1. July 15, 20031 Postmarketing Safety Evaluation of Approved Drugs and Risk Management Victor F. C. Raczkowski, MD, MS Director, Office of Drug Safety July 15, 2003

2. 2 CDER Mission CDER assures that safe and effective drugs are available to the American people

3. July 15, 20033 Mission: Office of Drug Safety The Office of Drug Safety (ODS) evaluates drug risks and promotes the safe use of drugs by the American people

4. July 15, 20034 Safe Products* All medical products are required to be safe Safety does not mean zero risk A safe product is one that has reasonable risks, given the magnitude of the benefit expected and the alternatives available *Managing the Risks from Medical Product Use Report to the FDA Commissioner from the Task Force on Risk Management U.S. HHS FDA; May 1999

5. July 15, 20035 Issues (I) Postmarketing surveillance –SRS/AERS, passive, signals Traditional FDA role –approve/withdraw, label More needed in some cases –unacceptable levels of M&M due to errors, poor quality, etc.

6. July 15, 20036 Issues (II) Need for systemic approach to reducing errors, improving safety –assessment, control, prevention, communication, evaluation FDA role in larger risk management system –consumers, HCP, pharmacists, insurers, HMOs, industry, other government agencies

7. July 15, 20037 Tools used by ODS Adverse Event Reporting System (AERS) Drug utilization databases Cooperative agreements CERTs Program Other collaborations (e.g., VA system)

8. July 15, 20038 Adverse Event Reporting System Signal-detection system Computerized database Adverse event reports –sponsors (mandatory reporting) –health care providers & consumers (voluntary reporting through MedWatch) –medication error reports

9. July 15, 20039 AERS Strengths and Limitations Strengths –Can identify uncommon adverse events –Can identify adverse events in special populations –Provides information on real-world use Limitations –Does not provide rates of adverse events –Limited information in case reports

10. July 15, 200310 Data Resource Procurements IMS Health Databases –number of prescriptions, demographic information, context within which ADEs occur Premier: Inpatient Information AdvancePCS: Longitudinal Outpatient Information (CHCA): Pediatric Inpatient Information Child Health Corporation of America

11. July 15, 200311 Risk Management

12. July 15, 200312 Risk Management: One “Definition” * Continuing process Minimize risks throughout lifecycle Optimize benefit-risk profile *PDUFA III Concept Paper: Risk Management Programs; March 3, 2003

13. July 15, 200313 Risk Management Plans Clear specified goals and objectives Evaluation of Program

14. July 15, 200314 Education and Outreach Beyond professional labeling (“package insert”, PI) HCP letters and other public notices Training programs and CE for credit Patient-oriented labeling –Medication Guides (MG) –Patient Package Inserts (PPI)

15. July 15, 200315 Systems Guiding Prescribing, Dispensing, Use Patient agreements/informed consent Enrollment of one or more stakeholders in special program Practitioner certification programs Special conditions of dispensing –special packaging –limited supply / no refill –check mechanisms to assure appropriate prescribing

16. July 15, 200316 Restricted Access Systems Designed to enforce compliance with program elements May include registration/enrollment of physicians/pharmacists/patients May include documentation of safe use conditions (such as lab tests) before dispensing to patients

17. July 15, 200317 Suspension of Marketing With or without application withdrawal

18. July 15, 200318 Selecting and Developing Tools Consider: Stakeholder input: feasibility, acceptance Consistency: with existing/accepted tools Evidence: past success in same or related objective Variability, validity, reproducibility

19. July 15, 200319 Risk Management: Evaluation Assess effectiveness of program & its tools — Before implementation (pretesting) — Periodically after implementation Ensure efforts are expended on effective interventions Guide adjustments to RM Programs

20. July 15, 200320 Outcome Measures or Metrics Apply to tools, objectives, or goals Measure changes in or absolute levels of: –Patient health outcomes –Surrogates of health outcomes –Process measures or behaviors –Behavioral components Comprehension, Knowledge, Attitudes