Pharmageddon (19 page)

A prime indicator of good medical care is an ability to detect treatment-induced injury. When an injury can be traced to a drug side effect, a clash with the pharmaceutical industry is set up. Just as in the struggles between medicine and the tobacco or chemical industries, the interaction between medicine and the pharmaceutical industry has had an extraordinarily nasty side when self-interest is seen to be at stake, with companies using gag orders, appealing to trade secrets, concealing their views as to the risks their drugs pose behind a veil of attorney-client privilege, settling legal actions out of court to hide data and documents, sometimes stalking and harassing academic critics, and co-opting universities with funding.
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But in this domain there is another factor not found with tobacco or industrial chemicals that isolates doctors who attempt to bring the hazards of a drug to light. The problem is that the medical body has now been infected with what could be called a clinical immunodeficiency virus (CIV). The infection enters in the drip feed of science. With industrial chemicals, the best studies systematically point to hazards where they exist, with a number of inferior, often company- sponsored “pseudo-studies” vigorously promoted to create doubt. But with pharmaceuticals, often the only studies are those of the drug companies themselves, and these studies, as one might expect, all seem to point to the benefits of an ongoing use of the very chemicals that may in fact be causing the problem.

There is another side to this infection. If the free market worked properly, given the amount of chemicals being pumped into patients in medicine, doctors eager for their fifteen minutes of fame should be hovering above their patients ready to write articles on any signs of problems stemming from treatment. But instead the literature on treatment-induced hazards is drying up, even though there are estimates that medical treatment is now one of the leading causes of death in hospitals.
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Instead there is a growing silence, and the censorship that brings about this silence is all but invisible.

For most academics it likely seems inconceivable that scientific journals and meetings might be censored, although some might concede that political maturity requires some accommodation with commercial sensitivities. A kind of de facto censorship, for example, occurs because of the premium put on controlled trials—the hazards of treatments are virtually never discovered in controlled trials, and faced with a choice between a ghostwritten account of a controlled trial demonstrating a trivial benefit or a detailed account of a new and potentially serious hazard in a small number of patients, journals will opt for the controlled-trial account each time.

But there is more to the censorship process than this. The best way to bring home what is at stake is to turn to a series of personal examples, from one domain—the risks of SSRI-induced suicides—to illustrate a larger issue.

In 1999, having agreed to testify in a case involving homicide and suicide on Prozac, I learned of company documents showing that Lilly had been aware for years that Prozac might make some people suicidal and indicating the lengths to which the company went to avoid warning of the risk. Although the documents were in the public domain, few people were aware of them. My immediate thought was to write an article outlining the material for the
British Medical Journal.

After the question of Prozac-induced suicide was first raised in 1990 and the first legal actions filed against Lilly, in 199i the
British Medical Journal
carried an article by Charles Beasley and a series of Lilly-only authors. Despite the fact that the data in the article show a 1.9-fold increased risk of a suicidal act on Prozac compared to placebo, this article was widely spun as evidence that there was no risk from the treatment.
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It drew a response from one academic who had a history of difficulties with the pharmaceutical industry: “The BMJ is a journal of distinction and, dare I say it, perhaps also of some innocence. At a time when in the United States the manufacturer of fluoxetine [Prozac] is facing litigation, the corporate defense attorneys will be pleased by the journal having published a piece authored wholly by the manufacturer's employees.”
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But even he seemed unaware the article had appeared in the very week Lilly was facing hearings at the FDA about the risk of suicide on Prozac.

The initial response from the then-editor of the
British Medical Journal
, Richard Smith, to my draft article appeared to recognize that the journal had had a role in the “mistake” in 1991. He seemed to welcome my submission and suggested reframing it as a discursive debate article rather than a data-driven research article. The reframed article was sent to a reviewer, who was apparently not told that it was an article about company behavior and not an evidence-based assessment of the case for Prozac-induced suicidality. The reviewer suggested the article had not established the case for treatment-induced problems— which it had never attempted to do. The editor rejected the piece on this basis. Mystified at the mismatching messages, I appealed, but in vain: in a phone call Smith stated that no matter what revisions I made nothing would be published.
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This article was published unaltered in the
International Journal of Risk and Safety in Medicine
, whose editor, Graham Dukes, also editor of the most authoritative book on drug-induced side effects in the field,
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commented: “It seems to me your approach is original and fair…. I also agree with your remarks about the failure of the present overall research approach to elicit a reliable picture of adverse effects and the sometimes unrealistic defenses put up by industry when their products are the subject of injury litigation.”
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A year later, in 2000, having conducted a blind and randomized trial in healthy volunteers, in which two volunteers had become suicidal on Zoloft, I again contacted the
British Medical Journal
about a submission. Nobody had ever accused Richard Smith of being in the pocket of the pharmaceutical industry; there are in contrast many journals whose editors have previously been employees of the pharmaceutical industry. For those who think conflict of interest is at the heart of all therapy-related problems, the prediction is clear—the
British Medical Journal
should be much more likely to take this article than a journal whose editors have been so closely linked to industry. In fact, even without review, the
British Medical Journal
declined to take the article. So I then sought publication instead in a journal whose editors had a pharmaceutical company background, which seemed to make them less rather than more nervous about offending industry. The paper was peer reviewed and rapidly published.
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What is going on? The following examples help clarify the possibilities. In Spring 2000, the
Hastings Center Report
, a leading bioethical journal, published a special issue, “Prozac, Alienation and the Self,” featuring five articles on the drug.
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Two of these articles suggested that Prozac was so wonderfully effective that it would be a mistake to restrict its use simply to people who are depressed; it should be available to anyone who responded to it. Two further articles argued that even though Prozac was very effective, its use should be restricted to people who are depressed. The fifth article, by me, argued that impressions of Prozac's efficacy stemmed in great part from the fact that negative trials were left unreported, that data on the hazards of the drug were concealed, and that this state of affairs was linked in part to the fact that articles on Prozac and on other psychotropic drugs were increasingly ghostwritten.

Following the publication of this issue of the journal, Lilly, at the time the biggest single outside funder of the Hastings Center, withdrew support, charging that the Center had “published articles that Lilly felt contained information that was biased and scientifically unfounded and that may have led to significant misinformation to readers, patients and the community.”
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Subsequently, in 2003, using the Current Medical Directions portfolio of Zoloft articles noted earlier, I submitted an article to the
British Journal of Psychiatry
on ghostwriting, whose key finding was that a majority of articles that deal with pharmaceutical products in leading journals are likely to be ghostwritten and that these articles do not faithfully report the data on hazards. A clearly nervous journal staff used at least five reviewers (instead of the usual two) and had the revised article re-reviewed—making up to ten reviews. The article was subsequently referred to the journal's legal department and after that the journal's copyeditors pored over the final version for longer than any other article I've ever written. It was finally published after a change in editors.
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A bit earlier, in 2001,
Contemporary Psychology
requested a review of Joseph Glenmullen's
Prozac Backlash
, a book that outlined some of the hazards of treatment with SSRIs. My review outlined the book's key points, without endorsing or countering the position of the author. I also noted that I was in possession of five highly critical reviews of the book written by distinguished American psychiatrists, disseminated by public relations agencies working for Lilly who urged media outlets not to feature the book. I sent the review and the accompanying documents to the editors. Having initially been accepted, the review failed to appear. On enquiring I was told that the journal could not find a balancing reviewer and that they thus could not carry my review. The response made little sense.

In 2004 two journals,
Open Minds
and
Young Mind
, requested articles on the subject of antidepressant-induced suicidality in pediatric populations. Both journals then declined to publish what I submitted on the basis, I was told, of legal advice. They said they did not have the resources to handle any difficulties that might arise with pharmaceutical companies as a result of the articles, and this could put them out of business.

The issues here do not just affect academic journals. In 2005 the
Times Higher Education Supplement (THES)
featured a series of articles on the case of Aubrey Blumsohn, the man described above who had “blown the whistle” on Proctor and Gamble over the ghostwriting of articles and concealment of data on patient responses to Actonel, their blockbuster treatment for osteoporosis.
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I wrote to
THES
to make it clear that Blumsohn's case was not unique. In the new world of medicine, data were routinely withheld and companies threatened to sue periodicals that reported on treatment risks.
THES
offered to publish an amended version of the letter, but the changes they wanted stripped the letter of its meaning. When I suggested their revisions made the letter pointless,
THES
responded, “We have also had to run these letters past our lawyers as this is, as you are aware, a very sensitive issue, and there are certain legal amendments we had to make.” The key amendment seemed to be that the letter could not state that anything the journal published on this issue was constrained by threats of legal action. They did not publish my letter.
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A more striking instance took place in 2007, when I was approached by
Index on Censorship
for a piece outlining evidence “that pharmaceutical companies are not transparent and that medical journals allow this to happen…. I think to an outsider who has certain expectations of science (that data is widely available and that access to data is fundamental in terms of any credibility) it's a baffling and shocking state of affairs.”

The resulting article covered the evolution of ghostwriting and the lack of access to clinical trial data, focusing on Study 329, the biggest study undertaken of the use of Paxil in children who were supposedly depressed. After much back and forth, the editor commented, “Our lawyer's just taken a look at your piece—and I do need to ask you for more chapter and verse on some points.” I complied, and eventually heard this: “I realize this is taking up more of your time than you bargained for and do apologize—lawyers must make you weary by now—but am sure you'll understand that it's necessary.” The process ended with this assertion: “The documents made interesting reading— and certainly answered the concerns—along with the cuts. But I've still got worries about running the piece…. I regret how things have turned out very much. I've appreciated all your help in finding documents and in cooperating with all my requests. As I've said before—it's a hugely important subject and we should be covering it.”
Index on Censorship
self-censored.

Leemon McHenry from Los Angeles and Jon Jureidini from Adelaide in Australia also tried to publish a paper on Study 329, “Clinical Trials and Drug Promotion: Selective Reporting in Study 329,” initially in the
Lancet
and later in the
British Medical Journal.
The
Lancet
sent the paper to GlaxoSmithKline, who objected, and the journal backed down. The
British Medical Journal
then contacted them saying they had heard of their paper and wanted to fast-track its publication. Six months later, the
British Medical Journal
indicated their lawyers still had concerns and they would not publish. They finally published a heavily modified version several years later.
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In 2005, the
British Medical Journal
had a new editor and I submitted an article on how the data on suicide and antidepressants had been manipulated. The peer reviews I received back were longer than the original paper. After answering all queries from two rounds of peer review, the paper was accepted, and proofs of the paper due to appear in the journal two weeks later were sent to me. In the middle of correcting the proofs, I received an email from the editor: “Thank you very much for all your hard work on this article. I'm afraid we've run into a legal wall with our libel lawyer reluctant for us to publish your piece…. I remain supportive of publication but obviously can't do this against legal advice.”