Seth's Blog

Joseph Biederman is a professor of psychiatry at Harvard. He recently received a far-too-mild sanction for behavior that included this:

Biederman was then placed in charge of the institute and began a study of 40 children between 4 and 6 years old who were given Risperdal [made by Johnson & Johnson] and Lilly’s Zyprexa, another antipsychotic. At the time, Harvard and MGH [Massachusetts General Hospital] rules forbid researchers from running trials with [drugs] if they receive more than $10,000 from a company that makes the drug.

Dr. Jay Amsterdam, a professor of psychiatry at the University of Pennsylvania, recently lodged a very interesting complaint against five authors of a 2001 study that compared Paxil to another drug and placebo for treatment of bipolar disorder. The paper reports research paid for by SmithGlaxoKline, the makers of Paxil.  For a subgroup of patients, it says, Paxil worked better than the other drug and better than placebo. Paxil supposedly had fewer side effects than the comparison drug. Amsterdam accuses the five academic authors of plagiarism — meaning they put their names on a paper they didn’t write (like a student who buys a paper). He also says the paper grossly misrepresents the results (because the subgroup analysis was completely ad hoc and the side effects description utterly wrong). So if they did write it . . .

The paper has been cited hundreds of times.  Given the actual results — Paxil had worse side effects than the other drug, and the subgroup result means little — this is no small matter.

As Spy magazine has said, if you cheat your customers, don’t fire anyone. Email included with Amsterdam’s complaint suggests he was upset because he was not an author on the paper. Why? Well, the study was done at many sites and there could be only one author per site — according perhaps to SmithGlaxoKline. At Penn, the work (enrolling subjects) was first given to a junior faculty member named Laszlo Gyulai. However, Gyulai couldn’t enroll enough subjects. Amsterdam was asked to help and paid for doing so. He ended up enrolling more subjects (12) than Gyulai (7). Yet Gyulai was an author and he was not! This greatly bothered him. He considered it  “misappropriation” of his data, said Gyulai had engaged in “the theft and publication of a professor’s data”, and wanted Gyulai censured. Perhaps Gyulai had considered Amsterdam’s non-authorship okay because many professors who contributed subjects were not authors. Whatever the reason, it appears that authorship was determined by the firm that did the ghostwriting, Scientific Therapeutics Information, presumably following orders from SmithGlaxoKline.

I don’t know why Amsterdam waited ten years to complain. Since 2001, however, the ghostwriting problem has become much clearer. In 2001, Amsterdam complained to his department chair, Dr. Dwight Evans, about the situation. In 2010, Amsterdam learned that Evans had benefited from ghostwriting. That’s how common it was.

There’s also this:

POGO [Project on Government Oversight], in a letter to President Obama [related to Amsterdam's complaint], asked that he remove Amy Gutmann, president of the University of Pennsylvania, from her position as chairman of the Presidential Commission for the Study of Bioethical Issues, until the two cases involving Dr. Evans are fully investigated and resolved.

Chairman! Another indication how common and tolerated ghostwriting is. It is as if an obesity expert, appointed head of the most important obesity committee in the country, charged with recommending how to stop the obesity epidemic . . . is fat.

Perhaps British journalistic phone-hacking has been more common than misrepresentation of results by med school professors but the latter, I’m sure, has done more damage.

Attachments to the Amsterdam complaint. Pharmalot weighs in. Some of the accused defend themselves.

While Forest [Laboratories] applied to the FDA for pediatric use of Celexa [the anti-depressant] and was eventually denied, the company admitted it had marketed the drug to doctors by hiring speakers to tout its benefits for young patients. Forest also admitted it had suppressed the negative results of research in Europe that found Celexa was no more effective in treating depressed children and adolescents than a sugar pill. Fourteen young patients in that study attempted suicide or contemplated suicide, compared with five in the placebo group, court records show.

From this article. Is Forest Laboratories worse than other big drug companies? Probably not. What’s horrible is how this sort of thing — suppression of negative results — keeps happening. It suggests that the evaluation of drugs should be taken entirely out of the hands of drug companies.

In August 2010, John Farber, a reporter at the Milwaukee Journal Sentinel, wrote an article about how a medical device called Infuse, used for spinal surgeries, “went from revolutionary advance [2002] to public health alert [2008].” Bad side effects were common when Infuse was used, far more common than when it wasn’t used. Infuse is a hugely profitable product of Medtronic, the largest medical device company in the United States.

How did the high rate of bad side effects go unnoticed? Farber went on to find that there were unreported conflicts of interest in the journal articles about Infuse. The authors of the articles had received (before and after publication of the articles) large payments from Medtronic, on the order of $5 million per person. The articles themselves greatly underreported side effects. Moreover,

Evidence has accumulated suggesting that the superior clinical results reported by doctors with financial ties to Medtronic have not been replicated when the device was used by doctors who receive no payments from Medtronic.

A whole issue of The Spine Journal has been devoted to the problem and a Senate committee is investigating.

Thanks to Zachary Hamaker.