May 02 2008
Part V of this Blog argued that the NCCAM-sponsored trial of the “Gonzalez regimen” for cancer of the pancreas is unethical by numerous criteria.† To provide an illustration, it quoted a case history of one of the trial’s subjects, who had died in 2002.¹ It had been written by the subject’s friend, mathematician Susan Gurney. A similar story was told on ABC 20/20 in 2000, albeit not about a trial subject. Each of these cases demonstrates the wide breadth of Gonzalez’s quackery, as did his brush with the New York medical board during the 1990s.
This entry addresses some aspects of how those in charge of the trial failed in their duty to protect human subjects. By implication, it suggests what is necessary to prevent similar travesties in the future. It also addresses, to the small extent that the information exists, what appear to be the final ethical violations: first, that the trial will never be completed, thus having “expose[d] subjects to risks or inconvenience to no purpose.” Second, that Columbia University and the responsible investigators have no intention of explaining why.
Science and Medical Need, not Politics, should Determine Human Studies Agenda
Recall that the impetus for the government to fund a trial of the Gonzalez regimen came not from the NIH itself or from any legitimate scientist, but from the office of an old Laetrile warrior, Indiana congressman Dan Burton. Burton is a well-known bully and shill for implausible medical claims. Stephen Barrett of Quackwatch has justifiably called him “quackery’s best friend in congress.” Burton is a sponsor of the annually-defeated “Access to Medical Treatment Act,” which is a euphemism for Freedom to Defraud You. To illustrate how cozy he is with the tiny world of politically-connected quacks, consider Burton’s glowing recommendation of Rashid Buttar, about whom Dr. Gorski wrote on Monday.
For years, Burton was the chairman of the powerful House Committee on Government Reform. Hearings of that committee, particularly during the 106th and 107th Congresses, were littered with pitches for implausible medical claims and diatribes against immunizations and other rational public health measures. Together with Senator Tom Harkin (D-IA), the creator of the NCCAM, Burton and a few other congressmen have managed to scare NIH scientists and administrators away from their proper concerns with scientific and ethical issues. Thus Richard Klausner, the former director of the National Cancer Institute, eventually caved to the pressure, as reported in Part IV of this blog. So did Claude Lenfant, the former director of the National Heart, Lung, and Blood Institute (bullied here by Burton; caved here).
Shortly after the late Stephen Straus was appointed the first director of the NCCAM in 2000, he revealed in an interview with Science Magazine that he, too, now viewed the scientific and ethical rules of human studies as optional:
Yet principles aside, Straus also has to follow the mandate of Congress–and some of its, well, less-than-scientific members. NCCAM is stuck funding a 5-year, $1.4 million trial of an unusual protocol designed to treat terminal pancreatic cancer by physician Nicolas Gonzalez. The so-called Gonzalez Protocol–a hodgepodge of pancreatic enzymes, coffee enemas, and up to 150 dietary supplements a day–caught the attention of Representative Dan Burton (R-IN), who in 1998 encouraged the National Cancer Institute (NCI) to study it. Even though Straus considers the evidence just an “aggregate of interesting anecdotes,” he defends the trial –albeit lukewarmly. “I’m more comfortable and find it easier to approach and fund things that already make a lot more sense to me,” he admits. “But the mandate here is … to be willing to take more risks for things that are novel.”
Except that Straus did not have to follow the mandate of Congress to its inevitable collision with human studies ethics. Political pressure, “mandates,” alleged popularity of a method, and even laws may not force biomedical scientists to expose human subjects to risks and discomforts that would not otherwise occur. The Helsinki Declaration, which is, in effect, the consensus of world opinion on the subject, addresses the issue explicitly:
Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their own countries as well as applicable international requirements. No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.
Such language did not happen by accident. It was a purposeful response to the infamous excuse offered at the Nuremberg Trials. Did it occur to Dr. Straus that a very small number of ignorant Congressmen were attempting to require hapless, desperate human subjects, such as Ms. Gurney’s friend, to “be willing to take more risks?” In the US, any NIH scientist not wishing to violate human studies ethics may simply refuse to do so or, if necessary, resign his post. He needn’t worry about being shot.
In less public circumstances, Dr. Straus did not appear to have qualms about the ethics of the trial. At a meeting of the Cancer Advisory Panel for Complementary and Alternative Medicine in 2001,
A long discussion ensued about the Kelley/Gonzalez criteria and efficacy of study; and the potential dampening effect of a failure of this study. Dr. White noted that the eligibility criteria may be too strict. Although the study has been highly publicized, only about 10% of referrals qualify. Possible solutions were discussed without clear answers, since publicity has not been the problem. Dr. Straus noted that in the future, with best case series data, we can have other trials with easier recruitment of patients and less stringent criteria…. Dr. Straus said, “Our ability to reach out and be open-minded about alternative therapies is constantly impugned by traditional medicine and others. We must press on, because this is groundbreaking and important.”
The “it’s out of my hands” plea at the NIH was also apparent at Columbia. Michael Specter, author of the 2001 New Yorker article about Gonzalez, interviewed Karen Antman, who at the time was the chief of Columbia’s division of medical oncology and a past president of the American Society of Clinical Oncology:
I asked if it would be right to infer that she thought the trial wouldn’t work. She shook her head. I asked if she had an idea why it might work. She said no. Did she have any opinions at all about the potential of nutritional therapy or the Gonzalez regime? “I have lots of opinions,” she told me, “but none of them matter.”
Could any reader who imagines that a chief ought to be a chief, or who is aware of the concept of clinical equipoise (discussed last week) not shudder at such an abdication of professional and ethical responsibility? John Chabot, the principal investigator, suggested on several occasions that he was not happy with the trial (here and here, and contradicted his own claim of equipoise here) but proceeded anyway. Susan Gurney argued that the refusal of such authorities to come clean with their views had contributed to the suffering of her friend:
He was an artist—a painter and a sculptor—and he had little scientific knowledge. When Dr. Chabot was neutral about the Gonzalez protocol, and when Dr. Antman said nothing adverse about it, my friend assumed that they must genuinely believe that the treatment could work.¹
Ms. Gurney later wrote me about something she had not included in her article: that James Gordon, the chairman of the White House Commission on Complementary and Alternative Medicine Policy at the time, had “paid a personal visit to my friend’s house – and praised the Gonzalez protocol to him.” The poor subject was a victim of both government-sponsored experts and government appointed pseudo-experts. He could not have known the difference, of course.
The Non-Outcome of the Gonzalez Trial
In anticipation of this blog series I wrote Susan Gurney to ask if she had a copy of the consent form and if she had learned more about the trial over the past few years. I was surprised, but not terribly so, by her reply:
I do not have the Gonzalez consent form….Columbia Presbyterian has been completely consistent in refusing to come forward and publish the study results, or air any of this sad business. John Chabot, the principal investigator, is now head of the Pancreatic Center of Excellence, and in between ski trips I hear that he supposedly does perform skillful and agressive surgery on pancreatic cancer patients. Al Neugut, head of the Herbert Irving Cancer Center, shrugs and says it wasn’t his idea, and pointed the finger at Karen Antman, who I think is now Provost at BU Medical School, and thriving. Victor Grann is in charge of the data, and is helping cover it up and won’t talk. William Sherman, who initially warned me about the study, but in the end could do nothing to stop it and wasn’t willing to rock the boat over it, is still practicing oncology to the best of his rather admirable ability, but it is a sore point and when we speak – which is now infrequent- I do not mention it.
I have called four reporters, written to two, obtained partial records from the NIH, and even paid a lawyer who said he could get me a story – and I have failed completely to get this study reported to the public in any way.
I know from the web that Gonzalez is as active politically about the rights of free trade, vitamin business, etc. as ever – I can only imagine that he is also thriving.
I wondered whether Columbia “refusing to publish the study results” was nothing more than the usual, long delay between the end of subject accrual and the publication of the paper. Gonzalez himself, however, had provided the answer more than a year ago, in an interview for Alternative Therapies:
AT: Let’s talk about the NCI study on your work. Has that been completed?
Dr Gonzalez: I’ve been working on this for more than 7 years. In 1998, we got the first approval for the study, and I started the project in 1999. I thought the project was designed incorrectly from the beginning. The administrators of the study initially set it up as a randomized study in which patients would be randomized into our treatment or chemotherapy. The patients had no choice about treatment. The administrators insisted the study had to be designed this way.
I argued that no one’s going to agree to do that because patients who are interested in the study only want to get my therapy….They spent a year trying unsuccessfully to get it to work as a randomized study. No one wanted to enter, so eventually they had to change the format so patients could choose the therapy they wanted, either ours or chemo. We ran into many other problems, including the predictable bias from the oncology profession. Many patients were discouraged from considering this study by their original oncologists, and a number were discouraged from continuing even after they had entered.
There was a constant undercurrent of hostility toward the study that really had a deleterious effect. Right now, the project is on hold, and government officials are looking into the way the study was set up and run by the people at NCI and Columbia. I can’t go into the details at this point, but I certainly would have run it differently. Our input regarding the design was very often ignored, so there were design flaws in the study that I believed helped undermine the study.
AT: You’re not hopeful some of those issues will be resolved and you’ll be able to move forward with the study?
Dr Gonzalez: I don’t think so. Right now, as far as I’m concerned, it won’t happen. What the NCI or the National Institutes of Health will decide to do, I can’t say, but I’ll tell you, after spending 7 years trying to get the study to work and fighting at every step, I would not want to go through that again….If I really felt that the NCI was serious about looking into alternative therapies, I would reconsider. But after 7 years, I believe they’re just not interested if the treatment wasn’t developed by them or at a major academic institution…
AT: Is it politics or a particular bias?
Dr Gonzalez: I think it’s a question of research bias and experts who surprisingly can’t do anything outside of their particular area of expertise. Natural treatments like mine are not just another chemotherapy, and you can’t design clinical studies to test them as if they were. We don’t offer a chemo drug, where the patient shows up and gets to watch TV and eat ice cream while nurses inject the medication. In our case, the patient has to change his or her entire life, so compliance becomes a major issue. You’re held hostage by patient compliance… This was chemo vs Gonzalez, and the oncology profession by and large rallied against it…For this study to have worked, the NCI needed to rise to the occasion and deal with the pervasive bias within the oncology profession. But they never did. They never did anything. I don’t know whether it was indifference or that they just didn’t care. But they didn’t do what needed to be done, in my opinion.
AT: Is this a case of the methodologies not being appropriate for this type of research or these types of protocols?
Dr Gonzalez: That’s correct. The NCI operates on a drug model and wants natural products to fit into a drug model, and natural therapies don’t. With chemotherapy, patients need only show up. With our therapy, patients have to change their whole life. Should the NCI ever wish to test an alternative dietary or nutritional approach again, they must ensure that the bias of the oncology profession, which in our case influenced accrual and compliance of accepted patients, be effectively countered.
AT: Have you considered writing a book about your treatment plan?
Dr Gonzalez: We’ve just finished a book about the NIH clinical study because so many people wanted to know what happened after 7 years of work. I was asked by some of my congressional supporters to document all the mistakes that were made, and it turned into a book. And we think that should be published.
It is hard to imagine, reading Dr. Gonzalez’s words, that he and Susan Gurney were talking about the same trial. Yet they appear to agree that it has come to a dead end. Gonzalez seems to believe that the reason has to do with “the pervasive bias within the oncology profession” convincing subjects not to be compliant with his regimen. Ms. Gurney’s information suggests a different take: the academics at Columbia were at first altogether too willing to foist patients into the trial, but when it became clear that it was a horrible experience they had second thoughts. Possibly because they realized what a terrible mistake they had made, but almost certainly because the OHRP (Gonzalez’s “government officials,” apparently) came knocking for the third time, Columbia decided to circle the wagons:
…for the record, although Sherman warned me about the trial to begin with – in the end nobody would come forward. I will be happy to be quoted about the sad situation – I have spoken to Chabot in person, who will not come forward and say anything publicly ‘according to the advise of his lawyers’ -which from what I understand are the Columbia Institution lawyers. This is simply being covered up – and the data are not going to be released- publicly – is what I believe. As well, they think that Gonzalez has friends in Congress – so they claim that he would only make Columbia look bad again and they wouldn’t defeat him – only end up taking the blame.
‘Enlightened self-interest’ I believe is the term I heard used.
‘Spineless wonders’ is the phrase that I myself would use.
Gonzalez claimed that the “oncology profession” had influenced not only compliance, but accrual of subjects. The latest OHRP determination letter, however, suggests that there were at least 62 subjects and possibly more than 113—a range consistent with the originally planned goal of 90. So why will there, apparently, not be a report? We have suggested a possible reason above, but that does not deal with the fact that there still must have been outcomes. Even Gonzalez’s claim, that subjects were not compliant, does not excuse the investigators from reporting the results. An “intention to treat” analysis is all the more important for a method that is notoriously difficult for subjects to complete.
What if the outcomes were what most experts would expect, ie, that subjects on the Gonzalez regimen did no better that comparable patients with cancer of the pancreas who were untreated, and worse than those who received standard treatments? That would present an obvious, but embarrassing conclusion: that the New York Office of Profession Medical Conduct had been correct about Gonzalez all along. The only reasonable actions would now be for New York to strip him of his medical license, for the NIH and Columbia University to admit publicly that they had made a terrible mistake in making him responsible for experimental subjects in an NIH-funded trial, and to thereby expose fundamental ethical problems with human trials of implausible medical claims. If the responsible institutions find themselves at odds with Gonzalez’s “friends in Congress,” so be it. Let the debate go public.
It seems that Columbia and the NIH have backed themselves into a corner: the “potential dampening effect of a failure of this study.” Will we be hearing from them anytime soon?
1. Gurney S. Socially Harmful but Unapparent Effects of the NCCAM-Columbia University-Gonzalez Protocol. Sci Rev Alt Med 7 (2):74-77 (Fall/Winter 2003-4)
†The “Gonzalez Regimen” Series:
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