Anti-Infective Drug Advisory Committee Meeting December 4, 2014 Reshma Ramachandran Co-Chair, NPA FDA Task Force MD/MPP Candidate at Brown Medical School and Harvard Kennedy School
National Physicians Alliance Putting Health at the Heart of Medicine The National Physicians Alliance was founded in 2005 to strengthen physicians’ civic engagement on behalf of patients and to build community within the profession. United across medical specialties, we believe every person has the right to quality, affordable health care and that America should provide equal opportunity for health. Focused on the core values that called us to the profession, we advocate for a health care system that puts patients first. To help restore trust and integrity in medicine, the NPA accepts no funding from pharmaceutical or medical device companies. DISCLOSURE: I have no financial relationships with a commercial entity producing health-care related products and/or services.
We need NEW antibiotics… • But NOT at the expense of patient safety and drug efficacy • Bottleneck in antibiotic R&D is NOT regulatory – Highest rates of regulatory agency approval – Almost 50% of anti-infective agents make it through market approval • Lower for other therapeutic classes (e.g. MSK, anti- cancer)
DiMasi, J.A., Success rates for new drugs entering clinical testing in the United States. Clin Pharmacol Ther , 1995. 58(1): p. 1-14.
No reward for cutting trials • Eastern Research Group – Shortening clinical trials would only give an economic incentive if trials were cut by 75% PERCENT – Impossible without compromising patient safety Sertkaya A, Eyraud J, Birkenbach A, Franz C, Ackerley N, Overton V and Outterson K. “Analytical Framework for Examining the Value of Antibacterial Products.” Eastern Research Group. April 2014. Available at: http://aspe.hhs.gov/sp/reports/2014/antibacterials/rpt_antibacteri als.cfm#_Toc382830308
Approval standards for new antibiotics are already too low, use too few patients – Bedaquiline • 5-fold increase in mortality in treatment group • Approved based on alternative endpoints (sputum positive → sputum negative) – Dalbavancin • Did not qualify for CMS new technology add-on payments – CMS: “…the NTAP application process and approval requires a demonstration of significant clinical improvement, which is not inherent in FDA’s regulatory process…” – Tigecycline • 2005 – received expedited approval • 2010 – associated with increased risk of death
Tiered Approval – NOT Adequate Also NOT sufficient for safety FDA: Not sufficient for safety and efficacy and efficacy • Tier B • Tier C – one phase 3 body site trial – small comparative and/or noncomparative studies with inference testing without statistical inference demonstrating effectiveness testing and safety in the one body – NOT sufficient for FDA’s site and descriptive studies in requirements for safety and patients receiving the new efficacy investigational drug • Tier D – Patient factors ≥ Organism – animal rule approach factors – NOT sufficient for FDA’s – Upjohn v Finch (1970) – case requirements of safety and studies not substantial efficacy evidence for drug efficacy
What should be done? • STRENGTHEN, not undermine the FDA approval process – When drug is more effective, fewer patients are needed for clinical trials. – System for sharing historical control data – NIH clinical trials network • Remove COI in setting standards for antimicrobial susceptability – Transparency, independent of COI, based on patient- centered outcomes – Only 3 of 14 members of CLSI group reported no financial COI
Thank you! Questions? Email me at reshma.ramachandran@npalliance.net
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