July 2, 2013

Triggering the Alltrials campaign

The New York Times has a detailed story about one of the triggers for the Alltrials campaign, the missing studies of Tamiflu

He was curious about one of the main studies on which Dr. Jefferson had relied in his previous analysis. Called the Kaiser study, it pooled the results of 10 clinical trials. But Dr. Hayashi noticed that the results of only two of those trials had been fully published in medical journals. Given that details of eight trials were unknown, how could the researchers be certain of their conclusion that Tamiflu reduced risk of complications from flu?

Only about half of all randomized clinical trials are published, despite regulations requiring publication, and the requirements of the Declaration of Helsinki

Authors have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports.

Since the obvious conclusion is that the unpublished studies are less favorable than the published ones, patients and the medical community cannot be sure about the benefits of even the most promising treatments.  The uncertainty always matters at least to a small group of patients, but in the case of Tamiflu it matters to the whole world. The 2009-2010 influenza pandemic was relatively minor, but still killed more than 250000 people worldwide (by most estimates, more than the Iraq war). The 1918 pandemic was at least twenty times worse. Before it happens again, we need to know which treatments work and which do not work.

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Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »

Comments

  • avatar
    megan pledger

    It’s all very well to say the studies have to be published but how many times do you have to submit before giving up as noone will publish negative results.

    11 years ago

    • avatar
      Thomas Lumley

      Megan,

      If I recall correctly, the follow-ups of cohorts of research projects approved by a single ethics committee (John Simes did one in Sydney, and Kay Dickersin did one in the US somewhere) suggest that failure to submit, rather than failure to accept is the bottleneck.

      Either way, it doesn’t matter, though. Journals such as Trials explicitly promise to publish negative results, and in any case the Alltrials petition is not requiring publication in a peer-reviewed journal, just release of the summary results. GSK, the only big pharma company to sign up, is releasing all its results on a website, and that’s fine.

      11 years ago

  • avatar
    Megan Pledger

    Yea, it’s easier now to get negative stuff published. But even strongly positive results can go unplublished or be hard to get published – I was involved in a pharmaceutical trial in a university setting and it was hard to get the trial published as it was funded by a pharmaceutical company. The positive results with that funding source just made editors go (I assume) “I don’t want to have to deal with this – pass”.

    Self-publishing that would have just added to the appearance of lack of credibility.

    11 years ago