Mark McClellan, former head of both the FDA and CMS, and Scott Gottlieb, current head of FDA, are two of the stars of the Washington health policy world.
A few weeks ago, FDA published a request for proposals with the government prerogative of making it a "sole source" offer - to McClellan's Margolis policy center, located at Duke with a DC branch.
FDA reversed course "after it became aware" that potentially other centers could apply for the funding, which is to help FDA convene public stakeholders and experts on matters of interest, such as improved structured risk-benefit assessment. As WaPo noted, the award budget will be $4.2M.
- See Endpoints News, here, May 17.
- See Politico, here, May 16.
- See WaPo, here, May 16.
- WaPo notes that FDA made a single source grant to Brookings Institute Engelberg Center in 2013 (here).[*]
In WaPo, Jerry Avorn, a Harvard health policy expert and frequent contributor to NEJM and JAMA, stated his surprise that FDA would view the topic as one leading naturally to a sole-source RFP.
The Actual RFP
The original RFP (RFA FD 18 013) was withdrawn from its online status but is available on Google Cache (as of 5/20/2018) here and a cloud copy of the original here. Note a simple remark on page 8 that entitie(s) eligible to apply are: "Duke University - Margolis Center."
It was reissued as award FD 18 025, online here. The new application cycle is May 17-July 18. See "Part 2, Section I," for research objectives, specific research interests, and the anticipated approach. (I've also posted a cloud copy here.) The award budget is stated as about $850K in each of 5 years (FY2018 - which will nearly be over by the award date), 19, 20, 21, 22).
It was reissued as award FD 18 025, online here. The new application cycle is May 17-July 18. See "Part 2, Section I," for research objectives, specific research interests, and the anticipated approach. (I've also posted a cloud copy here.) The award budget is stated as about $850K in each of 5 years (FY2018 - which will nearly be over by the award date), 19, 20, 21, 22).
Topics include - well, almost everything the FDA does, in a lengthy bullet point list, from "enhancing regulatory science and expediting drug development" to "enhancing the use of real world evidence" and "the patient's voice in drug development and decision-making."
The two areas receiving the most highlight, in paragraph form, are enhancing PFDD - patient focused drug development - and structured risk-benefit assessment.
Structured Risk Benefit
While "regulatory science" is a very broad domain, the core principle is to make risk/benefit decisions, such that benefit is greater than risk. This is tortuous for several reasons. For one thing, risks and benefits are incommensurate - Viagra has one set of benefits, but a completely different sets of risk (e.g. stroke).[**] Scientifically, when is one great than the other? For a second thing, trial design and statistics are completely different. Benefits are usually very tightly defined endpoints with hard statistics (survival increases 8 weeks ± 1 week.) Risks are random, unpredictable, and have little statistical weight because they are ad hoc and observational - two patients had a heart attack, one had new migraines, and one had a stroke.
Traditionally, FDA advisory boards see a 100 slide presentation of benefits, get a coffee break, see a 100 slide presentation of risks, then chat for a while and vote. That's hardly "structured." FDA has posted some "qualitative structured" templates, but the ones I've seen are hardly more than putting benefits in a list on the left and risks in a list on the right - presumably what people were doing in their heads anyway. (The technique was published by Benjamin Franklin in 1791).
For some current FDA thinking on structured risk benefit, see here here here and here. For an 18 page 2017 Duke/Margolis white paper on the topic, here.
I wrote about the topic in this blog in 2014 (here). I revisited in 2015 regarding flibanserin, not to promote flibanserin but to note how openly disparate the "risks" and "benefits" were.
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[*] The 2013 award was to study a range of bullet-point initiatives (similar to the current award) with special focus on patient reported outcomes, on structured risk/benefit, and on standardizing and evaluating REMS. That award amount was $700K for one year, similar to a one-year budget in the new grant.
[**] In case it's not obvious, the risk benefit "equation" would be highly subjective, such as whether 12 sexual encounters per year are worth (say) 3% risk of stroke. (Discuss and explain your answer.)
