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:
The cornerstone of science-based medicine is, of course, scientific research. The integrity and quality of biomedical research is therefore of critical importance and to be thoughtfully and jealously guarded, if we care about maintaining an optimal standard of care. There are many threats and hazards to the institutions of medical research – mostly ideological. One that has not been discussed much on this blog but has been in the news recently is that of conflict of interest. Upon close examination this is a more complex issue than it may at first appear.
The most recent controversy over conflicts of interest were sparked by an article published in JAMA in which the authors allege that published studies that downplayed the risks of Vioxx (A Cox-2 inhibitor marketed as a pain killer that was removed from the market for increased cardiac risk) were in fact ghost-written by employees of Merck, the manufacturer of Vioxx. The names of two academic researchers were then attached to the studies to give them legitimacy. If true this is a damning episode, and no one would reasonably disagree with the contention that companies writing research on their own products represents an unacceptable conflict of interest. For the record, both Merk and the one surviving academic deny the accusations completely.
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.
This is a slight departure from the usual fare of pseudoscience, but a matter that should concern us because of the vulnerability this matter confers on medicine – the borderline practices of major medical centers. The article can be viewed here.
Several days ago the San Francisco Chronicle printed a second article about the plight of a 37 year old woman (EP) with an inflammatory breast cancer who was denied insurance coverage for an expensive treatment, high-dose chemotherapy with autologous bone marrow (or stem cell) transplant or infusion (HDCT/BMT or SDI.) The institution is the MD Anderson Cancer Center in Houston. The problem is that although the treatment is effective, it is no moreso than moderate dose HDCT without the marrow or stem cell infusion, and also is more expensive and has significant morbidity.
Inflammatory breast cancer is a highly aggressive form that is usually regarded as “advanced” when diagnosed, that is, spread beyond the breast and regional lymph nodes. One cannot tell from the article whether EP’s cancer spread is documented or implied. But because of the poor prognosis and presumed incurability in either case, options are limited. In the 1980s -90s, HDCT/BMT was thought to be a promising method on the basis of studies that showed a prolonged disease-free and overall survival compared to results of prior studies using more conservative treatment. The problem then was that the studies were uncontrolled.
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
In January I had the pleasure of attending TAM 5.5 in Fort Lauderdale. On the last day of the conference the JREF had an open house where anyone interested could come see the inner workings at the JREF facility. Since I had a rental car I decided to go through the lobby to see if anyone needed a ride, and sure enough one Dr. Harriet Hall took me up on my offer.During the 20 minute drive that I had Harriet captive we were able to have a pleasant and illuminating (for me) conversation, during which I told Dr. Hall about an experience I had with a chiropractor in my neck of the woods. This got me thinking about honesty and purposeful deception in alternative medicine, and for this reason I’m going to start this blog entry off with a personal anecdote about an incident that occurred some years back just after I graduated from Nursing and had become a full-fledged registered nurse.
After having some back problems I decided to go to a respected chiropractor in Calgary (a city of about 1 million people). Since it was my first visit I needed to go through a full ‘assessment’ and the chiropractor took my blood pressure, had me step on two scales (one for each foot) so that he could weigh both sides of my body simultaneously, and he also took a single anterior X-Ray of my chest/spine (anterior means an X-Ray taken straight on with my back against the photographic plate – actually I think the technical term for that is an AP or anterior-postero X-Ray).
Phrenology was a 19th century pseudoscience that claimed to associate brain areas with specific personality traits. It was based on palpating bumps on the skull and was totally bogus. New brain imaging procedures are giving us real insights into brain function in health and disease. They are still blunt instruments, and it is easy and tempting to over-interpret what we are seeing. In his book The New Phrenology William Uttal warns that “the excitement of these new research tools can lead to a neuroreductionist wild goose chase” and that we must be careful not to succumb to new versions of the old phrenology.
The Amen Clinics, founded by Daniel G. Amen, MD, offer SPECT (single photon emission computed tomography) scans to help diagnose and manage conditions such as attention deficit disorders (ADD), mood disorders, anxiety and panic disorders, autistic spectrum disorders, obsessive compulsive disorder (OCD), substance abuse, toxic exposure, brain trauma, memory problems, temper problems, and relationship and marital struggles.
The scans generate colored pictures of the brain that show “areas of your brain that work well, areas that work too hard, and areas that do not work enough.” They do not actually provide a diagnosis, but “must be placed in the context of a person’s life, including their personal history and mental state.” “The goal of treatment is to balance brain function, such as calm the overactive areas and enhance the underactive ones.” (more…)
I’m on the record multiple times as saying that I reject the entire concept and nomenclature of “alternative medicine” as being distinct from “conventional” medicine as a false dichotomy, when in reality there should be just “medicine.” Indeed, if there is one major theme to which this blog is dedicated it’s that medicine should be as much as possible science-based, a concept that takes into account not just clinical trials, which are prone to all sorts of false-positive results in the case of modalities that have no plausibility from a scientific perspective. In essence, I advocate treating “alternative” medicine the same as “conventional” medicine subjecting it to the same scientific process to determine whether it has efficacy or not, after which medicine that is effective is retained and used and medicine that fails the test is discarded. Where it comes from, the “alternative” or the “conventional” medical realm, matters little to me. All that matters is that it is based on sound science and that it has been demonstrated to have efficacy significantly greater than that of a placebo.
Given that, you’d think I’d be all in favor of subjecting alternative medicine, be it woo or more credible, to rigorous scientific testing. In many cases, you’d be right. My sole caveat is that, when testing alt-med, priority should be given to modalities that have at least a modicum of scientific plausibility, even if a bit tenuous. Herbal remedies would thus be at the front of my line to be tested, while obvious woo whose core principle on which it is based is so utterly ridiculous and scientifically implausible (like homeopathy, for instance) would be relegated to the back of line, if it’s ever tested at all. More implausible modalities that might work (albeit by a method that has nothing to do with the “life energy” manipulation that is claimed for it) like acupuncture would be somewhere in the middle. It’s a matter of resource prioritization, in which it makes little sense to test blatant woo before more plausible therapies are examined. Indeed, it’s arguable whether blatant woo like homeopathy should even have resources wasted testing it at all, given its extreme scientific improbability. Finally, regardless of what modality is being tested in scientific and/or clinical trials, it has to be done according to the highest ethical standards, on adults fully cognizant of or able to be taught about the questions being asked, the issues involved, and the potential risks who are thus able to give truly informed consent.
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…)
You Can’t Foo’ Stu with Woo!
A Spitzerian (“pointed”) analysis
Last week’s inaugural game elicited several amusing and penetrating analyses, including that of the hands-down Gold Medal Winner, Stu. His was the first entry, introduced in a concise and alliterative imperative, and was both hilarious and timely. It implied most of the points discussed by others. This distinctive combination has moved me to grant Stu a legacy here at the W^5. In the future there may be, undoubtedly no more than once in a very long while, entries that live up to the Soaring Standard of Stu®. If so, they will be Duly Acknowledged. (more…)