PUBLICATION & CITATION BIAS IN FAVOR OF INDUSTRY-FUNDED RESEARCH?
In last week’s column (www.doctorwascher.com/Archives/9-21-08.htm), I raised the issue of potential biases being introduced into the publication of clinical research studies when the manufacturer of a drug or medical device provides funding for such research projects. Multiple previous assessments have reported that industry-sponsored studies far more frequently come to favorable conclusions regarding the products manufactured by their sponsors than similar studies (including other studies that have evaluated the very same devices and drugs) that have been funded by government or non-industry philanthropic sources. Moreover, manuscripts from studies that report “positive” findings (i.e., studies that report a beneficial effect of a treatment being studied) are more likely to be published in leading medical journals than similar studies with “negative” conclusions. Interestingly, this “positive publishing bias” has been confirmed for submitted manuscripts irrespective of the source, or sources, of research funding utilized to conduct these clinical research studies.
Now, a newly published research paper in the journal Circulation adds further objective evidence that the increasingly common trend of conducting clinical research with industry dollars significantly improves the likelihood that such research will be accepted for publication in the most prestigious medical journals, and that such studies will also receive far more widespread distribution in the world’s medical literature than comparable studies underwritten by government and non-industry philanthropic sources.
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The results of this study were eye-opening, and potentially very worrisome. The median (midpoint) number of citations per year for research trials funded entirely by for-profit industry sponsors was 46, while the median number of citations per year for studies jointly funded by for-profit and not-for-profit sponsors was 37. More strikingly, compared to the median of 46 citations per year for purely industry-sponsored studies, the median number of citations per year for published research studies funded solely by government grants was a meager 29.
When the authors of this study then looked specifically at those cardiovascular medicine research studies that found the new treatments to be better than standard treatments, the bias against studies not sponsored by for-profit industry sources became even more dramatic. The median number of citations per year for the for-profit industry-sponsored “positive” research studies was 52, while similar research studies that were funded by government and other not-for-profit sources managed only 25 citations per year in the world’s published medical literature!
As if the data presented so far wasn’t provocative enough in suggesting that industry-sponsored “positive” research studies get a much larger share of the limelight in the world’s medical literature (i.e., compared with non-industry-sponsored research), when the authors of this newly published analysis then looked at the number of citations per year being reported for “negative” studies that identified a worse outcome with the new treatments being studied, the results, once again, strongly suggested that a powerful publishing and citation bias exists in favor of industry-sponsored “positive” research studies. Among those clinical research studies that identified a worse outcome associated with new treatments, the median number of citations per year was 33 for industry-sponsored “negative” trials and 41 citations per year for the “negative” studies that were funded by not-for-profit sources.
All of the above biases in favor of for-profit industry-sponsored clinical research studies, and against government-sponsored studies, held true even when the same clinical issues and treatments were being addressed by both types of studies, and even when both types of studies were published back-to-back in the very same journal!
Perhaps you are not surprised by these findings, or perhaps, on the other hand, you may wonder what these apparent publication and citation biases have to do with the price of tea in China (or, say, with the way that Medicine is practiced by the doctors who care for you and your loved ones…)? In fact, these biases, which continue to strongly favor the publication and citation of research underwritten by for-profit companies (and whose products are being assessed in these very same studies), can indeed have a profound impact on how your doctor may choose to treat you and his or her other patients.
Like most doctors these days, I try to ensure that my clinical practice guidelines for various diseases follow an evidence-based approach. That is to say, I rely heavily upon recently published research studies, and particularly those studies that have been published in the world’s most prestigious medical journals, to inform me about the safest and most effective way to treat the illnesses that patients come to see me about. Thus, if these exalted sources of cutting-edge clinical research information are preferentially publishing clinical research studies that are underwritten by the very same companies that manufacture the drug or device being studied, while at the same time they are apparently declining to publish similar research studies that have been funded by unbiased governmental funding sources, then I, and with most other doctors, become far more likely to recommend treatments that are being underwritten by the very drug or device companies (and who are clearly not unbiased) that manufacture and market the same treatments being evaluated in these studies.
Unfortunately, clinical researchers, and their academic institutions, are under enormous pressure to accept research funding from the deep pockets of for-profit industry sponsors. Because of a continuing decline in the availability of government-based funding for clinical research (and especially for the younger generation of clinical researchers who may not already have an elaborate history of previous government grants), many researchers find themselves between the proverbial rock and a hard place. In the end, many clinical researchers end up making rather Faustian deals with industry sponsors because they cannot find alternative (non-profit) sources of funding. Although the precise impact of these publication and citation biases on the quality and cost of medical care is difficult to measure, multiple drugs and medical devices have recently been taken off the market by the FDA due to belated findings of severe, and even lethal, side effects associated with treatments that were originally lauded within industry-sponsored clinical research trials, and which, after being published in some of the world’s most exalted medical journals, were then expeditiously approved for marketing by the FDA.
Despite recent efforts of the editorial boards of many of these same prestigious journals to demand, from all researchers, full disclosure with respect to their funding sources, the deck still remains stacked against the publication and citation of important clinical research that has been conducted with funding from government agencies and non-industry not-for-profit philanthropists, and most especially for those studies concluding that a new treatment is inferior to existing (and often less expensive) treatments. The best way to rectify this pernicious and potentially harmful source of bias is quite simple: provide qualified researchers with adequate sources of government-based funding to allow them to conduct meaningful clinical research studies.
Government-based sources of funding could also be further supplemented by not-for-profit philanthropic organizations that are able to prove that they have no potential conflicts of interest with regards to the treatments being evaluated, and that will agree to completely abstain from attempting to influence the conduct of the research, the interpretation of the resulting data, the composition of the study’s manuscript, and the submission of the manuscript to specific medical journals.
In addition to all of these initiatives, the editorial boards of all medical journals need to come together and jointly agree to eliminate their continuing biases in favor of industry-sponsored studies, as well as their ongoing biases against otherwise high quality research studies that reach negative conclusions about the treatments that they are assessing. It is only in this way that we can reduce the risk of skewing the world’s published medical literature in ways that are very likely to drive up both the risks and costs associated with providing medical care in our already over-burdened and under-funded healthcare system.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
Dr. Wascher's Archives:
9-21-2008: Does TylenolŪ (Acetaminophen) Cause Asthma?
4-27-2008: Stents vs. Bypass Surgery for Coronary Artery Disease; The “DASH” Hypertension Diet & Cardiovascular Disease Prevention; Testosterone Therapy for Women with Decreased Sexual Desire & Function
4-6-2008: Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality