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Robert R. Fenichel |
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Professional Activities ConsultingIn the past two years or so, I have been paid for activities directly affecting the interests of Allergan, Astellas, AstraZeneca Pharmaceuticals LP, Bayer, Boehringer-Ingelheim Pharmaceuticals, Cardiome, Cebix, Chelsea Therapeutics, Corthera, Daiichi Sankyo Pharma, Dainippon Sumitomo Pharma, Epix, Essentialis, Forest, Galenea, GeNO, Graceway, GTx, Hyperion, Ikaria, Janssen Pharmaceuticals, Ligand, H. Lundbeck A/S, Lux Biosciences, The Medicines Company, Pharmacopeia Drug Discovery, Roche, Sanofi-Aventis, Sequel, Synosia, TAP Pharmaceutical Products, VIA Pharmaceuticals, and two pharmaceutical companies that insist on anonymity. About 80% of my work has been for drug developers, large and small; about 13% has related to litigation; about 4% has been with potential investors in pharmaceutical development; and the remainder has been a miscellany. Overall, about half of the time I am trying to help victims of regulators' ignorance, most frequently with respect drug-induced changes in ventricular repolarization. An increasing fraction of my work has entailed the collaborative production of documents, and some notes on that process are here. I recently had the opportunity to serve on the data-safety-monitoring board (DSMB) of a clinical trial. As part of this work, I composed a spreadsheet to facilitate optimum use of the expertise of (a) the DSMB members and (b) the contract employees doing most of the legwork. I expect to modify the spreadsheet for use with other trials, and so may you. My fee schedule and billing practices are described here. It was the best of Times, it was the worst of Times, but not in that orderI was one of many FDA-associated people interviewed by a Los Angeles Times reporter doing a series on recent drug withdrawals. When the series appeared on 20 December 2000, I realized that he and I had not talked about many of the key concepts behind modern pharmacotherapy, drug development, and drug regulation. Some of these concepts are non-obvious, as demonstrated by both the thrust of the articles themselves and by some of the quotes that the author gathered from FDA insiders & outsiders. I felt compelled to send the author a long email message. The posted email message led to an interview with Denise Grady and an article in the New York Times on 6 March 2001. The CATHEDRAL TrialSeveral recent hard-endpoint trials have demonstrated that treatment with HMG-coA-reductase inhibitors ("statins") reduces the incidence of atherosclerotic events in high-risk middle-aged adults. At a meeting organized by the Duke Clinical Research Institute in December of 1999, we discussed the difficulty of extrapolating these results to younger patients. We sketched the outlines of a feasible trial to answer some of the open questions, but the matter was left hanging. I'd love to pull together the logistic and financial support that might be needed for such a trial. The ideas were loosely described in a manifesto, but after a certain amount of trolling I doubt that anyone can be found to support it. How antihypertensive drugs are approved for marketing in the United StatesI contributed chapters on this topic to the first and second editions of Oparil & Weber's Hypertension (Philadelphia: Saunders and then Elsevier Saunders, 2000 and 2005). Not much of my text changed between editions, but the paragraphs Applications for new antihypertensive drug products come to the FDA's Division of Cardio-Renal Drug Products (DCRDP). As of early 1998, the staff of DCRDP included 18 physicians, 15 toxicologists, and 11 administrative and technical personnel. In addition, there were at that time 11 chemists, 6 biopharmaceutical reviewers, and 6 statisticians who — although not formally members of DCRDP — were assigned full-time to the support of the Division. . . . A Nonapprovable letter must describe the deficiencies in the application that led to the Agency's negative conclusion.
At the other extreme, an Approval letter is usually short and simple. The third type of Action Letter, the Approvable letter,
is used for a product which appears to be safe and effective, but with respect to which there remain minor gaps in the
chemistry description, unsettled portions of labeling, or other deficiencies that appear to be straightforwardly reparable.
Marketing of the product is not permitted until the issuance of an Approval letter. were updated to Applications for new antihypertensive drug products come
to the FDA's Division of Cardio-Renal Drug Products (DCRDP). As of late 2003, the staff of DCRDP included
11
physicians (down from 16 in
1999), 13 toxicologists (down
from 15), and 12
administrative and technical personnel (up
from 11). In addition, there
were at that time 8
chemists, 8
biopharmaceutical reviewers, and 5 statisticians who — although
not formally members of DCRDP —
were assigned full-time to the support of the Division. . . . The third type of Action Letter, the
Approvable letter, was
originally used for products
which appeared
to be safe and effective, but with respect to which there remained
minor gaps in the chemistry description, unsettled portions of labeling, or
other deficiencies that appeared
to be straightforwardly reparable.
The typical Approvable letter was then followed by no more than a few weeks of
faxes and meetings before the predictable appearance of an Approval letter.
More recently, apparently as a response to time constraints imposed upon the
Agency by the Prescription Drug User Fee Act, Approvable letters have been less
closely coupled to ultimate approval. The total elapsed time from the Division's
receipt of the application to its issuance of the Action Letter averaged
about 14 months in
the late 1990s. The Division declines to release any newer statistics, and
such statistics would in any event be difficult to interpret, in view of recent
changes in the use of Approvable letters. Describing PatientsStarting in 2002, I was a volunteer mentor for second-year Georgetown Medical School students during their first experiences of interviewing and examining hospitalized patients. The students wrote up their findings, I annotated their reports, and we discussed the issues that arose. Some of the same problems occurred from year to year, and I started assembling my old annotations into handouts. Georgetown Medical School did not make things easy for an irregular faculty member like me, so I have not worked with their students since 2004. The last version of the collected handouts is here. Page revised: 05/19/2010 21:30 |