Coffee Mugs or the Medical Literature: Why Do Doctors Make the Decisions They Do?

Jonathan Leo, PhD / Jeffrey Lacasse, PhD
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In The New Republic, psychiatrist Sally Satel recently reviewed Carl Elliott’s new Book, White Coat, Black Hat: Adventures on the Dark Side. Satel and Elliot have entirely different views about the complex relationship between clinicians and the pharmaceutical industry and the forces at work on the decision making process that clinicians go through when deciding on the best treatment for their patients. Like many others, Elliott is concerned about the problematic role that money is playing in what should be scientific based decisions.  Satel, a fellow at the American Enterprise Institute, does not see a problem with the relationship and provides a less than flattering review of Elliott’s book.  However, following the law of unintended consequences, Satel’s review presents somewhat of a problem for academic medicine, because instead of successfully knocking down his book, she has essentially provided even more evidence to support Carl Elliot’s thesis – that clinical decisions are not strictly based on evidence.  Satel seems to ignore all the countless newspaper articles, magazine exposes, lawsuits, and editorials from the leading medical journals, all of which have revealed the growing problem of commercial influence within the medical literature. 

When it comes to the problematic relationship between doctors and pharmaceutical companies, there are two areas of concern.  If you have ever been a patient, you are probably fully aware of the first problem – the ever present freebies and other trinkets, such as pens, clocks, and tape dispensers that are in many doctor’s offices. Satel is correct that there has been a noticeable effort by everyone involved to move away from this practice, however the free trinkets are not the major problem.  To think that this is the major problem is to miss the forest through the trees. There are probably very few physicians who prescribe drugs because they want a new coffee cup.

Certainly most physicians, including Satel, prescribe a certain medication because they believe it is safe and effective- often because they are persuaded by a peer-reviewed journal article.  All the better if they read the article in a top tier journal like the New England Journal of Medicine, or the Journal of the American Medical Association, authored by a professor from Harvard, Princeton, or Yale.  Satel states: “It is one thing to scorn emblazoned mouse pads and other tchotchkes, but quite another to denounce academic-industry relationships.” In other words, she has it totally backwards. What Satel apparently does not understand, but which Elliott documents clearly in his book, is that the peer-reviewed literature is the real problem – the idea of the sacrosanct “peer-reviewed literature” is quickly becoming more myth than reality.  Prozac and the other antidepressants didn’t become a household name because clinicians thought that the coffee mugs were neat; the antidepressants became household names because the medical literature said they were efficacious and that the side-effects were minimal.  However, we now know that the antidepressants do not work very well in the short term, at least according to the clinical trial literature, and that long-term use of antidepressants appears to have problematic outcomes. 

Given all that has been published over the past several years about the problems with the medical literature- such as ghostwriting and selective reporting of study results- only a very naïve clinician could really believe that the peer reviewed clinical trial literature is an accurate reflection of the true evidence base about a drug. Indeed, medical journal editors are increasingly skeptical, the FDA is skeptical, and medical school deans are skeptical, yet Satel is not? 

You could pick virtually any recent blockbuster drug to illustrate the point that the medical literature is biased, but since they have been in the news lately let’s take the atypical antipsychotics. When Risperdal was coming on the market in 1992 the FDA told Johnson and Johnson that “We would consider any advertisement or promotion labeling for RISPERDAL false, misleading or lacking fair balance under section 502 of the Act if there is a presentation of data that conveys the impression that Risperidone is superior to haloperidol or any other marketed antipsychotic drug product with regard to safety or effectiveness.”  Yet this drug, which according to the FDA, was no better than the older drugs, and cost 30 times more, went on to become Johnson and Johnson’s 4th most profitable drug in 2004. But if the companies couldn’t advertise it as better and safer how did it achieve this success? 

 Risperdal became a blockbuster because the companies could hire prominent physicians and scientists to say the newer generation drugs were better (even though it would be illegal for the company to run an advertisement making this claim).   At company talks, clinicians would hear Key Opinions Leaders (KOLs) tout the drug, and they could read academic articles, supposedly authored by KOLs but often really written by company employees, saying that the newer drugs were better. Such experts certainly should have known the biased and flawed nature of the evidence that they were citing to support the superiority of the new drugs.  And now, somewhat unsurprisingly, a decade later, through various government funded studies, we now know that the atypicals have not lived up to the companies’ claims.  When the results came out, Robert Rosenheck, one of the researchers, said: “What you have is both industry and opinion leaders claiming this is a breakthrough drug. And then three large government-funded studies come out, and none of them finds evidence of a breakthrough.” 

We are now at a point where multiple State Attorneys General are suing antipsychotic manufacturers, claiming that the states were misled into paying for medications that cost more but were no better than the cheaper ones.  Johnson and Johnson just lost a $257.7 million jury verdict over misleading claims about the safety of Risperdal, and the other atypicals are involved in similar suits because of misleading marketing practices.  And to top it off, in spite of the fact that it is hard to find defenders of the practice, the medical community is now prescribing the atypicals to the two most vulnerable populations: children under five, and the elderly.  Ironically, Satel mentions that we need to punish and police the wrong doers. This brings up an uncomfortable question for academics in psychiatry: Rather than suing the pharmaceutical companies, shouldn’t the Attorneys General sue the academics who the companies hired to say exactly what the FDA forbid the companies from saying? 

Although Satel insists that academic-industry relations are not a problem, ghostwriting, perhaps the most egregious practice of all takes place at the nexus of industry and the academy. Take Study 329, a clinical trial of paroxetine for pediatric depression.  The study failed to find a positive effect on any of eight protocol-defined outcome measures  but the resulting publication selectively reported that paroxetine was “generally well tolerated and effective for major depression in adolescents.” The author list included the biggest names in child psychiatry, yet it’s now known that the true author was a ghostwriter. (This came out in court proceedings; we have no idea how many other studies published in the last 15 years were also ghostwritten). When critics pointed out the problems with the study to the editor of the journal, she published an angry reply denouncing the critics - if she only knew what was coming.  The study she defended has gone on to become the quintessential example of the corruption of the medical literature and academic medicine, as subsequent internal company documents were eventually published showing that the company knew that the study was negative, but they were still able to find professors to put their name on a paper which said the findings were positive.  David Healy has said that the research into the use of SSRIs and childhood depression represents possibly the greatest divide in all of medicine when one compares the published studies to the unpublished data.

Unfortunately, the marketing of SSRIs within medical journals is not unique.  No one knows the true extent of ghostwriting but some have suggested that virtually all the clinical trial literature has been ghostwritten. Ghostwriting is not something that happened every now and then with just a few drugs.  As the table attached to this blog posting shows, almost all the blockbuster medications that have been embroiled in lawsuits and fines have had marketing plans which utilized the services of ghostwriters.

Satel also suggests the need for studies to look at prescribing habits before jumping to conclusions: “Only prospective data on the prescribing habits and rationales of real physicians in real medical settings will answer the question.”  But we already have loads of data on the fact that numerous prescriptions for numerous medications have been prescribed for millions of people with little scientific rationale. Pick your drug.  Vioxx was prescribed unnecessarily to millions of people, expensive blood pressure medications continue to be prescribed even though in many cases cheaper diuretics work just as well, the atypicals are prescribed to children under three, Lexapro is prescribed for depression when the only significant difference between it and Celexa is that it costs more. 

Satel also says that all of this in the past.  In her words, “The wild-west days of free ranging-drug salesman, unfortunately keeps alive the impression that corruption, both subtle and overt, is rife.” Elliot’s book does document many instances of obvious (or likely) corruption; for instance, a surgeon who recently testified in front of Congress regarding proper treatment for injured soldiers who was secretly a paid lobbyist for a medical devices company; the death of Jessie Gelsinger in a clinical trial of gene therapy; and again, the fact that peer-reviewed medical journal articles are routinely ghost-authored by pharmaceutical companies. To most, these examples (among many others that could be cited) would seem to obviously point to the fact that corruption is still a problem, but Satel misses the big picture. While most of the general public can’t even comprehend the idea that professors have their articles written by company employees, very few Universities have placed into effect policies that control ghostwriting. And, professors who are known to have been involved in ghostwriting are not scorned for working for pharmaceutical companies in the pages of medical journals to the detriment of evidence-based medicine. Furthermore, several major psychiatry departments in major medical schools are led by chairpersons with a history of being involved in ghostwriting.  The author list for Study 329 included professors from numerous institutions.  Satel says that one solution is for junior faculty to only meet with pharmaceutical reps in the presence of senior faculty members.  But where is the evidence that the senior faculty are more adept at critically thinking about conflicts-of-interest?  In fact, the KOLs come from the ranks of senior faculty members, not the junior members. 

One area that we agree with Satel about is the misguided idea that just because someone has a conflict of interest that they are automatically presumed to be wrong.  But, just because someone has a conflict of interest does not mean that what they say about a medication is tainted. Someone with a large conflict could certainly be correct.  However, there is a flip side to this belief, and quite possibly one reason that the general public is skeptical.  Namely, that when someone is found to be making false statements, or selectively reports favorable data, and subsequently it is determined that they have an undisclosed conflict, surely people will speculate that money is the source of the problem.  Surely this is not the case all the time, but if there were not so many examples of this, then possibly the medical editors, medical school deans, and the general public would not be so skeptical.

Sally Satel’s view of academics and companies working together for the betterment of the patients is a noble one but, when one thoughtfully considers what has gone on during the last ten years, as Elliott has done, it is unfortunately not a realistic view of how academic medicine is functioning. And, even more unfortunately, it will be difficult to solve the problems at the industry-academia interface as long as some are whistling past the graveyard, insisting that the problems do not exist in the first place.

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Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.

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