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After the ALLHAT trial results announcement in December 2002, the 7th Joint National Committee on hypertension is expected to convene. Important standard of care advances have been made since the last committee report in 1997, and we are looking forward to updated treatment recommendations. Such a forum might also take the opportunity to promulgate a mandate on how the important drug trials that influence practice standards are conducted.

At the 17th annual scientific meeting of the American Society of Hypertension on May 17, 2002, Neil Kurtzman1 delivered a critique of recent drug trials with a clarion call for new rules of study design adequacy. Certainly a plethora of recent experiences have demonstrated the ethical dilemmas and missed opportunities associated with the tilt of pharmaceutical sponsorship toward a marketing strategy in trial design.

Kurtzman pointed out four potential practicechanging studies randomizing proteinuric diabetics for 2–4 years to trial arms utilizing medications other than an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a regimen including an ARB. These trials appeared to demonstrate benefit in type 2 diabetes in the regimen based on an ARB compared to one that did not include an ACE or an ARB.2–5 The legitimizing rationale that the protection against renal decline of ACE inhibition in diabetic nephropathy had only been proved for type 1 diabetes runs counter to the National Kidney Foundation and American Diabetic Association recommendation inclusive of all diabetics. In fact, such an argument lends credence to the assertion that “medical ethics” may have been used as an excuse to avoid an ethical course of action.

Business prerogatives probably led to the premature closure of one clinical trial whose conclusion fell just short of statistical significance,6 the misleading truncating of data from another trial,7 and difficulties publishing results from negative studies.8 Recently, a national survey9 concluded that when partnered with industry sponsors, medical schools routinely fail to adhere to guidelines for investigator participation. The “powerlessness” of academic participants expressed by interviewees in this survey coincides with increasing pharmaceutical industry utilization of competing nonacademic contract research organizations which are cheaper and more compliant.10

In his provocative dissertation, Kurtzman1 asserted two core principles, and offered a potential solution. Referring to the recent ARB trials, he stated that “evidence-based medicine cannot be used as a shield to evade the standard of care.” In a similar vein, “the legitimate need to develop profitable new compounds needs to be balanced against the obligation to compare them to established and effective, but cheaper agents.” Trials conceived in this fashion would more likely influence the practice styles of physicians who have become increasingly skeptical of drug companysupported trial design.

A panel representing pharmaceutical companies, academic institutions, and drug regulators was proposed to write new rules of study design adequacy. The level of acquiescence could then be assessed by journal editors who receive trial data for publication. Judging by the attention at the national meetings and in the literature, there is grass roots support for fundamental change. The expected convening of the 7th Joint National Committee on Hypertension would be a powerful forum to advance a much-needed mandate for reform in the study design of hypertension trials.

References

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  2. References
  • 1
    Kurtzman NA. Conflicts of interest and ethical issues in the design and reporting of clincial issues. Seventeenth Annual Scientific Meeting of the American Society of Hypertension. New York , NY ; May 17, 2001.
  • 2
    Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345: 861869.
  • 3
    Lewis EJ, Hunsicker LG, Clarde WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851860.
  • 4
    Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870878.
  • 5
    Lindholm LH, Ibsen H, Dahor B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:10041010.
  • 6
    Sica DA. Premature termination of clinical trials—lessons learned. J Clin Hypertens. 2002;4:219225.
  • 7
    Hrachovec JB. Reporting of 6-month vs. 12-month data in a clinical trial of celecoxib [letter]. JAMA. 2001;286:2398.
  • 8
    Moser M. Comments on medical research and the publication of scientific papers. J Clin Hypertens. 2001;3:277278.
  • 9
    Schulman KA, Seils DM, Timbie JW, et al. A national survey of provisions in clinical-trial agreements between medical schools and industry sponsors. N Engl J Med. 2002; 347:13351341.
  • 10
    Davidoff FD, de Angelis CD, Drazen JM, et al. Sponsorship, authorship, and accountability [editorial]. N Engl J Med. 2001;345:825826.