Saturday, April 9, 2011

Conflict of interest 2: Clinical practice guidelines and Deans

My last blog post was about conflict of interest (COI) in medicine; there has been some recent literature on the subject, so I am providing a second posting on the topic.

In “Conflicts of interest in cardiovascular clinical practice guidelines[1], in the March 28, 2011 issue of Archives of Internal Medicine, Mendelson and colleagues reviewed the 17 most recent guidelines regarding the diagnosis and management of heart disease promulgated by the American College of Cardiology (ACC) and the American Heart Association (AHA), the most important issuers of such guidelines. These clinical practice guidelines (CPGs) are important, as not only do physicians use them as authoritative sources to inform their patient care, but increasingly payers – and courts -- are looking at whether they were followed to determine payment and bonuses, or culpability in malpractice cases. While thorough review of the published (and unpublished) evidence is required (indeed is a sine qua non) in the issuance of guidelines, these panels of experts are convened to allow their collective experience and knowledge fill the gaps where there is no evidence. The authors point to the 2009 Institute of Medicine (IOM, a group of distinguished physicians and medical scientists convened by the National Academies, which are private citizens gathered with federal support to advise on science and technology) report from its Committee on conflict of interest in medical research, education and practice, which states that there is insufficient study of COIs in guideline reporting, as the fact that both ACC and AHA have “recently placed restrictions on official participation in educational events and guidelines production”.

Using the concept of an “episode” to mean that 1 person participated 1 time in production of 1 guideline, there were a total of 651 episodes by 498 people in the production of the 17 guidelines. Overall, 56% of individuals (277) had some COI, and (coincidentally) a COI was present in 56% (365) of the total episodes, with a range among the 17 guidelines of 13% (2 of 15) to 87% (13 of 15). Interestingly, actual members of the guideline committees, as opposed to those who just reviewed the guidelines (“peer reviewers”) were more likely (63%, a level reaching statistical significance for those who care, p=.006) to have COIs, as were the chairs of the committees (or first authors) compared to committee members, 81% (p=.03). Only 6 of the 17 guideline committees reported whether the COIs were “modest” or “significant”; the authors found that of those 54% were modest and 29% significant. Perhaps more important, according to the authors, was that it was only a few companies, presumably those with the greatest economic stake in the outcomes, who were involved in most of the COIs. They also note that this is “a particular cause for concern given the fact that many of the newest ACC/AHA guideline recommendations are based more on expert opinion than on clinical trial data”.

Dr. Steven Nissen, commenting on the article in the same issue (“Can we trust cardiovascular practice guidelines?”[2]), calls the “depth and breadth of industry relationships reported in this article…extraordinary,” in that they go beyond scientific collaboration to include significant stock ownership and serving as promotional speakers, and states that “no conceivable logic can defend [this] practice.” He continues “Such relationships are so antithetical to the academic mission that many medical schools have now forbid such relationships for their faculty. To allow such individuals to write CPGs defies logic.” I imagine his use of the word “extraordinary” is in the sense of “amazing”; since this is the first such study, we do not know if such COIs are indeed “extraordinary” in the sense of “well out of the ordinary”, or if they are, indeed, quite typical. Indeed, Mendelson et al cite a 2002 study by Choudry et al[3] in which the found that of the 52% of the authors of 100 CPGs for a variety of adult diseases who responded to their survey, 87% had “some type of relationship with the pharmaceutical industry” (and we would not imagine that the 48% who didn’t respond had fewer!) Dr. Nissen, who is from the Cleveland Clinic, reveals his own potential COIs, including research support from a number of companies and honoraria for speaking which he has turned directly over to charity. As covered in the New York Times (Duff Wilson, “Study finds conflict among panels’ doctors”, March 28, 2011), Dr. Nissen calls for “banning most of these conflicts rather than just disclosing them”.

But sometimes COIs are not even disclosed. The same issues of Archives of Internal Medicine contains a “research letter” titled “Failure by deans of academic medical centers to disclose outside income[4]. The authors, Freshwater and Freshwater, looked at holdings of deans of allopathic and osteopathic medical schools on the Morningstar directory of US corporate directors and executives, and EDGAR, the Securities and Exchange Commission database. They found that while there were only a few deans who served as directors of public companies involved in health care (9 of 161, with one serving as a director of 2 companies and one of 4), this information was not always disclosed on the schools’ websites, nor was the compensation received. This compensation for each directorship ranged from $11,250 to $386,439 with a mean of $217,454, with one dean who served on multiple companies receiving $640,038. “One dean’s official Web page disclosed the 2 directorships, but it did not disclose the compensation. Two medical schools’ Web sites disclosed 3 directorships, with one dean holding 1 and the other 2 directorships; however the Web sites underreported the deans’ compensation by 39%, 56%, and 80% compared with the compensation calculated from the companies’ EDGAR forms.” These deans are the same people who are expected to enforce the rules against COIs that Nissen refers to above. In a commentary[5], Lo (who was the chair of the 2009 IOM committee) et al, say that disclosure is not enough, and that “Some relationships need to be managed or even prohibited”. They do not go so far as to suggest that all should be banned, although I would note that 152 of 161 deans seem to do OK without serving as corporate directors.

So should all such conflicts, whether deans serving on boards of directors, guideline authors having financial relationships such as major stock holdings or speakers’ fees, or receiving grants from corporations, be disclosed or prohibited? I think that there is clear consensus that disclosure is the de minimis requirement. As I have noted before, without disclosure there is no way for the consumer of information in a research study to decide if their might be bias; this is at least as important for are those writing CPGs or presiding over our academic medical centers. But, as Nissen states explicitly and Lo hints at, disclosure is not sufficient. To extend the metaphor of the judge referred to by Howard Brody in his article Professional Medical Organizations and Commercial Conflicts of Interest: Ethical Issues and cited by me in The AAFP, Coca-Cola, and Ethics: Serving the public interest? August 20, 2010, knowing that a judge in a case you are party to owns large amounts of stock in the company you are suing is not sufficient to make you feel alright about her presiding in the case.

Mendelson et al note that “It has also been argued that relationships with industry may also bring a breadth of perspective and experience, especially if individuals have relationships with multiple different companies. Theoretically, these individuals may be less conflicted than those with fewer industry affiliations…”. Right. Taking graft from many sources makes you less beholden to any one of them. Unfortunately, if you buy this argument, then their study should disappoint you, as only a much smaller percentage of the CPG authors had more than one COI.

Come on. Prominent scholars take money from industry for the same reason that others do. They like the money. Perhaps they are eminent enough that their heads are so swelled that they can believe both that they are being paid solely for their wisdom, and not for any bias they might bring to the deliberations of academic groups like those writing CPGs or in the administration of medical schools, and that, in any case, they are so distinguished that there is no way they would demonstrate such bias. If so, they are deluded. No one else believes it, most especially the companies giving them money. These COIs need to be completely banned if we are to be able to trust their academic integrity and intellectual honesty.

[1] Mendelson TB, et al, “Conflicts of interest in cardiovascular clinical practice guidelines”, Arch Int Med 28Mar2011;171(6):577-85. (only abstract available on line without subscription).

[2] Nissen SE, “Can we trust cardiovascular practice guidelines?” Arch Int Med 28Mar2011;171(6):584-5.

[3] Choudhry NK et al, “Relationships between authors of clinical practice guidelines and the pharmaceutical industry”, JAMA 2002;287(5):612-17.

[4] Freshwater DM and Freshwater MF, “Failure by deans of academic medical centers to disclose outside income”, Arch Int Med 28Mar2011;1717(6):586-7.

[5] Lo B, Kelch RP, Grady D, “Illuminating physicians’ financial relationship with industry”, Arch Int Med 28Mar2011;1717(6): 587-8.

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