Friday, March 13, 2009

Massachusetts fraud case exposes deep flaws in our system of medical research and publication

The news that a Massachusetts anesthesiologist fabricated data in at least 21 studies (and probably more) is disturbing on several counts. First, it raises serious questions about the credibility of the peer review process at all the supposedly respectable journals this doctor published in. Second, it sets in sharp relief what happens when journals do not require researchers to disclose their conflicts of interest, i.e., their financial ties to the drug or medical device companies who stand to benefit from their work. And third, it makes you wonder: where were the institutional review boards at Baystate Medical Center and Tufts Medical School when Dr. Scott S. Reuben (who was affiliated with both institutions) was faking all this research?

In sum, the case of Dr. Reuben, who has been apparently been faking research data for more than a decade, highlights the serious shortcomings in our current system of conducting and disseminating medical research. It also spotlights why the much-heralded disclosure regulations recently promulgated by the state of Massachusetts are not as effective and far-reaching as state officials would have us believe.

The facts first. Baystate Medical Center in Springfield discovered Reuben's extensive fraud last spring after a routine audit of research summaries revealed that Reuben had failed to obtain approval of the hospital's institutional review board for two of his newer studies. As Anesthesiology News was the first to report,"What ensued was the unraveling of what medical ethicists are calling one of the largest instances of research fraud ever reported, a massive scandal that has led to the withdrawal of as many as 21 journal articles."

Many of the studies that were found to have been fabricated are positive findings about painkillers like Vioxx, Celebrex, Bextra and Oxycontin, two of which have since been withdrawn from market because of their untenable side effects (an increased risk of heart failure). Also tainted is a study purportedly showing the value of Effexor, an antidepressant, in reducing pain among patients who underwent a mastectomy because of breast cancer. Now, Reuben may or may not have been getting money from Wyeth, the maker of Effexor, but we do know that, according to The Boston Globe, he was a long-time member of Pfizer's speaker bureau. That means he was getting speaking fees from the drug company that makes Celebrex and Bextra at the very same time he was reporting positive findings about the drugs. Yet none of these conflicts of interest were disclosed in the journal articles he published about these controversial painkillers.

That, to me, is an egregious oversight. It's all well and good if the leading medical journals like the New England Journal of Medicine and JAMA require conflict of interest disclosures from their researchers. But most doctors publish their work in less rigorous journals, among them Dr. Reuben, who published the bulk of his phony research in such second-tier journals as Anesthesia and Analgesia and the Journal of Pain and Symptom Management. The fact that Reuben's results did not raise red flags at these journals says as much about the inadequacy of their peer-review process as it does about their shoddy disclosure policies around conflicts of interest.

The Reuben case is just one more pressing reason why we need a federal Physician Payment Sunshine Act that requires drug and medical device companies to routinely disclose such conflicts of interest to the American public. If Reuben's conflicts of interest had been more transparent, there's a possibility that someone in the field of pain medicine might have questioned sooner why all of his studies seemed to find positive benefits to the drugs he was studying. (Obviously, this kind of scrutiny was not going to come from Pfizer and other drug companies who were only too happy to reward Reuben for his glowing results).

The Reuben case also illustrates the weaknesses in Massachusetts' new regulations banning free gifts to doctors and requiring the disclosure of payments (over $50) to health-care professionals involved in sales and marketing of drugs or medical devices. There is a big loophole in these regulations: they exempt the disclosure of payments to doctors "in conjunction with genuine research and clinical trials," according to the rules posted on the state's Department of Public Health website. What this means is that Reuben (or any researcher) could have been paid a consulting fee to help drug companies plan and disseminate the results of his research to other doctors (at conferences and in journals) and these payments might not have to be disclosed. In an interview, Tom Lyons, a spokesman for the Mass Department of Public Health, said he thinks that consulting payments after a clinical trial is finished would have to be disclosed, but payments while the trial was ongoing would not have to be. "This kind of thing will have to be decided on a case by case basis as questions come up," he said.

One other thing: in the interview with Anesthesiology News, Baystate officers insisted that no patients were harmed by Reuben's fraud. That's a ridiculous assertion. Based on research done by Reuben and others, many patients were given drugs like Vioxx, Celebrex and Bextra, all of which have serious side effects, and they may well have been harmed as a result. If I were a patient who had a heart attack after taking one of these nonsteroidal anti-inflammatory painkillers, I might want to re-examine the culpability of all of the players in this horrendous case of scientific fraud.

4 comments:

tgibbs said...

It is a common misconception that the peer review system is designed to protect against deliberate fraud. Peer reviewers do not normally inspect primary data or conduct site visits of research laboratories. Peer review is an honor system designed to evaluate the interpretation of data; the data themselves are normally accepted at face value. Fabrication of data is likely to be detected by peer reviewers only if the fraudster makes blatant errors such as duplication of data or statistical errors.

Reporting potential conflicts of interest, while a good practice in that it enables readers to evaluate possible bias on the part of an investigator, also offers little protection against fraud. Most people with potential conflicts of interest are not engaged in fraud. Moreover, the motivation for fraud is not limited to receiving private funding; professional advancement and obtaining government grants are also potential motives.

Jerrold Lerman said...

Ms. Bass' assertion that physicians (in this case anesthesiologists) do not disclose conflict of interests when publishing manuscripts or delivering lectures is wrong. With all the disclosures today, it would be the exception that such disclosures did not accompany a published article. However, journals do not investigate whether authors have lied about this matter. Regarding the Institutional review board, most do not have the funds to monitor the conduct of research studies. This is left to the sponsoring company. It is inconceivable to me that the well-known pharmaceutical firms did not audit his research during his ten year term.

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