November 28, 2020

The Niche

Knoepfler lab stem cell blog

FDA outlines potential crackdown on Clinicaltrials.gov offenders

Clinicaltrials.gov is a wonderful resource for its many users, whether a patient searching for a clinical trial to actually participate in or someone doing research as I have done, but it’s not perfect and some sponsors have been breaking the rules regarding its use. It’s a major problem in fact.

Based on new draft guidance it seems that the FDA and NIH are teaming up in a big new way to punish those who are non-compliant with the Clinicaltrials.gov-related regulations and laws, including potentially with large fines.

What do sponsors of specific listings do that’s so bad?

Figure 2, NEJM, Anderson et al on Clinicaltrials.gov 2015
Figure 2, NEJM, Anderson, et al. on reporting compliance of studies listed on Clinicaltrials.gov 2015

There are a variety of problems including submitting false information or certifications as well as failure to post results in some cases as documented in a 2015 NEJM Anderson, et al. pub by the FDA itself, and other issues. See Figure 2 from the Anderson pub showing the poor reporting compliance of results.

Years ago I noticed that some stem cell-related listings were not real clinical trials but instead were listings from for-profit, unproven stem cell clinics. It’s become clear since then that a number of clinics use their listings on Clinicaltrials.gov as a marketing tool by portraying it as some kind of NIH seal of approval, which it clearly isn’t.

I’ve been thinking even more about the trial site ever since I did a surprising interview with its Director at that time, Dr. Deborah Zarin, almost exactly 4 years ago. In the interview Zarin made clear that there is only limited vetting of submitted listings prior to them going up live on the site:

“We specifically ask for IRB info (menu of options includes: pending, approved, exempt)—and don’t allow studies to go into “recruiting” or “open” status until they have stated that they have IRB approval. We ask for, but don’t systematically enforce, a copy of at least one IRB letter.  We don’t investigate other aspects of regulatory or legal status—it’s just something that the responsible party has to “certify” to us.  We list the oversight authority as a service so that if there is an alleged problem the public (or we) know what entity might have oversight. This is especially true for non-US studies, for which we might not know anything about the regulatory system.”

There’s also no mechanism by which Clinicaltrials.gov indicates to users of the site that a given listing has no IND, charges for participation, or has other potentially important complicating issues. In fact, as far as I know a trial listing remains on the site even if the FDA sends the sponsor a warning letter or takes other major action, and there isn’t even any indication on the listing that anything happened.

Shortly after my interview with Zarin, I raised an alarm about the site’s mission being at risk from for-profit, non-compliant “trials” in the stem cell arena. Over the years, others have weighed in about this as well. Furthermore, broader issues with the way many sponsors behave have been discussed including the failure to follow the law regarding posting trial results in a timely manner after trial completion.

The new FDA draft guidance suggests a crackdown on trial scofflaws. It’s hard to navigate the verbiage in the draft guidance and without reading the important associated documents it’s not entirely clear how this crackdown might play out, but the guidance suggests a tough new stance.

I don’t know that it will necessarily have any impact on the stem cell clinics that misuse Clinicaltrials.gov, especially since they generally operate outside of the IND-based system, but it might and I hope it does. If, for instance specific clinics have certified to the site that they are compliant when they aren’t, that could be a violation of the guidance. On the other hand, these clinic listings might escape any action.

Beyond fines, I think the for-profit, non-compliant stem cell clinic listings should be delisted, but I’m not sure there’s even a mechanism for that in the laws/regs pertaining to the site in general and I didn’t see anything about that in the new draft guidance.

We’ll have to see how this plays out as the guidance hopefully goes from draft to finalized version and gets employed in the real world. The impact will go far beyond the stem cell arena.

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