A Reminder…

…of why we keep harping on this. A couple of days ago The Scientist reported that the “economic stimulus package” may include a windfall for the NIH:

Senate OKs big NIH bump

Posted by Bob Grant

[Entry posted at 4th February 2009 04:12 PM GMT]

The US Senate, which is furiously debating the details of the economic stimulus package making its way through Congress, passed an amendment yesterday (Feb. 3) to add $6.5 billion in National Institutes of Health funding on top of the $3.5 billion already allotted to the agency in the bill…

Exactly how an NIH funding increase will be spent remains to be determined.

You can bet that if this happens, the NCCAM will be licking its chops for some of that lettuce. Let’s continue to explore why it shouldn’t get any…

NCCAM Insiders Join the Fib Fest

In the last post, we saw abundant evidence that the late NCCAM Director Stephen Straus and Deputy Director Margaret Chesney had stretched the truth in objecting to a critical 2006 Science article by Drs. Donald Marcus and Arthur Grollman. In that article, Marcus and Grollman had mentioned a lost opportunity to submit the Center to responsible scrutiny:

In 2002, the Institute of Medicine (IOM) was commissioned by NIH and the Agency for Healthcare Research and Quality to “explore scientific, policy and practice questions that arise from the significant and increasing use of CAM [complementary and alternative medicine] therapies by the American public.” One of three tasks assigned to the IOM Committee was to “Identify major scientific, policy and practice issues related to CAM research.” Seven of the 17 committee members were CAM practitioners or directed CAM and integrative medicine centers…Unfortunately, the IOM committee did not evaluate the quality of NCCAM-funded trials or the value of spending hundreds of millions of dollars on CAM research.

Those comments apparently got under the skin of academics who feed at the NCCAM trough, because a couple of months later a letter appeared in Science, authored by 7 of them: Susan Folkman, Brian Berman, Stuart Bondurant, David Eisenberg, Aviad Haramati, Mary Jo Kreitzer, and Fredi Kronenberg (Bondurant, Berman, Eisenberg, and Folkman had been members of the IOM Committee). They wrote:

Marcus and Grollman miss the mark…The processes through which proposals are submitted, reviewed, funded, and managed are all consistent with standard NIH practice.

Marcus and Grollman’s comment that the NCCAM research agenda is shaped more by politics than by science is gratuitous, as is their suggestion that the Institute of Medicine (IOM) report, Complementary and Alternative Medicine in the United States, was flawed because some of the members of the panel were NCCAM grantees.

No: Marcus and Grollman were exactly correct, as abundantly shown by the history of the NCCAM, the memberships of its advisory councils, the projects that it has funded, including the chelation trial and the Gonzalez trial, and much more that has been discussed or referenced on this site. To call the pro-“CAM” IOM report “flawed” is not gratuitous. It is an understatement.

The “CAM” 7 asserted the fundamental scientific and ethical fallacy of human trials of implausible claims:

Because CAM is already in the public domain, used by millions of people at a cost of billions of dollars each year and with health effects that largely have not yet been scientifically evaluated, it is appropriate that a significant focus be on clinical research.

In this context, “clinical research” means human trials. I have previously explained why the “popularity” rationale is wrong: here, under The Fallacy of Popularity, and here, under Human Studies Ethics and CAM.

The 7 offered a curious justification for why negative trials of implausible claims, such as those discussed in Part II of this series, shouldn’t deter the NCCAM from pursuing more studies of the same claims:

As is true in clinical trials with new conventional drugs, we should expect that many trials of CAM treatments will not show definitive efficacy, and as with most research on understudied agents, multiple studies are often needed to develop a research base adequate for mature judgment concerning efficacy or the lack thereof. We need to be patient and use our best tool, that is, science, to understand and evaluate these widely used health practices. We believe that NCCAM has established a standard not for advocacy, but rather for rigorous objectivity.

Readers not familiar with the science and ethics of human trials, or with the misleading language of “CAM” advocates, might not recognize the deceptive content of that statement. First, drug trials, unlike their “CAM” counterparts, begin with plausible hypotheses. That is because good science demands it, but also, as explained by the Declaration of Helsinki, because

Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.

Next, it is true that many clinical trials of new “conventional” drugs don’t show “definitive efficacy”; in almost all such cases, however, those drugs are quickly discarded. It is only when early trials do suggest efficacy that “multiple studies are often needed” or even justified.

In their attempt to blur those distinctions, the “CAM” 7 inadvertently exposed NCCAM processes as not being “consistent with standard NIH practice.” According to the NIH Grant Policy Statement,

To be eligible for NIH funding, all clinical research involving INDs [Investigational New Drugs], drugs approved for a different indication, or experimental combinations of drugs must meet FDA’s IND regulations, FDA’s human subjects’ protection requirements, and HHS’s human subjects’ requirements.

Here is language from the FDA’s regulations entitled “INVESTIGATIONAL NEW DRUG APPLICATION“:

Sec. 312.21 Phases of an investigation.

(c) Phase 3. Phase 3 studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase 3 studies usually include from several hundred to several thousand subjects. [Emphasis added]

That regulation is not merely a definition. There are compelling scientific, ethical, and public policy reasons for not pursuing wild gooses of the sort that almost all NCCAM-sponsored trials chase. It’s rare enough for people with pretty good ideas about how nature works to generate fruitful hypotheses, as discussed here under Most Hypotheses are Wrong… . Human trials require a much higher prior probability of the hypothesis being correct than do laboratory trials: it is not ethically acceptable to exploit human subjects to test what Emanuel et al termed “trifling hypotheses,” nor is it ethical to allocate scarce research funds to such notions.

The Trial to Assess Chelation Therapy (TACT), named by Drs. Marcus and Grollman as deserving of comment and discussed at some length in the last post, is a Phase III trial of a combination of drugs for which there are not only no laboratory or animal studies suggesting effectiveness, but for which there is preliminary laboratory and substantial human evidence suggesting ineffectiveness and danger: see here, under RCTs Revisited and The Risks for Na2EDTA Chelation and Supplements. This is hardly “consistent with standard NIH practice.” The TACT, like the Gonzalez trial and the NCCAM itself, was shaped by politics and rationalized by misrepresentations of science, as documented here, here, here, and here.

The “CAM” 7: Fools or Frauds?

We must wonder how the “CAM” 7 could not have known at least some of these facts. Are the 7, purportedly clinical researchers all, ignorant of the Declaration of Helsinki (the consensus world opinion on human studies ethics), adherence to which almost every major medical journal expects as a condition of publishing research findings? Is it possible that Fredi Kronenberg, who heads Columbia University’s CAM” program, was unaware of the origins or the fate of the Gonzalez trial, as we wondered last week about Straus himself? It was Kronenberg who, according to Victor Herbert, had first hired Gonzalez to give lectures at Columbia.

Brian Berman was a member of the NCCAM Advisory Council that, in 2000, passed the “concept” of a trial of “EDTA Chelation Therapy for Coronary Artery Disease,” by a vote of 11 in favor, none opposed, and 2 abstentions. So was Ted Kaptchuk, David Eisenberg’s Right-Hand Man at Harvard Medical School. Were Berman, Kaptchuk, and the rest of the Council aware of the history, science, and politics of chelation advocacy? If so, how could they not have opposed a trial? If not, why were they chosen to pass judgment on such a trial (to be funded by taxpayers), and why did they not recuse themselves? Either way, the “CAM”7’s above-quoted charges about “missing the mark” and “gratuitous” comments are categorically false, and they know it.

Brian “Boondoggle” Berman

Dr. Berman is the Director of the University of Maryland Center for Integrative Medicine. He is the first author of the NCCAM-funded “landmark study” of acupuncture for osteoarthritis of the knee, discussed at some length last week. Recall that within 3 years of the report’s publication in 2004, its claimed findings, equivocal to begin with, had been disconfirmed: first by another controlled trial twice the size of Berman’s, and shortly thereafter by a meta-analysis co-authored by…Berman!

From his bio on the U. Maryland website, we learn that “Dr. Berman is one of the most highly funded National Institutes of Health (NIH) researchers in the area of integrative and complementary medicine, receiving over $30 million over the past 14 years.” We also learn that he still considers his “landmark study [to have shown] acupuncture to be a safe and effective therapy for osteoarthritis of the knee.” He told the same thing to the New York Times only last fall. Has he repudiated his recent meta-analysis?

Berman reports that he has been a major player at the OAM and the NCCAM from their beginnings, and was a member of the IOM panel on “CAM.” He was the “first chair of the Consortium of Academic Health Centers for Integrative Medicine” and received “the prestigious Bravewell Leadership Award.” It is ironic that Berman worked for years with R. Barker Bausell, a statistician who eventually concluded, even without considering prior probability, that “CAM” research is Snake Oil Science and that “CAM” treatments are “nothing more than cleverly packaged placebos.” After Bausell’s book was published, according to the Baltimore Sun (quoted here),

Dr. Brian Berman…said he skimmed the book, calling its arguments “misleading about what the state of research is.” He called any conclusions about the value of CAM premature.

Let’s see: in 2007, Dr. Berman co-authored a meta-analysis that demonstrated acupuncture to be ineffective for osteoarthritis of the knee; in 2008 he declared that his 2004 “landmark study”—one of nine included in his meta-analysis—“establishes that acupuncture is an effective complement to conventional arthritis treatment.” Whose arguments are misleading about the state of “CAM” research?

If, moreover, “any conclusions about the value of CAM [are] premature,” there can’t be any justification for spending public moneys to create “integrative medicine” centers for the purpose of

  • Integrating evidence-based complementary therapies into clinical care to help people achieve and maintain optimal health and well-being.

Can there? Dr. Berman’s most recent new hire, by the way, is Margaret Chesney, the NCCAM Deputy Director who had helped Director Stephen Straus stretch the truth in responding to Drs. Marcus and Grollman.

Incest is Best

The remainder of the paragraph in which the “CAM” 7 accused Drs. Marcus and Grollman of “gratuitous” comments is this:

In fact, like NIH, the IOM has procedures for recognizing and managing conflicts of interest. Those of us who participated in it were very mindful of any potential conflicts of interest and guarded against them in our deliberations. Further, the report was carefully reviewed by external, independent reviewers before publication.

Only in a world of shruggies could such a blatant and insulting disregard for common sense—the sense, for example, to know a “made guy” when we see one—not trigger a scandal. Does anyone really buy that this tiny clique of academic fools (or frauds) is not wallowing together in one big vat of oily schmooze, oozing with conflicts of interest?

Posted by Kimball Atwood