Committee Meeting December 4, 2014 Reshma Ramachandran Co-Chair, - - PowerPoint PPT Presentation

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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

SLIDE 1

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

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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.

National Physicians Alliance

Putting Health at the Heart of Medicine

DISCLOSURE: I have no financial relationships with a commercial entity producing health-care related products and/or services.

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We need NEW antibiotics…

But NOT at the expense
f 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)

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DiMasi, J.A., Success rates for new drugs entering clinical testing in the United States. Clin Pharmacol Ther, 1995. 58(1): p. 1-14.

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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

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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

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Tiered Approval – NOT Adequate

FDA: Not sufficient for safety and efficacy

Tier C

– small comparative and/or noncomparative studies without statistical inference testing – NOT sufficient for FDA’s requirements for safety and efficacy

Tier D

– animal rule approach – NOT sufficient for FDA’s requirements of safety and efficacy

Also NOT sufficient for safety and efficacy

Tier B

– one phase 3 body site trial with inference testing demonstrating effectiveness and safety in the one body site and descriptive studies in patients receiving the new investigational drug – Patient factors ≥ Organism factors – Upjohn v Finch (1970) – case studies not substantial evidence for drug efficacy

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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

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