This conversation is closed.

That doctors and the public are misled by unpublished drug trials

I believe this presentation is misleading for the follwoing reason.

I worked in the drug industry for 20 years conducting Phase II and III (Premarketing) trialson new drugs. The data from these trials were submitted to the national drug licensing agencies (e.g. FDA in the USA). It was incumbent upon us to submit ALL data from these trials and serious efforts were made to do so. It is on the basis of these data, NOT the published data, that a drug is given a licence for marketing or not. If a drug comapanyfails to submit all the data it has, it is obviously culpable and may have committed fraud (though given the amount of data, human error is also possible - usually several large trucks were required to carry the volumes of paper to the regulators.)

The problem of publication bias is another problem altogether and it is serious for the reasons Ben Goldacre gives. But it's probably true that most doctors are less 'nerdy' than him and don't feel the need to personally examine all the trial results, being content to leave this task to the agencies set up for the purpose. I ran several nagative trials and was keen to get them published. I provided the results of our analyses to the investigators, they had their own copies of the original data, but few were interested in doing the work necessary to produce a publication because they knew that the chances of a journal accepting it were very low. THis problem was compounded by another factor that Dr Goldacre does not mention. Most of these trials were multicentre studies where many doctors co-operated on the same study protocol in order to obtain sufficient patients to achieve a statistically reliable result. Doctors need publications to pad out their CVs and get ahead in their careers. So, oftentimes, doctors wrote up and published the results obtained in their own small subset of patients, especially if that subset happened to give a positive result in the context of an overall negative study. I couldn't stop this.

Closing Statement from John Collier

Yes, the User fees are a big problem because of the conflict of interest they create. In theory our public servants should be abovethis influence but these days it's hard to have this confidence any more. If I understand correctly, even if the industry pays for the review of its data (and in a way, what's so wrong with that?) the review of the data still rpoceeds independently and there are no penalties that the FDA might be subject to. If that's not so, then there really is a problem which goes right back to the democratic process in the US.

The other comment about not adding anything: if every individual doctor wants to make his or her own assessment of the value or otherwise of a new drug this is individualism gone mad and moreover hints at delusions of grandeur in the doctor. The amount of data and the several different disciplines (not just medicine but pharmacology, toxicology, pharmacy, etc) involved make this a ridiculous idea. Having worked with my fellow physicians I know that there are those who consider themselves to be multidimensionally omnicompetent but most of us would rather delegate this analysis to a team of specialists working in a non-commercial setting e.g. FDA or the Medicines Control Agency. SO, whether or not a drug is approved for marketing should require that all the data on the drug are submitted to the agency that makes the decision not necessarily that they are all published, even though this is a good idea - not that all data are published but perhaps at least the medical trial data. Still this begs a question: what about the toxicology data?

  • thumb
    Oct 2 2012: I also urge people to read this exchange of letter in the New York Review of Books.
  • thumb
    Oct 2 2012: Dr.Angell is an outspoken critic of the FDA. In the April 6, 2009 edition of The Boston Globe there is an editorial by Dr. Angell titled, "Charting a new course at the FDA", wherein she offers a list of seven thing that she thinks would return the FDA to its rightful purpose, "to ensure that [drugs] are safe and effective."

    First, Congress should repeal the Prescription Drug User Fee Act.
    Second, consultants for drug companies should no longer be permitted to serve on FDA advisory panels.
    Third, the agency should see that the post-marketing studies it mandates are actually carried out.
    Fourth, the FDA should review generic drugs as fast as brand-name drugs.
    Fifth, Congress should give the FDA the authority to require drug companies to compare new drugs with existing drugs of the same type.
    Sixth, the FDA should stop approving me-too drugs on the basis of surrogate endpoints.
    Finally, the FDA should prohibit direct-to-consumer advertising for three years after drugs are approved.
  • thumb
    Oct 2 2012: Dr Marcia Angell, Former NEJM Editor-In-Chief And Current Harvard Medical School Professor, writes, "But in 1992, Congress put the fox in the chicken coop. It passed the Prescription Drug User Fee Act, which authorizes drug companies to pay "user fees" to the FDA for each brand-name drug considered for approval. Nearly all of the money generated by these fees has been earmarked to speed up the approval process.

    In effect, the user fee act put the FDA on the payroll of the industry it regulates. Last year, the fees came to about $300 million, which the companies recoup many times over by getting their drugs to market faster.

    But while it's a small investment for drug companies, it's a lot of money for the agency, and it has drastically changed the way it operates -- creating a disproportionate emphasis on approving brand-name drugs in a hurry. Consequently, the part of the agency that reviews new drugs gets more than half its money from user fees, and it has grown rapidly. Meanwhile, the parts that monitor safety, ensure manufacturing standards, and check ads for accuracy have languished or even shrunk."