditions More people are using medical products, and multiple products than ever before –aging population –improved therapies (non-sedating antihistamines, inhaled steroids, SSRIs) –new therapies for previously untreatable conditions (hair loss, erectile dysfunction, PMS)

5 RECENT STUDIES HAVE RAISED PUBLIC CONCERNS Deaths due to adverse drug effects Medical errors

6 CURRENT PRACTICE: Spontaneous Reporting Passive surveillance –physicians or consumers voluntarily report adverse effect to product manufacturer or FDA directly All reports end up in FDA data base Huge numbers per year –250K: drugs and therapeutic biologics –100K: medical devices –13K: vaccines

7 CURRENT PRACTICE: Active Surveillance In some cases, manufacturer does “phase 4” study after product is marketed An agreed-on number of patients is treated with new product, with active follow up by manufacturer Annual reports to FDA; rapid reporting of serious events that were previously unobserved

8 CURRENT PRACTICE: RETROSPECTIVE STUDY Identify cases of interest in available data base –Health maintenance organization –Medicaid –National Death Index Define and identify a reasonable control group from same or other data source Study association of exposure and outcome using case-control methodology

9 WHAT TO DO WITH SPONTANEOUS REPORTS Several simple methods have been proposed over the years All have important limitations; none is considered “standard” practice Recent development of Bayesian data-mining approaches shows promise for signal identification

10 BIG QUESTIONS Is there more that could be done? Are there other, as yet untapped, sources of data that would be helpful? How can we promote more research in this area?