Scott Gottlieb, M.D.
The behavior of the New England Journal of Medicine (NEJM) is a case in point, when it rushed onto its Web site a limited and flawed analysis of safety concerns around the diabetes drug Avandia. The publication was timed to get ahead of the Food and Drug Administration's more careful evaluation of the same issues. The journal seemed bent on beating the FDA to the punch. The goal? Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals. The journal's motives were made bare by its own editorial on the matter.
While there are "questions" whether Avandia is associated with certain heart risks--so far unsupported by more rigorous, randomized studies and extensive review by the FDA and other authorities around the world--the NEJM study doesn't add much new insight into those issues because of its own limitations. But you wouldn't know that from the way the Journal hyped its analysis to the media or opined about the study's significance. These facts weren't lost on clinicians and even NEJM's competitors. The Lancet, NEJM's British sister publication, said of the study, "Alarmist headlines and confident declarations help nobody." A top American medical researcher told WebMD, "I can't help but wonder if the NEJM is functioning more like the mainstream press than a scientific journal at this point."
At what cost do political machinations of the medical journals come? When editors pursue a political agenda, it's public health that pays a price.
NEJM said it rushed to post the study on the Web because of its medical importance, but the FDA, which would need to act on any safety issues, wasn't even given a heads up about the study's publication or its findings. Rep. Henry Waxman (D., Calif.), however, seems to have known in advance that it was coming because he issued a substantive press release immediately after the study was posted online. He was even ready with the date and location of oversight hearings aimed at probing the FDA's "handling" of the drug safety issues. Mr. Waxman is trying to add new restrictions to the FDA's drug approvals. The study's primary author, Cleveland Clinic cardiologist Steve Nissen, admitted to the Wall Street Journal that he was in touch with Congress while preparing his analysis. Three days after the study was submitted to NEJM, and before it was published, the FDA commissioner received a letter about Avandia from members of the House Energy and Commerce Committee that seemed to reference the NEJM study.
At what cost do political machinations of the medical journals come? NEJM editors have long favored more drug regulation. But medical journals have also historically played a special role in helping to define medical practice standards. Even decisions they make on how prominently to place a study, let alone how they editorialize about it, are seen as strong signals to clinicians on how doctors should weigh the evidence. So when editors pursue a political agenda, it's public health that pays a price. Degrading an institution that doctors depend on for balanced analysis and fair-minded editorial judgments isn't good for anyone.
In the case of the Avandia study, NEJM editors gave short shrift to the study's flaws. The paper, which re-analyzed the results of 42 earlier studies of the drug found on the Internet, revealed that Avandia might cause a small increase in the absolute risk of a heart attack. But the study that the authors did, called a "meta-analysis" because it aggregates results from lots of studies to generate a larger sample, contained a number of serious limitations.
Among other things, the authors of the NEJM study based their conclusions that Avandia caused a higher heart risk on just a handful of cardiac events, none of which they could go back and verify, because, unlike the FDA, the authors didn't have access to confidential patient records. A few heart events either way might have changed the study's findings. The way data was misused by NEJM will give pause to companies that agreed to more transparency around results of medical studies and who now post their clinical trial data online.
These shortcomings didn't stop NEJM from spinning the preliminary data into the conclusion that Avandia was a troubled drug mishandled by the FDA and comparing it to Vioxx, the pain drug withdrawn by Merck two years ago because it increased risk for heart attacks. Vioxx "represented a similar regulatory failure to insist on large trials of public health importance in a timely fashion," NEJM's editorial states.
Absent was any discussion by NEJM of the drug's benefits, or advice from diabetes experts on how doctors should counsel their patients based on the information.
There have now been too many instances where one of the major medical journals has used editorial decisions about publication and placement of bottom-line medical information as a tool to primarily influence political discourse, rather than informing medical practice. Many journals still hold the line and stick to scientific standards in their decision-making, but face political risks themselves in declining politically minded submission tactics. When it comes to the issue du jour, drug safety, no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval. Yet NEJM and other journals have tried on other occasions to upstage FDA investigations through well-timed but much less complete publications.
Nor is this the first time that NEJM timed release of a deceptive publication to influence political debate. Its now-infamous December 2005 editorial on the Vioxx affair, titled "Expression of Concern," advanced factual distortions that internal NEJM emails later revealed were timed to divert attention away from a damaging deposition that one of the NEJM editors had given in a Vioxx trial and, instead, place blame on Merck.
I have worked on the staff of two leading medical journals, the British Medical Journal and the Journal of the American Medical Association. These institutions fill an invaluable role informing clinical practice and maintaining standards for how rigorous clinical research ought to be conducted. There is a problem when some journals let antipathy for business interests and left-leaning views interfere with the medical decisions that they make, bending standards or stepping outside their mandate, using their prestige and influence in ways that distort medical facts in the aim of influencing political outcomes.
Prestigious biomedical journals are important public health tools, provided they stick to their core business of weighing medical evidence and informing physicians of important practice advances. When they use shortcuts and shoddy analysis to fabricate criticism and doubt of drug regulation, they're no better than some politicians they increasingly comport with.
Scott Gottlieb, M.D., is a resident fellow at AEI.