It took some legal arm-twisting from New York State's attorney general, prodding from the American Medical Association (AMA), and threatened action by medical journal editors. But finally, the healthcare industry looks to be on the verge of asking the government to set up a comprehensive registry of clinical drug tests.
The registry would include not only positive trials that drug manufacturers like to tout, but also any tests that show drugs to be harmful or ineffective. The move could go a long way toward addressing public concerns that such studies are being suppressed, especially after recent revelations about the effects of an antidepressant on children and teens, observers say. But by itself, a registry won't counteract the influence drug companies hold on the marketplace, they add.
"We should not delude ourselves into thinking it will overcome the enormous promotional clout that the companies already have," says Jerry Avorn, a professor of medicine at Harvard Medical School and author of the forthcoming book "Powerful Medicines: The benefits, risks, and costs of prescription drugs." Even if such a registry were magically in place tomorrow, Dr. Avorn says, "the companies would still have a very large say in what published information is brought to the doctor's office in a convenient, colorful, glossy, well-illustrated package."
Concerns about clinical trials arose earlier this month after Eliot Spitzer, New York's attorney general, sued GlaxoSmithKline. The suit charges, among other things, that the British drug firm had suppressed clinical studies showing that its antidepressant drug Paxil was ineffective in children and teenagers and possibly could cause suicidal behavior. Glaxo released the studies.
Then last week, apparently reacting to growing public concerns that negative trials were being hushed up, the AMA called for a comprehensive government registry of all clinical trials, ensuring that information on trials with negative results would be widely available. The AMA proposal followed on the heels of news reports that the International Committee of Medical Journal Editors was considering a requirement that any articles published in its member publications be based on trials listed in such a database. That could pressure drugmakers to register all their trials, since they count on reports in prestigious medical journals to influence the choices physicians and patients make when choosing prescriptions.
The drug industry's trade organization, the Pharmaceutical Research and Manufacturers of America (PhRMA), has yet to decide whether to endorse the concept of a registry. It is waiting to see a final draft of the AMA proposal and to learn whether the medical editors formally act, a spokesman says.
Drug companies are already committed to communicating negative trial results, says Alan Goldhammer, PhRMA's vice president for regulatory affairs, noting that PhRMA is on record with a general expression of support. That statement calls for "timely communication" of the results of clinical trials "regardless of outcome."
One of the difficulties for drug companies, Dr. Goldhammer says, "is that it's hard to publish negative results because the journals tend to not want to publish them." But even without publication, negative outcomes of drug trials are still presented at scientific meetings, he adds. "The devil's in the details." he says, noting that PhRMA's members are concerned that such a registry "may end up confusing physicians more than helping them - and we don't want to see patients not prescribed the medicine they might need."
While PhMRA as a whole is hesitating, some drug companies are quickly making concessions. Glaxo said it would publish the results of its trials on its website, and Merck indicated it would support a government registry.
Still, close observers who favor a registry say it will not be a panacea.
The idea of a registry is a good one, but it has to be well thought out and without "a lot of little tiny studies that aren't representative of anything," says Jerome Kassirer, a former editor-in-chief of the New England Journal of Medicine who now teaches medicine at Tufts and Yale universities. Hard questions remain about the registry's funding, its format, and whether it would be mandatory, he adds. And making more negative studies available to journals doesn't mean they will be published. Editors aren't "terribly excited about publishing the second or third negative study. It becomes boring," he says.
The call for a registry has brought to light another issue. "Where were the doctors who were involved in these [negative] studies when the studies were suppressed?" asks Dr. Kassirer. "Why weren't they out front saying to the medical community that there are studies here that contradict the drug companies' assertions? ... My guess is that either they were cowed by the industry or they had a financial conflict of interest with the industry, and they didn't want to rock the boat."
Critics say Congress may have to compel drug companies to register all their trials. "The power to control what studies get released and what studies don't get released is enormous, because you then can influence the perceptions of the public and of the prescribing physician at will," Avorn says. "That's why they have not done it willingly thus far, even though the idea has been around for years."
Concern over the lack of full disclosure comes at a time when more and more drug trials are being conducted by private industry. The share of private investment in biomedical research rose from 32 percent 1980 to 62 percent in 2000, while the federal government's share fell, according to a study at Yale, published last year in the Journal of the American Medical Association.
"There is strong and consistent evidence that industry-sponsored research tends to yield pro-industry conclusions," said Justin Bekelman, the lead author. Industry-sponsored studies, the report said, reached pro-industry conclusions 3.6 times as often as other studies.
But even if a registry does become available, physicians won't necessarily use it, Avorn says.
"Most docs are not able to spend an hour in front of the computer doing searches for all the drugs they prescribe every day," he says. "That's why I don't see this as a panacea."