“Why aren’t there more clinical trials studying the effect of CAM on cancer?” cries the CAM advocate

I’ve lamented time and time again just how much money the National Center for Complementary and Alternative Medicine (NCCAM) wastes on basic research and clinical trials of modalities that are, from a scientific viewpoint, so highly implausible that the chances of finding a clinically useful or relevant–or even a consistent statistically significant–effect (for example, homeopathy or reiki) or on therapies for which there is already abundant negative evidence (chelation therapy, for example) are vanishingly small. In this fifth year of a flat or declining NIH budget and of scientists facing the most unfavorable paylines for getting funded since the early 1990s, it strikes me as utterly irresponsible to be devoting over $120 million a year to mostly badly designed studies to test if woo works.

Sadly, what I didn’t know until fairly recently is that NCCAM isn’t the only source of NIH money going to fund woo. There is in fact an Institute in the NIH that actually spends more money studying woo than NCCAM. Indeed, in FY 2007, it spend $121,932,765 million on CAM-related research, funding 461 projects in the form of grants, cooperative agreements, supplements or contracts, compared to the $121,400,000 spent by NCCAM. Really, it’s true, and its CAM portfolio represents 2.5% of its total budget. So what is this Institute funding lots of “complementary and alternative medicine” (CAM)? Can you guess? I’ll be happy to tell you.

It’s the National Cancer Institute. Alright, I’m sure virtually everybody figured out the answer based on the title of this post, but I had to generate some suspense somehow, didn’t I? In any case, ensconced deeply in the NCI, there is an office known as the Office of Cancer Complementary and Alternative Medicine (OCCAM). Even though I was disappointed to learn this, I nonetheless looked at the highlights of OCCAM-funded research and then at OCCAM’s entire research portfolio for last year, including 151 open clinical trials and 145 closed trials. Although my overall gestalt was that it looked a lot like the usual list of CAM trials funded by NCCAM, there were several trials immediately visible that weren’t obviously CAM trials by their titles, and there were plenty of trials of nutritional supplements or dietary manipulations on cancer development or treatment, showing once again how CAM has somehow managed to appropriate the scientifically legitimate area of nutrition and diet research as somehow being “alternative.” Actually, I don’t mind this sort of research so much, as long as it’s testing hypotheses that are supported by sound basic science and preclinical data. I just resent that somehow such research is now considered “CAM” when nutritional research has long been a major area of “conventional research.” Ditto the study of natural products and herbs with useful pharmacological activity, an area of research in pharmacology since time immemorial. There’s no scientific rationale why such studies should be segregated away as “alternative”; they could and should be evaluated just like any other scientific study, and, even worse, segregating them into the CAM ghetto devalues them and by association with the woo also being funded under the rubric of “CAM” makes them look like woo too.

Unfortunately, there also appears to be a fair amount of woo in the OCCAM portfolio, such as studies of healing touch and reiki–at the Cleveland Clinic, yet!–in cancer patients. Worst of all, OCCAM is funding a trial of homeopathy! This trial happens to be at the Oklahoma University Cancer Institute, which suggests to me that I may have to add OU to my Academic Woo Aggregator at its next (long overdue) update. It’s all very depressing, especially because, as I peruse the list of open trials today and compare it to the list of closed trials, I get the distinct impression that the open trials include more woo, implying to me that OCCAM is getting less scientifically rigorous in what it is willing to fund. On the other hand, somehow in the closed trials are a whole bunch of trials of antineoplastons, a highly improbable and dubious therapy; so maybe my impression is wrong. I must say, however, that my confidence in the scientific rigor of the entire OCCAM enterprise was not boosted by my encounter with an OCCAM representative at the AACR Meeting three weeks ago that I never blogged about. Suffice it to say that he went on about “royal herbs” and couldn’t provide a good rationale why anyone should conclude that impure mixtures of compounds would be more effective or reliable than pharmaceuticals. When he started going on about “emperor” herbs and “assistant” herbs, I couldn’t take it anymore.

Be that as it may, no matter how much money OCCAM throws at CAM studies, CAM advocates are not happy. Oh, no, they’re not happy at all. It’s not enough, you see! Indeed, published at that repository of all medical crankery and quackery, NaturalNews.com, recently appeared an article entitled Analysis: Virtually Zero Alternative Cancer Research Occurring. The article cites an “analysis” done for a non-peer-reviewed newsletter called CancerWire published by Michael Horwin, MA, JD. Now, you’re probably wondering how this analysis can conclude that there is “virtually zero alternative cancer research” going on, given that I just showed hundreds of billions of dollars a year worth of alternative cancer research being funded by OCCAM. Easy. Just complain that it’s not the right kind of CAM research that’s being funded:

The authors found that of the 7,080 clinical trials for cancer currently ongoing, over 3,000 are focused on chemotherapy — a treatment that already has over 50 years of research to its credit with relatively little practical return on investment. Of the remaining trials, over 2,000 were focused on more advanced biological treatments such as anti-angiogenesis drugs, which work to cut off the blood supply to tumors.

In all, only 123 of the trials deal with any type of alternative or complementary treatment. “These 123 represent only 1.7% of the total and included trials of various foods, herbs and modalities such as: soy, ginger, Valerian, Curcumin, acupuncture, Reiki, meditation, garlic, Green tea, and Tai Chi,” the authors state. An optimist might find comfort in the fact that the number at least reached the triple digits, but closer analysis reveals an even less tolerable situation.

“The overwhelming majority of these trials examined questions that did not focus on whether these approaches alone improved survivability from cancer,” the authors report. What this means is that the treatments were actually being evaluated not as treatments, but as adjunctive therapies to improve the rate and intensity of symptoms among those patients already undergoing conventional therapy.

In other words, because the vast majority of these clinical trials did not test alternative therapies alone against cancer to see if they show objective evidence of anti-tumor activity that can lead to tumor shrinkage and measurable increases in survival, Adam Miller is unhappy. Of course there’s a very good reason why these therapies are not being tested alone, and it’s simple ethics. It is highly unethical to perform a trial in which one arm receives a treatment that the investigators doing the study do not have a strong reason to believe to be effective. Indeed, in cancer trials at least, even new drugs that investigators have good reason to anticipate to be effective are usually not tested alone in anything other than phase 1 trials. Instead, usually they are tested in addition to the standard of care or in addition to a known effective treatment regimen. The reason is that many new drugs that have made it through the preclinical gauntlet of basic science experimentation, testing in animal models, and safety testing in phase 1 trials still fail to demonstrate objective evidence of efficacy in phase 2 or phase 3 trials. Consequently, it is considered unethical to expose cancer patients to the risk that the new drug they are taking will turn out to be a dud without a “back up” of getting a treatment known to be effective. Imagine now subjecting one group of cancer patients in a clinical study to various forms of woo without standard of care therapy or even known effective therapy. It’s obvious to me how unethical that would be, and it would be equally obvious to any clinical researcher worth a damn. Moreover, even if the researcher conducting such a study really, really believed that the “alternative” therapy being tested could cure cancer (thus making the trial ethical to him), any Institutional Review Board worth a damn evaluating the study for approval would shoot it down. Finally, did it ever occur to Miller that testing a drug in combination with another known effective drug is looking for an effect over and above that of the effective drug, indicating additivity of the effects of the two drugs and an independent therapeutic effect of the “add-on” drug while making sure that patients in all treatment groups get effective therapy? There’s more to clinical trial design than just the science, but does Miller or Horwin understand that?

Nope.

Of course, it’s very clear where Horwin is coming from by taking a look at his newsletter. He begins lamenting the “conventional” paradigm in cancer treatment, which he characterizes thusly:

Cancer is caused by personal choices, genetics and acts of God. Scientists around the country are making important discoveries that are getting us closer to a cure every day, but more money and research is needed. When it comes, a cure for cancer will come from a large pharmaceutical company. Only a deeply researched expensive drug can cure cancer. Anyone who is serious about alternative or nutrition-based therapies is ill advised, a multi-level marketer, or a quack. Alternative therapies are ineffective, unproven or disproven and a waste of money.

Ah, yes, the typical altie straw man characterization of how scientific medicine approaches cancer. At least Horwin spared us the usual “cut, burn, and poison” refrain about the dreaded “conventional” or “allopathic” medcine that we typically hear from Mike Adams, Whale.to, and their ilk. However he does then next launch into a glowing story about Dr. Andrew Ivy, the doctor who pushed the dubious cancer therapy known as Krebiozen back in the 1950s and 1960s. Basically, Krebiozen was claimed to be a hormone isolated from horse blood, and injections of this concoction were claimed to cause dramatic tumor shrinkages and even remissions. Naturally, Horwin sees the lack of acceptance as “orthodox” medicine “suppressing” a cure, and even goes so far to claim:

Today, Drs. Ivy’s insights may be better appreciated. In the last 20 years, mainstream science may have caught up with the insights of this physician. According to a leading medical treatise, “Animal studies have conclusively shown that the immune system can recognize and eliminate malignant tumors in vivo.”(14) In recent years, billions of dollars have been invested in isolating and synthesizing interleukin, interferon, and other cytokines-all natural immune-related substances which can kill or arrest cancer and that are found in the blood of mammals including horses and man.

What any of this has to do with a dubious substance isolated from horse blood is not explained. What is explained at Quackwatch is just how improbable Dr. Ivy’s claims were and how incompetent and bogus his Foundation’s clinical research was, for example:

In 1962, California physician decided from what he had seen and read that krebiozen research was not a bona fide clinical investigation. He wrote to ask for krebiozen for a patient who had had a bilateral pneumonectomy. Bilateral pneumonectomy (the removal of both lungs) is incompatible with life. No questions were asked, however, and krebiozen was sent with the usual request for $9.50 a vial. When the physician didn’t pay, he received rebillings at monthly intervals. When he reported this to the FDA, further investigation followed.

In March, 1963 another physician wrote deliberately stating his patient had had a bilateral total pneumonectomy, the unambiguous removal of both lungs. This is inconsistent with life and with common sense, but the Krebiozen Research Foundation, whose principal scientific consultant, Dr. Ivy, is a distinguished physiologist, sent 8 ampules of krebiozen and a bill for $76.

And, most tellingly:

Samples of krebiozen were reluctantly provided on two occasions to the National Cancer Institute, and on one occasion to the FDA in the form of dry powder. In September, 1961, the material was labeled as pure krebiozen, and this identification was confirmed and reiterated as late as March, 1963. All three samples, on analysis by the FDA, consultants from several universities, and by studies at the National Cancer Institute proved to be creatine monohydrate, a normal constituent of muscle and a common laboratory compound purchasable for $.30 a gram, approximately $10 for a 1-ounce bottle.

As you might expect, the Krebiozen Research Foundation had an answer for this set of observations, too. They implied that the FDA had misinterpreted the data and overlooked the important facts –that the creatine monohydrate was just a contaminant in what had previously been labeled pure krebiozen, and that trace quantities of real krebiozen were there.

The very fact that Horwin would cite Dr. Ivy as a victim of orthodoxy run amok “suppressing” cures shows that he is credulous in the extreme. This leads him to lament this:

…if one includes Dr. Burzynski’s antineoplaston studies, a total of 27 clinical trials out of 7,080, less than half of one percent are focused on alternative and complementary therapies as a stand alone treatment to assess survival. If one considers the Burzynski trials as a separate category, then only 3 of 7,080 or .04% are focused on this question.

These numbers speak volumes. Alternative therapies represent a small minority of cancer clinical trials and only a smaller number of these are focused on whether they are viable treatments. While there were 3,198 chemotherapy trials, a treatment that has been experimented with for over fifty years, less than 30 trials were focused on natural approaches. This analysis suggests what many observers have been reporting for some time that alternative therapies – stand alone natural cancer treatments have been co-opted into the conventional paradigm. They are no longer seen as potentially powerful treatments in their own right, but rather “add-ons” to ameliorate the side effects or improve the quality of life for patients who receive the toxic conventional treatments.

From my perspective, barring compelling evidence to persuade me otherwise, that is actually entirely appropriate, both scientifically and ethically. Indeed, believe it or not, I find Horwin’s complaint about CAM research in cancer to be somewhat heartening. It suggests to me that the infiltration of woo into the NCI is still fairly low. That doesn’t mean it isn’t troublesome, though. For one thing, the approximately $122 million that the NIH spends a year on CAM research could easily fund 50 to 75 clinical trials or R01 grants studying hypotheses that are based in plausible science and thus far more likely to produce a concrete benefit to cancer patients in terms of improvements in treatment efficacy and/or symptom relief than spending that money on modalities that are at best of dubious plausibility and at worst as improbable as homeopathy. That’s a lot of lost opportunity, but as a total percentage it’s perhaps not as bad as I had feared. Even so, even if the funding as a percentage of total trials by the NCI is small considerable damage to scientific medicine can be done. By funding utterly implausible and not better than placebo modalities like homeopathy, healing touch, and reiki, even if it’s only a handful of trials, the NCI gives such woo as reiki, therapeutic touch, and even homeopathy an undeserved patina of scientific respectability. Worse, it tends to encourage medical schools, which are hurting now as they chase after an ever-shrinking pool of NIH grant money, to chase after CAM dollars by doing such research, perhaps even joining the list of centers of quackademic medicine in my Academic Woo Aggregator.