"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.
I think the idea is that the number of studies unpublished because of negative results is a constant across all time scales.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.
> It stands to reason, then, that this is standard industry practice.
It only looks like this because people who have no intent of publishing their papers probably don't register the trials at all, rather than registering them late.
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.)
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).
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?
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.
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.
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.