Post-Marketing Safety Information on Medical Products: Potentials for Improvements

1. Post-Marketing Safety Information on Medical Products: Potentials for Improvements Overview for perspective Marc K. Walton, M.D., Ph.D. OPPL / FDA The views expressed are those of the author, and do not represent an official FDA position

2. Postmarketing safety information • Requirements stated in regulations (21CFR 600 & 314) • Review – promptly review all AE information (any source) • Reporting – PM 15d Alert Reports • Serious & Unexpected AE • Follow-up information • Reporting – Periodic Reports – All additional AEs yearly (quarterly first 3 yrs) – primarily spontaneous reporting • Added to FDA AERS database • Includes MEDWATCH direct repots to FDA • PM Studies - Typically as agreed between FDA and manufacturer; primarily for topics with known basis for reasonable concern

3. Postmarketing safety informationCurrent chief sources • Agreed-upon PM studies – limited to issues where there is a basis for reasonable concern • Spontaneous reports • Relationship of AE to drug may not be recognized, and thus not reported • Substantial underreporting • Weak ability to estimate relevant denominator

4. Existing Methodology • Can be useful to refine understanding of known or clearly suspected AE related to drug • Can be useful to detect clinically notable AE that occur in a manner revealing relationship (e.g., events with temporal characteristic, rechallenge, otherwise rare) • Weaknesses in other situations widely discussed • One FDA approach to improving medical product safety is termed the ‘Sentinel Network’

5. The Problem • The effectiveness of Federal government postmarket surveillance and risk communication efforts have been constrained due to limitations in the: • Quality of data • Quantity of data • Timeliness of data receipt and analysis • Capacity to rapidly conduct postmarket safety studies, when needed • Risk communication tools used • Available resources

6. A Proposed Solution • The private sector has taken steps that can facilitate surveillance activities: • Developing new information technology tools • Exploring informatics methods and applications • Creating the capacity to conduct postmarket safety assessments • Therefore, link private and public sector efforts to address these limitations through better integration of the nation’s postmarket medical product safety activities to create a “Sentinel Network” – a virtual, integrated, electronic medical product safety network

7. Sentinel Network • The network would foster the seamless, timely, electronic flow of medical product safety information from electronic databases and surveillance reporting systems, through risk identification and analysis processes, to healthcare practitioners and patients at point-of-care, while protecting patient privacy • The network would be assembled through public-private partnerships and build on existing efforts rather create entirely new systems • The network would use national and international standards

8. Components of the Sentinel Network • Data Collection • Integrate clinical practice and adverse event surveillance • EHRs • Integrated databases • Risk Identification and Analysis • Integrated research networks • Data mining tools • Reach agreement on methodologies • Conduct subgroup analyses and identify biological/genomic markers • Risk Communication • Leverage medical community’s expertise • Integrate new risk information into the workflow of clinical practice (e.g., decision support systems)

9. Legislative Initiatives • FDARA • PDUFA, MDUFA reauthorization • Multiple other potential FDA procedural, organizational, responsibility aspects • Senate version has been passed • House version in committee • Final enacted version yet to be determined

10. S. 1082 Drug Safety • FDA shall work to establish within 2 years a system(s) for drug safety surveillance • Described with similar data collection, analysis characteristics as were used for Sentinel Network • Goal of 100 Million patients by July 2012

11. S. 1082 Drug Safety – Qualified Entities • ‘‘(aa) has the research capability and expertise to conduct and complete the activities under this paragraph; • ‘‘(bb) has in place an information technology infrastructure to support adverse event surveillance data and operational standards to provide security for such data; • ‘‘(cc) has experience with, and expertise on, the development of drug safety and effectiveness research using electronic population data; • ‘‘(dd) has an understanding of drug development and risk/benefit balancing in a clinical setting; and

12. Data Sources and Adequacy • Claims data • EMRs • ‘Compatability’ of data needs with data sources • Richness of detail • Common granularity, format, meaning to permit combining information from multiple systems • Informatics systems in development can be planned to satisfy needs • Data needs driven by clinical question and analytic methodology