Chicago, IL -Although they should be congratulated for testing their antihypertensive drugs in trials, pharmaceutical companies cannot and should not be relied on to answer public-health questions, a new commentary asserts [1]. The authors, no strangers to tackling provocative issues, call into question whether recent large comparative trials such as LIFE, INVEST, VALUE, and ASCOT can be used as the basis for public-health decisions.

"Industry sponsors have no obligation to serve the health of the public," the authors, Dr Bruce M Psaty (University of Washington, Seattle), Dr Noel S Weiss (University of Washington) and Dr Curt D Furberg (Wake Forest University School of Medicine, Winston-Salem, NC), write. "They have a fiduciary duty to their shareholders and a right, circumscribed only by the ethics of human studies, to fund the studies of their choice. As a result, the design of large, long-term comparative studies may, in some instances, function as commercial speech rather than compelling science."

The commentary is published in the April 12, 2006 issue of the Journal of the American Medical Association.

In an interview with heartwire, Psaty said, "Sponsors ought to be congratulated for testing their products in trials; that's absolutely essential." However, he said, "sponsors can compete in a number of ways; they can compete in marketing, and they can compete in clinical trials."

The commentary points to four trials in particular, the LIFE [2] trial, which compared the angiotensin receptor blocker (ARB) losartan vs a beta blocker, atenolol; the VALUE [3] trial, which pitted amlodipine, a calcium antagonist, vs another ARB, valsartan; INVEST [4], comparing the calcium antagonist verapamil with atenolol; and ASCOT [5], which compared amlodipine- and atenolol-based therapy in patients with hypertension, as examples of this phenomenon.

"Trial results affect guidelines and practice, and the trial designs affect the questions that get asked and answered," Psaty said. "The choices of comparison treatment and composite end points, I think, from the point of view of public health, would not have been the same as the choices that were made in some of these industry-sponsored studies."

The authors contend that the choice of atenolol as a comparator in three of the four studies, for example, "does not address key public-health questions. The fundamental principle of active-control trials is the scientific obligation to use the best available treatment for the control group," Psaty said, which, in the authors' view, is low-dose diuretics.

They base their assertion on results of the ALLHAT trial [6], which compared amlodipine and the ACE inhibitor lisinopril against the diuretic chlorthalidone, on which Furberg was chair of the steering committee. The primary end point of the trial was not different for the three treatments, but chlorthalidone was superior to the other drugs on some secondary outcomes.

"The number of people who are on a single agent using, say, atenolol is very small—probably in single digits," Psaty said. "So many of these trials picked that as the comparator, and it just doesn't answer a key question. They don't contribute a lot to public health."

The authors point to a document published last year by the National Heart, Lung, and Blood Institute Working Group on Future Directions in Hypertension Treatment Trials [7]. One of the proposals there is a trial that would begin with all patients on a low-dose diuretic and then compare which agents would be best as second-line therapy among those not controlled on diuretics alone.

"So what questions do you want answered, and what are the important public-health questions?" Psaty concluded. "I think the [National Institutes of Health] NIH has done a terrific job of setting up trials that ask those questions."

Asked for comment on the paper, Dr Stevo Julius (University of Michigan, Ann Arbor), principal investigator of the VALUE trial, declined to engage in the debate. "The position of Drs Psaty and Furberg is well known and does not call for additional comment," he told heartwire.

Other principal investigators of these studies approached for comment had not responded at this writing.