Dr Scott Gottleib has reviewed Trick or Treatment? Alternative Medicine on Trial for Wall Street Journal. He also recounts an intriguing anecdote from his own experience.
When I was practicing medicine in the Elmhurst section of New York about five years ago, my colleagues and I confronted an epidemic of liver damage among the recently arrived Chinese immigrants who live there. We put these patients through an exhaustive battery of tests for conventional sources of hepatitis, the most likely culprit, but found none. The mysterious illness, we decided, must have been caused by the folk therapies, usually herbal, that our patients often used but rarely disclosed to their doctors. There was little we could do but counsel them to stop. Instead of following our professional advice, though, they usually just added new herbs to their regimen, hoping to solve their liver problems but sometimes making themselves even more ill.
The Elmhurst epidemic was a classic example of the clash — both cultural and scientific — between “alternative” and conventional medicine. In this case, the inability of doctors to treat a liver ailment strengthened the false faith of patients in other cures. Usually, alternative medicine is a harmless distraction. And some treatments actually do offer benefits. But going outside modern medical practice also carries dangers.
There are many contributory factors as to why the patients in this epidemic decided to ignore their medical advisors’ advice and sought to rectify matters by adding in yet more herbs. One of the interesting features is what has been described before now as “the politics of elixirs”. Charlotte Gray explores why expert advice and grounds for scepticism count for so little when they are up against something that captures the imagination of the public or politicians in such a powerful way.
Dr Luigi Di Bella was an italian medical doctor and physiology professor who claimed to have developed and implemented a successful treatment for cancer. The treatment was a cocktail of vitamin A retinoids, somatostatin and melatonin with other ingredients that varied according to the needs of the patient. The treatments were subsequently tested and found to be ineffective. Silvio Garattini commented that the treatment protocol was “a totally irrational association of drugs supported by absolutely no scientific evidence”, and that it had “the same dignity as Lourdes water”. Di Bella’s haphazard approach to record-keeping did not enhance his claims for scientific rigour.[a]
Oncologist Paul Hoskins participated in a delegation to examine di Bella’s work (pdf) and reported that he saw records that contained scant clinical details; observations took the form of notes that the patient “felt fine”. Plainly, despite patients’ desperation, there wasn’t enough material or evidence to recommend that trials of the Di Bella Multitherapy should be initiated in Canada.
However, the existence of a cure hyped as a miracle fomented controversy both in Italy and Canada (pdf), amongst other countries. Kamran Abbasi is not alone in characterising the desperate eagerness of patients and their families to obtain Di Bella’s “miracle cure” as a “public frenzy”.
Not content with Italy, the Di Bella publicity machine has gone global. Di Bella spoke to the European parliament, claiming that he had also cured Alzheimer’s disease, multiple sclerosis, and retinitis pigmentosa with somatostatin.
In Italy, the political, legal and social agitation around the notion of patient choice and freedom combined into an irresistible pressure that led to some very expensive[b] multi-centre, uncontrolled phase II trials that involved 8 different types of cancer and only 386 participants. According to Gray, in 1998, the trials were budgeted to cost close to $20 million (Canadian) — “the same as the entire annual budget for chemotherapy treatments for the BC Cancer Agency’s 13 000 patients”. The costs were so substantial that the italian parliament passed a special act to fund it.
Unfortunately the brief time-scales, sense of urgent scrutiny and other pressures resulted in substantial flaws in the design and execution of the studies. For many observers who had been polarised in the preceding controversy, these flaws mitigated the power of the negative results and the authors’ recommendation that the outcomes did not “warrant further clinical testing”. When the results were published, Marcus Müllner wrote a powerful accompanying editorial: Di Bella’s therapy: the last word?
The design of these studies is flawed; the results are already known; and Di Bella and his followers probably would not accept the findings, even if the studies had been randomised, double blind, and placebo controlled. So, why are we publishing this paper in the BMJ? Firstly, even though the results have appeared in the media, these studies and their design have not been formally published. Secondly, we should acknowledge this swift concerted action against a bogus therapy of nationwide importance. Thirdly, treating this topic seriously may prevent future cases—both of the implementation of treatments with unknown efficacy and side effects and of studies of weak design to answer important questions.
Inevitably, of course, Müllner’s 3rd point did not happen. When the findings did not support the Di Bella Multitherapy Di Bella and others rejected the negative findings and claimed that the results were sabotaged by mainstream doctors for the benefit of Big Pharma. Predictably, there are footholds on the internet and throughout the world where people believe that Big Pharma didn’t want the world to learn that Di Bella Multitherapy is a cure for cancer and a variety of other intractable diseases.
There is also a more pernicious outcome of cases such as this that continues to wreak its harm in several ways for an unpredictable amount of time. The way in which the discussion became polarised between science and emotion/desperation seem to undermine trust in both health officials and doctors. Doctors seemed remote, uncaring, lacking in empathy and compassion when they called for trials and some desperate people interpreted this as obstruction rather than a drive to investigate the matter thoroughly for the best advantage of patients. Like other enthusiasms for ‘miracle cures’ (e.g., laetrile), the emotional tone of the public discussion result in unwise and ill-considered political action.
Gray highlights one of the unintended and potentitially damaging consequences when she discusses the impact of the Di Bella trials on the reputation of somatostatin research. Some canadian researchers thought that somatostatin might have some potential as a preventive cancer therapy. One of the researchers was oncologist Professor Pollak of McGill University who had conducted some research with somatostatin; notably, to assess whether it reduced the risk of a recurrence of breast cancer. He was apprehensive that whatever the outcome of the Di Bella Multitherapy trials, it had the potential to undermine research in a useful drug. Either because a successful trial outcome would make further research on somastatin seem null and void and ludicrously slow by comparison; or because of a taint of association if the trial were to fail.
Fads can be remarkably damaging to a field of endeavour or research that might be worthwhile but the taint of pseudoscience can be so strong that it creates a scorched earth that is doomed to destroy all attempts at cultivating it. Orac expressed a similar concern in his series of posts about the hype surrounding DCA as a possible cancer treatment. He captured the clash between patients who were begging doctors to allow them to try DCA because they felt that they had little to lose and researchers who knew that the results were too preliminary to allow anyone to recommend safe dosages, far less appropriate regimens: Dichloroacetate (DCA): A scientist’s worst nightmare?
I remain of the mind that hypesters like Jim Tassano, although he seems to think that he’s doing good, are in fact not only putting patients at risk, but putting the very clinical trials necessary to demonstrate the utility of DCA against cancer at risk. Thanks to Jim Tassano, idiots like Dave Scot egging him on, and the general Kevin Trudeau-style “cure for cancer that ‘they’ don’t want you to know about” blogospheric meltdown, the taint of quackery has descended upon a new chemotherapeutic drug (and, indeed, a new overall approach to treating cancer in general) that is promising and the study of which could utimately yield a whole new class of anticancer drugs.
This last point was pithily recast by Orac in his exploration of Searing stupidity about “complementary and alternative medicine” (CAM) in Slate.
Worse, legitimate evidence-based scientific medicine, again such as nutrition or natural products, were unjustly “ghettoized” by CAM when they were coopted by woo-meisters and relabeled as “CAM.” The association with woo has made legitimate scientific modalities that have fallen under the CAM rubric take on the taint of pseudoscience.
Some patients don’t trust doctors. Some doctors find it difficult to work with patients who reject their treatment recommendations. What Ernst identified as a “repetitive pattern” means that trials resolve nothing for some people and the therapy continues with a lower profile.[c] As we’ve argued on several occasions, nutritionism and the poor scholarship of Patrick Holford and other media nutritionists is undermining the reputation of nutrition as a serious academic discipline and nutrition in general. The cultural and scientific clash between CAM and medicine can create far-reaching ripples of harm and has many casualties.
Di Bella had boasted that his personal files contained proof that he had cured thousands of patients. In June, however, his credibility was shaken by an analysis of 3076 of his records. According to the National Institute of Health, 1,553 (50%) contained no documentation that the patient had cancer or lacked other essential information. Of the rest, 918 were excluded from further consideration because they lived in areas where tumor registries were not available, which meant that reliable survival information was not available. Out of 605 patients living in areas covered by local tumor registries, only 248 had sufficient documentation of diagnosis and treatments. However, 244 of them had also received conventional treatments, which meant that no favorable conclusion could be drawn.
A[n]…important point relates to a repetitive pattern in the scientific investigation of “bogus” therapies. Proponents first manage to mobilize supporters to campaign in their favor. This brings financial gain. When skeptics ask about the evidence, the burden of proof is swiftly put on their shoulders, and the lack of evidence is made to look like a “conspiracy” of orthodoxy against the alternative. If scientists then decide to rigorously test the method, its proponents would celebrate this as a breakthrough for their method. Again, this amounts to financial gain. Subsequently, a study may prove that the method is ineffective. Proponents now claim that the research was flawed, did not adhere to their protocol, or was wrongly analyzed. The press coverage yet again brings financial gain. This pattern repeats itself with depressing regularity, e.g., when Laetrile or Di Bella’s cancer cure were promoted.
One of the remaining concerns is that the trials have had some effect in dampening the hyperbole but the controversy will continue for years. Part of the responsibility for this lies with the tremendous pressure to perform trials that were unsatisfactory. In the same way that the Mayo Clinic trials failed to replicate Pauling’s protocol (using oral rather than IV route of administration for Vitamin C) and thus failed to be a “fair test”, the flaws of this trial might allow others to argue that malice rather than incompetence or undue haste sabotaged these trials and their outcome should be discarded. Cancer UK has a decent overview of the controversy surrounding the ‘replication’ of the vitamin C trials.
 Gray C. Dr. Luigi Di Bella and the politics of elixirs.. CMAJ. 1998 Jun 2;158(11):1510-2.
 Abbasi K. Di Bella’s miracle method. BMJ 1998 May 23; 316(7144): 1617.
 Italian Study Group for the Di Bella Multitherapy Trials. Evaluation of an unconventional cancer treatment (the Di Bella multitherapy): results of phase II trials in Italy. BMJ. 1999 January 23; 318(7178): 224–228. There is an additional review which is a thorough-going exploration of the trial. Traversa G, Maggini M, Menniti-Ippolito F, Bruzzi P, Chiarotti F, Greco D, Spila-Alegiani S, Raschetti R, Benagiano G. The unconventional Di Bella cancer treatment: A reflection on the Italian experience. The Italian Study Group for the Di Bella Multitherapy Trials. Cancer. 1999 Nov 15;86(10):1903-11.
 Müllner M. Di Bella’s therapy: the last word? The evidence would be stronger if the researchers had randomised their studies. BMJ. 1999 January 23; 318(7178): 208–209.
 Ernst, E. (1999). Response to Chelation Therapy for Vascular Disease. Circulation;99:164-167.