By Keir Liddle
It can be frustrating knowing that something is happening but not knowing exactly what it is or what it means. For critics of the Burzynski clinic knowing he is under audit but not knowing the details has been one of those frustrations.
That the clinic was being audited was revealed through a patient blog, as detailed here, a few days ago and later confirmed by is he/isn’t he PR guru for the clinic Wayne Dolcefino in an interview with David James of the East England Skeptics. There are three kinds of FDA audit:
- Bioequivalence Audit
-when 1 study is the sole basis for approval
- Study-related Audit or ROUTINE
– primary efficacy studies
– studies submitted to FDA for NDA, marketing, license, etc
Investigator-related Audit or FOR CAUSE
– interest or concern regarding a specific investigaton
The first type of audit is not applicable to the Burzynski clinic so which of the other two is it?
Supporters of the clinic and Dolcefino have claimed that the audit is simply part of the normal post-trial process and that there is no other reason for them to be there. The FDA does indeed carry out routine inspections following a New Drug Application (NDA) submission (over 80% of their inspections are conducted for this reason) and the clinical investigators who enroll the most patients in the NDA’s pivotal trials are the most likely candidates for a routine inspection. Burzynski certainly has applied for a New Drug Application and does claim to have enrolled thousands of patients in clinical trials. However he applied for his New Drug Application in 1983 and after several legal wrangles was allowed to start treating patients with antineoplasteons as part of “FDA approved” clinical trials.
That is just one reason to suspect that this inspection is not at all routine and may indeed be a “For Cause” inspection. Another reason is that this inspection appears to have been going on for around two months, which is beyond the scope of a routine inspection, and it seems that ANP clinical trials have been suspended.
“For Cause” inspections are much more infrequent and generally arise only when the agency receives reports of, or otherwise becomes aware of, suspicious behavior by a clinical investigator.
Approaching the FDA is likely to be fruitless in confirming whether or not this is a routine inspection or something more serious as their website states:
“Inspections are classified (see Inspection Classifications) to reflect the compliance status of a firm. “
However we have uncovered some reasons to doubt this narrative (hat tip @frozenwarnings for the info) and we present these below as a possible scenario and invite you all to draw your own conclusions.
- Conducting a large volume of clinical trials;
- Conducting clinical studies outside of one’s field of specialization;
- Reporting significantly better efficacy, fewer adverse effects, or different laboratory results than other investigators studying the same drug;
- Having apparent access to too many patients with a specific disease state for the locale or practice setting;
- Complaints from a patient or sponsor of an alleged violations of the regulations, protocol, or human rights.
On the first point it is worth reminding everyone that the clinical trial registry of the US national institutes of health lists a total of 61 studies registered to one Stalislaw Burzynski or his clinic. One of these trials is registered as not currently recruiting, the much hyped phase 3 trial that is not all it seems to be, the status of 2 is “terminated” a further 7 have simply been withdrawn and the status of the remaining 36 is “unknown” (which means the clinic has not updated their records with the clinical trial registry for over two years) and only one has been completed.
It is also worth reminding everyone that Burzynski is not and never has been qualified as an oncologist regardless of his claims to have a Ph.Degree in Biochemistry. but the majority of the “trials” conducted at the clinic were for various forms of cancer. Which makes the second point salient also.
Critical followers of the Burzynski saga will also be aware that the “good” Doc has used his own definitions for success and recovery in his “trials” as reported on cancer.org:
The United States Congressional Office of Technology Assessment (OTA) reviewed medical journal articles describing cases of cancer patients whom Dr. Burzynski had treated with antineoplaston therapy
The OTA report criticized Burzynski’s research process and noted that his definitions of advanced cancer and of complete and partial cancer remission were not used in accordance with generally accepted definitions. One example they pointed to was a patient said to have had a complete remission after treatment with antineoplastons. The report concluded that this claim was inappropriate because the cancer had been removed by surgery before the antineoplaston treatment was started.
Point four is not to my knowledge relevant here and I am not aware of any complaints from trial sponsors about research practices at the Burzynski clinic. However he was issued with a warning letter by the FDA for unethical practices in relation to his internal review board and patients have complained in the past even taking him to court. I am also vaguely aware that a number of American skeptics and critics of Burzynski did raise concerns with the FDA. However in spite of that I am not 100% convinced this is what motivated the FDA to action. What did may remain a mystery though one popular explanation is provided here.
Those are some reasons to assume that this inspection is more important and much more serious than some of the clinics more vocal and paid supporters would have us believe.
Know we will not be 100% sure until the FDA publishes it’s findings but when it does there are three potential classifications of their findings:
- NAI: No Action Indicated
Site is in compliance. Acknowledgment letter will be sent to site and no response required
- VAI: Voluntary Action Indicated
Objectionable practice having minimal effect on study integrity (data or/or subject protections) noted. A formal letter will be sent to site and response is required.
- OAI: Official Action Indicated
Objectionable conditions identified requiring sanctions. Site response/action required and re-inspection likely.
Feel free to place your bets as to whether action will be taken, again, against Burzynski or whether he will somehow evade sanction yet again.