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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by SLS on January 18, 2008, at 17:11:54
Hi.
My impression is that this behavior has been condoned by the FDA for many years such that it became accepted as standard practice by the pharmaceutical companies.
- Scott------------------------------------------------
Study Identifies Bias in Favor of Publishing Positive Antidepressant TrialsMedscape Medical News 2008. © 2008 Medscape
These findings are published in the January 17 issue of the New England Journal of Medicine.
January 17, 2008 A study of Food and Drug Administration (FDA)registered clinical trials of 12 antidepressants found a bias toward publication of positive results. Almost all studies viewed by the FDA as positive were published. The clinical trials that the FDA deemed negative or questionable were largely not published or, in some cases, were published as positive outcomes.
For each of the 12 drugs, at least 1 study was not published or was reported in the literature as positive despite a conflicting judgment by the FDA.
The overall effect size of the antidepressants (vs placebo) that was reported in the published literature was nearly one-third larger than the effect size for these agents that was derived from FDA data.
"Selective reporting of clinical-trial results may have adverse consequences for researchers, study participants, healthcare professionals, and patients," they conclude.
Evidence-Based or Biased Evidence?
"You might get the impression from the published literature that [these drugs] are consistently effective; however, the outcome of this study is that they are effective, but inconsistently so," lead study author, Eric H. Turner, MD, from Oregon Health and Science University, in Portland, Oregon, told Medscape Psychiatry.
"Evidence-based medicine is valuable to the extent that the evidence is complete and unbiased," he noted, adding that selective publication of clinical trials can alter the apparent risk/benefit ratio of drugs, which can affect prescribing decisions.
The current study sought to examine how accurately the published literature conveys data on drug efficacy to the medical community.
The team identified the phase 2 and 3 clinical-trial programs for 12 antidepressants approved by the FDA between 1987 and 2004, which involved 12,564 adult patients. They also determined whether the FDA judged the studies to be positive or negative with respect to primary end points.
To identify matching study publications, the researchers conducted a systematic literature search and contacted the sponsors of the drug studies.
Among the 74 FDA-registered antidepressant studies, the team found that 23 trials (31%) had not been published.
Among the 38 of 74 studies (51%) that the FDA deemed to be positive, 37 were published.
The remaining 36 studies (49%) were deemed to be either negative (24 studies) or questionable (12). Of these 36 studies, 22 were not published, 11 were published as positive, and 3 were published as negative.
Posted by Larry Hoover on January 18, 2008, at 18:51:21
In reply to Bias in publishing of antidepressant trials?, posted by SLS on January 18, 2008, at 17:11:54
> Hi.
>
> My impression is that this behavior has been condoned by the FDA for many years such that it became accepted as standard practice by the pharmaceutical companies.
>
>
> - ScottHey Scott. As I understand it, it's irrelevant to the FDA. They want to see all research, as part of their approval process. Should we extend FDA control over the publication industry?
I saw an interesting question raised, with respect to a possible confound to this review of publication bias. How likely are journals to publish failed trials? Unless they determine whether these negative trials were submitted for publication, then this study is itself biased.
Lar
Posted by SLS on January 18, 2008, at 20:48:02
In reply to Re: Bias in publishing of antidepressant trials? » SLS, posted by Larry Hoover on January 18, 2008, at 18:51:21
Hi Larry.
> > My impression is that this behavior has been condoned by the FDA for many years such that it became accepted as standard practice by the pharmaceutical companies.> Hey Scott. As I understand it, it's irrelevant to the FDA. They want to see all research, as part of their approval process. Should we extend FDA control over the publication industry?
Good point.
> I saw an interesting question raised, with respect to a possible confound to this review of publication bias. How likely are journals to publish failed trials?I guess it's not sexy enough.
> Unless they determine whether these negative trials were submitted for publication, then this study is itself biased.
I think I understand what you are saying. I guess articles submitted to peer-reviewed journals are subject to the reviewers' determining the effectiveness of the trial reported. A failed study would be judged to be ineffective, and therefore has no reason to be published.
- Scott
Posted by Larry Hoover on January 18, 2008, at 22:06:51
In reply to Re: Bias in publishing of antidepressant trials? » Larry Hoover, posted by SLS on January 18, 2008, at 20:48:02
> > Unless they determine whether these negative trials were submitted for publication, then this study is itself biased.
>
> I think I understand what you are saying. I guess articles submitted to peer-reviewed journals are subject to the reviewers' determining the effectiveness of the trial reported. A failed study would be judged to be ineffective, and therefore has no reason to be published.
>
>
> - ScottI probably could have said it better.
In the late 80's and through the 90's, medical journals competed to be the first to publish the latest breakthrough. Submissions often numbered ten or more times what could ever be put into print. Before peer-review, even, editors tossed most of what they were offered. A study with a failed hypothesis doesn't stand much chance of seeing print.
What I'm getting at is that it's not appropriate to blame the pharmaceutical companies for an effect that was subject to a number of independent decisions made by third parties with their own motives.
Lar
Posted by Larry Hoover on January 18, 2008, at 22:27:49
In reply to Re: Bias in publishing of antidepressant trials? » SLS, posted by Larry Hoover on January 18, 2008, at 22:06:51
> What I'm getting at is that it's not appropriate to blame the pharmaceutical companies for an effect that was subject to a number of independent decisions made by third parties with their own motives.
....unless they were never submitted.
Posted by Phillipa on January 18, 2008, at 23:29:31
In reply to Re: addendum, posted by Larry Hoover on January 18, 2008, at 22:27:49
Are they effective or not? Will we ever know why some respond to one right away and some never? Just asking unscientifically. Phillipa
Posted by SLS on January 19, 2008, at 5:29:27
In reply to Re: Bias in publishing of antidepressant trials? » SLS, posted by Larry Hoover on January 18, 2008, at 22:06:51
Thanks for the clarification, Larry.
I don't wish to insult you, but we are in agreement. I don't know how that might portend to your future reputation.
:-)
- Scott
> > > Unless they determine whether these negative trials were submitted for publication, then this study is itself biased.
> >
> > I think I understand what you are saying. I guess articles submitted to peer-reviewed journals are subject to the reviewers' determining the effectiveness of the trial reported. A failed study would be judged to be ineffective, and therefore has no reason to be published.
> >
> >
> > - Scott
>
> I probably could have said it better.
>
> In the late 80's and through the 90's, medical journals competed to be the first to publish the latest breakthrough. Submissions often numbered ten or more times what could ever be put into print. Before peer-review, even, editors tossed most of what they were offered. A study with a failed hypothesis doesn't stand much chance of seeing print.
>
> What I'm getting at is that it's not appropriate to blame the pharmaceutical companies for an effect that was subject to a number of independent decisions made by third parties with their own motives.
Posted by Glydin on January 19, 2008, at 10:14:55
In reply to Re: addendum, posted by Phillipa on January 18, 2008, at 23:29:31
> Are they effective or not?
~~~ Sometimes they are and sometimes they're not. Defining what effective means varies.
> Will we ever know why some respond to one right away and some never?
~~~ Probably not in our lifetime, IMO.
> Just asking unscientifically.
~~~ My opinions, purely unscientific.
Posted by Phillipa on January 19, 2008, at 19:08:19
In reply to Re: addendum » Phillipa, posted by Glydin on January 19, 2008, at 10:14:55
But a good opinion never the less. Phillipa
Posted by Larry Hoover on January 23, 2008, at 17:01:02
In reply to Re: Bias in publishing of antidepressant trials? » Larry Hoover, posted by SLS on January 19, 2008, at 5:29:27
> Thanks for the clarification, Larry.
>
> I don't wish to insult you, but we are in agreement. I don't know how that might portend to your future reputation.No worries, mate. That's good company.
After seeing how many different articles were written about this issue, I finally got around to accessing the original, in the New England Journal of Medicine. The first sentence of the conclusions, in the abstract, reads: "We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both."
The *only* reason I can fathom, to have such an important issue ignored by reviewers, is to provide an opportunity to impugn Big Pharma. Not that they don't deserve it for some things, but this is uncalled for. Moreover, it made me have to think more than I needed to.
Anyway, we already knew that there was substantial unpublished clinical trial information in the FDA database. I can't see how this particular study advanced our knowledge one iota.
Lar
Posted by Jamal Spelling on January 27, 2008, at 11:21:40
In reply to Re: Bias in publishing of antidepressant trials? » SLS, posted by Larry Hoover on January 23, 2008, at 17:01:02
Perhaps it is not the fault of pharmaceutical companies when "negative" studies are rejected for publication by journal editors. But what about the 11 studies that were deemed by the FDA to be "questionable" or "negative", but portrayed in the literature as "positive"?
Pharmaceutical companies are not scientists pursuing an altruistic quest for truth. They are businesses who are interested in maximizing their profits. Of course they are going to try to portray their products in a positive light, as much as the rules allow them, and then some.
This is the end of the thread.
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