Sunday, July 7, 2013

Getting Drug Companies to Release Clinical Trial Data

There’s a tension in our society between openness and confidentiality. On the one hand, we celebrate openness and full disclosure. Men like Julian Assange and Edward Snowden who allegedly break laws and release confidential or classified information are lauded as anti-establishment heroes. The media doesn't allow politicians, celebrities, and other people in the public eye any privacy. On the other hand, laws like HIPAA restrict our ability to acquire health care information about other people. I recently blogged about the inability of parents to find out about their children’s mental health treatment.

A change has been occurring regarding public access to pharmaceutical clinical trial data. A recent New York Times article talks about the efforts of researchers to push drug companies to release unpublished clinical trial data.

The article profiles Peter Doshi, a M.I.T.-educated researcher, and Dr. Tom Jefferson, a British epidemiologist. They collaborated to determine if the anti-flu drug Tamiflu was effective. Jefferson had earlier concluded that Tamiflu reduced the complications of flu. His review was based on a study that pooled the results of 10 clinical trials. Only 2 out of these 10 trials had been published in medical journals, however. Taking another look at the data, Jefferson approached Roche, the manufacturer of Tamiflu, for the results of the 8 missing trials. Roche declined to cooperate, citing Jefferson’s refusal to sign a confidentiality agreement.

Due to the missing data, Jefferson’s team published an article in the British Medical Journal that concluded that Tamiflu was only moderately effective against influenza-like symptoms, and cannot be shown to reduce complications of influenza (e.g. pneumonia and hospitalization). The journal also did its own investigation, concluding that Roche had hired ghost writers to author some of the articles involving Tamiflu, pressuring the writers to highlight positive aspects of the drug.

After the British Medical Journal articles appeared, Roche turned over partial copies of study reports. The European Medicines Agency also turned over documents from 19 trial reports to Jefferson and colleagues. These documents allowed researchers to discover the importance of clinical study reports, which are thousands of pages long, and contain details such as descriptions of trial protocol and design, and ingredients of placebo pills. This April, Roche further relented, agreeing to make available clinical study reports for all Roche-sponsored trials of Tamiflu.

“All these years later, and we still don’t know if Tamiflu is effective,” said Dr. Harlan Krumholz, a Yale cardiologist. “It’s perplexing to have a billion-dollar drug, and you’re not willing to share everything you’ve got to know whether this thing is effective and safe.”

Prodding from Doshi and others led the pharmaceutical company GlaxoSmithKline to announce that it will share detailed data from all company-sponsored trials dating to 2000. This would amount to more than 1000 trials involving more than 90 drugs. Due to past misdeeds, Glaxo needed an image rehabilitation. Last year, it pleaded guilty to criminal charges and agreed to pay $3 billion in fines. It had been accused by the U.S. Justice Department of failing to report safety data about its diabetes drug Avandia, and publishing misleading information about the antidepressant Paxil. The settlement, which also involved civil penalties over marketing of other drugs, was the largest ever involving a pharmaceutical company.

Publication bias of studies involving antidepressant drugs is a topic in Irving Kirsh’s book The Emperor's New Drugs (which I review here). Kirsh had used the Freedom of Information Act to obtain unpublished clinical trial studies of antidepressants from the FDA.

Not everyone in the pharmaceutical industry is happy with the new openness. The Pharmaceutical Research and Manufacturers of America (PhRMA), a major industry group, and other drug companies oppose releasing clinical trial data. John J. Castellani, chief executive of PhRMA, said that “[i]f you dump onto the sidewalk all the data and you include commercially protected information, then you’re essentially giving to competitors what we invested billions of dollars in.” U.S. federal law restricts what information can be released, especially data that can reveal personal or commercially confidential information.

My view is that the public has a right to know all the results of studies of a particular drug, both positive and negative. It’s the pharmaceutical company’s obligation to provide this data. They certainly have a right to withhold commercially protected information, and private research participant data, but they don’t have the right to only publish positive studies, and hide negative studies. I applaud Doshi, Jefferson, Kirsh and others who have helped push drug companies to release clinical trial data.

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