Former Medical Journal Editor Outlines Conflicts of Interest

The pharmaceutical industry's corrupting influence on our medical care system usually gets the most attention. Now its corrupting influence on medical journals has come under fire. Yes they're full of drug ads that prompt the usual suspicions about financial dependency. But that's the least of it, according to Richard Smith, MD, who resigned last year as editor-in-chief of the BMJ (British Medical Journal).

In a recent commentary for the Public Library of Science, a free online medical journal, Dr. Smith identified the less obvious conflicts of interest that surround the most respected form of research, the randomized clinical trial. Whenever a large trial is published in a high-profile journal, it has that journal's implicit stamp of approval and may well receive global media coverage thanks to drug company-financed PR.   A trial with favorable results will generate far more money for the drug companies than a multi-page advertising campaign, according to Dr. Smith, and that's why they spend “upwards of a million dollars” on reprints of the trial to send around the world. Doctors won't necessarily read the reprints, he acknowledges, but the name of a highly respected medical journal will impress them.

Here's the most disturbing element of this scenario: More and more drug companies are getting the results they want because the trials are often rigged. Most drug trials are now sponsored by the drug companies. They can, and often do, design a trial in such a way as to get results that prove a drug's benefit. In fact, several reviews have already found that most of the industry-funded trials have findings that favor the drug. Between two-thirds and three-quarters of trials published in the major journals—Annals of Internal Medicine, JAMA, Lancet, New England Journal of Medicine—are funded by drug companies.

To get FDA approval, a company need only prove its drug is better than nothing (a placebo). But even more profits can be made in that relatively uncommon instance when a drug company compares its newer drug against a competitor's older less expensive drug. The trials can be rigged in a variety of ways, according to Dr. Smith. The comparator drug is purposely given in a weak dose so the sponsoring company's drug will appear more effective. Or, the drug will be compared against a treatment already known to be inferior. Another common technique is designing a trial with multiple endpoints, or goals, such as reductions in stroke, hospitalizations, and then select for publication only those that favored the drug.

How to Misrepresent with Statistics

What's more, medical journals allow trial results to be published in relative risk reduction terms, which make the drug appear more effective than it truly is. A classic example: The top-selling cholesterol-lowering drugs called statins will reduce the risk of having a heart attack by 25%. Would you be inclined to take the drug if the same results were expressed this way? The heart attack rate in the placebo group was 4% and the rate in the statin group was 3%. (The 25% is the difference between the two groups.) Worse, the drug companies often provide journals with incomplete data from their trials regarding drug-related harms.

Some journal editors are fighting back. Last year, a new policy was announced by 11 editors of the world's most prestigious journals, including the New England Journal of Medicine, The Lancet, and Canadian Medical Association Journal. They will not publish results of any trial that has not been registered in a publicly available database before the first participant is enrolled. The policy is aimed at foiling researchers who change the goals of a study while it's in progress and to stop drug companies from withholding the existence of trials that show negative results.

The likelihood of trial results favoring the trial's sponsor is not limited to pharmaceutical research. In a 2003 review of all studies that looked at total hip arthroplasty implants, 75% were commercially sponsored, of which 93% reported positive outcomes; whereas independently funded researchers reported good results in only 37% of the studies.

Dr. Smith calls for more public funding of trials that do head-to-head comparisons of all available treatments for the same condition--that would leave journals to concentrate on critically assessing the trials. He is now chief executive for the European division of UnitedHealth Group, the largest health insurance company in the U.S. , and a board member of   the PLoS Medicine journal.

It remains to be seen whether all medical journals will follow the lead of the 11 that called for the registration of all trials. Success is dependent upon participation of all journals.   How carefully will medical journal editors scrutinize a major trial likely to generate worldwide media attention if their own financial well-being is at stake? When the sale of reprints can have a profit margin of 70%, writes Dr. Smith, “an editor may … face a frighteningly stark conflict of interest: publish a trial that will bring in $100,000 of profit or meet the end-of-the-year budget by firing an editor."

Dr. Smith reports that it took him a quarter of a century editing for the BMJ to wake up to the fact that he was being manipulated. ±

More About the Public Library of Science ( PLoS ) Medicine

When this free online medical journal published its first issue at the end of last year, Dr. Smith noted, "The launch of PLoS Medicine provides an opportunity to reinvent medical journals. Publishers have made money by restricting access to research and limiting the development of new ideas. And I hope that free access to research will encourage greater public understanding of science. It will certainly be a boon for patients, many of whom are even more eager than doctors to access the latest research."   Go to www.plosjournals.org

More About the Registration of Clinical Trials

Last month, the International Committee of Medical Journal Editors updated its policy about the registration of clinical trials. The journals represented by this committee will not publish trials that are not publicly registered by July 1, 2005. The editors have given the drug companies until September 13, 2005 to register ongoing trials. Other journal editors have now joined the committee.

Congress is considering legislation, entitled Fair Access to Clinical Trials Act, which will mandate the early registration of clinical trials.

Maryann Napoli, Center for Medical Consumers © June 2005