PharmalotBy Ed SilvermanNovember 16, 2015As a US Senate committee meets on Tuesday to consider Dr. Robert Califf for the top job at the Food and Drug Administration, an open question remains whether he is biased toward industry. Califf is held in high regard by drug makers and academics alike. A cardiologist by training, he spent years as a professor at the Duke University School of Medicine and is one of the most influential biomedical authors in the world. He’s also run numerous clinical trials and served on various FDA advisory committees. But ever since Califf was named a deputy commissioner at the FDA in January and then nominated to be chief regulator in September, his long-standing working relationship with the pharmaceutical industry has prompted debate. Among those opposing his nomination are Democratic presidential aspirant Bernie Sanders and Public Citizen, a consumer advocacy group.
Califf was the founding director of the Duke Clinical Research Institute, which conducts studies for companies. Last year, six drug makers — including Merck and Novartis — partly supported his salary, and several others paid him for consulting work. He has also authored numerous papers with industry researchers. No other commissioner in the recent past has held such close ties to pharmaceutical manufacturers. [The last commissioner, Margaret Hamburg, for example, was a career public health administrator.] All this has led some to challenge whether Califf can be an honest broker. “I do think hard questions should be asked,” said Daniel Carpenter, a Harvard University political scientist, who has studied the FDA but has not taken a position on Califf. “He will have a fair amount of power to push for change”…
Boston GlobeBy Sheila KaplanNovember 17, 2015
Supported by Johnson & Johnson Pharmaceutical Research and Development and Bayer HealthCare…
Dr. Califf, receiving consulting fees from Kowa, Nile, Orexigen, Sanofi Aventis, Novartis, and Xoma and grant support from Novartis, Merck, and Amilyn/Lilly and having an equity interest in Nitrox…
I would prefer that Dr. Califf were as clean as a whistle and had no financial connections with any pharmaceutical company. And I would be much happier if he didn’t bother messing with drugs of convenience. Even reading his paper, I wouldn’t take or recommend Xarelto®. My focus would be on being either being the patient or the doctor in the situation when there was a bad car wreck, and I’d say to hell with convenience if I could save a life with a Vitamin shot instead of watching someone bleed to death, I don’t mind insisting on the countless routine blood tests it took to keep that possibility open. But that’s my clinical decision, that would be made in concert with my patient when we’re both playing with a fully informed deck of cards – including this study. I said that to my friend [which was the whole point of my even looking at the paper], and he chose Xarelto® anyway. That’s what his doctor recommended, and that’s what he did [by getting a needed scholarship from J&J]. Their choice. But my friend was fully informed, so I did my job. And in so far as I could tell, so did Dr. Califf [I hope. See this article by the POGO Editor in Chief: Drug Problems: Nominee to Head FDA Led Clinical Trial FDA Faulted].
Looking at other things I’ve written about Dr. Califf, the one real negative was guilt by association [predictable repetitions…]. It was an editorial in the New England Journal of Medicine, Revisiting the Commercial–Academic Interface, by Dr. Jeffrey Drazen supporting Dr. Califf for FDA head [see also a contrarian frame of mind…, wtf?…, wtf? for real…, a narrative…, not so proud…]. In the first place, since when is the editorship of the NEJM a position from which to weigh in on such matters? And Dr. Drazen’s recent showing with his editorial and series on industry-tainted authors writing review articles was an outrageous rationalization, worthy of considering a change in his employment. He’s the paradigm of an industry-friendly guy who assured us fifteen years ago that his PHARMA-connections were behind him and it was… well, it just wasn’t true [sleeper cell comes to mind]. I have no idea how he and Dr. Califf are connected, but I don’t have a bit of question about Dr. Drazen’s Conflicts of Interest. So I see that endorsement from Dr. Drazen as a major black-mark on Dr. Califf’s resume.
But when it’s all said and done, I don’t really think that the FDA is a major problem except in two areas. I don’t like the fact that the boss over-rode the opinion of the evaluator on drugs like Zoloft or Latuda, but those aren’t my main beefs. They are that the FDA continues to honor industry’s claim that Clinical Trial data and the submitted Clinical Study Reports or Individualized Participant Data are proprietary – keeping secrets for industry – and have made none of the moves towards data transparency like those occurring in the European Medicines Agency. My second complaint is that the trials known as Phase IV [post-marketing] Trials which should be rigorous and ongoing are essentially worthless. They’re done by PHARMA, and rarely mentioned. In reading about a drug, even late in its patent-life, we still mostly hear about those PHASE III Clinical Trials done to get the various approvals. We need to know how the drugs perform [or don’t perform] once they’re out there, and we don’t know – at least in any formal way. The whole Contract Research Organization industry was built to get drugs approved. Once approved, they’re in the hands of the marketeers and then later the Civil and Federal Courts. The latter may be getting better at punishment, but that’s hardly the point.
What matters is what happens once the drug is in general use. I can "vet" products I order on-line from Amazon.com not long after they appear [Amazon.com is the major store for those of us who line in the woods], but even as a doctor, I can’t do that with drugs until they’re almost out of patent except by word of mouth or trial and error. Dr. Healy’s giving it a really serious try with RxISK, but he’s going to need a lot of help. The FDA has a reporting system but it’s woefully lackluster.
Data Transparency and post-marketing Trials. I doubt they’ll be asked, but I sure hope they are. And when it comes down to it, the real question is whether Dr. Califf is a person of integrity who will make the right hard decisions when the issues that really matter come across his desk [two of my favorite unlikely heros, James Comey and Earl Warren, come to mind]? Or will he follow Dr. Drazen’s sleeper cell mentality? Will the Office make the man? I don’t know how one knows something like that in advance…Boston GlobeSheila KaplanNovember 17, 2015
Regulatory AffairsBy Zachary Brennan17 November 2015
Washington PostBy Brady DennisNovember 17, 2015
I am sure that this is all high drama, but at a practical level it doesn’t really mean much.
Any time that you have a scientific committee voting by a wide margin to not approve the release of a drug and the drug is released anyway based on the fact that the pharmaceutical company jumped through all of the hoops it illustrates the problem. You can obviously have a government bureaucracy that does what it wants independent of science and common sense.
Not only that but following the trail of what happened is generally impossible on one of the government’s most poorly organized web sites. Bureaucrats are like politicians – you might be able to figure out what happened someday, but that is usually long after they are retired or dead. Most of these decisions won’t even come close to the Director’s desk. Everyone in a position like this expects plausible deniability. If I was a candidate and looked at some of the recent approvals – I would insist on it.
That’s far from my main beef with the FDA. A far bigger problem is their interference with the right to try to live. They won’t let the dying take drugs that are in early clinical trials. The compassionate use program after HIV success was supposed to change that but only one percent get access unless they are in a study and (rightly) there are a lot of exclusion criteria for comorbidity.
Think about the fact that many states have right to die laws but not a right to try experimental drugs.
One million Americans a year are told by their doctor there’s nothing you can do. That’s a much bigger issue than nanny state bickering over which SSRI is better.