Burzynski’s Export Drive
The saga of Dr Stanislaw Burzynski and his antineoplastons (ANPs) is in danger of turning into a soap opera. Well actually it probably already has, as it has gone on for decades with no real plot and no end in sight. Many bloggers have been as puzzled as I as to why the US regulator, the FDA, allows this to continue. Admittedly, from time to time the FDA takes some sort of action, but it is never decisive – he is always allowed to carry on charging desperate patients vast sums to receive an unproven drug. First, let’s look a little more at what is happening here in the UK. I am indebted to Liz Woeckner of Citizens For Responsible Care and Research, who has identified at least 10 British patients who have travelled to Burzynski’s clinic in Houston, started treatment, and then returned home with supplies of antineoplastons (ANPs) in their luggage – apparently complete with IV administration sets. Liz has also compiled a pack of documents obtained form the FDA under Freedom of Information requests, which demonstrate the long history of serious regulatory violations at Burzynski’s facility. I’ll leave you to digest that lot.
Well, here is the list of UK patients that we have collated so far:
Luna Petagine (Raglan Gardens, Oxhey): http://www.lunapetagine.co.uk/diary
Amelia Saunders (Reading, Berkshire): http://www.ameliasmiracle.com/2.html. Note that Burzynski’s `exemption’ trial (ie patients could be treated outside an approved protocol) closed in 2006, and this patient was born in 2008 so must have been treated under an approved protocol.
Billie Bainbridge: http://www.billiebutterflyfund.org/billies-story/
Claire Faulkner: http://www.clairefaulkner.co.uk/
Hannah Bradley: http://teamhannah.com/
Laura Hymas: http://www.hopeforlaurafund.co.uk/
Chiane Cloete: http://helpmefightcancer.co.uk/
Supatra Emily Adler: http://supatrascancerfight.blogspot.com/p/home_10.html
Andrew Sherwood: http://www.thesherwoodfoundation.org.uk/Home: Site has now been taken down.
Once I had this list, my first question was: if these patients are all taking ANPs (and apparently under FDA approved protocols), have UK physicians obtained ethics approval? Let me remind you that worldwide all clinical trials of investigational drugs must be reviewed by an independent ethics committee, and must have approval from the national drug regulatory authority. Not only does the ethics committee review the protocol, it also must review all patient-facing documents, including any advertising for recruitment to the study. That would include any websites.
Joan Kirkbride, Director of Operations, National Research Ethics Service, told me:
We have searched our database using the search terms: antineoplastons; A10 (Atengenal, Cengenal); AS2-1 (Astugenal, Fengenal) and Burznyski and have not returned any results.
“However Dr Burznyski would not be permitted to be a Chief Investigator for a trial in the UK as he is USA based and it is a requirement that such a person be based in the UK.
“My understanding is that there are other mechanisms to provide investigational medicinal products outside a clinical trial protocol eg for compassionate use but the MHRA would be able to provide further information in this regard.
Now hang on a minute, there are these trade names Atengenal and Cengenal. While surfing with those names, I also came across another one, Astugenal. Two of these, Atengenal and Astugenal, are being actively marketed by a California company Pediatrica USA, but not to US consumers. The company “acts as a patient’s representative so that these experimental yet potentialy (sic) life-saving drugs may be made available to developing countries. US residents cannot use this website.” Needless to say, the company operates in association with Burzynski. I would really like an expert oncologist to review the material on this site, in particular the descriptions of the mechanisms of action. But whether or not there is substance to the claims, the scenario is clearly one of exporting an investigational drug without a full dossier on efficacy, safety and quality. Is it not interesting that `developing countries’ are targeted? Would it not be more lucrative to export to say the EU? But of course, it also has tough regulatory legislation. The export drive is set out in this SEC filing, which lists the countries involved, and for which this contract engages a marketing company, Carigen.
I also spoke to the UK regulator, the MHRA, and learned that there had been no submissions for regulatory approval for ANP studies in the UK. I had already checked the EudraCT database and found nothing, although this is notoriously incomplete. The fact remains that if certain UK doctors are involved, they are not simply prescribing an unlicensed drug, they are acting as investigators for a drug classified by the FDA as in development.
I had another go at the FDA about these UK patients, but the reply (from the Center for Drug Evaluation and Research) totally avoided the question, and simply reiterated that ANPs are investigational drugs. Although I didn’t ask about illegal promotion, I did get this:
The FDA has sent an Untitled Letter to The Burzynski Research Institute (BRI) and The Burzynski Clinic for promotional and marketing claims about the safety and efficacy of its antineoplastons, investigational new drugs that have not been approved by the FDA. The unapproved promotional claims made by BRI violate the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA regulations. The promotion of investigational new drugs is prohibited by law and the agency is concerned BRI’s promotional claims will mislead patients about the safety and efficacy of the unapproved antineoplastons. FDA plays an important role in ensuring sponsors provide accurate information about their investigational drug products to patients and health care professionals.
FDA requested that BRI submit a written response to the Untitled Letter by November 1, 2012, stating whether BRI intends to comply with FDA’s request that it cease the dissemination of violative promotional materials for antineoplastons, and explain its plan for discontinuing use of such violative materials. We are currently reviewing BRI’s response. Because this is an open case, we are unable to share additional information at this time.
That was on 7th November 2012 (sorry, there is so much stuff that this post took a long time!). Others I think have already picked up on the FDA’s warning letter, referring to this earlier website and also to the Burzynski Research Institute site. The two sites appear to have removed all promotional claims, but the Burzynski Clinic site still links to the patient group site, where you can find all the usual hyped-up claims.
Naturally I pressed CDER for an answer about exporting ANPs, and was simply referred to the legislation. It seems impossible to get a direct answer. But from exports, we move to imports, or the lack of them. This import refusal was issued by the FDA over two years ago. It appears that Burzynski was trying to get ANPs made abroad.
The FDA seems to be under fire from both sides. The patient groups constantly press for immediate approval of ANPs, as exemplified by this package sent to the Clinton administration (shows how long this has been going on). Look at page 31 – the FDA quite rightly refused to consider a submission for marketing approval from a single investigator.
Well this is a rather disparate collection of facts, but it reflects the vast complexity of Burzynski’s operations. To boil it down to essentials, there must be some UK doctors under whose care patients are receiving ANPs, and it’s not clear whether the imports and exports of ANPs are lawful. So far we have one name, Dr Simon Berrisford, cited by the parents of Burzynski patient Andrew Sherwood (site taken down as noted above). I do not know any more than that, indeed I do not know Dr Berrisford’s role, and I would not presume to ask him to breach patient confidentiality. But I am still curious as to what his role is. If he is operating as a co-investigator of Dr Burzynski, then he needs approval from a UK ethics committee and from the MHRA. There are no records of those approvals. If he is not operating as a co-investigator, then research data on an investigational drug are not being collected, as required by the FDA.
I have been looking at Burzynski’s study protocols, cached here. I am way out of date it seems – we have here 72 protocols listed. At www.clinicaltrials.gov there are only 62. Burzynski gives his protocols internal numbers, which don’t appear on clinicaltrials.gov, so it’s extremely difficult to work out whether we are talking about the same studies. However to take one example at random, protocol BT-7 is entitled “Antineoplastons A10 And AS2-1 In Patients With Glioblastoma Multiforme”, and was dated originally 1996. On clinicaltrials.gov study 60 has the same title, and is stated to have started in 1998. My suspicion is that here we have a bizarrely large number of studies, which are created to accommodate whatever patients come through the door (look at the vast range of conditions), and go on for decades. If that is not the case, I’ll be perfectly happy to publish a correction, but it’s up to Burzynski to show how I am wrong. Note the large number of changes to this protocol logged on clinicaltrials.gov, over the period June 2005- August 2008. Most of these are trivial, but I did notice that in 2007 the primary study indication was changed from “Recurrent Adult Brain Tumor” to “Brain and Central Nervous System Tumors”. This is quite unusual in my experience, and again suggests that protocols are being customised to suit patients.
I was deeply shocked by this paragraph in the informed consent section of protocol BT-14:
If your child is injured as a result of participation in this treatment, emergency care will be made available by the hospital and billed to you as part of your medical expenses. No financial consideration or compensation will be provided for a research related injury.
I have never heard of any such clause in any study, let alone receiving ethics approval. All clinical trials of investigational drugs are required to have insurance in place against drug-induced injury. This protocol is about as unethical as it’s possible to get. We already know that the institutional review board (IRB – or ethics committee in European parlance) is attached to the Burzynski Research Institute. Indeed it is called the Burzynski Research Institute IRB. It is quite clear that this IRB does little or nothing to protect patients. We also know that it received a damning inspection report from the FDA in 2008, but when I asked the FDA whether that had been closed out I got the usual stone wall. But again CIRCARE has the story. Some 10 months after the inspection, the FDA issued a warning letter, in October 2009. There is nothing on public record since then.
I have also been looking again at the investigator site inspection which the FDA carried out in 2001. Note that this was a `directed’ inspection, what we call these days `for cause’. It must have been in response to something that raised their suspicions. A possible cause could have been the detailed report published in The Cancer Letter in 1999, reproduced at QuackWatch with permission. Worth reading if you have the time. Anyway, here are the warning letter, the inspection report, and Burzynski’s response. The heavy redactions are of course excessive, and reflect the US obsession with secrecy. Note that item 6 of the warning letter states that Burzynski failed to include mandatory wording in the informed consent information. This demonstrates that ethical review is essential, and that it simply wasn’t happening. So far, I have been unable to identify any further action from the FDA, but as a clinical research professional here are my observations:
- The inspection report shows that Burzynski was at that time very clearly an incompetent investigator. International standards for Good Clinical Practice (GCP) say that everyone involved in clinical trials must be qualified by education, training and experience. Burzynski is not a board certified oncologist, which I would have thought was essential for what he is doing (I looked on the Texas Medical Board database). Why has he not been listed by the FDA as a debarred investigator?
- There is no mention anywhere of independent study monitoring. This is frankly baffling. It is a GCP requirement that three roles are in place, sponsor, investigator, and monitor. The last is normally carried out by a clinical research associate (CRA), who does inter alia the checking of case report forms versus source documents. They also check drug accountability, another major violation at the site. Obviously nobody was doing that, yet the FDA did not ask who should have been doing it. At inspections, it isn’t mandatory for the CRA to be present, but the documents on site must include a log of monitoring visits carried out. The inspector should check those to ensure the visits did happen. Everything checked by the CRA should have a signature to verify they did it. There’s not a word about any of this in the report.
- None of the documents includes the letters from the FDA which Burzynski claims give permission to treat patients off-protocol. I think it is very important to clarify what is going on here. If there is no such permission, then GCP applies to everything he is doing, wherever it is in the world.
- The FDA inspection report mentions that Burzynski was charging patients for ANPs. Yet they don’t list this as a violation. So why mention it? They seem to think it was unusual. The clue may be that the matter doesn’t come up in the warning letter, most likely because the FDA was not confident that such an allegation would stand up in court – in the light of Burzynski’s track record through the courts.
This post could easily go on for another four pages, so I think I need to stop here and let you assimilate it. More to come.
STOP PRESS! Just saw the post from Josephine Jones that suggests the BRI studies are on clinical hold. No point in asking the FDA for more news of course, we’ll have to wait and see. A while back I asked readers to press the FDA to inspect Burzynski, and now it seems they are. But I am intrigued as to the legality of suddenly shipping a vast load of ANPs to this patient – for which presumably they will get a huge bill.