Stanislaw Burzynski versus regulations protecting human research subjects

It’s been a long time, been a long time, been a long lonely, lonely, lonely, lonely time.

Well, not really, although it has been a while since I’ve discussed Dr. Stanislaw Burzynski. Specifically, I last dedicated a post to him following the death of one of his famous patients, Billie Bainbridge, who incidentally had become famous because her family had managed to raise hundreds of thousands of pounds with the help of some U.K. celebrities. Burzynski, as regular readers will recall, became a frequent topic on this blog last fall after one of his lackeys decided to issue vacuous legal threats against skeptical bloggers who had called attention to his activities. These activities have included administering an unproven therapy that he calls antineoplastons to patients under the auspices of dubious clinical trials that appear mysteriously rarely to accrue sufficient patients and have not produced significant publications in several years. (Not that Burzynski’s earlier publications were ever particularly impressive.)

In the process, he developed a cult of personality, in which his false promise of “natural” and “non-toxic” therapy that can cure the incurable, has attracted desperate cancer patients from all over the world, as long as they can come up with the tens (or hundreds) of thousands of dollars that the Burzynski Clinic charges. It’s also managed to blind journalists, who should normally be a lot more skeptical, to the unethical nature of what he is doing. Mixed in with antineoplastons, Burzynski also claims to have cracked a nut that world-renowned cancer centers have yet to crack, specifically providing “personalized, gene-targeted cancer therapy” that works. Burzynski’s “personalized” therapy also puts the lie to the claim that his therapy is natural, because, as I explained before, based on the results of a commercial test Burzynski uses very expensive chemotherapeutic drugs and targeted therapies, all of which have significant toxicity. As I pointed out before, Burzynski doesn’t know what he’s doing; what he’s really doing is “personalized cancer therapy for dummies,” as I’ve put it before. Moreover, in doing so, he’s managed to co-opt an orphan drug.

So why am I revisiting Burzynski? After all, nothing much new is happening that hasn’t been happening for the last 30 years, particularly since legal maneuvering has delayed his appearance before the Texas Medical Board to determine whether he should be stripped of his license. Rather, I was made aware of a post by Keir Liddle entitled Investigating Burzynski, which revealed documents that I hadn’t seen before related to Burzynski’s activities. True, the documents are about a decade old, but they reveal some truly disturbing things about how Burzynski operates. In particular, they strongly suggest that Burzynski operates in much the same way that vaccine/autism quacks Mark and David Geier operate when doing their “clinical research.”

What has always been puzzling to me, ever since I became interested in Burzynski and his antineoplastons, is why Food and Drug Administration (FDA) not only continues to let Burzynski set up phase II clinical trial after phase II clinical trial, nearly all of which never accrue enough patients to publish. The last time I checked, there were over 60 clinical trials listed on ClinicalTrials.gov under Burzynski’s name. There still are. Even more puzzling to me is why the FDA apparently approved a phase III clinical trial of antineoplastons (A Randomized Study of Antineoplaston Therapy vs. Temozolomide in Subjects With Recurrent and / or Progressive Optic Pathway Glioma). The trial was submitted in December 2010 and is not yet open for recruitment, which strikes me as a rather long time given that the study start date was listed as having been scheduled to be December 2011. The study was then to have run until December 2015. In any case, the reason that this is an issue is that Burzynski apologists have been pointing to this study as “evidence” that there must be something to antineoplastons, the rationale being that otherwise the FDA would not have given the trial the go-ahead. Given that there is no good clinical data published by Burzynski that I’ve been able to find to support a phase II clinical trial, this has puzzled me and other skeptics, at least one of whom suspects that, however he persuaded the FDA to approve this trial, it suits Dr. Burzynski just fine that it has not opened yet. It is a suspicion that I share. Think about it. This phase III trial is the biggest and most effective club that Burzynski apologists have to beat skeptics over the head with. If Burzynski actually started accruing to the trial, its results would, by law, have to be posted to ClinicalTrials.gov. An approved but not yet accruing trial is an infinitely better weapon than a trial that accrues and produces no results. It’s also interesting to note that this clinical trial includes chemotherapy.

Be that as it may, what interested me the most were three documents: a letter to the Burzynski Clinic Institutional Review Board (IRB) from 2001; a report of a site visit to the Burzynski Clinic by the FDA Southwest Regional/District Office, Dallas District; and a warning letter from the FDA’s Human Subjects Protection Team, Division of Scientific Investigations, Office of Compliance dated 2009.

The first thing that leapt out at me is an offense that, to my mind, is identical to the offense committed by Mark and David Geier. Basically, the chair of the Burzynski Research Institute IRB is Carlton F. Hazlewood, PhD, who just so happens to be on the board of directors of the Burzynski Research Institute. Given that the Burzynski Clinic is trying to commercialize antineoplastons, this is a profound conflict of interest. Think of it this way: What would Burzynski’s defenders say if they found out that a sitting member of the board of directors of Merck, for example, was serving on the IRB that approves Merck’s clinical trials? This is the same thing. True, it’s not quite as bad as having the principal investigator of a study sitting on the IRB that approves his study, as Mark Geier has done, but it’s still quite dubious.

And there’s more, unfortunately, so much more. For instance, this report lists the following deficiencies:

  • Enrollment of subjects into antineoplaston study protocols prior to the protocol-specified interval following prior chemotherapy and/or radiation therapy.
  • Failure to report all serious adverse events (SAEs) and adverse events (AEs) to the agency and/or IRB.
  • Failure to follow proper informed consent procedures.
  • Failure to maintain adequate drug accountability records.
  • Discrepancies between case report forms and source documents.

Of note, there is another interesting admission in the report as well, specifically:

He [Burzynski] stated that the majority of prospective patients that present to the clinic do not qualify for entry into a study protocol and, therefore, are treated with traditional FDA-approved drugs/treatments; i.e., radiation or chemotherapy. Dr. Burzynski then added that approximately [REDACTED] of his patients were treated with antineoplastons.

Later, Burzynski admitted:

I asked Dr. Burzynski what other treatments are offered/done/given at his clinic. He stated that all other treatments are FDA-approved treatments, such as chemotherapy or radiation therapy.

Wow! I wonder if Suzanne Somers knows about this. Do Burzynski’s alt-med apologists know about this? Burzynski actually told FDA inspectors that he uses FDA-approved chemotherapeutic drugs for most of his patients. I also wonder if they know about some of the SAEs reported, such as hemorrhagic cystitis, serious diarrhea, pancreatitis, central line sepsis, pneumonia, renal acidosis, and even death. These are SAEs that weren’t even reported, as well. Whether they weren’t reported because Burzynski was intentionally hiding them or because he and his medical staff were clueless about what constitutes an SAE that must be reported, I don’t know. Even more amazingly, Dr. Burzynski didn’t seem to know that tumor measurements had to be reported on case report forms!

This report describes Burzynski IRB operations, including quite a few deficiencies:

  • Failure to keep a copy of the study protocol and informed consent form.
  • Failure to receive and/or require progress reports from the principal investigator for the study.
  • Failure to receive and/or require a final report from the principal investigator for the study prior to removal from the IRB’s active list of studies.
  • Failure to assure that FDA approval was obtained by the principal investigator for the study prior to the treatment of a patient under a special exception.
  • Approval of special exceptions via expedited review.

What I’d really like to know is who is on the Burzynski IRB. For instance, if Dr. Hazlewood, who has a massive conflict of interest, was allowed to serve as IRB chair since 1993, who else on the IRB has a conflict of interest? Inquiring minds want to know! They also want to know how, seven years later, the same problems (and even worse ones) were still going on at the Burzynski Research Institute and the Burzynski Clinic, as enumerated in this FDA warning letter:

  • The IRB approved research without determining that the following criteria were met: That risks to subjects were minimized and That risks to subjects were reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.
  • The IRB Failed to prepare, maintain, and follow written procedures for conducting its initial and continuing review of research.
  • The IRB failed to ensure that informed consent would be sought from each prospective subject or the subject’s legally authorized representative.
  • The IRB failed to ensure that no member participated in the initial or continuing review of a project in which the member had a conflicting interest.
  • The IRB failed to conduct continuing reviews.

And, as mentioned before, Dr. Hazlewood has a massive conflict of interest:

For the (b)(4) study, you (IRB Chairman, Carlton F. Hazlewood, Ph.D.) are listed as a clinical investigator on the “Certification: Financial Interests and Arrangements of Clinical Investigators”; you are also listed as being an ex-officio advisor to the (b)(4)/IBR Central Registry Control Committee/Data Monitoring Committee. Therefore, you had a conflict of interest.

Minutes of the August 8, 2008 IRB meeting indicate that you attended this meeting and participated in the discussion of the (b)(4) study. At this meeting, the IRB voted to draft a letter to (b)(4) to inquire about the status of the animal toxicity studies. According to the minutes, all members were in favor, none were opposed, and none abstained. Minutes of the October 24, 2008 IRB meeting indicate that you attended the meeting and participated in the discussion of the (b)(4) study. At this meeting, the IRB voted to draft a letter to (b)(4) informing them that their application was on hold. The vote on this action is recorded as unanimous; therefore, according to the minutes of these two IRB meetings, you participated in the review of this study and voted on it even though you had a conflict of interest. We also note that you signed off on all correspondence sent by the IRB to Dr. (b)(6) and the sponsor in regard to this study.

And:

Our inspection revealed that, in some instances, when an IRB member had a conflict of interest for a particular study, another person, who was not an IRB member, was allowed to take the place of the conflicted member and participate in the IRB’s action. There is no provision in FDA regulations for this type of action.

In other words, the IRB played fast and loose with its membership roster.

Talk about the fox guarding the chicken coop! Is anyone willing to bet that there’s more than just this? This is the conflict of interest that could be documented on paper, a COI for which Hazlewood screwed up. I’d be willing to bet that Hazlewood has his hooks in many of Burzynski’s studies, just not as a co-investigator of one study. After all, he’s worked for Burzynski since the early 1980s and has been IRB chair since 1993. At the risk of being repetitive, I think it’s absolutely appropriate to point out one more time that Burzynski’s fans would go absolutely nuts if they discovered that a scientist who is listed as a co-investigator on a study for a drug company served on the IRB overseeing his study not just as a member, but as the chair of the committee!

OK, OK, I’ll stop now. I realize I might be pounding this point too hard. I hope you’ll understand, though. Being a clinical investigator myself, my mind just boggles thinking about this, and I can’t comprehend how Burzynski and Hazlewood have been able to get away with playing fast and loose with human subjects protection rules at least since the 1990s. I just can’t. That the FDA apparently approved a phase III clinical trial for any disease at the Burzynski Clinic after finding these violations is something I have even more trouble understanding. I’ve heard of whole medical schools being in danger of having their ability to do clinical research shut down until they corrected violations this serious; yet somehow Burzynski continues.