Drug companies must share trial data, Paxil saga shows

A Paxil pill.handout

This story was produced by Stat, a national publication from Boston Globe Media Partners that will launch online this fall with coverage of health, medicine, and life sciences. Learn more and sign up for Stat's morning newsletter at Statnews.com.

Some people can keep secrets much better than others. Among them are the folks who run the world’s biggest drug companies. For years, they have sequestered clinical trial data containing precious information about their medicines. But a recent development might accelerate efforts to bring about greater transparency.

Last week, in an unusual look behind the pharmaceutical curtain, a team of researchers released an independent analysis of trial data from a 1990s-era study of the Paxil antidepressant in teenagers. And what they found is, well, depressing.

Their conclusion contradicts the upbeat claims the pill was safe and effective for youngsters. Yet, GlaxoSmithKline, the company behind Paxil (known generically as paroxetine), touted the original findings as a marketing tool to persuade physicians to write more prescriptions, even though the medicine was not approved to treat teens at the time. All the while, concerns began to grow that Paxil and similar antidepressants were tied to suicidal behavior in this age group.

The new analysis, published in the journal BMJ, confirms the link to suicidality and indicates that the drug wasn’t even helpful in the first place. It caps more than a decade of recriminations, lawsuits, and government probes that cast a harsh spotlight on Glaxo.

Three years ago, for example, the drugmaker paid $3 billion to settle criminal and civil charges that, among other things, its 2001 study — led by Martin Keller, a psychiatrist at Brown University — was misleading and that results from two other trials showing Paxil was ineffective were never disclosed.

The saga is now largely over, and few doctors are likely to prescribe Paxil to teenagers anymore. But the fact that it took so many years to get to the truth underscores a significant problem plaguing medical research: namely, the extent to which the pharmaceutical industry properly discloses trial data, information that is regularly used to promote medicines.

And so, this new study will increase needed pressure on the pharmaceutical industry to open its books. Nothing less than the hot-and-cold relationship between drug makers and patients is at stake.

“This analysis has provided a window into a fundamental problem with the way in which we evaluate medicines,” said Peter Doshi, an assistant professor of pharmaceutical health services at the University of Maryland and an associate editor at BMJ.

Researchers must be able to replicate results and analyses of clinical trials; if they can’t conduct these kinds of exercises, outstanding questions about the safety or effectiveness of a drug may linger.

“This is not really about any one drug or any one trial or any one condition,” said Dr. David Healy, one of the researchers who analyzed the Glaxo trial data and a professor of psychiatry at Bangor University in Wales. “It’s really about access to data. Because if you don’t have access, you can’t see how a company can manipulate data and, therefore, miss the harms” a drug may cause.

Glaxo did not dispute the new analysis. Instead, the drugmaker maintains that the findings “appear to be in line with the long-standing view” that Paxil and similar antidepressants cause an increased risk in suicidal behavior in youngsters, according to a company spokeswoman. “This is widely known” and has appeared on product labeling for years, she wrote in an e-mail.

To its credit, Glaxo provided the researchers with some 77,000 pages of detailed patient data that was contained in case report forms. In response to the settlement with the US government, the drugmaker established a mechanism for researchers to seek access to its trial data and convinced several other companies to join its effort.

But while some other drugmakers have created access schemes, they’ve done so in varying degrees, because these are voluntary efforts.

Not all, for instance, are willing to make older data available, given the logistics and expense involved in digging up files. And in general, the pharmaceutical industry still balks at releasing any data that it says would compromise trade secrets.

Getting investor attention is one way to force change. That’s why Sense About Science, a British nonprofit that launched the AllTrials campaign to widen access to data, is working with 85 asset managers and pension funds to assess steps taken by drugmakers to provide trial information. A report is expected as soon as next month.

A key question is the extent to which dissecting the Paxil trial data will spark similar efforts by other researchers. To be sure, there is growing interest in reexamining scientific research, especially as more retractions are made by medical journals.

But the Paxil study required nearly two years of effort on the part of a large team of researchers, and they did so without pay.

What’s needed is money. Even if a new look at old data simply confirms original results, doctors and scientists must be able to show that the data can stand up to scrutiny.

“I don’t think it’s as grim as it seems, but it’s no small task” to attempt such an undertaking, said Dr. John Nardo, a retired psychiatrist in Jasper, Ga., and one of the authors of the BMJ paper. “I guess every little bit counts, and I hope this is enough impetus to get a few more little bits out there. But it’s going to take more than just the faithful few to take this to the next step.”

Drug makers may have a fiduciary responsibility to shareholders, but that commitment can be hard to uphold if an underlying moral responsibility to patients remains unfulfilled.

If clinical trial data are liberated, patients will benefit. That should be a win for everyone.