Healthy Skepticism Library item: 1072

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

MacPherson K.
Pharmacia denounced for halting drug study : Research questioned its medicine's value
Star-Ledger Staff 2003 Apr 23

Full text:

A major drug company that for “commercial reasons” pulled the plug early on a long-running clinical trial involving high blood pressure came under extraordinary criticism yesterday from the medical community.

In a lengthy editorial in the most recent edition of Journal of the American Medical Association, the editors condemned the drug giant, the Pfizer-owned, Peapack- based Pharmacia, as unethical for aborting the trial comparing its hypertension drug with water pills.

Journal editors also took the unusual move of publishing the incomplete results drawn from the study, which indicated that the drug verapamil, known as a calcium channel blocker, was no better than diuretics in preventing heart attacks and stroke when the study was halted.

“Medical research, even if it is conducted by the pharmaceutical industry, is not solely a commercial enterprise designed to maximize personal gain or company profits,” the editorial said. “The responsible conduct of medical research involves a social duty and a moral responsibility that transcends quarterly business plans or the changing of chief executive officers.”

The federal government often pays for the huge costs associated with running clinical trials to test the safety and effectiveness of medicines. Increasingly, private firms are underwriting the cost of such trials as government budgets shrink and the quest for new drugs expands, creating new ethical quandaries.

The unpaid volunteers, who wanted to learn what was the best treatment for their hypertension as well as to advance the cause of science, were treated poorly, according to Bruce Psaty, a physician-researcher at the University of Washington in Seattle who co-authored the scathing editorial. “They were not only deprived of personal benefit from the completed trial, but also the social benefit of genuine scientific contributions from an adequately powered study,” Psaty said.

Pharmacia, which was acquired last week by Pfizer in New York, also broke its pact with researchers and society through its actions, he said.

Pfizer spokesperson Vanessa McGowan said the company had limited information on the study and could not comment on it.

Fred Hassan, the former CEO of Pharmacia who became Schering- Plough’s CEO earlier this week, said he not yet seen the critical JAMA editorial and the research report. Speaking at a session with reporters yesterday in Woodbridge after Schering-Plough’s annual meeting, he said the trial was stopped because it was losing statistical value. But he believes science was served by the effort: “I felt we had a much deeper knowledge” of the drug as a result of the study, he said.

Physicians managing the study said there were no data problems with the trial.

The study began in 1996 and was stopped in December 2000, two years shy of its completion. Henry Black, the physician from Rush Medical College in Chicago who supervised the study, said he was told by Pharmacia executives that business considerations forced the trial’s closure.

“That’s all we were told — commercial reasons,” he said.

By that time, he noted, the company had spent $50 million on the study. There is no evidence to suggest that the company knew the results of the study at the time the trial was halted, he said.

Verapamil, known commercially as Covera, was originally made by G.D. Searle, which later became part of Pharmacia.

Patients diagnosed as having hypertension are often given a calcium channel blocker like verapamil to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. With its 16,000 patients, the study, known as The Controlled Onset Verapamil Investigation of Cardiovascular End Points Trial or CONVINCE, was designed to put these issues to rest.

According to international guidelines set out for the conduct of experiments involving humans, trials should only be halted for ethical reasons or if the study is not of adequate “power,” meaning that statistically significant conclusions cannot be drawn because of low numbers of patients enrolled or the lack of significant medical events.

Ethical rationales for halting a trial would include knowingly giving trial participants a drug that would harm them or continuing them on a course of treatment that is known to be inferior either because of revelations made during the trial or from outside research reports.

Bioethicist Arthur Caplan agreed that the company’s conduct in this case was unethical and harmful to society at large. “The subjects in this case were flat-out betrayed,” said Caplan, director of the Center for Bioethics at the University of Pennyslvania. “In the long run, if more of this happens you’re going to discourage people from joining studies.”

Last month, physicians managing another large study, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), concluded that the calcium channel blocker amlodipine was not superior to the diuretic chlorthalidone in reducing the rate of coronary heart disease or stroke and was associated with a higher rate of heart failure.

The news sent sales of calcium channel blockers dipping. Diuretics, which help the body get rid of water and sodium, cost about 10 cents a day. Alternatives like verapamil cost about 10 times as much, but millions of dollars in pharmaceutical marketing have, until recently, helped keep them dominant.

Psaty, the editorial author, hopes to stop what he sees as a growing trend.

Over the past several years, several companies have stopped clinical trials for commercial reasons, including Bristol-Myers Squibb, Hoechst Marion Roussel, Sandoz India Ltd and Novartis, according to Psaty. “This isn’t right,” he said.

If patients switch to water pills, the editorial concluded, it would: “one prescription change at a time, whisper an evidence-based reminder to the pharmaceutical industry about the social value and the public health importance of large long-term trials that are successfully brought to completion,” the JAMA editorial concluded.

Staff writer Susan Todd contributed to this article.