BMJ  2003;327:E107-E109 (4 October), doi:10.1136/bmjusa.02050002 (published 23 August 2002)

BMJ USA: Editorial

Brains, claims, and the pharmaceutical industry

Conflict of interest in perspective

This article originally appeared in BMJ USA

In this issue the journalist Jeanne Lenzer draws attention to the uneasy alliance between industry, science, and policy (BMJ USA p 283). She explores the relationship between Genentech, the manufacturer of alteplase (tPA), and the decision of the American Heart Association (AHA) to give that drug a class I recommendation as thrombolytic therapy for stroke. She accuses the AHA and Genentech of overstating the trial evidence for tPA, creating the "stroke attack" ad campaign to promote the drug, denying the existence of a guideline panel member because he disagreed with its recommendation, barring access to trial data, and delaying release of information from another trial.

Whether these assertions are true is not the focus of this editorial. Saver and colleagues (BMJ USA p 291) suggest that her characterization of the evidence may not be entirely accurate. Since the publication of the National Institutes of Neurologic Disease and Stroke trial, numerous other studies support the efficacy of this therapy.^{1 2} Moreover, the AHA recommendations are consistent with those from the National Stroke Association, American Academy of Neurology, Brain Attack Coalition, and Stroke Belt Consortium.^{3 4} Lenzer warns about the high mortality reported in a community-based study of tPA, but protocol violations in that study occurred in half the patients, compared with 15% in other studies. Most stroke experts believe that tPA is an important treatment for acute ischemic stroke, but they also agree that it should only be used in clinical settings with the expertise, training, protocols, and support systems to use the drug safely.

Lenzer raises a familiar concern about the influence of industry money on clinical research. There are well known instances in which pharmaceutical companies have impeded investigators from releasing data with unfavorable results,⁵ fueling speculation that industry-sponsored research as a whole cannot be trusted to present all the facts. But is there evidence for this generalization? Constraints on federal grant money mean that many important studies and investigators must be funded by industry. An estimated $1.5b from industry flows annually into academic institutions. It would be wrong to dismiss this work without evidence of a flaw in its methodologies. While studies indicate that pharmaceutical-sponsored studies are significantly less likely than publicly funded studies to report negative findings, ^6-8 it is unclear that the methodologic quality of industry-funded studies is inferior.⁷ The pattern may simply reflect the sponsorship of investigations with a greater promise of return⁹ and the reluctance of pharmaceutical companies to publish negative results. The resulting skewing of evidence is troubling, but no less so than the publication bias of journal editors, who are also less likely to publish negative trials.¹⁰

Studies suggest that the composition of practice guideline panels influences recommendations. ^11-13 It is therefore reasonable to ask what influence arises when panel members have financial ties with industry. Lenzer reports that Genentech contributed $11m to the AHA, including $2.5m for its national headquarters building, and that six of the eight panelists involved in the tPA guideline had ties to the manufacturer (eg, lecture fees, grant support). A recent study reported that 87% of guideline panel members have some association with the pharmaceutical industry.¹⁴ Only 7% of these authors felt that the relationships influenced their recommendations, but empirical evidence suggests that a bias is possible. Stelfox et al showed that authors who supported the use of calcium-channel antagonists were more likely than neutral or critical authors to have financial relationships with a drug manufacturer.¹⁵

Guideline developers face competing tradeoffs in dealing with this problem. One school of thought is for guideline panels to be composed of generalists who are skilled in the critical appraisal of evidence but who are not experts on the topics under consideration. Their distance from the topic gives them a fresh perspective and the advantages of not having a vested interest in the outcome of the recommendations, a preconceived view of the evidence, or ties to relevant industry.

Although some groups, such as the US Preventive Services Task Force, have adopted this approach, many guideline bodies are uncomfortable with this model because of concerns that the panelists will not understand the topic and that the guideline will lack credibility if the panel members are not recognized experts. It is therefore customary for guideline panels to include leading researchers on the topic, but this often means that the participants will have received a grant or some other industry support at some time in their careers. Making these individuals ineligible for guideline panels often eliminates the leaders in the field.

The crucial issue is not whether a panel member has received a lecture fee or a grant but whether that individual is capable of looking objectively at the evidence and recommending what is best for patients. Panel members can fail miserably at this task without any ties to industry. Staunch proponents or critics with fixed viewpoints can have intellectual conflicts of interest that make them incapable of viewing the evidence fairly. It is proper that panel members disclose the nature of their financial and intellectual conflicts of interest to other participants at the start of the guideline process, recuse themselves if they have substantial conflicts, and disclose conflicts to readers.¹⁴ Readers can make their own judgment. However, those who have served on guideline panels know that the content and quality of the final publication depends on multiple variables, including the actual data, analytic methods, and the past experiences and personalities of the participants.

Northwestern University Feinberg School of Medicine, Chicago (m-alberts{at}northwestern.edu)

Northwestern University Feinberg School of Medicine, Chicago, Chicago Veterans Administration Healthcare System and the Veterans Administration Midwest Center for Health Services Research and Policy Studies (cbe282{at}merle.it.northwestern.edu)

BMJ USA and professor of family practice and preventive and community medicine, Virginia Commonwealth University, Fairfax, Virginia (swoolf{at}vcu.edu)

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Education and debate BMJ USA p 283

  MJA has received grant support, speaker fees, and honoraria from AHA, Genentech, and other pharmaceutical companies. CLB has no ties to Genentech but has received funding from manufacturers of antiplatelet drugs for stroke prevention. SHW has no financial ties to Genentech or other pharmaceutical companies.

Alteplase for stroke (Lenzer), p. 283, http://bmj.com/cgi/content/full/324/7339/723#art

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