
Non-publication of large randomized clinical trials - gabemart
http://www.bmj.com/content/347/bmj.f6104
======
pflats
_" Finally, we excluded trials that were registered with ClinicalTrials.gov
more than one month after beginning enrolment, in order to ensure that the
decision to register a study occurred separately from the decision to publish
the study results. This decision was made because it has been shown that in
spite of guidelines endorsing prospective trial registration, trials are often
not registered for many months after the initiation of participant enrollment.
In some of these cases, the registration of the trial is performed in
preparation for publication and after the decision is made to publish the
results. To the extent that this occurs, the inclusion of trials with delayed
registration would bias our results. We limited this source of bias by
focusing on trials for which registration was not delayed."_

I worry that the article is still examining a biased group. As it stands, over
two thirds of the large trials (3710 out of 5427) were eliminated for
registering after enrollment. It stands to reason, then, that this is standard
industry practice. The remaining 10% that was studied is clearly bucking the
common practice and I'd therefore suggest it's not a representative sample.

That said, I commend them for the study and can't suggest a better way to
mitigate bias. I think it clearly shows a pervasive problem in the industry.
I'd just be wary of citing the percentages too fervently.

~~~
andrewla
I think the idea is that the number of studies unpublished because of negative
results is a constant across all time scales.

The data here are probably sufficient to do this meta-analysis; looking at
publication rate as a function of time between starting the study and
registration, rather than looking at an arbitrary cutoff.

------
zetazzed
29% of large, randomized trials did not have published results. This is
actually a much better stat than I was expecting, given the significant
incentives for industry to hide bad outcomes. There's still an unquantified
pile of hidden results that stem from studies that never register with
ClinicalTrials.gov in the first place. (E.g. studies done outside of the US.)

~~~
Aloisius
_There 's still an unquantified pile of hidden results that stem from studies
that never register with ClinicalTrials.gov in the first place. (E.g. studies
done outside of the US.)_

How many studies done outside the US are not registered at ClinicalTrials.gov?
If you intend to use your post-phase 1 trial for FDA approval, you have to
register within 21 days of signing up your first person. Since the US is where
drug and medical device companies make all their profits, I can't imagine why
you would spend the money to do a trial just to have to rerun the trial later
for FDA approval.

Plus if you ever intend on publishing in any of the major journals, you _have_
to register _before_ your trial starts or you'll be ineligible to publish
(including phase I trials).

~~~
janzer
It doesn't make sense to me then why over 2/3rds of the trials this study
looked at were excluded because they registered >1 month after enrollment
started. Have they all found exceptions to, or ways to work around, the above
restrictions?

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colinbartlett
"Non-publication was more common among trials that received industry funding
(150/468, 32%) than those that did not (21/117, 18%)".

Oh, how unsurprising, BigPharma. When someone with an agenda discovers results
that do not support that agenda, bet to bury those and never publish.

~~~
viraptor
Is it really that malicious? Of course either way the result is the same, but
I seeing some corporate actions I would expect that people are simply
reassigned from failing trials and there's noone left to finish. If there's no
incentive to publish the result and the producer doesn't get anything from it,
why would they continue? It's not even malicious or stupid - it's just
business as usual.

Providing some incentive that applies even when the study is not continued
would be great. But the only thing I can come up with is escrow for some sum
of money until the results are sent in. But that's also an incentive for
fabricating any results once it's known that the trial is going to fail.

~~~
andrewla
If a clinical trial is failing, and the corporation decides to reassign
people, then the scientists involved still have an obligation to publish a
result, even if that result is a short note saying "we broke the blind and the
test results are useless".

The notion of having to register early in a study is an excellent one. In a
perfect world, the FDA should interpret an unpublished clinical trial as
"EVERYONE WHO TOOK THIS DRUG CAUGHT FIRE AND DIED" and factor that in to the
decision to approve or deny a potential drug/device/methodology.

