Saturday, June 28, 2008

Alison Bass's SIDE EFFECTS: Another Hall of Shame candidate

The most recent book on Pharma issues that I've seen is by Alison Bass, formerly of the Boston Globe, called Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial (Algonquin Books, Chapel Hill, NC, 2008). Essentially it tells the story of Paxil and the suit filed by then-NY-Attorney-General Eliot Spitzer in 2004, charging GlaxoSmithKline with fraud in state court for concealing unfavorable evidence about the antidepressant's effectiveness and adverse-effect profile in children. She particularly profiles Rose Firestein, the assistant AG in Spitzer's office who led the GSK suit; and Donna Howard, a whistleblower who revealed the concealment of adverse research outcomes in the key Paxil study in adolescents. (She also discusses Martin Teicher, a Boston psychiatrist who reported the first cases of suicidality related to SSRI drugs and was roundly vilified by his colleagues as a wacko or anti-psychiatry cultist.)

At one level the book tells us experienced Pharma watchers little that we did not already know. In HOOKED, I suggested that the filing of the New York suit against GSK in the spring of 2004 might have been a critical tipping point, after which the momentum that had previously favored the influence and dominance of the pharmaceutical industry first started to swing in the opposite direction. Many would have said that this was silly, an the real tipping point came later, on September 30, 2004, when Merck withdrew Vioxx from the market and admitted its link to excess heart attacks. So it is at least somewhat reassuring to read a book that views the New York AG lawsuit as a critical event. Bass even goes so far as to suggest that the way Merck elected to deal with the Vioxx expose later that same year was predicated in part on the drubbing that GSK had taken in its legal tussle with the NY AG; so that the two "tipping points" are more closely linked than might at first appear. Still, the "smoking guns" in the GSK suit seem rather cool to the touch; for example, we discover that Rose Firestein became aware of the single most incriminating internal GSK memo, on how the critical negative study of Paxil in kids was spun deliberately to make it seem positive, by the simple expedient of reading an article about it in the Canadian Medical Association Journal--whose editor kindly then faxed her a copy of the original memo itself.

At another level, the book solidifies the case against another academic psychiatrist whose ties to Pharma seem to have reached legendary proportions. Dr. Martin Keller, chair of psychiatry of Brown University and the principal investigator of the major Paxil study in adolescents (the now-infamous Study 329), was originally outed by Bass years ago in the Boston Globe, as earning the princely sum of nearly a half million dollars annually in drug company money, on top of his salary as department chair. The book makes a strong case to show that Keller acquiesced, at the very least, in a ghostwritten version of the study that re-spun a study that actually was negative and made it appear to be positive. Moreover, the testimony of the Brown whistleblower suggests just as strongly that Keller deliberately concealed and misclassified serious adverse reactions among study participants--saying, for instance, that teens who had to stop taking the drug because of suicidal impulses or serious bizarre behavior quit the study due to "non-compliance" rather than due to adverse effects.

Dr. Keller refused to be interviewed for Bass's book. Brown University responded to Bass's query by stating that "Brown takes seriously the integrity of its scientific research. Dr. Keller's research regarding Paxil complied with Brown's research standards." When a prestigious Ivy League medical school says that its research standards support ghostwriting and suppression and misclassification of data, then somebody has some explaining to do. (I know that some of our esteemed colleagues who are affiliated with Brown have protested this situation, based on information that was publicly available even before Bass's book was published.)

Bad News--Other Countries Also Have FDAs of their Own

The ever-alert Jon Judeidini sent this link out through the Healthy Skepticism network:

This is a news article and not a medical journal publication, but the claim is that the Swedish pharmaceutical regulatory agency, their version of the US FDA, is colluding with psychiatrists who are well known to be heavily beholden to the pharmaceutical industry, to publish a study that purports to show that antidepressants really do work very well and that studies that seem to indicate that they are little if any better than placebo are bunk. The article was of such stunning scientific quality that the two journals to which it was first submitted, Lancet and BMJ, both rejected it forthwith. The study then experienced a soft landing at European Psychopharmacology (I guess psychopharmacology on that continent is different from everywhere else, requiring a separate journal) , edited by Dr. Stuart Montgomery. According to the reporter, Dr. Montgomery is apparently the European version of our own Dr. Charles Nemeroff (see previous post, Dr. Montgomery was described as being almost singlehandedly responsible for previously concealing data on the paroxetine withdrawal syndrome.

Now, just to be up front about the whole matter, I would like to go on record as admitting that I have somewhat the same reaction as the Swedish psychiatrists who are in bed with Pharma. In my years of practicing family medicine, during which I wrote a lot (in hindsight probably way too many) of scripts for newer-generation antidepressants, I did see a number of patients who had very significant therapeutic responses. In the best cases, they stated that they felt like their normal selves again for the first time in years. For this subgroup of patients, it might have been a placebo effect for all I could know scientifically, but it was a darn impressive placebo effect if so. I also saw a number of cases where the drugs did not work or seemed to stop working after about 6 months; and I saw a good many cases where the patient complained that the side effects ("I feel like a zombie" was a pretty common way to express them) were as bad or nearly as bad as the depressive symptoms. So my own very limited clinical experience is inconsistent with the notion that these drugs are no good at all. It is consistent with the assertion that the side effects of these drugs have been chronically underreported in the literature as well as in the curbside conversation of my colleagues, in both psychiatry and in primary care.

Anyway, back to Sweden--I suppose one element of incurable romanticism among Americans is that we imagine that other countries are wiser than we are and have solved many of the problems that continue to plague us (like providing universal health care). So it is sad to realize that other advanced countries have their own versions of the same issues with "regulatory capture" that we do in the U.S.