Friday 25 November 2011

The weird world of US ethics regulation

There has been a lot of interest over the past week in the Burzynski Clinic, a US organisation that offers unorthodox treatment to those with cancer. To get up to speed on the backstory see this blogpost by Josephine Jones.
As someone who spends more of my time than I’d like grappling with research ethics committees, there was one aspect of this story that surprised me. According to this blogpost, the clinic is not allowed to offer medical treatment, but is allowed to recruit patients to take part in clinical trials. But this is expensive for participants. The Observer piece that started all the uproar this week described how a family needed to raise £200,000 so that their very sick little girl could undergo Burzynski’s treatment.
I had assumed that this trial hadn’t undergone ethical scrutiny, because I could not see how any committee could agree that it was ethical to charge someone enormous sums of money to take part in a research project in which there was no guarantee of benefit. I suspect that many people would pay up if they felt they’d exhausted all other options. But this doesn’t mean it’s right.
I was surprised, then, to discover that the Burzynski trial had undergone review by an Institutional Review Board (IRB - the US term for an ethics committee). A letter describing the FDA’s review of the relevant IRB is available on the web. It concludes that “the IRB did not adhere to the applicable statutory requirements and FDA regulations governing the protection of human subjects.”  There’s a detailed exposition of the failings of the Burzynski Institute IRB, but no mention of fees charged to patients. So I followed a few more links and came to a US government site that described regulatory guidelines for ethics committees, which had a specific section on Charging for Investigational Products. It seems the practice of passing on research costs to research participants is allowed in the US system.
There has been considerable debate in academic circles about the opposite situation, where participants are paid to take part in a study. I know of cases where such payments have been prohibited by an ethics committee on the grounds that they provide ‘inducement’, which is generally regarded as a Bad Thing, though there are convincing counterarguments. But I am having difficulty in tracking down any literature at all on the ethics of requiring participants to pay a fee to take part in research. Presumably this is a much rarer circumstance than cases where participants are paid, because in general people need persuading to take part in research. The only people who are likely to pay large sums to be a research participant are those who are in a vulnerable state, feeling they have nothing to lose. But these are the very people who need protection by ethics committees because it’s all too easy for unscrupulous operators to exploit their desperation. Anyone who doesn’t have approval to charge for a medical treatment could just redescribe their activities as a clinical trial and bypass regulatory controls. Surely this cannot be right.


  1. I think you're spot on here, Dorothy. As a member of an ethics committee myself, I agree that the way in which Burzynski's studies are clearly taking advantage of vulnerable patients, when they should be respecting their rights, is thoroughly unethical. It does appear that there is something questionable about the way Burzynski's IRB has been operating, given the concerns expressed by the FDA. I would love to know what enforcement action they have taken, but I suspect that any action they may have taken was inadequate.

    I'm not sure why this isn't making more news in the mainstream media as a terrible scandal.

  2. Dorothy, that is a truly bizarre case. Thanks for highlighting that. Steve

  3. I don't know why Google insists on me being unknown? I tried my google account ...

  4. +1 to Adam Jacobs's comment about being spot on. I find the whole "pay to take part in trials" notion to be deeply disturbing and dangerous.

  5. I am hoping that this story will hit the mainstream media soon. It certainly ought to.

  6. On the other hand, I know of a UK researcher who studied drug addiction and who was for a long time not allowed to pay his addict volunteers money in case they spent it on drugs.

    But then the REC changed their mind, decided that was unfair discrimination against addicts, and said that he had to pay them money if he was paying the controls money.

  7. I would hazard a guess that Burzynski may well have it fixed so that there is no specific charge on any bill identified as "a cost for being enrolled in the trial' - it is more that all their patients are 'enrolled in a trial' as this is how they get around other restrictions put on how they operate. But it does sound like people pay dearly for everything (see e.g. this account from some very pro-altmed folks).

    The whole Burzynski clinic story is awful, really, and the IRB stuff deeply troubling. But apparently the ethical review system in the US has always been pretty lax if you are working outwith the university/university-affiliated hospital mainstream. When I worked at the NIH a dozen years ago in a gene transfer lab, one of the common topics of discussion was that the private industry trials of human gene transfer were very minimally regulated. In contrast, if you were funded by federal tax dollars (i.e. by the NIH) you had to have the full panoply of ethical, IRB and regulatory approvals.

  8. Thanks for this-- my reaction was similar (as someone with a similarly professional interaction with research ethics committees).

    I'd note that the guidence linked to on the page you refer to ( does lay down some restrictions on when one can charge for an Investigatory Medicinal Product.

    On a quick look, the rule appears to be that you can charge, but only to recover the cost of the drug and only where that is necessary for the trial to go ahead and the cost of the drug is extraordinary. You also have to show that the drug has potential to 'provide a
    significant advantage over available
    products in the diagnosis, treatment,
    mitigation, or prevention of a disease or

    Importantly, it seems that the trial Sponsor (i.e. the organisationt that takes overall responsibility for the trial) has to get FDA approval for charging.

    One presumes that the chap in question has got the necessary authorisation.

  9. It's kind of allowed, but kind of not really - the .pdf explains it, and you do have to get a waiver and you can't profit.

    Where the whole Burzynski thing comes into play, and what I haven't seen mentioned in articles yet, is that while they claim to be running clinical trials, a quick looksee at indicates that the trials were registered in the late 90s, and anything that is listed as "open/still recruiting" hasn't been updated since (at latest) 2009. These are all moving on towards being listed as abandoned, and the vast majority of said "trials" have been terminated or are listed as incomplete.

    What this means is that chances are very good that this "clinic" is operating outside of what is allowable by the FDA - if there are even any valid clinical trials going on, which I strongly doubt.

    (I think those listings primarily exist to allow the "clinic" to say that they have clinical trials running - taking some time to read thru everything that's been canceled or abandoned or otherwise ignored suggests they were never enrolling as many people into the trials as they claim. And for better or worse, people can pay what they want for woo.)

  10. So I guess the inclusion for the study specify 'ability to pay $$$$' . Interesting take on possible selection bias. A really nice teaching example, but what an awful reflection on this Institutions ethics.