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.
Part IV of this blog ended by observing that the NIH-funded trial of the “Gonzalez regimen” for cancer of the pancreas,† to have begun in March, 1999, was in trouble almost as soon as it started. As originally designed, it was to have been a randomized, controlled trial comparing gemcitabine, the standard chemotherapy, to the “Gonzalez regimen” of pancreatic enzymes, “supplements,” twice-daily coffee enemas, and other purported methods of “detoxification.” By June, 1999, according to Dr. John Chabot, the Columbia University surgeon acting as Principal Investigator (PI) of the trial, only 3 of the first 50 potential subjects had agreed to be randomized, and none of the three met the eligibility criteria. By January, 2000 it had become clear that the trial would not accrue a sufficient number of subjects if it remained randomized, because almost all of the potential subjects were intent on being in the “nutritional,” ie, the Gonzalez arm.
Trouble with Randomizing
The investigators at Columbia therefore decided to change the protocol to a “single-armed, non-randomized case-cohort study where patients will only be enrolled in what was the nutritional arm.” Paradoxically, PI John Chabot had recently explained, at the 1999 Comprehensive Cancer Care Conference of James Gordon’s Center for Mind-Body Medicine, why this would not be a scientifically sound design:
A Review; then Back to the Gonzalez Regimen†
Part I of this blog introduced the topic of the “Gonzalez regimen” for treating cancer: “Intensive Pancreatic Proteolytic Enzyme Therapy With Ancillary Nutritional Support” and “detoxification” with twice daily coffee enemas, daily “skin brushing,” “a complete liver flush and a clean sweep and purge on a rotating basis each month,” and more. The topic was occasioned by the federal Office for Human Research Protections having recently cited Columbia University, for the second time, for violations of human subject protections in its NIH-funded trial of Gonzalez’s method as a treatment for cancer of the pancreas.
Part I discussed the implausible and bizarre regimen and cited Gonzalez’s troubles with malpractice suits and with the New York medical board during the 1990s. It ended by wondering what could have induced the NIH to give a $1.5 million grant to Columbia University to study the method.
Parts II and III began to answer that question, tracing some of the key events and individuals from the Laetrile wars in the 1970s to the NCI-funded trial of Laetrile reported in 1982, to the ”immuno-augmentative therapy” (IAT) battles of the mid-’80s, to the Report on “Unconventional Cancer Treatments” by the Congressional Office of Technology Assessment (OTA) in 1990, which in turn led to the NCI adopting its “Best Case Series Program” in 1991.
The end of Part III hinted that the conspiracy mongering that had greeted every attempt by the government to explain its positions on implausible cancer treatments, from Laetrile to the OTA report, ultimately led to the creation of the Office of Alternative Medicine (OAM) at the NIH, also in 1991. There is plenty of evidence for that, both from the conspiracy mongers themselves and from more level-headed observers. Each time the government acted—to fund a trial of Laetrile, to solicit the OTA report and propose a study of IAT, to establish the NCI “Best Case Series” program, and to establish the OAM—it was not because of scientific or medical considerations, but because of political pressure. More on that from time to time, but now back to Dr. Gonzalez.
A Reminder (Mainly to Myself): this Blog will Eventually get back to Discussing the NIH Trial of the “Gonzalez Regimen” for Treating Cancer of the Pancreas†
Which, if you’ll recall, is an arduous dietary and “detox” regimen that includes 150 pills per day, many of which contain pancreatic enzymes, two “coffee enemas” per day, ”a complete liver flush and a clean sweep and purge on a rotating basis each month during the 5 days of rest,” and more. In Part II I ventured off on a tangent about Laetrile and government sponsorship of trials of implausible cancer “cures.” That became more involved than I had planned (but also more enlightening, or so I hope), and Part III continues on that tangent.
The Politics of “Alternative Cancer Treatments”: the Lamentable Legacy of Laetrile (cont.)
The whole tide is beginning to turn toward metabolic therapy for degenerative disease and preventive medicine. Laetrile…has been the battering ram that is dragging right along with it…B-15,…acupuncture, kinesiology, …homeopathy and chiropractic…And we’ve done it all by making Laetrile a political issue.”
-Michael Culbert, editor of The Choice, the newsletter of the Committee for Freedom of Choice in Medicine. Quoted in 1979.¹
Laetrile and the Politics of NIH-Sponsored trials of “Alternative Cancer Treatments”
Part I of this blog ended by asking how, in light of the implausible and arduous nature of the “Gonzalez regimen” for cancer of the pancreas, and the unconvincing “best case series,” the NIH could ever have decided to fund a trial of it.† This entry will begin to answer that question. In so doing it may seem to veer from the original subject, but hold on to your seats: what you’ll find here is a piece of the treasure map that leads to the Mother Lode of Fool’s Gold that is government-sponsored “CAM” research.
All historical accounts of the encroachment of implausible claims into the research agenda of the NIH must begin with Laetrile. By that is meant all implausible claims, not merely those having to do with cancer. Elsewhere we have traced the history of “chelation therapy” for coronary artery disease, and have shown that its origins as a political movement, eventually leading to an unethical, $30 million, 2000 subject NIH trial, were intimately associated with people and organizations advocating Laetrile—the most lucrative health fraud ever perpetrated in the United States. In that essay we offer evidence that the creation of the NCCAM itself was at least partly attributable to the history of Laetrile and its advocates. Several good histories or partial histories of the Laetrile debacle are available online, including here, here, here, here, here, and here. The best,¹ but one that does not seem to be available online, is by the recently deceased dean of historians of American quackery, James Harvey Young. (more…)
Blogger’s note: This blog, which is rough going in places, will be presented in either 2 or 3 parts (I won’t know which until next week). I’ll post a part each week until it is complete, but due to overwhelming popular demand I promise to maintain the every-other-week posting of the far more amusing Weekly Waluation of the Weasel Words of Woo/2.
On Feb. 25, 2008, the federal Office for Human Research Protections (OHRP) cited Columbia University Medical Center (CUMC) for violating Title 45, Part 46 of the Code of Federal Regulations: Protection of Human Subjects (45CFR§46). The violations involved Columbia’s administration of the NIH-sponsored trial of the bizarre “Gonzalez Regimen” for treating cancer of the pancreas.† The OHRP’s determination letter to Steven Shea, MD, the Director of the Division of General Medicine and Senior Vice-Dean at CUMC, cited ethical problems of a serious kind:
We determine that the informed consent for the 40 of 62 subjects referenced by CUMC was not documented prior to the start of research activities, nor was the requirement for documentation waived by the CUMC IRB for subjects in this study.
It was the second time that the OHRP had cited Columbia for its dubious management of the “Gonzalez” trial. The first occurred in Dec. 2002, after investigators had determined that the trial’s consent form “did not list the risk of death from coffee enemas.” The OHRP listed several other violations at that time, but “redacted” them from the letter that it made available to the public. (more…)
I promised readers the “Advanced Course” for this week, which undoubtedly has you shaking in your boots. Fear not: you’ve already had a taste of advanced, subtle, misleading “CAM” language, and most of you probably “got” it. That was R. Barker Bausell’s analysis of how homeopathy is “hypothesized to work.” In the interest of civility, let me reiterate that I don’t think of Bausell as a horrible person or an ignorant boor for having written that statement. Rather, I think of him as having been so steeped in the de rigueur “CAM” language distortions of the 1990s that he is largely unaware of their insidious power. I suspect too that he, like most of us who grew up when schools no longer stressed the rigors of English composition, has an underdeveloped sense of the relation between the craft of writing and the integrity of its content. That doesn’t excuse him from writing honest prose, of course.
Last week’s post cited blatant language distortions of “CAM”—euphemisms, slogans, and outright falsehoods—and some that were more subtle: question-begging, misrepresentation, and derogation. It would require a semester’s worth of seminars to delve into the overlapping categories of misleading “CAM” language, but here we can consider a few. Then, perhaps, we’ll engage in an amusing diversion—more about that at the end of this post. (more…)
The Best Policy
From time to time I have been reiterating that correct use of the language has much to do with logic; I should add that it entails also honesty. I use the word “honesty” in its broadest sense…
Concision is honesty, honesty concision—that’s one thing you need to know.
—John Simon. Paradigms Lost: Reflections on Literacy and its Decline. New York, NY: Clarkson N. Potter, Inc.;1980. pp. 48, 52
In 1983, a naturopath in Alberta inserted balloons into the nostrils of a 20 month-old girl and inflated them. The child died of asphyxiation. Subsequently, a judge described the treatment—dubbed “bilateral nasal specific” by the chiropractor who had invented it—as “outright quackery.”  Fast-forward 15 years: a woman presented to the otolaryngology clinic at the University of Washington in Seattle “complaining of severe midface pain and epistaxis” (nosebleed). She had suffered nasal septal fractures caused by a similar treatment, by then renamed “NeuroCranial Restructuring” (NCR). In their case report, the surgeons who had treated the woman at U. Wash discussed the claims of NCR and explained that the relevant anatomy predicts that it is implausible and risky. They also reported that it is expensive: “$2000 to $4800 for a standard course (of 4 treatments).” They concluded:
This case report of a complication after a CAM procedure called NCR highlights the wide range of treatment options available to patients. It is important for otolaryngologists to be aware of the spectrum of CAM therapies that patients may pursue and be aware of potential complications from these procedures.
An accompanying editorial used similar language.
How is it that in 1983 a judge could offer a concise summary of the essence of such a method, whereas scarcely a generation later 5 highly-trained medical doctors, even after presenting the sordid facts, could only obscure it with bland euphemism? (more…)
This is actually the second entry in this series;† the first was Part V of the Homeopathy and Evidence-Based Medicine series, which began the discussion of why Evidence-Based Medicine (EBM) is not up to the task of evaluating highly implausible claims. That discussion made the point that EBM favors equivocal clinical trial data over basic science, even if the latter is both firmly established and refutes the clinical claim. It suggested that this failure in calculus is not an indictment of EBM’s originators, but rather was an understandable lapse on their part: it never occurred to them, even as recently as 1990, that EBM would soon be asked to judge contests pitting low powered, bias-prone clinical investigations and reviews against facts of nature elucidated by voluminous and rigorous experimentation. Thus although EBM correctly recognizes that basic science is an insufficient basis for determining the safety and effectiveness of a new medical treatment, it overlooks its necessary place in that exercise.
This entry develops the argument in a more formal way. In so doing it advocates a solution to the problem that has been offered by several others, but so far without real success: the adoption of Bayesian inference for evaluating clinical trial data.
Homeopathy and Science: Discussion, Summary and Conclusions
I was not surprised by a couple of the dissenting comments after Part IV of this blog. One writer worried that I had neglected, presumably for nefarious reasons, to cite replications of Benveniste’s results; another cited several examples of “positive” homeopathy studies that I had failed to mention. I answered some of those points here. I am fully aware of such “positive” reports, including those seeming to support Benveniste. I didn’t cite them, but not in some futile hope of concealing their existence from the watchful eyes of the readership. I also didn’t cite several “negative” reports, including an independent, disconfirming report of one of the claims of David Reilly, whose words began this series,* and the most recent of several reviews (referenced here) to conclude that “the clinical effects of homoeopathy are placebo effects.” I didn’t cite those reports for the same reasons that I didn’t cite the “positive” studies: they are mere footnotes to the overwhelming evidence against homeopathy.
To explain why, it will be necessary to discuss some of the strengths and weaknesses of the project known as “Evidence-Based Medicine.”