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The Ethics of “CAM” Trials: Gonzo (Part VI)

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.

Epilogue

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:

1. The Ethics of “CAM” Trials: Gonzo (Part I)

2. The Ethics of “CAM” Trials: Gonzo (Part II)

3. The Ethics of “CAM” Trials: Gonzo (Part III)

4. The Ethics of “CAM” Trials: Gonzo (Part IV)

5. The Ethics of “CAM” Trials: Gonzo (Part V)

6. The Ethics of “CAM” Trials: Gonzo (Part VI)

7. The “Gonzalez Trial” for Pancreatic Cancer: Outcome Revealed

8. “Gonzalez Regimen” for Cancer of the Pancreas: Even Worse than We Thought (Part I: Results)

9. “Gonzalez Regimen” for Cancer of the Pancreas: Even Worse than We Thought (Part II: Loose Ends)

10. Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 1

11. Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 2

Posted in: Cancer, Clinical Trials, Medical Academia, Medical Ethics, Science and Medicine

Leave a Comment (18) ↓

18 thoughts on “The Ethics of “CAM” Trials: Gonzo (Part VI)

  1. David Gorski says:

    That this whole trial was green-lighted in the first place is incredibly disturbing, but it’s even more disturbing that the data won’t even be published or reported. What happened to NIH rules that require that the results of all federally-funded clinical trials be reported, whether the clinical trials are positive or negative? What about Freedom of Information Act requests?

    In a way, this guy’s worse than Rashid Buttar. Dr. Buttar makes no pretense of being scientific or even really wanting to test his quackery scientifically. He’s easy for scientifically-minded people to spot as a fraud. Dr. Gonzalez, on the other hand, helped by credulous, woo-friendly idiots like Dan Burton and Tom Harkin and officials at Columbia who turned a blind eye and abrogated their ethical responsibilities in the pursuit of research grants, has wasted $1.4 million of taxpayer money on an unethical and indefensible clinical trial that didn’t do a single patient any good and may well through its onerous requirements harmed patients. In the process, he gave his protocol far more scientific credibility than it deserves by any reasonable standard. Worse, we can’t even salvage something out of the ruins of this trial, such as evidence that the Gonzalez protocol does no good and may well do harm, because the investigators holding the data are not showing any signs of wanting to publish it and no one is holding their feet to the fire to release the data to let someone else analyze it.

    Where on earth was Columbia’s IRB during all this?

  2. pmoran says:

    The results MUST be published. If they aren’t it will be very damaging to the healthfraud cause. It will certainly be portrayed as the suppression of something that “doctors don’t want you to know”.

    If the study was performed with adequate rigour in terms of patients selection and follow-up, prior probabilities detemrine that all patients in the Gonzales arm of the trial would have displayed cancer progression within 3-6 months. That is what pancreatic adenocarcinoma does without effective tretament. No patient is likely to have shown objective remission.

    That would be extremely useful information for cancer sufferers, as most would not be too keen on taking on such an arduous program with that knowledge.

    If the study was not performed well enough to give information that score, then we have the right to be even more exasperated with those who designed a 1.4 million dollars trial so naively. Even Gonzales was shrewd enough to predict that patients interested in entering such a trial would have prior sympathies towards alternative medicine, and they would all want to join the “alternative” arm.

    If the study did show patients remitting in the Gonzales arm — well, we need to look closely at the data.

  3. Wallace Sampson says:

    Excellent summary of events of a story that I felt would not give us an end in the near future.

    I had some misgivings on publishing Susan Gurney’s paper in the form we did because I had encouraged her to use real names. It was chancy for obvious reasons, including the lack of paper proof of the sequence of events and because I had been treatened before with legal action for defamation, libel, etc.

    And, although dangerous to say even now, as I recall, it was my idea to publish the story, which was all we could offer at the time – we had no information about violation of NIH and other regulations by Columbia. It was a human story.

    Credit to Kim and his sources for digging up the ethical violations in the case, which finally round it out. Togethe with the Cha/Wirth story it ts a serious shadow on the whole program at Columbia. Yet the original “CAM” program is still in place, and Mehmet Oz’s program in cardiac surgery is active, although it seems to havebeen toned down some (it began with the Touch for health program.)

  4. David Gorski says:

    Yet the original “CAM” program is still in place, and Mehmet Oz’s program in cardiac surgery is active, although it seems to havebeen toned down some (it began with the Touch for health program.)

    Mehmet Oz is still on Oprah’s show regularly and does radio ads in the NYC media market for his woo. He’s still quite famous, thanks to Oprah.

  5. oderb says:

    Unlike any of the other posters I am and have been a patient of Dr Gonzalez for 18 years. I had a bronchial carcinoid resected in the late 1980′s, which spread to the liver in 1990. I am still alive and well on the Gonzalez protocol. That obviously is not proof of anything except my good luck and judgement in learning of him and rigorously following his program for all these many years. (I know that patients can live for some years with carcinoid in the liver….but 18 years..possible but quite quite rare.)

    I am utterly appalled at many of the closed minds who write on this site. To say there is no science behind his work is to ignore the work of Dr Beard and others, to disparage coffee enemas is to ignore that they were endorsed in the Merck Manual for decades, to claim that there is no evidence the pancreatic enzymes survive the digestive tract is just untrue (I don’t have a citation but I can find it if anyone cares to ask.)

    I will keep this post brief and simply make two more points.

    First that I have spent about 40 hours with Dr Gonzalez over the past 18 years and find him to be a man with compassion, tremendous knowledge, and enormous dedication to healing his patients. When I call him he always gets back to me the same day. He patiently explains the rationale for everything he does when I ask – and I’ve asked him hundreds of questions over the years. He has helped me with innovative and yes – unorthodox – approaches to health issues other than cancer a number of times.

    But most importantly he has always said to me – and in public – that all he ever wanted was to have a fair test of his protocol and that if it showed no benefit – as virtually everyone on this site vehemently assumes – that he would readily abandon his protocol, if not his practice.

    How many doctors – conventional or alternative – would have such an attitude? What in the world would he gain fighting for years to test his protocol if he wasn’t utterly convinced based upon his experience treating thousands of patients that it is efficacious?

    What possible motivation would one have to take the abuse and barrage of ridicule that undertaking such a study would lead to from the conventional oncology community? He has a thriving practice and international recognition (at least among alternative practitioners) now.

    This question in no way proves that his therapy works, anymore than my own survival does, but I would hope it might at least make some of the readers here pause before they continue with their angry condemnations of a man who simply is trying to shine the spotlight on 20 years of dedicated work treating people in need.

    I am heartsick myself that the data from this trial has not and maybe will not ever be made public. It is in the interest of all – true believers like myself and skeptics like most of you – that it be released and closely scrutinized.

    If anyone wants to discuss this post with me privately I can be reached at hrb885@aol.com

  6. CAMCENTRAL says:

    Just to correct a few of the facts on this discussion. First, Dr. Gonzalez had presented a best case series to the NCI prior to Congressman Burton’s hearings and interest. There was significant interest in conducting a study well before 1999.

    The reason there has been no data published is that the study was poorly managed by the NIH and Columbia. The principal investigator at Columbia has been found guilty by the Office of Human Subject Protections for among other things failing to follow federal guidelines on obtaining written informed consent from patients for a majority of the patients. Among the many problems that doomed this study were that the principal investigator, Dr. John Chabot, not Dr. Gonzalez was in complete charge of patient referral to the nutritional arm and repeatedly referred patients who did not fit within the protocol and who never fully participated in the treatment. The truth on this will one day come out, but the fault on this study lays clearly at the fit of the NIH staff responsible for managing this study and of the principal investigator Dr. John Chabot…that he continues to be allowed to be involved in clinical trials is a real travesty.

    While I know that Dr. Atwood is a part of the quackbuster network and that there is nothing that anyone can say that will open your mind to any alternative therapy, including the facts, I hope that the general reader will remember that while Dr. Atwood has provided an eloquent dissertation of his opinion, and Dr. Wallace Sampson a colleague of his within the quackbuster network has seconded, it does not mean they presented a fully accurate representation of the issue.

    I have on occasion met a number of patients of Dr. Gonzalez who conventional medicine sent home to die, and only because of his protocol and their personal investment in following it dilligently were they alive 5 – 10 and sometimes 20 years later. How many inoperable pancreatic cancer patients who use chemotherapy are alive 10 or 18years later? Please stand up and be heard.

  7. Harriet Hall says:

    Is there a quackbuster network? Where can I join?

  8. pmoran says:

    CAMCENTRAL, we all agree the study was ill-conceived and poorly managed.

    But there is nothing to stop Gonzales publishing the results of any patients who he treated optimally during the present study. In fact, I defy him to do so. I predict that no case meeting the trial criteria survived five years, and suggest that this is why Gonzales is not pushing for the available results ot be published.

    (I don’t believe your own claims about knowing such patients for a moment — I have tried to get such information out of Gonzales without success.)

    http://www.users.on.net/~pmoran/cancer/Alternative_studies.htm

  9. David Gorski says:

    I’m with Dr. Moran, CAMCENTRAL. I challenge Dr. Gonzalez to push for publication of the results of his trial.

    I, too, also want to join the quackbusters’ network, but first I need to find out if my big pharma paymasters will increase my monthly kickback if I put forth the extra effort required.

  10. Joe says:

    Harriet and David,

    Joining the “quackbuster’s network” is easy, and approved by the Big Pharma overlords. Simply go to your copy of “The Big Pharma Handbook and Guide to Poisoning Children with Vaccines.” Turn to Appendix 3 (don’t tell you removed it out of habit) and modify the application for the “disease-producing ray-gun” (that keeps you in business). Scratch that out and replace it with “quackbusters’ network.” It also qualifies you for an upgrade (when appropriate) from your dark-blue (not black!) helicopters to Lear Jets (when appropriate).

  11. CAMCENTRAL wrote:

    Just to correct a few of the facts on this discussion. First, Dr. Gonzalez had presented a best case series to the NCI prior to Congressman Burton’s hearings and interest. There was significant interest in conducting a study well before 1999.

    This discussion was presented in 6 parts, and includes a history of Gonzalez’s claims, including more than one critique of his “best case series.” Please read each part before presuming that pertinent facts were excluded.

    More interesting is that you, CAMCENTRAL, imply that you have information about the non-publication of the trial that is unavailable for public scrutiny. If so, please share it with us or explain why you won’t. As taxpayers, we have a right to know.

    KA

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