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Prescription for trouble

http://www.technologyreview.com/articles/wo_jonietz070104.asp?trk=nl

British regulators say it's now OK to buy potent cholesterol-busting drugs without a prescription, but medical experts wonder if such easy access is a good idea.

By Erika Jonietz
July 1, 2004

Starting this month, British consumers will be able to buy a powerful, cholesterol-lowering drug without a doctor’s prescription. The U.K. government has billed the move, the first time a member of the class of drugs known as statins has been available over-the-counter, as a boon to public health, sure to help prevent Britain's number one killer: heart disease. But within days of the May 13 announcement, doctors began vocal criticism of the decision, raising doubts about both the safety of and motivations behind it. And a similar step by the U.S. Food and Drug Administration seems inevitable, as drug companies are for the third time requesting permission to sell two different statins without prescriptions.

In a press release announcing the approval of the nonprescription sale of simvastatin, sold by Merck as Zocor, British Health Secretary John Reid noted that the Committee on Safety of Medicines had concluded the benefits of the shift outweighed the risk. “This new move will allow more people to protect themselves from the risk of coronary heart disease and heart attacks,” he said.

But a May 22 editorial in the British medical journal The Lancet said the decision to allow over-the-counter sales of the drug was made with little evidence on either the safety or efficacy of offering it to the public without physician monitoring. The U.K. Department of Health, the journal said, was turning the population into “guinea pigs in this large-scale OTC experiment.” The British Medical Association has publicly questioned not only the wisdom of the move but also the motives behind it, saying that the government is attempting to shift the cost of heart disease prevention from the National Health Service onto individual patients.

The decision and its outcome are being closely watched in the United States. Last November, reports surfaced that Merck was planning to ask the FDA to review Mevacor, the first statin sold and now off-patent, for OTC status. In 1997 and again in 2000 the FDA had rejected over-the-counter marketing applications from Merck for Mevacor and Bristol-Myers Squibb for Pravachol, another related statin, citing safety concerns. But the agency has softened its position: in 1997, regulators called all statins unsuitable for over-the-counter sale. Although the agency again rejected OTC sales of the statins in 2000, it withdrew that statement, leaving what some see as an opening for future approval.

“I do think eventually we’ll have over-the-counter statins,” says Joshua P. Cohen of the Tufts Center for the Study of Drug Development; Cohen is an expert in switches of drugs from prescription to over-the-counter status. But, he cautions, there are concerns over efficacy, safety, and cost.

While statins do effectively lower cholesterol, they can't simply be taken like antacids or allergy medications. For one thing, the same dose won’t work for everyone. And unlike allergy or pain medication, where symptom relief is clear, “cholesterol levels are not an easily diagnosed condition,” says Cohen, leaving open the question of how patients taking the drug without a doctor’s supervision will know what’s best for them.

A study published in the April 8 New England Journal of Medicine, for example, found that patients who received high doses of statins had 16 percent fewer cardiovascular events than a control group. But the British government approved only the lowest dose of simvastatin—10 milligrams—for over-the-counter sale. In fact, prescription data from health data company IMS Health suggests that fewer than 30 percent of simvastatin prescriptions in Britain are for the 10-milligram dose; most simvastatin patients take 20 milligrams, and more than 25 percent take 40 milligrams. Doctors worry that without regular monitoring, patients may not find the right dose to affect their cholesterol levels.

Side effects are also a concern. Doctors routinely monitor patients taking statins for liver damage. And 31 patients taking the statin Baycol died from rhabdomyolysis, a rare but dangerous muscle breakdown that can lead to kidney and other organ damage; these deaths led to Baycol’s recall in 2001. “You certainly don’t want people taking an over-the-counter medication and dying from it,” says Cohen. “I wouldn’t be too alarmist about it, but that’s a real concern.”

Doctors also worry about harmful interactions with drugs heart patients may already be taking, including other cholesterol-lowering drugs, anticoagulants, antifungals, and even common antibiotics. This could be a bigger problem in the United States than in Britain, where simvastatin will actually be sold in a special class of over-the-counter drugs for which pharmacists act as gatekeepers. Although a cholesterol test will not be required, patients will have to answer questions to allow pharmacists to determine their risk of coronary heart disease, as well as what other drugs they are taking. But the advent of such a system doesn’t seem likely in the United States. There is a small fee for pharmacist counseling in Britain, and U.S. patients won’t want to pay for it, says Peter Jones, codirector of the Lipid Metabolism and Atherosclerosis Clinic at Baylor College of Medicine in Houston. “If I’ve got a $10 copay to see my doctor, why should I pay $10 for the pharmacist to tell me this when I maybe trust my doctor better?” he asks. “I don’t think the U.S. is ready to have that tier.”

Still, most experts feel that risks of adverse effects are small. Of more concern is that patients will lose the chance for more comprehensive counseling from their doctors on risk factors such as diet, exercise, weight, and smoking. "Some people feel that taking a Lipitor [statin] and eating a Big Mac at the same time is somehow going to offset one another," says Cohen. "And you wouldn't want that to happen on a large scale."

Perhaps the major objection of British doctors, though, is cost, says Cohen. About 1.8 million Britons currently have prescriptions for statins, costing the National Health Service more than $1.2 billion a year; that figure is predicted to grow to more than $3.6 billion a year by 2010. Doctors worry that many patients who currently receive the drugs for free will be unable to afford the predicted monthly cost of roughly $18 to $27 for a drug usually taken for years.

Even in the United States, where most patients already pay for at least part of their prescriptions, cost could be a problem, according to Cohen. “These are daily medications,” he says. “It can be anywhere between $20 and $60 a month or more, maybe $100 a month.” Insurance companies might follow the model seen recently with allergy medications, taking newer, more expensive statins off the list of covered drugs if an older statin becomes available over the counter—in effect, shifting the cost of the drugs to consumers.

But despite the risks and costs, many believe over-the-counter statin sales would have benefits in helping to prevent coronary heart disease. Wider availability of the drugs could, for instance, help shift consumer spending away from “nutraceuticals,” over-the-counter supplements with questionable health benefits. Says Jones: “There are people who would spend the same amount of money as you can spend on a statin taking garlic pills, which do absolutely nothing.”

Allowing over-the-counter sales of statin drugs could increase their use, ultimately helping a huge number of people. “Anyone with risk beyond the most trivial level will, somewhere around the age of 50 or 60, see the benefit of a statin far outweigh the risks,” says cardiologist Richard A. Stein, associate chair of medicine at the Singer Hospital of Beth Israel Medical Center in New York and a spokesperson for the American Heart Association. Less than one-third of Americans with elevated cholesterol are being treated, according to the association. “The current model is leaving untouched and at high risk a substantial amount of our population,” Stein says. Buying a statin drug in the drug store “isn’t a good alternative to seeing a physician,” Stein emphasizes. But he believes that there are large numbers of people who don’t get into the medical system and whose risk of heart disease and heart attack would be reduced if they took the pill. “Since it’s the major cause of death and disability in the United States, a 10 percent reduction in that risk is extraordinary in terms of its health care implications.”

An FDA decision to give statins over-the-counter status in the United States could come within the year—or not for several years. In the meantime, experts say, they’ll be closely watching how things go on the other side of the Atlantic. “In Britain we’ll have a nice test model,” says Stein. “We’ll be able to look at, five years down the road, how widely it’s used, what’s happening to the overall risk of heart attacks, and we’ll have a very nice model to see if it works.” To their benefit or not, it seems that British consumers will indeed be serving as test subjects in a massive medical experiment.