1. Life Sciences Research Office (LSRO) Evaluating Adverse Event Reporting Systems for Dietary Supplements January 30-31, 2003 “Open Portion of Meeting”

2. Goals for AERS meeting January 30-31, 2003  Introduce importance, controversial nature and complexity of project  Present LSRO’s objectives  Begin to formulate plan to achieve objectives

3. Phase I Review and qualitatively compare AER in Metabolife and FDA databases Determine the usefulness of these AER as signals for product safety

4. Phase II Review systems for reporting adverse events for dietary supplements In a detailed LSRO report, recommend features of an AERS to the dietary supplement industry --How to collect, document, and respond to AER --How to evaluate aggregate data to obtain useful and reliable signals of potential problems

5. Critical issues that may be considered: AER systems for OTC drugs, foods and dietary supplements Models for evaluation of data Type of data necessary Additional data Responsibilities of consumers and healthcare providers Signals generated by evaluations of AER Types of responses associated with these signals

6. FDA CFSAN database of AER associated with dietary supplements containing ephedrine alkaloids Docket Number 00N-1200

7. FDA CFSAN AER associated with dietary supplements – Each AER is assigned a 5 digit case number – Each case has a chart – The chart has up to 9 sections

8. FDA CFSAN AER Chart Sections 1.Section 0 Incoming Report 2.Section 1 Affidavits 3.Section 2 Label Sample 4.Section 3 Outpatient Medical Reports 5.Section 4 ER/Urgent Care Records 6.Section 5 Hospital Record Summaries 7.Section 6 Hospital Medical Notes 8.Section 7 Hospital Surgical Reports 9.Section 8 Other (e.g., Autopsy Report)

9. FDA CFSAN AER Ephedrine Alkaloid-Containing Dietary Supplements (1990 through 11-3-99)  Total 1176 minus duplicates = 1164  Distribution by year (n=1126)  Ranked by frequency of product reported (n=499)

10. Pre-Case Seriesn=14 Prior to 6-1-97 (and not in docket 95N-0304) New Case Seriesn=140 6-1-97 to 3-31-99 Post Case Seriesn=119 4-1-99 to 12-31-99 FDA CFSAN AER Ephedrine Alkaloid-Containing Dietary Supplements (Docket 00N-1200 obtained for LSRO review, n=273)

11. New Case Series (n=140)  Attributablen=22 [e.g., used as directed, temporal, de/rechallenge, signs and symptoms consistent with known effects of ephedrine]  Supportiven=38 [e.g., incomplete medical record, other confounding factors]  Insufficient Datan=72  Not Evaluatedn=8