Small field, big numbers, exciting work for Brown's pharmacoepidemiologist

Kate L. Lapane, an associate professor at the Medical School who specializes in drug use by the elderly, is one of the world's few pharmacoepidemiologist - someone who crunches numbers to see what medications are being used for what purposes.

by Wendy Y. Lawton

Think of Kate Lapane (below) as a prescription drug detective. Finding clues in colossal, computerized data sets, Lapane sniffs out who gets drugs, who doesn't, and how prescription patterns affect people's health - for better and for worse.

This field is pharmacoepidemiology, which combines the disease-tracking methods of epidemiology with the prescription drug know-how of pharmacology. Who gets life-saving prescriptions for heart disease? Mostly white men, pharmacoepidemiologists can tell you. Is that new acne medication safe? No, they learned in the case of Accutane, which can cause birth defects. So the warning label changed.

How many Americans should get the smallpox vaccine?

In the wake of the anthrax attacks three years ago, the government decided that everyone in the United States should get the smallpox shot. But an expert committee, led by a pharmacoepidemiologist, determined through biostatistics that mass vaccination would pose more health risks than benefits. Today only 50,000 Americans, mostly health workers, will get vaccinated for smallpox.

With the ability to change public policy and pull drugs off the market, pharmacoepidemiologists are powerful. As a group, however, they are puny.

The International Society for Pharmacoepidemiology claims about 700 members who monitor drug side effects and track drug use for pharmaceutical companies, the government and in academia.

That makes Kate Lapane a rare bird. She is the Medical School's only pharmacoepidemiologist. In a ceremony in France next month, she will become one of only 62 fellows inducted into the international society.

"It's a small field, but it's exciting work," Lapane said. "You work with huge numbers but can affect the health of individuals."

Lapane is 38, with a ready laugh and black hair graying at the temples. Her office in the Department of Community Health, where she is an associate professor, is stuffed with boxes from a recent move. Her bookshelves are cluttered - "Bayesian Statistics" shares space with "The Merck Manual" and "Chemical Physics." A starry, serene Van Gogh print hangs above her desk.

Lapane's biggest drug-detecting tool is her laptop, which she uses to crunch data culled from government and insurance files on millions of patients. "l confess," she says. "I love numbers. And big numbers? Even better."

After earning a bachelor's degree in math and statistics at Boston University in 1987, Lapane landed an analyst job at Blue Cross & Blue Shield of Rhode Island, where she was surrounded by huge mainframes spitting out insurance claim forms. She began to notice patterns in the claims - which patients' jobs were dangerous, who could afford medical care.

She began, in short, to see the world as an epidemiologist. This mindset was cemented when she went to work for the Pawtucket Heart Health Program, a massive research project aimed at reducing risk factors for cardiovascular disease in Pawtucket residents. Analyzing data for the study, based at Memorial Hospital from 1980 to 1991, had a profound impact on Lapane.

"I got to work with doctors, psychologists, statisticians, epidemiologists," she said. "I got to be curious. I was learning all the time. I just fell in love with health care and research."

After earning a master's degree in statistics from the University of Rhode Island, she enrolled in Brown's Ph.D. program in epidemiology. Prescription drugs, so ubiquitous in medicine, became a fascination.

In her first major journal article, published in Epidemiology in 1995, Lapane and other researchers found a link between antidepressants and heart attacks. Although the authors did not draw a clear cause-effect relationship, Lapane got calls and letters from people saying they stopped taking their depression drugs because of the findings.

This was a wake-up call, she said, about the impact of her work. In 1998, she was reminded again, when she contributed to a paper in The Journal of the American Medical Association providing evidence that many nursing home patients dying of cancer were going without adequate pain medication and that more than a quarter - particularly minorities and patients older than 85 - got no painkillers, not even aspirin.

Results wound up on the front page of the New York Times and even in the comic strip "Doonesbury." The research sparked discussion and nursing home policy changes across the country.

Lapane wants her future work to make similar waves. What's the use of pointing up problems, she says, if the research doesnÕt change reality? Lapane is also mulling a move from strict numbers, hoping to include interviews and other qualitative methods into her nursing home research.

"Numbers can only take you so far," Lapane said. "You need to go into homes and talk with people to truly understand the situation." She paused: "The more I learn, the more questions I have."

A 'field sprung out of crisis'

In Europe in 1957, doctors began prescribing a pill to pregnant women to ease morning sickness. In 1961, scientists discovered that the drug - thalidomide - caused severe birth defects, stunting the growth of arms, legs, hands and feet in thousands of babies.

The result was an international uproar. In the United States, the Food and Drug Administration worked to keep thalidomide off pharmacy shelves; other countries pulled it from the market.

Because the drug was never tested in animals, the incident pointed out the need for more rigorous drug testing. Pharmacoepidemiology was born.

"The field sprung out of crisis," said Brian Strom, director of the Center of Clinical Epidemiology and Biostatistics at the University of Pennsylvania and editor of the classic textbook "Pharmacoepidemiology."

Arguably the world's leading pharmacoepidemiologist, Strom said the field has continued to grow because of safety scares. Pharmacoepidemiologists have delivered on their duty to protect patients, Strom said, doing side-effect surveillance that forced several unsafe drugs off the market.

One example is Rezulin. In 2000, it was voluntarily withdrawn from the market by the drug maker after pharmacoepidemiologists learned it can cause liver disease.

Sebastian Schneeweiss, an assistant professor in the Department of Epidemiology at the Harvard School of Public Health, said the boom in drug development and increasing concerns about drug safety have created an enormous demand for pharmacoepidemiologists. Schneeweiss said he gets at least one job offer a week from drug companies.

But only a handful of universities in the world offer specific degrees in the field. (Most practicing professionals hold a combination of advanced degrees in areas ranging from medicine and pharmacology to biostatistics and epidemiology.)

"We don't have enough training programs," Strom said. "And there's a crying need." - Wendy Y. Lawton