Post-marketing safety signal detection and refinement for medical products 醫醫醫醫療療療療 品品品品的的的的上上上上 後後後後安安安安全全全全信信信信息息息息徵徵徵徵測測測測及及及及快快快快速速速速評評評評估估估估 產產產產 巿巿巿巿 陳建煒 K. Arnold Chan 臺大醫院醫學研究部 臺大醫學院 2014.10.24 ICPE 11 Potential conflict of interest (cid:1) Faculty of a public university (cid:1) Consultant to private companies (cid:1) Fees go to an education and research account 2014.10.24 ICPE 2 Outline (cid:1) Current view about regulation of medical products (cid:1) Safety surveillance (cid:1) Methods (cid:1) Examples (cid:1) Q & A throughout 2014.10.24 ICPE 3 - Benefit-Risk Assessment of a medical product - Continuous assessment / monitoring throughout a product’s life cycle Improve public health U $$$ Blockbuster Moderate benefit Approval threshold $ Moderate return on investment Neutral value Public health disaster A threshold for withdrawal? New Indications and Risk Management IND NDA 2014.10.24 ICPE 44 Why? (cid:1) Some historical examples (cid:1) cisapride (cid:1) troglitazone (cid:1) rofecoxib (cid:1) SSRIs use among adolescents (cid:1) aprotinin (cid:1) rosiglitazone 2014.10.24 ICPE 5 Strom. JAMA 2006; 295: 2072-5, Figure (cid:1) 2014.10.24 ICPE 6 FDA Amendment Act and The Sentinel Initiative www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf We are seeing the emergence of a science of safety. This science combines the growing understanding of disease and its origins at the molecular level (including understanding of adverse events resulting from treatment) with new methods of signal detection, data mining, and analysis, enabling researchers to generate hypotheses about, and confirm the existence, and causal factors, of safety problems in the populations using the products. 2014.10.24 ICPE 77 FDA Amendment Act and The Sentinel Initiative www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf In addition, personalized medicine is generating information about the unique genetic and biologic features of each person that some day will help determine how he or she responds to treatment. Using these tools, FDA has increasingly adopted a life-cycle approach to product development and evaluation. 2014.10.24 ICPE 88 FDA Amendment Act and The Sentinel Initiative www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf This kind of approach should be used for all medical products so that safety signals generated at any point in the process can be evaluated along with relevant benefit risk data to inform treatment choices and regulatory decision making. FDA regards improving risk and benefit analysis to be one of the important facets of the science of safety that urgently requires additional development. 2014.10.24 ICPE 99 Some general concept (cid:1) Public health practice vs. ivory tower academic research (cid:1) Safety should never be considered alone (cid:1) Benefit-Risk evaluation (cid:1) Continuous assessment (cid:1) Product life cycle management (cid:1) Surveillance within the therapeutic risk management framework (cid:1) Science of Efficacy and Science of Safety 2014.10.24 ICPE 10