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The Minimal Impact of a Big Hypertension Study
The surprising news made headlines in December 2002. Generic pills for high blood pressure, which had been in use since the 1950s and cost only pennies a day, worked better than newer drugs that were up to 20 times as expensive.
Dr. Paul K. Whelton, president of Loyola University Health System and the current chairman of the Allhat steering committee, said that Pfizer and other drug companies “took what was in their best interest and ran with those, and conveniently didn’t mention other things.”
Pfizer defends its actions. Dr. Michael Berelowitz, the head of Pfizer’s global medical organization, said that in the trial’s design, heart failure was merely one component of a broader measure of various cardiovascular problems. And in that broader measure, Dr. Berelowitz said, there was no difference between Norvasc and the diuretic. Also, he said, the label for Norvasc already contained a precaution about heart failure.
“Further action regarding the heart failure finding was therefore not considered necessary,” he said in a statement in response to questions.
Pfizer was not the only company promoting its drugs. The drug giant Novartis, for example, was spending heavily to market Diovan, a leader among a class of hypertension drugs called angiotensin receptor blockers, which were too new to have been included in Allhat. Diovan, which had more than $5 billion in sales last year, sells for $1.88 to $3.20 a pill on drugstore.com, compared with 8 to 31 cents for a diuretic.
No company, though, was spending money to promote generic diuretics. So the federal Heart, Lung and Blood Institute recruited Allhat investigators, provided them with training and sent them to proselytize fellow physicians. In all, 147 investigators gave nearly 1,700 talks and reached more than 18,000 doctors and other health care providers.
But it was a coffee-and-doughnuts operation compared with the sumptuous dinners that pharmaceutical companies used to market to doctors. Moreover, the steering committee’s outreach program did not get under way until about three years after the results were published.
Dr. Stafford of Stanford said the outreach seemed to have had a slight effect on increasing the use of diuretics.
The results of Pfizer’s efforts are easier to quantify. Norvasc sales continued to grow to $4.9 billion in 2006, falling only after the drug lost patent protection in the United States in 2007.
Tangles and Strife
Tensions about industry influence reached even the study’s own steering committee. Dr. Furberg, the chairman, bluntly accused some members of the committee of being agents of the industry.
One member, Dr. Richard H. Grimm Jr. of the University of Minnesota, had been receiving tens of thousands of dollars a year from Pfizer since at least 1997, according to reports that pharmaceutical companies file in that state.
In 2003, the year after the Allhat results were published, Dr. Grimm’s payments from Pfizer soared to more than $200,000 — an increase that The New York Times reported in 2007.
Dr. Grimm said in a recent interview that about half those fees in 2003 came from giving about 100 Pfizer-sponsored talks to doctors about Allhat. Dr. Grimm said he gave mainly the standard Allhat-sanctioned talk. But instead of saying diuretics were outright better than the other drugs, he said they were as good or better.
Meanwhile, Dr. Grimm had led an effort to remove Dr. Furberg from his position on the grounds that he had not been impartial.
“He had a vendetta against the calcium channel blockers,” Dr. Grimm said. Dr. Furberg had been publicly questioning the safety of those drugs based on some studies he did in the 1990s. The effort to oust Dr. Furberg failed in 2001. But in August 2004, Dr. Furberg resigned as chairman, contending that there had not been enough effort to disseminate the Allhat message.
Dr. Whelton, who took over as chairman, said that the study’s message was never compromised by industry ties on the steering committee.
“Curt is a wonderful guy who is a crusader,” said Dr. Whelton, who did not have industry ties and was not involved in the effort to unseat Dr. Furberg. “He has certainly rubbed a lot of people, even good friends, the wrong way.”
Changing Practice
Experts see several lessons to be learned from Allhat.
One is that “all trials have flaws” that leave the results open to interpretation, said Dr. Robert M. Califf, a cardiologist at Duke who served on the safety monitoring committee of Allhat.
Another is that providing doctors information is “necessary, but not sufficient” to urge them to change their practices, said Dr. Carolyn M. Clancy, director of the federal Agency for Healthcare Research and Quality, which itself conducts studies comparing different medical treatments.
And while insurers can influence practice through reimbursement policies, they did not seem to have pushed strongly for diuretics after Allhat, in part because some of the other drugs had become generic.
Even the cost-conscious medical system at the Department of Veterans Affairs did not require diuretics, because too many doctors would probably have requested exceptions, said Dr. William C. Cushman, chief of preventive medicine at the department’s medical center in Memphis.
Dr. Cushman, a member of the Allhat steering committee, said diuretic use in the system was still “much lower” than he thought it should be.
Dr. Clancy said that her agency was now mainly using insurance records to judge how treatments perform. While clinical trials are the gold standard, she said, they are costly and time-consuming.
And, she added, “You might be answering a question that by the time you are done, no longer feels quite as relevant.”