Thursday, August 14, 2008

A Review of Side Effects, by Alison Bass

I finally got a chance over this past weekend to sit down and read Side Effects, the new book by former Boston Globe reporter Alison Bass. I read the book cover to cover, which surprised me, because I was expecting that this would be an information-heavy repetition of the same territory covered by other recent books, such as Claude Barber’s Comfortably Numb or Marcia Angell’s The Truth about Drug Companies.

But Side Effects is different and more riveting, because it tells the story of several individuals, peering into details of their professional and personal lives as the events unfold. It reads like a John Grisham thriller, but it teaches you everything you need to know about how some drug companies have used their marketing and legal muscle to lie about science.

The centerpiece of the book is study 329, a placebo-controlled clinical trial of Paxil (paroxetine) for the treatment of children and adolescents with depression. This study, first-authored by Martin Keller, then and now the chairman of Brown’s Department of Psychiatry, was published in the leading child psychiatry journal in 2001. Here is the abstract from the Journal of the American Academy of Child and Adolescent Psychiatry. As you can see, the conclusion reads: “Paroxetine is generally well tolerated and effective for major depression in adolescents.” As it turns out, it was neither tolerated nor effective.

Bass describes the experience of the lead investigating attorney, Rose Firestein, as she first read study 329:

Downloading the study onto her computer, Firestein read the full text of the report and read it again. And again. She grew increasingly baffled. It appeared as if the positive conclusion in the abstract simply did not correspond to the actual data.

One of the fun things about this book is that you can participate in solving the mystery as you read. Thus, I, too, downloaded the study and tried to see the problems Firestein detected—and believe me, it wasn’t easy, because so many different outcome variables were analyzed that it’s like cutting through a jungle with a machete to figure out where the relevant result are.

This, of course, was part of the problem. The study went on a fishing expedition after the data came in, looking for a measure that would make Paxil look good, because the two primary outcomes were negative. This has been compared to changing the score of a football game by moving the goalpost after the last quarter.

But such manipulations are already so well known that they are no great surprise. What is surprising is how deliberately the drug company went about deceiving us. In a confidential memo from GSK’s Medical Affairs team that was revealed anonymously, we learn that the company knew exactly what it was doing. To quote again from Side Effects:

The memo acknowledged that study 329 had “failed to demonstrate a statistically significant difference from placebo on the primary efficacy measures.” Even so, “a full manuscript will be progressed,” the memo’s authors wrote. “It would be commercially unacceptable,” they added, “to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.”

And it goes on. I don’t want to steal any more thunder from this magnificent book, so I encourage you to get your own copy. Just don’t expect to get much sleep for a couple of days after you start it, because you won’t be able to put it down.

7 comments:

therapyfirst said...

I've read books like this, including the other two you mention by Kroop and Angell, so I personally do not need to read another. The reality of this matter, which I know you either won't say or can't say, is that too many of our colleagues are out of touch with the reality of responsible health care interventions, and with the ever growing negativity that goes on about our field in the press, internet, and general discussions on the street, WHEN our field has been deemed irrelevant by the masses, we will have mostly ourselves to blame.

When S Preskorn, from Kansas who is a well know psychopharmacologist (had a column in the journal J of Psychiatric Practice for years up to around 2001), wrote in a column around 1997 that suggested that paroxetine's high affinity for 5HT reuptake receptors was not the most positive attribute to this drug, I heard that and began to use it a lot less; now I hardly prescribe it unless it is fully warranted and a third line + choice. Well, sorry to sound a bit arrogant, but good for me and my patients! As I have written here for months, WHEN we learn more of Seroquel's toxicities being known but supressed, I wait with glee when our colleagues who have written for it like pez get nailed to the wall. I hope you give some more thought to write about this when it occurs.

As always, appreciate and enjoy your work. Keep 'em coming!!!

STILL HATE THE WORD VERIF PROCESS!

Stephany said...

Thanks for the review! I recommend watching the film "The Constant Gardener" next

Anonymous said...

This is all really depressing. I am tempted to ask my internist for a prescription for an anti-depressant! Nah, I will just go back and see my former analytic psychiatrist ( a dying breed) for some good old fashioned "working through." Seriously, if your article (and the book) is true, just how does Keller become a Chair of Psychiatry at an Ivy League institution (or any other university, for that matter)? Have these people no shame? Or, has "academic psychiatry" become an oxymoron?

Iowa Doc said...

I have also felt at times that it is futile to try to change the thinking of my colleagues nationally. It sometimes seems that they are hopelessy mired in narcissistic denial. However, I recently attended a meeting of our state psychiatric society that changed my opinion on this somewhat. This was a relatively small meeting of our leadership. We discussed the public's perceptions regarding our society's relationship with Pharma. Initially, there was some resistance to my suggestion that we distance ourselves from Pharma. After all, it was argued, we are so dependent on their funding that we could not possibly sustain our educational meetings without it. But after further assessment of the numbers and options, it began to sink in that maybe we could still pull this off without Pharma money.

It has been my experience that physicians do not respond well to direct challenges or allegations when it comes to their Pharma connections. You can get a lot more traction when you stress the PUBLIC PERCEPTION of this relationship. So then, we can stipulate that the gifts and favors don't have any effect on the physician's judgment, but we remain very concerned that acceptance of these gifts may lead the general public to grow concerned about a conflict of interest. In other words, even if it is all harmless, it doesn't look very good.

My colleagues locally, like most physicians nationally, are all basically good people with honorable intentions. But some of them have been sucked in so far by Pharma that they have lost their perspective. They sometimes don't realize just how corrupt this looks to the average citizen who is on the outside looking in. Books like this may not offer anything new to those of us who already know the score, but they will add even more momentum to the public's desire for change and accountability.

Michael S. Altus, PhD, ELS said...

Danny,

Thank you for your helpful reporting of Side Effects' reporting of study 329's reporting of side effects. Turns out that there’s a lot more reading (and thinking) to do about study 329.

Author Alison Bass described follow-up comments about study 329. Read her June 14, 2008, post, Drug company under fire for Paxil research at http://tinyurl.com/5gthzy.

Anonymous said...

Iowa doc wrote:
"It has been my experience that physicians do not respond well to direct challenges or allegations when it comes to their Pharma connections. You can get a lot more traction when you stress the PUBLIC PERCEPTION of this relationship."

Ah, the classic tactic for dealing with narcissists. Very astute. :-)

Gina Pera said...

therapyfirst wrote:

STILL HATE THE WORD VERIF PROCESS!

--------
Surprise...I agree with you. :-)

Google shows rampant disregard for the time wasted with these idiotic "verifications."

This is what you get, though, when you assemble too many people without empathy in one company. They don't give a damn how much of other people's time they waste--as long as they keep getting their free organic lunches and narcissistic supply.

Some researcher calculated that the collective human energy wasted on these "verifications" totals tends of thousands of hours DAILY. He decided to harness the valuable energy by improving OCR recognition as old periodicals are converted to digital format. Just FYI.

But better that we stop taking what these companies hand out to us without question. It's always dangerous to let machine-like people dictate society's norms.