Over the last decade some 30,000 women with late-stage breast cancer received an expensive therapy known as autologous bone marrow transplantation. The treatment, costing $50,000 to $100,000, involved high doses of chemotherapy and the transplant of bone marrow cells in an attempt to arrest the disease. It offered hope but little evidence that it would prolong or improve the quality of life.
Doctors, hospitals, patients and their advocates, all with a stake in the procedure, fought for its use while insurers resisted on the grounds that it was experimental--that there was little proof that it worked. Battles between insurers and patients over the procedure made national headlines: A Southern California jury in 1993 awarded millions to the family of a breast cancer patient who died after her HMO refused to pay for ABMT treatment.
Two years ago, results from four clinical trials showed that insurance companies--some of which had bowed to public pressure and had begun paying for the procedure--had been right all along. The lack of evidence for ABMT is hardly an isolated example. If you look closely at many of the things done to patients, the evidence for their use often is soft or even nonexistent. For decades physicians placed tubes in the ears of kids with chronic ear infections in the belief that they would improve hearing and language development. A recent review of the evidence, however, shows that tubes don't have much of an effect after all.
Several studies show that the proportion of medical interventions firmly grounded in evidence is much smaller than most people realize. "The public is shocked when they hear that 80% of medical practice is not based on evidence," says Dr. Gregg Meyer, who directs the Center for Quality Improvement and Patient Safety at the federal Agency for HealthCare Research and Quality. Much of what doctors do is based on opinion and consensus but that doesn't always produce the best outcomes and highest quality care. However, says Meyer, consensus "isn't always bad. There has never been a randomized controlled trial of penicillin for strep throat but we know it works."
But sometimes consensus is scary, especially when sellers of new treatments, tests, drugs and devices take to the airways to shape public opinion. Doctors are part of the public too. With help from the media, sellers sometimes promote treatments whether or not research has proved them effective. In 20 seconds Oprah can generate more demand for a medical procedure than one or two well-done clinical trials reported in the New England Journal of Medicine. Hype, promotion and public relations can overwhelm whatever science there is, and if there isn't any, they become a substitute.
The arthritis drug Celebrex and its cousin Vioxx, which is prescribed for arthritis as well as acute pain, show what can happen. Celebrex is now the sixth bestselling drug, generating more than $4 billion in sales since its debut in early 1999.
"The question prescribers have to ask is how did Celebrex reach $1 billion in sales at a time when there wasn't a single controlled trial published that looked at the effectiveness in treating arthritis and pain compared to similar drugs," says Larry Sasich, a pharmacist who works with the Public Citizen Health Research Group. "What sources of information do prescribers use to choose drugs? In the case of Celebrex, because there was no science, the decision had to be based on promotional materials."
Meyer says his 6-year-old son, who watches fewer than three hours of television each week, can hum the Celebrex song. So can I, and I watch almost no TV and have no need for the drug. Doctors can, too, and that's when marketing that implies greater safety or efficacy than may be warranted becomes dangerous.
When Celebrex came on the market, Searle, which then made the drug, pointed to clinical trials that showed the drug caused fewer stomach ulcers than comparable medicines, known as nonsteroidal anti-inflammatory drugs, or NSAIDs. Indeed, its apparent gastrointestinal safety became its promotional raison d'etre.
However, the studies did not reflect strong enough evidence for the FDA to allow Searle to market the drug without a warning--also carried by other NSAIDs--that it could cause gastrointestinal bleeding and should be avoided by people with severe liver and kidney problems.
At the time, a study at the University of Pennsylvania, which was funded by Searle, discussed the possible risk of blood clotting that could result in heart attacks and strokes and recommended larger clinical trials. The study's senior author said the findings raised a red flag. But Searle dismissed the study as reaching "highly speculative conclusions." That study got little media attention.
The science is beginning to accumulate on Celebrex and Vioxx, which is manufactured by Merck. A study reported last July in the Annals of Internal Medicine found that both drugs reduced kidney function in older people who were otherwise healthy. And a scientifically valid study of Celebrex in the Journal of the American Medical Assn. last fall raised questions about its gastrointestinal advantages compared to similar drugs.
"There was no significant safety advantage in the GI tract," says Dr. M. Michael Wolfe, chief of gastroenterology at Boston Medical Center and a member of FDA's advisory panel on gastrointestinal drugs. However, Judith Glova, a spokeswoman for Pharmacia, which now makes Celebrex, said that "additional analysis showed clinically meaningful results."
A trial involving Vioxx found that it was easier on the stomach than naproxen, another NSAID sold under the brand names Naprosyn and Aleve. But this study raised a new red flag. Patients taking Vioxx had four times the risk of heart attacks as patients taking naproxen. "We're not sure whether Vioxx was associated with more heart attacks or naproxen was acting as aspirin to prevent heart attacks," Wolfe says.
Although warnings have surfaced, early hype for the drugs may be getting in the way of sound medical judgment. A doctor friend of mine tells of an 80-year-old patient who was in a rehabilitation facility after a minor fall. She had a history of arthritis, heart and kidney problems. The facility's cardiologist prescribed Celebrex, and soon the woman developed symptoms of heart and renal failure.
When my friend asked doctors at the facility if Celebrex could have caused her problem, at first they said no, replying that the drug did not have a "side effect profile." Later they conceded it could have been the culprit. "This fits the definition of an adverse drug event that went unrecognized," my friend says. Apparently doctors were confusing the advertised gastrointestinal advantages of the drug with other potential problems that received little publicity.
More than a decade ago, David Eddy, a physician and medical commentator, wrote in the journal Health Affairs: "Physicians can do more to admit the existence of uncertainty both to themselves and to their patients. While this will undoubtedly be unsettling, it is honest, and it opens the way for a more intensive search for ways to reduce uncertainty." Patients, he said, "can push the process by asking questions. There are few things better than asking questions to force research to get the answers."
With the explosion in technology and sophisticated marketing techniques, Eddy's comments are even more relevant today.
Trudy Lieberman is the author of "Consumer Reports Complete Guide to Health Services for Seniors" (Three Rivers Press, 2000). Send comments to: firstname.lastname@example.org. Health Matters appears on the third Monday of the month.