Dr. Susan Molchan responds to the second and third pieces of a series by New England Journal of Medicine national correspondent Dr. Lisa Rosenbaum: Understanding Bias –The Case for Careful Study, and Beyond Moral Outrage –Weighing the Trade-Offs of COI Regulation. Last week, she was one of the first critics of part one of the series.
In part two of her New England Journal of Medicine series on financial conflicts between physicians and industry, Dr. Rosenbaum questioned the evidence suggesting that these conflicts have negative effects on patient care. She went through considerable theoreticizing, invoking authoritative psychologists and even a lawyer. But for all her more than 9,000 words, I think she missed the big picture. That is that the pursuit of the next blockbuster drug, the test that can screen millions, has become the end for much medical research. Even then, effectiveness and safety have become secondary at best. Take stomach ulcers as an example. When Barry Marshall proved that a bacterium was responsible for most of them, this threatened the multi-billion dollar antacid market of cimetidine and raniditine. Drug companies were not interested in what he had to say about curing ulcers, their interests were in keeping them a chronic disease. As ulcers inevitably dropped out of the picture as people were treated with antibiotics, we saw the rise of GERD, formerly known as heartburn, the replacement chronic condition. Drug companies need doctors to get the word out on conditions like this, to write prescriptions. Also in the research literature, good luck if you’d like to know how non-drug measures like exercise compare to drugs for bone or heart or mental health.
Dr. Richard Horton, editor-in-chief of The Lancet, touches on the point of harms of conflicts in a commentary published last month in The Lancet. He cites financial conflicts as one of the major reasons that half of biomedical research simply can’t be trusted.
The Brits seems to be coming around to this a bit more quickly than those of us on this side of the pond. Dr. Richard Smith, who served almost 25 years as editor of the British Medical Journal, wrote a paper entitled, “Medical journals are an extension of the marketing arm of pharmaceutical companies.” He said it took him a while to see the many and often subtle ways that trial data can be manipulated. He has suggested that journals stop publishing clinical trial results, and that protocols and results be published in an online registry. Various authors could then discuss the validity of the results
Another missed point: Dr. Rosenbaum cites a 1998 study of calcium channel blockers for treatment of hypertension, noting that those supporting use largely had financial ties to industry, but subsequent randomized trials nevertheless supported their conclusion that the drugs were safe and effective for the treatment of hypertension. Yes, but other, less expensive drugs, which for some patients are often better clinically too, were also available. The large NIH-funded Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates this well.
Another example of harm from smarmy physician-industry relations, in my opinion, fits into the category of child abuse. The numbers of children treated for bipolar disorder increased 40-fold from 1994 to 2003. Antipsychotics are often used for treatment, and these can cause obesity, diabetes, heart disease, breast development in boys, and possibly shortened life expectancy. Sudden death has occurred in a few cases in very young children. The financial relationships between pharma and the psychiatrists popularizing the diagnosis, primarily from Harvard, with the ring leader being Joseph Biederman, weren’t disclosed until 2008 when Congressional investigations revealed he’d taken over a million dollars in undisclosed consulting fees from the manufacturers of antipsychotics. He had even told colleagues at Johnson & Johnson that studies he’d planned would yield results that would benefit its products.
As Dr. Allen Frances said, “Whenever there is an apparent explosion in the prevalence of any mental disorder, the safe bet is diagnostic fad—not real change in people.” The causes of this one? “ . . . a combustible combination of overly influential thought leaders, aggressive drug company marketing, desperate parents, and gullible doctors.” Frances is the former chair of the task force responsible for the 4th edition of psychiatry’s Diagnostic and Statistical Manual (DSM-IV).
Dr. Rosenbaum notes that many sources of bias exist among scientists, and that is indeed true, as for any human being. The best we can do is to try to be open and transparent about these, and while this may not always help the situation, the alternative is being secretive about it. It’s hard to see how that can be better.
Most people, including myself are not under the delusion that financial conflicts will ever go away. But I can’t help but reflect on Dr. David Sackett’s death last week. He was considered by many to be the father of evidence-based medicine. I guess that some might have called him a “pharmascold” (a term Dr. Rosenbaum dredged up in her series). Sackett and Andrew Oxman authored a literal prospectus on how clinical trial evidence can be warped to “accentuate the positive.” In the abstract, they note, “We’re combining the world’s oldest and second oldest professions, cashing in on our reputations, and distributing this confidential prospectus for our new company, HARLOT plc.” OK, it was in the Christmas issue, which has a tradition of including satirical pieces, but it is satire with a powerful message.
Addenda on May 26:
On his BMJ journal review blog, Dr. Richard Lehman wrote: “The NEJM has the highest reputation of any medical journal, so it’s impossible not to feel dismay when it lets its standards slip towards the near-nonsensical. When the first part of Lisa Rosenbaum’s three-part series on conflicts of interest appeared, I wondered if it might be some kind of elaborate joke: but sadly it seems not. I hate to see it when a clearly talented young writer is encouraged to write below standard, and at great length for no obvious reason. This final article, “Beyond Moral Outrage,” is an attempt to describe people who worry about conflicts of interest as beyond rationality. …Is Lisa actually suggesting that the pharmaceutical industry just flushes away used American flags and has never harmed anyone or concealed harm? But there I go—I am responding to wholly unserious arguments seriously, which I suppose must be the purpose of this exercise. I think theNEJM has shot itself in the foot. And also exposed some awful editorial decisions. Please, if you are going to publish someone attempting to persuade us against bias, don’t let through a sentence like “Being a pharmascold conferred the do-gooder sheen many of us coveted.” The only unbiased words in it are “being,” “a,” “the,” and “of.” ”
And Roy Poses, MD, wrote on his Health Care Renewal blog, “Say It Ain’t So: Logical Fallacies in Defense of Conflicts of Interest … in the New England Journal of Medicine?”
Addenda on May 29: