BMJ  2006;332:991 (29 April), doi:10.1136/bmj.332.7548.991

News

US scientists urge overhaul of clinical trials to restore confidence

London

The US government's top biomedical scientists have called for an overhaul of clinical trials to protect the public and to restore trust in medicine. After a summit at the National Institutes of Health (NIH), in Maryland, the institutes' director, Elias Zerhouni, warned that failure to spot serious side effects of drugs quickly enough was gradually eroding public trust. He announced an eight point plan designed to improve clinical trials and reduce the likelihood of side effects being swept under the carpet.

A key recommendation is for equal weight to be given to determining the safety as well as the efficacy of medicines. The NIH committee cited the scandal surrounding the painkiller Vioxx (rofecoxib) as evidence that safety needed to be stepped up. Merck withdrew the drug in 2004 after it emerged that users were at increased risk of heart disease and stroke. Earlier this month, a jury in New Jersey ordered the company to pay $13.5m (£7.6m; 10.9m) in damages to a 77 year old man after Vioxx was found to have contributed to his heart attack, and Merck had failed to warn about the dangers of taking the drug (BMJ 2006;332: 927, 22 Apr[Free Full Text]). The company is facing thousands of other lawsuits in the United States.

The NIH committee called for longer term follow-up, increased powers for the Food and Drugs Administration to do postmarketing surveillance, and more effective dissemination of information relating to adverse events.

Superior court judge Carol Higbee at the 2006 hearing which ruled that Merck had failed to warn of Vioxx's risks Credit: MARY GODLESKI/AP/EMPICS

 

The committee's recommendations, published in PLoS Medicine (2006;3: e144), also call for researchers to treat prior observational evidence with greater scepticism, pointing to combined oestrogen-progestogen hormone replacement therapy. For years doctors were convinced that the treatment protected women from heart disease and stroke, on the basis of limited observational studies. But in 2002, the women's health initiative trial showed that it actually increases the risk of circulatory disease. Selection bias in the original observation studies was to blame, says the National Institutes of Health—women taking hormone replacement treatment were likely to be fitter and more educated and less likely to smoke.

The committee also singled out a tendency to mislead both patients and practitioners with statistics. In particular, the committee noted that presenting drug efficacy in terms of relative risk alone can be misleading. It cited publicity for an antiosteoporosis drug that simply said that in 12 months the treatment cut vertebral fractures by 68% compared with placebo. But this was the relative risk. In absolute terms, the proportion of vertebral factures was 0.738% for patients given placebo compared with 0.238% for patients given the drug—a difference of half a percentage point.

A British expert, Joe Collier, professor of medicines policy at St George's Hospital Medical School in London, told the BMJ that the proposals probably did not go far enough. "A lot of the things suggested are laudable. But we've known for years that they're needed."

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