Clinical Trial Ads, Informed Consent, And Half-Hearted Regulation
By Paul Ivsin
Both of these things are true:
- FDA guidance on clinical trial recruitment specifies that “Advertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.”
- Many clinical trial ads routinely emphasize payment in larger and bold type.
What is the cause of this? Scofflaws running amok in pharma?
Not really! The root of the problem is the very guidance I mentioned in #1, FDA’s 1998 classic, Recruiting Study Subjects. That document belongs to a special category of government work: the half-hearted regulation.
The core of the guidance’s half-heartedness is also the most-quoted line in it:
FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process. Advertisements should be reviewed and approved by the IRB[.]
The IRB is responsible for reviewing and approving a site’s informed consent process. If advertising is the start of that process, then the ads must also be reviewed.
This makes perfect sense… except when it doesn’t. The guidance clearly pictures a scenario where a site is looking to enroll a particular trial.
But there is another extremely common scenario where ads about trials arise: when an advocacy group, or patient recruitment service, or even an individual site builds a database of interested patients who may be evaluated for a match to multiple trials. As long as the recruitment is done in a way that spans more than one protocol, the IRB no longer has the authority to review the ads. IRBs don’t have legal power to monitor the business operations of sites and recruitment vendors — and they certainly have no authority over patient advocacy groups!
We are left with two categories of clinical trial ads: protocol-specific ads that need to be reviewed by IRBs and follow the assortment of rules laid out in the FDA guidance, and everything else, which doesn’t really need to be reviewed by anyone and can more or less make up their own rules.
So, how does the guidance address this seemingly very problematic second category?
It does not.
It simply — through a failure of imagination? a complete lack of interest? — does not contemplate the existence of trial ads that are not “the beginning of the informed consent process.” It just seems to assume, half-heartedly, that of course all ads would be subject to IRB review.
And whether FDA feels like acknowledging it, this is a bit of a problem. When I wrote about this before, the trend was going in the obvious direction:
It feels like the current two-tier system can’t last long. Bypassing the IRB is cheaper, faster, and has a lot fewer pesky rules to worry about! So even if people feel that IRB review is better, competition and market forces would seem to push hard against that as a standard practice. And it absolutely does seem like no-IRB ads are proliferating.
Understanding The FDA’s Trial Ad Guidance
It is a common criticism of the 1998 guidance that it’s old — after all, it hasn’t been updated in 28 years. But then again, most guidance documents are designed to remain relevant even as times change: They articulate general principles and standards. For example, the guidance on Screening Tests Prior to Study Enrollment also came out in 1998, and it seems perfectly appropriate to a trial running today.
That said, I cannot emphasize enough how weird the trial ad guidance is. Unlike the screening tests guidance, it is strangely hyper-specific to its time and place. It cites individual websites, including one (ACTIS) that has since gone defunct. It recognizes the existence of “listings of clinical trials on the internet” but fails to even consider the possibility that there might be advertising on the internet. This is all very odd, because even in 1998 people mostly knew that internet sites came and went and that ads were starting to appear everywhere.
And then it wraps up by taking an off ramp, dedicating the final 15% of its content to “receptionist scripts.” But that section doesn’t actually talk about the content of scripts (or mention why only scripts for receptionists were an issue); instead, it exclusively talks about handling of sensitive patient information.
As a whole, it reads like a collection of notes from a meeting, not an actual official regulatory document. It makes an extraordinary claim — that ads are part of informed consent — then simply refuses to consider that might have broader implications. Instead, it just drops a semirandom assortment of rules and prohibited phrases (“no-cost health examination” is fine, but “free medical treatment” is a no-no).
So, not only is IRB authority granted half-heartedly, the guidance itself is half-hearted.
And to this day, IRBs have simply taken the guidance at face value, enforcing the few rules that it provides. To be fair, it’s unclear what else they could do? The FDA makes it clear that it expects IRBs to review trial advertising, so IRBs have done that across the subset of trial ads where they actually can, and mostly just ignored the ads it has no remit over.
An Opportunity To Fix The Problem
Not all guidance documents can be perfect, of course.
Fortunately, FDA had a golden opportunity to address this issue with its comprehensive update to the Informed Consent guidance in 2023. With a couple of decades of hindsight, surely it could tackle this large and growing discrepancy.
Did they? No, they did not.
The 1998 guidance is cited as authoritative, and the wording is only lightly edited:
FDA considers advertising used to recruit subjects into the clinical trial to be the start of the ongoing consent process, and the information provided in any online or hard copy recruitment materials should be consistent with the informed consent document.
The guidance tries to incorporate advertising into a broader concept it calls the “consent process.” The process starts with advertising and continues… well, somewhat indefinitely. The actual informed consent form and accompanying conversation(s) with site staff are referred to as the “consent document” and “consent discussion,” respectively.
But you can tell the FDA’s heart really isn’t in this distinction.
Most of the guidance doesn’t even pretend that advertising is part of the “consent process.” Here’s a fun example:
FDA regulations authorize the IRB to observe or have a third party observe the consent process.
I don’t think FDA gave any thought to figuring out how to enable IRBs to monitor every patient’s reading and click behavior on Facebook ads! This sentence only makes sense if “consent process” doesn’t actually include ads and is just restricted to the ICF and discussion with the site staff.
Even when the guidance is explicitly invoking a broad, sweeping use of “ongoing process,” it is often still clearly not thinking about the alleged “start” of that process. There’s no way to understand this passage if advertising is truly part of the ongoing process:
FDA notes that informed consent should be viewed as an ongoing process throughout the course of a subject’s involvement in the research. Therefore, FDA recommends that whenever subjects who do not understand English are involved in research, appropriate interpreter services be made available throughout the course of the research.
“Whenever” in this paragraph can only be read as “whenever, but not before the ICF and consent discussion.” Ads don’t come with interpreter services!
FDA’s inconsistency about whether ads are inside or outside of the informed consent process highlights just how odd and unsustainable the ads-are-the-start-of-consent position really is. But once again, FDA commits to the half-hearted position that some ads are reviewable and some are not, and they don’t want to talk about it.
Where Do We Go From Here?
To summarize the current situation, then: We have a set of rules that a) only applies to some trial ads some of the time, and b) is pretty incoherent relative to the rest of the rules regarding informed consent.
What would be the best way to fix this? The FDA could either update its advertising guidance to be more generally applicable to all ads, or it could simply scrap that guidance and take IRBs out of the ad-approval business.
When I discuss these options with other people in the industry, they invariably recoil at the second option. The consensus is: Don’t open the door to more unreviewed ads. Figure out how to increase compliance.
I sympathize a lot with this take. Even though the guidance is decidedly less than great, do we really want to just give up and let trial advertisers post whatever they want? That doesn’t feel like a path to good quality.
But the nagging problem is: I don’t think this discrepancy is fixable. The FDA cannot regulate what patient recruitment companies or sites say about their businesses — not because they don’t know how, but because they simply don’t have that level of legal authority. The laws establishing the FDA’s jurisdiction and powers are pretty clear, and they do not extend into business operations that aren’t directly related to testing, manufacturing, or selling a particular drug.
And even in the implausible scenario that Congress goes forward to create laws expanding the FDA’s authority, their actual ability to stop advertising will be limited. A series of federal court cases from 2011-2015 greatly restricted the FDA’s ability to regulate truthful promotional speech, and this would certainly still apply to any new trial ad regulations.
The key question then becomes: What would happen if the guidance were simply withdrawn and IRBs were given no special authority to review any pre-consent materials?
In reality, the ads may not change that much. They would still need to be fundamentally truthful (there are still rules, from groups like the FCC, against outright lying in ads), so the changes would mostly be on areas of emphasis — ads would likely lean in more on potential benefits of trial participation, including compensation.
It is possible that some people would then get the wrong idea about what the trial was for and what was involved in participating. The good news: That’s what the informed consent document and discussion are for! An enormous amount of effort (maybe even too much) has gone into specifying all the ways that the ICF should work to prepare patients and ensure that neither coercion nor undue influence are factors in the decision to enroll. By clearing away rules about pre-consent communications, the FDA could put its whole heart into solidifying the ICF’s central role.
About The Author:
Paul Ivsin spends his days thinking about how to improve enrollment in clinical trials. Coincidentally, he is also the founder of First Patient In, a clinical trial enrollment consultancy, where he serves as principal and chief combobulation officer.