David's New Book

Thursday, October 21, 2010

More on FDA Thinking

In the Oct. 14 issue of the New England Journal, Dr. Susan Okie writes about Drs. Hamburg and Sharfstein’s efforts to “revive” the FDA (an interesting choice of words, don’t you think?).   In this article, Dr. Okie covers the FDA on rosiglitazone, medical devices, food safety, facility inspections and the tension within CDER between their Office of Surveillance and Epidemiology and their Office of New Drugs.  The surveillance folks claim that the new products folks are too focused on approving new drugs to pay sufficient attention to safety risks.  The new drugs folks feel that the surveillance office is too focused on safety to the detriment of valuable new products. Although Dr. Okie cites rosiglitazone as the contemporary example, she could easily have chosen the antibiotic telithromycin (Ketek) removed from the market for certain indications back in 2006.  Of interest, the FDA has apparently contracted with Harvard Pilgrim Health Care to develop and test a data mining system to survey electron medical records to answer safety questions.

Back in 2005, I worked with the Manhattan Institute to frame an approach to Janet Woodcock’s Critical Path proposal.  In this proposal, Dr. Woodcock exhorts sponsors to develop new tools using new genomic, proteomic and other novel scientific methods to push rapidly forward towards a new paradigm of drug development.  In this new paradigm, drug safety and efficacy studies would be informed by biomarkers developed and validated using the new scientific tools.  The task force at the Manhattan Institute examined the proposal and developed a white paper, Prescription for Progress; a Critical Path to Drug Development.  The context of the white paper was within the realm of biomarkers and, mostly, the development of drugs for oncology and inflammation.  But one general approach that we did present to the FDA still resonates for me and, I think, for some at the FDA.  We suggested that a drug could be conditionally approved based on favorable Ph. II data in a life threatening indication or where there was no other therapy available.  One example we used in our presentation to the FDA in 2005 was Vioxx.  If Vioxx were developed for use in patients with rheumatoid arthritis whose pain was unresponsive to other non-narcotic pain relievers in a phase II trial, the drug would then be approved for use only in that patient population.  A registry would then be required for all patients for whom the drug was prescribed to assure that the drug was not being used off label and to assess safety risk.  Thus, the drug would fill an important medical need only within the specific needy population.  The sponsor would sell the drug and recoup some costs while continuing into phase III trials that might study the drug in a wider population.  Before the drug would be approved, though, there would be considerably more use occurring outside the clinical trials than we usually have at the end of phase III.  Therefore, our understanding of the safety of the new drug in a larger population would be enhanced and this would reduce the safety risk going forward.  In the case of Vioxx, perhaps the cardiac risk would have become evident during its restricted use in the rheumatoid arthritis population.  The sponsor might have then been able to argue that the benefit risk ratio is still favorable within that population, and ultimately have had Vioxx approved in a narrow indication as opposed to the very broad indication for pain relief where hundreds of millions of prescriptions were written.

If we could study antibiotics in a very needy population, such as patients with serious infections caused by highly resistant pathogens, perhaps a new antibiotic could follow a similar route.  The questions as posed in a recent blog remain the same.  What would the details of such a study look like?  Will it be feasible or not? 

The article by Dr. Okie in the New England Journal did not even touch on antibiotics.  Hmmmm . . . .