It’s hard to even imagine the world of investigative medicine without the wonderful resource of Clinicaltrials.gov, the global hub for clinical trial listings. I recently interviewed the Director of Clinicaltrials.gov, Dr. Deborah Zarin here, which is a fascinating read.
As great as Clinicaltrials.gov is as a resource, unfortunately it faces a new, rapidly growing problem that is a serious threat to the site.
The Clinicaltrials.gov database is including a rapidly increasing number of for-profit clinical trials that are not by any stretch of the imagination traditional clinical trials. At present, the Clinicaltrials.gov rules largely allow any trial submitted to be listed in the database based on an honor system approach.
Dubious stem cell clinics are taking advantage of this loophole to get an air of legitimacy and often use their listing in Clinicaltrials.gov as a marketing tool to convince their potential customers that their trials are approved by the federal government (see hypothetical example below of such a web marketing approach), which at best is misleading.
Another level of strangeness to this situation is that although Clinicaltrials.gov is intended primarily to be a database for trials of experimental new drugs (keep in mind that stem cells products often are biological drugs), the dubious clinics–despite listing their “trials” on the site–claim that their stem cell products are not drugs.
As a result of this overall dubious stem cell trial problem, I believe that the Clinicaltrials.gov vetting system approach is in need of a major overhaul as soon as possible.
How a for-profit trial differs from a regular clinical trial, and how Clinicaltrials.gov can be used.
A traditional clinical trial is intended to evaluate new drug products for safety and efficacy, not to directly make the sponsor of the drug cash. If investigational drugs are proven both safe and effective, their use may go on to generate income and even a profit for a biotech company in the future, but the traditional trial is about evaluating the drug rather than directly raking in cash.
In contrast, a for-profit stem cell clinical trial today is a new breed. Such a trial itself is designed to directly generate a big profit for those running it. The profit from such trials comes not in the future should the drug be proven safe and effective, but rather right now regardless of whether the drug is any good or not.
So for these trials, a stem cell product, for example, could be unsafe and/or ineffective (and the trial sponsors may already even know that) and the stem cell clinic still potentially gets mounds of cash upfront. We are talking big profits as well, potentially in the tens of millions of dollars just from the clinical trial itself, again regardless of whether the product in question is safe or effective.
Vulnerable patients must pay to participate in such for-profit trials and they pay a premium so that the folks running the trial get what can often turn out to be a hefty profit. By and large, if you as a patient do not pay this hefty sticker price then your odds of getting to be in the trial are very low. Usually, you are out of luck.
Does Clinicaltrials.gov really want to list such trials in its database and in so doing be linked to, even if indirectly and unintentionally, the exploitation of vulnerable patients?
I doubt it.
So what can be done?
Clinicaltrials.gov needs to make some changes and do so now rather than later. I’ve explained my concerns to them and pointed out how they are being used by these stem cell clinics. I don’t know if they will listen to me or even if they agree with me whether they can overcome bureaucratic hurdles in the way of change to do something about this any time soon. Here are the key kinds of changes that are needed.
- 1. Competing interest declaration. At the very least, if a company is directly profiting from a trial itself then that competing interest should be prominently displayed in the Clinicaltrials.gov listing. Patients have a right to know.
- 2. No use of Clinicaltrials.gov listings as marketing tools. Clinicaltrials.gov should also have a policy about for-profits using the listing as a marketing tool on the company website. If dubious stem cell clinics, for example, convince patients to pay via website promotional material indicating that they are legit because their trial is listed on Clinicaltrials.gov, the listing should be deleted.
- 3. Keeping the FDA informed about new trials. Clinicaltrials.gov should provide information on all new trials to the FDA and the FDA should examine whether they need to investigate these new trials for compliance. This kind of interagency cooperation makes perfect sense, but will it happen?
If no changes are made at Clinicaltrials.gov to deal with this problem any time soon, at some point the database overall could be damaged. I hope that doesn’t happen as I am a big fan of Clinicaltrials.gov.
Until you posted the interview with Dr. Zarin, I also believed that there was government oversight of the clinicaltrials.gov site. It’s deeply disappointing to realize that this site, with .gov at the end, is being exploited by charlatans as an advertisement for lucrative bogus stem cell “trials.”
I would prefer oversight so that patients aren’t misled. I know that government money is tight, but how hard would it be for the site to tag each alleged trial with an “unverified” label, and mark those listings that charge patients with a big label to that effect?
Thank you for highlighting this important area of concern and proposing cost and resource effective solutions. Clinicaltrials.gov is seen by patients and many medical practitioners as a stamp of authenticity and we advise patients to make sure their trials are registered. A federal standard for IRBs and the mandatory training of the IRB members is critical also.
Most people are not aware that applying for a license for an IRB does not require much rigor.
If we are going to advise patients/participants that the trial needs IRB approval and clinicaltrials.gov registration is seen as a step in validation we need to make sure this means something.
The public is in need of ways to validate the research methods as many of the trials in question are offered with MDs as medical directors and patients have been taught to respect an MD’s authority which translates to if an MD has his/her name on it, it is in clinicaltrials.gov, the inventor has published papers and it went through an IRB this must be good research. Sadly this is not always true.
As for trial expenses, compensation for adverse events and costs for testing etc pre-trial as well as inclusion/exclusion criteria should be clearly laid out upfront and the terms of engagement standardised. For example if a patient in an FDA trial is expected to pay pre-testing and costs of the medical device etc but the trial itself is “free” how can they possibly differentiate when they are asked by a non FDA approved group to pay upfront and be included as part of a trial?
The argument that it would be ethical if they crowd source the expenses of a trial but are not given/guaranteed a place in the trial is pretty weak.
It is unfair to have well-meaning and often desperate and vulnerable patients jump through all the hoops and then inform them it is not enough.
The same issue goes for so called safety papers that are not up to FDA standards and even using non FDA approved interventions. Yet some of these are published in peer reviewed journals. Some of these use patient reported outcomes with very general terms which do not capture the concerns that may develop and therefore dilute the integrity of safety measures.
I agree with you in toto. Firstly, I have never believed in the concept of paid Clinical Trials for the simple reason that their safety & efficacy has not yet been proved & meanwhile you are raking in money.
Same Marketing gimmick is being carried out in this part of the world too.