AMSTERDAM, The Netherlands—New evidence shows that the outcomes in industry-sponsored nutrition research studies, as in industry-sponsored drug studies, are more likely to favor the sponsor's product, rekindling concern over the integrity of clinical trials research.

However, researchers also point out that industry funding, which exceeds research funding by the National Institutes of Health drives rapid expansion of research into newly recognized areas of promise. Martijn B. Katan, MD, comments in an editorial in Public Library of Science, Medicine (PLoS Medicine). "My personal experience makes me reluctant to support a blanket condemnation of industry-supported research, because collaboration with industry has allowed me to discover things that I could not have found otherwise."¹ Dr. Katan, Royal Netherlands Academy of Sciences professor of nutrition at Vrije Universiteit, Amsterdam, in The Netherlands, points to the discovery (in collaboration with Unilever PLC) of the effects of trans fatty acids on heart disease risk and the discovery (in collaboration with Nestlé) of the cholesterol-raising factor in unfiltered coffee as examples.

The data reported in PLoS Medicine by Lesser et al show that the odds of a favorable outcome were four-to-eight times higher for studies funded by the manufacturer of beverages tested than in studies not funded by industry.² A similar analysis in 2003 by Bodil Als-Nielsen, MD, and colleagues, of randomized drug trials found that industry-funded studies were five times as likely to recommend the experimental drug as treatment of choice in trials funded by that product's manufacturer as in trials funded by nonprofit organizations.³ Als-Nielsen et al write, "Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by the data."

In a subsequent systematic review of pharmaceutical industry sponsorship and research outcomes, Joel Lexchin, MD, and colleagues reported that industry-sponsored trials were four times more likely to report outcomes favoring the sponsor than were studies with other sponsors.⁴ The possible reasons include "the selection of an inappropriate comparator to the product being investigated and publication bias."

Kanu Okike, BA, and colleagues with the department of orthopaedic surgery at Harvard Medical School in Boston, Massachusetts, recently examined the associations between financial conflict-of-interest and study outcomes reported at all podium presentations given at the 2001 and 2002 Annual Meetings of the American Academy of Orthopaedic Surgeons.⁵ They report not only that funding influences findings but also that the nature of the financial conflict-of-interest matters.

Conflicts of interest related to research or institutional funding were not associated with increased likelihood of positive study outcomes. "Presentations authored by individuals with a conflict of interest related to royalties, stock options, or consulting or employee status were significantly more likely to describe positive findings," lead author Okike writes.

The magnitude of these associations is interesting. The rate of positive study findings was 98.4% for studies by individuals who received royalties from a sponsor (vs 88% for studies whose authors have no conflict of interest; relative risk 1.1, P = .02), 100% for authors with a conflict of interest related to stock options, and 97.8% in studies whose authors have a conflict of interest related to consultant or employee status.

To help overcome the problem of publication bias, Als-Nielsen et al argue for an international register of all initiated randomized clinical trials, which would include data from unpublished randomized trials, irrespective of funding source or results. Journal editors are increasingly considering lack of registration an absolute bar to consideration of a clinical trial report for publication. In a January 11, 2007, editorial in the New England Journal of Medicine, Jeffrey M. Drazen, MD, and Deborah A. Zarin, MD, describe a situation in which a paper was initially rejected because of incomplete registration on the Web site clinicaltrials.gov, but was ultimately accepted only because a duplicate registration included the needed information.⁶ Drazen and Zarin argue for "a single, informative registration record" which would include a single record for multisite studies, including those conducted in multiple countries.

"We urge investigators, including those who receive funding from the National Institutes of Health or other nonindustry sources, to ensure that the studies they conduct are registered with complete information and to check the registration records for accuracy....The message should be clear to all investigators participating in clinical trials: before you enroll a patient in a study, be sure that there is full and appropriate registration of the trial in a public database approved by the ICMJE (International Committee of Medical Journal Editors, www.icmje.org)."

Reference

1. Katan MB. Does industry sponsorship undermine the integrity of nutrition research? PLoS Med. 2007;4:e6. doi:10.1371/journal.pmed.0040006.
2. Lesser LI, Ebbeling CB, Goozner M, et al. Relationship between funding source and conclusion among nutrition-related scientific articles. PLoS Med. 2007;4:e5. doi:10.1371/journal.pmed.0040005.
3. Als-Nielsen B, Chen W, Gluud C, et al. Association of funding and conclusions in randomized drug trials. A reflection of treatment effect or adverse events? JAMA. 2003;290:921-928.
4. Lexchin Jl, Bero LA, Djulbegovic B, et al. Pharmaceutical industry sponsorship and research outcome and quality: a systematic review. BMJ. 2003;326:1167-1170.
5. Okike K, Kocher MS, Mehlman CT, et al. Conflict of interest in orthopaedic research. an association between findings and funding in scientific presentations. J Bone Joint Surg Am. 2007;9:608-613.
6. Drazen JM, Zarin DA. Salvation by registration. N Engl J Med. 2007;356:184-185.