What do a Boston psychiatrist, a Brown University administrator, and a diminutive, legally blind district attorney all have in common?

All three believed something was amiss with the marketing of selective serotonin release inhibitors (SSRIs) for children and adolescents. All three serve as the protagonists in Alison Bass’s new book “Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial” (Algonquin Books, June 2008).

Through the activities and assertions of McLean Hospital’s Martin Teicher, Brown’s Donna Howard, and attorney Rose Firestein, Bass outlines how the New York Attorney General’s office, under Eliot Spitzer, built a landmark consumer-fraud case against GlaxoSmithKline (GSK).

The controversy turns on whether clinical trials showed the drug was more effective than placebo. Some GSK trials showed an increased risk of suicidal behavior among teens; but those results took a while to reach the medical literature. The cumulative weight of the evidence is still debated in psychiatric circles. When the less-rosy Paxil results finally did reach the scientific community (and the news media) they triggered a new era of mistrust of drug companies and the physicians who work for them. That climate continues to this day, with Congress probing both individual Ivy League psychiatrists and their professional organization.

Soon enough, other cases came to light, including similar allegations of improperly marketed drugs, doctored data, and buried results from trials that didn’t turn out as sponsors desired. It’s all detailed—and we do mean detailed—in Side Effects.

Anonymous Call

As a health reporter at the Boston Globe, Bass got an anonymous call from an employee at Brown University, alerting her to the misappropriation of funds by a prominent psychiatrist-researcher. Bass was told that Martin Keller, chief of psychiatry at Brown, was accepting Massachusetts funding for studies he was not even conducting. He was also, the source said, playing fast and loose with study data on a Paxil trial being conducted on children and adolescents. Bass was unable to verify that information.

But soon her anonymous source—Donna Howard, an assistant administrator in the Brown psychiatry department—went on the record. Bass was able to confirm allegations about research and billing transgressions through interviews with other Brown employees. The Globe ran the story. Brown eventually returned more than $300,000 in funding to the Massachusetts Department of Mental Health.

Rose Firestein, in the New York State Attorney General’s office, soon started looking into the matter. She discovered that there were big problems with the Paxil study conducted at Brown. Turns out that trial was a pivotal study on which GSK had based much of the drug’s marketing related to children and adolescents. GSK is now under a federal probe by the U.S. Department of Justice for that study.

Undue Influence

In the book, the Pulitzer-prize-nominated Bass takes a critical look at the alleged misconduct around antidepressant trials and marketing, as well as the tangled relationships between drug companies and a) medical journals, b) not-for-profit advocacy groups like the National Alliance for Mental Illness, c) principal investigators and d) the FDA.

The troubling factor at the heart of all these relationships? Bass points to money and inappropriate influence on the scientific process, along with an FDA legally mandated to keep significant amounts of industry data secret. 

After a four-year foray into the industry, she has come away with strongly negative conclusions. “The industry itself is not going to change,” Bass said. “The FDA has got to. I think they should abolish direct-to-consumer advertising, and the FDA should do a better job of post-market monitoring.”

Bass’s Rx

In addition, Bass said, medical centers need to do a better job in regulating conflicts of interest. She believes doctors getting more than a specific amount of personal income (perhaps $10,000 to $20,000) from drug companies should not be allowed to conduct studies on drugs being developed by those particular companies. She defines personal income as consulting fees, speaking fees, and the like—not payment for conducting trials.

The New England Journal of Medicine apparently agrees with the main thrust of Bass’s book. In its June 26, 2008 issue, Richard Friedman, of Weill Cornell Medical College, wrote that Side Effects “used the case of Paxil to expose the unsavory and self-serving relationships among members of the pharmaceutical industry, psychiatrists, and members of the FDA.” He added that the book “should be widely read by members of the medical profession, many of whom continue to believe, despite all evidence to the contrary, that they are immune to the influence of drug companies.”

Industry Aftershocks

As readers will recall, GlaxoSmithKline negotiated with New York and agreed to post study results on its website. A dozen elite medical journal editors decided to require sponsors to register some trials on clinicaltrials.gov, making it harder for companies to change outcome measures later. Last fall, Congress took that further, selectively requiring trial results to be listed online.

Will any of that make a difference with politicians or the public? Maybe. But Bass says she thinks drug companies might find avenues around any reforms. “Where there’s a will, there’s a way,” she said.

Bass is now on a tour promoting Side Effects. What will she be working on when that wraps up? A novel.

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