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CHS Research News
Vol 18, Issue 1, Winter 2006

Feature Article

Dr. Bruce Psaty:
Long-time collaborator, known for his integrity and public service, officially joins the CHS faculty

By Katie Saunders

Major media outlets, attorneys, the Institute of Medicine, and even Congress are interested in Group Health Center for Health Studies (CHS) Senior Investigator Bruce Psaty’s opinions on drug safety. One reason is his impressive 20-year record as a researcher on the safety and efficacy of drugs for coronary disease and stroke. But it’s Psaty’s lack of financial ties to pharmaceutical companies that sometimes sets him apart. As MacColl Institute Director and early Psaty mentor Ed Wagner says, "Bruce’s effectiveness as an advocate begins and ends with the high quality of his science and his unshakeable integrity."

Whether he’s speaking out on the risks of Vioxx, a need for change at the FDA, or his latest findings in drug-gene interactions, the CHS is proud to claim Psaty, MD, PhD, as one of its own. CHS can’t take credit for Psaty’s preference not to accept drug company funding (he had a gut feeling as an internal medicine resident that accepting things from pharmaceutical companies was "just not right"), but the Center has played a major role in Psaty’s career as a pharmacoepidemiologist. Psaty has collaborated with Center scientists on case-control studies since 1984, first as a Robert Wood Johnson Clinical Scholar at the University of Washington (UW), and then as co-director of UW’s Cardiovascular Health Research Unit (CHRU), a post he still holds. The CHRU, established in 1991, consists of UW-based scientists who work with Group Health investigators and the Group Health "population laboratory" to study risk factors for heart attack, cardiac arrest, venous thrombosis, atrial fibrillation, and stroke. The CHRU and CHS have enjoyed a close relationship over the years, with Psaty maintaining an adjunct or an affiliate CHS investigator position since 1987 and joining the CHS faculty as a senior scientific investigator in 2005.

It was as a Robert Wood Johnson Scholar interested in drugs affecting the cardiovascular system that Psaty first worked with Ed Wagner, then the newly appointed Director of CHS. The two men have since collaborated on several case-control studies that made use of Group Health’s pharmacy database with its computerized records of all outpatient prescription fills since 1977.

Some of their earliest case-control studies related to beta-blockers, a class of antihypertensive medications. Two high-profile publications resulted from these studies early on. One published in 1989 showed that beta-blockers appeared to be effective in preventing coronary heart disease. The other, published in 1990, showed that subjects who abruptly stopped taking the medications had a transient four-fold increase in the risk of developing new angina or having a heart attack.

Safety was also the issue in another study by Psaty, a case-control study designed to examine the relationship between antihypertensive medications and myocardial infarction (MI). Psaty and colleagues found that short-acting calcium channel blockers, compared to diuretics or beta-blockers, were associated with a 60 percent increase in the risk of MI. Upon release of these findings in 1995, drug industry representatives immediately attacked Psaty’s integrity and used Washington State public records laws to demand "every piece of paper that I had ever touched," he recalls. After Wagner spoke with drug company officials, however, the request for information was eventually withdrawn. "It was very nice to have senior people who were reassuring, helpful, and supportive," Psaty says.

Drug safety was at the heart of another memorable Psaty analysis that relied on a novel data source—trial records. As an expert witness for the plaintiff in a lawsuit against Bayer, manufacturer of the statin Baycol, Psaty had access to trial documents showing that although the company knew that Baycol could cause a sometimes-fatal muscle disorder, it took no remedial action for at least a year. "In short, the company was almost completely irresponsible about safety. When I reviewed the trial records I was distressed by what I saw—the scientific inattention to the safety data. It turned out that I could use publicly available trial records to describe the problem," says Psaty.

His article on the subject appeared in the December 2004 issue of the Journal of the American Medical Association (JAMA). In a highly unusual move, the JAMA editorial board invited Bayer to respond to Psaty’s article and then printed this response and Psaty’s rebuttal virtually unedited so as to preserve the tenor of the debate. The JAMA editors came down on Psaty’s side, agreeing that the Baycol situation exposed some of the major flaws in the post-marketing drug safety surveillance system in the United States.

Psaty says one of the biggest problems with the drug safety system is the "almost insurmountable conflict of interest" it imposes on pharmaceutical companies. He writes that drug companies are "largely responsible for collecting, evaluating, and reporting data from postmarketing studies of their own products." This involves making an often subjective decision about whether an adverse event was actually caused by a medication or was coincidental to it, a determination that can be influenced by economic considerations. To protect the health of the public, Psaty and others have advocated for an Independent Office of Drug Safety under the Food and Drug Administration (FDA), one that would be separate from the FDA Office of New Drugs, which has responsibility for initially approving drugs.

One of the functions of such an independent FDA office would be to require pharmaceutical companies to conduct adequate postmarketing safety trials. Psaty is a proponent of large, long-term clinical trials designed to assess key risks and benefits over a 3- to 5-year period. Using antihypertensive medications as an example, Psaty explains that they are initially approved on the basis of whether they lower blood pressure among patients in small, short-term studies that compare the drug with a placebo. However, the purpose of antihypertensive treatment is not to reduce levels of blood pressure per se, but to prevent the long term complications of elevated blood pressure. Long-term trials are necessary to evaluate whether a drug that lowers blood pressure also prevents heart attacks and strokes and, if it does, whether there might be other adverse events that outweigh these preventive properties. Psaty notes that the scientific literature is rife with reports of industry-funded short-term trials, which do not provide information about health outcomes. As such, they serve more as "marketing tools" for drug companies than important scientific evidence, he contends.

Psaty made some of these points in his 2004 Congressional testimony with FDA whistleblower Dr. David Graham. Briefly, Congress was reviewing Graham’s charges that the FDA tried to suppress his findings that the arthritis drug Vioxx increased the risk of heart attacks. Psaty, who had no industry support suggesting conflict of interest, was asked to testify on the cardiovascular risks associated with the drug. In testimony described by CHS Director Eric Larson as a "masterful piece of scholarship," Psaty delivered a primer in epidemiology, a summary of Vioxx’ history that underscored the conflict-of-interest faced by its manufacturer, Merck, and his recommendations to prevent similar fiascoes in the future. Psaty has since been appointed to an Institute of Medicine panel charged with making recommendations about how to revise post-marketing drug surveillance in the United States.

Psaty believes independence from drug companies should be the norm for all pharmacoepidemiologists who study drug safety. "It’s a matter of culture," he says. "If you hang out with drug company executives or scientists and they provide funding for you and you give talks for them, are you a marketing tool for them or are you a scientist?" He points to the Vioxx situation as an example. After Merck voluntarily withdrew the drug from the market, a 32-member FDA Advisory Committee was formed to review whether the drug’s benefits sufficiently outweighed its risks so that it could re-enter the market. While the overall vote was a squeaker, 17-15 in favor of Vioxx’ return, the 10 committee members who had financial ties to industry overwhelmingly supported market re-entry.

Cardiovascular drug safety and efficacy are not Psaty’s only research interests. There’s also "the other CHS in my life"—the UW’s Collaborative Health Studies Coordinating Center, which conducts multi-center cohort studies. One such study, the Cardiovascular Health Study, has followed 5,888 older adults from four sites since the late 1980s in an attempt to identify risk factors, including measures of sub-clinical disease, for heart attacks and stroke. Psaty currently serves on the Steering Committee for that study.

In addition, Psaty works with CHRU’s Susan Heckbert, Nick Smith, and David Siscovick in an ongoing set of case-control studies of Group Health members. The group is pursuing studies that look for drug-gene interactions (pharmacogenetics)—work that he sees as a logical extension of earlier research in drug safety. "The idea here is to try to take some of the information that’s available from the Human Genome Project and make it useful," he says. Psaty explains that there may be people with genetic variants that make them more or less susceptible to a drug-related adverse event or beneficial effect, or more or less tolerant to a specific dose. For example, a prior study found that people with hypertension who have a particular genetic variant were more likely to avoid heart attacks and strokes if they took a diuretic medication. Noting that there are probably a limited number of important drugs and genetic variants, Psaty envisions a time when patients might be given a set of genetic tests to help determine appropriate dosage, medication etc. "That’s the underlying idea behind much of what we’re trying to do right now," he says.

Psaty deflects references to his newfound "fame" resulting from his Congressional testimony, saying that he thinks of himself as a "publicly-funded public health scientist with a certain level of expertise and competence." CHS Director Eric Larson put it a bit differently in his letter nominating Psaty for the University of Washington’s 2005 Outstanding Public Service Award, which Psaty went on to win: "Dr. Psaty’s far-reaching and life-saving influence in the area of cardiovascular drug safety, coupled with his clear sense of integrity and public service around this issue, make him an ideal candidate for this award."

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