arrow10 Comments
  1. antipodean
    Oct 13 - 6:19 PM

    Sneaky buggers…. thanks for that post Dave.

    I have personal experience of trying to be an honest player in publishing clinical trials. It is very very hard to get a negative trial published. Editors are quite willing to bend to inane reviewer comments when directed at a negative study- the same study if positive will be accepted forthwith.

    Any move toward the acceptance of trials for publication before the results are known (or by keeping the results out of the hands of reviewers until they decide whether it is a basically acceptable trial) would be something I would support wholeheartedly.

  2. David
    Oct 14 - 7:26 AM

    antipodean, thanks for the insight. Indeed, we all have experience where even the most relevant negative data is difficult to publish. Glad to hear that you have done your best to contribute to transparency.

    I don’t know the European drug registration process as well as in the US but it seems to me that FDA may have had access to the complete data when making their decision not to approve reboxetine in the States.

  3. JJM
    Oct 14 - 10:09 AM

    I am surprised that companies turned-over unpublished data.

    Antipodean, my first thought was your idea is good. However, if I understand it correctly what you are suggesting is to accept a manuscript based on approval of the protocol. It seems that paves the way to publication of inconclusive results (all CAM research concludes “Further research is needed) as well as accepting clinically insignificant results.

  4. [...] BMJ meta-analysis: Reboxetine “an ineffective and potentially harmful antidepressant” [...]

  5. antipodean
    Oct 14 - 7:06 PM

    JJM

    You could still be rejected for having your conclusions not match your data. And clinically insignificant results are not clinically insignificant because they highlight the lack of effect of that treatment. This is just as important to know as a large treatment effect.

  6. JJM
    Oct 16 - 7:09 AM

    Antipodean,

    Of course it is important to know when a treatment is ineffective, I was thinking, though, about publication in a top-line journal which eschews mundane, if useful, results. Also, some work is clinically insignificant simply because it is redundant (I know a chemist who revels in saying “We knew that 30 years ago”). Other times, work may be ‘justified’ by some convoluted logic that would not normally occur to someone; viz. using oral Mg Citrate solution to treat glaucoma.

    Overall, publication of negative results is good. Really important results (lack of effect of echinacea) is even acceptable to JAMA. If a journal has a policy of deciding the value of results (good or bad) there should be no need to blind reviewers.

  7. David Kroll
    Oct 16 - 10:01 AM

    antipodean and JJM: Funny that we should be having this conversation about the time that my German oncologist/scientist colleague, Martin Fenner, posted at his PLoS blog calling for a pre-print archive of clinical trials.

  8. JJM
    Oct 17 - 7:55 AM

    I like Fenner’s idea, I like antipodean’s idea, too; I just don’t think the complication of pre-approval of the protocol is necessary. Good journals should be open to publishing solid, negative results. And some are, they are just not usually the top journals (with exceptions, e.g., the echinacea study in JAMA).

  9. Martin Fenner
    Oct 17 - 6:07 PM

    David, thanks for mentioning my post suggesting a preprint server for clinical trials. The FDA since September 2008 requires reporting of clinical trial results within 12 months after the last patient has ben treated. I haven’t yet seen any report that analyzed the compliance with this policy.

    • antipodean
      Oct 17 - 8:46 PM

      Hi Martin

      Even in good faith it is very very difficult to report clinical trials in under a year. I realise an expert reviewer and guideline writer, such as yourself, will find this extremely frustrating. It is hard to get this done quickly to the requisite standard.

      JJM “Good journals should be open to publishing solid, negative results.” They should be. But they aren’t. The top journals will publish negative results only when they overturn a long held clinical or folklore tradition (i.e. the echinacea study). They have to be surprising or newsworthy. The bigger better study of a novel technique that overturns a previous smaller less rigourous study will often be rejected. You can see this clearly in citation practices as well- even when published in the same journal the smaller positive trial will be cited faster than the larger negative study.

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