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

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

July 15, 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

July 15, 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

July 15, 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.

July 15, 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

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

July 15, 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

July 15, 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

July 15, 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

July 15, Risk Management

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

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

July 15, 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)

July 15, 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

July 15, 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

July 15, Suspension of Marketing With or without application withdrawal

July 15, 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

July 15, 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

July 15, 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