September 21, 2012

Docs Don't Trust Pharma-Funded Studies

By Nancy Walsh, Staff Writer, MedPage Today

Published: September 20, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Physicians tended to be skeptical of clinical trials funded by the pharmaceutical industry, even if they considered the study design to be methodologically rigorous, an analysis based on hypothetical studies found.

In a survey of board-certified internists, participants expressed more willingness to prescribe a drug evaluated in a highly rigorous hypothetical study (OR 3.07, 95% CI 2.18 to 4.32, P<0.001) than if the trial design was considered to have low methodologic rigor, according to Aaron S. Kesselheim, MD, JD, of Harvard Medical School in Boston, and colleagues.

Yet they were less likely to view a trial as having a rigorous design if industry funding was disclosed -- regardless of the methodologic quality of the study -- than if no funding source was provided (OR 0.63, 95% CI 0.46 to 0.87, P=0.006), the researchers reported in the Sept. 20 New England Journal of Medicine.

Prominent medical journals have made major efforts in recent years to provide conflict of interest information for published studies, but considerable skepticism remains on the part of clinicians regarding potential bias.

To explore the effects of funding disclosures on physicians' perceptions of study credibility, the researchers asked 263 physicians to examine a series of abstracts describing drug trials for three hypothetical newly approved drugs, and to rate their impressions of the studies and their willingness to accept the results.

For each of the three drugs, the researchers constructed an abstract that reflected a highly rigorous trial -- being randomized, double-blinded, having a large sample size and long follow-up, and providing safety data -- as well as abstracts that would be considered as reflecting medium- or low-level rigor.

All the abstracts reported that the results were statistically significant.

Each abstract then was amended to report no funding, industry funding, or support by the National Institutes of Health (NIH).

The median age of survey participants was 48, and more than two-thirds were men.

Participants reported having read a median of four journal abstracts within the previous month that related to prescription drugs.

When presented with simulated studies having low, medium, or high degrees of rigorous design, clinicians were likely to correctly identify high-quality trials (OR 3.95, 95% CI 2.81 to 5.55, P<0.001).

They also reported being more confident in the results of studies they considered highly rigorous (OR 2.73, 95% CI 1.95 to 3.82, P<0.001), and that they would be more willing to prescribe drugs evaluated in these trials.

But they reported having less confidence overall in studies sponsored by industry (OR 0.71, 95% CI 0.51 to 0.98, P=0.04), and being less likely to prescribe drugs from those studies (OR 0.68, 95% CI 0.49 to 0.94, P=0.02).

Participants also said they were less willing to consider industry-sponsored studies as being "important" than those sponsored by NIH (OR 0.59, 95% CI 0.42 to 0.82, P=0.002).

Physicians' unwillingness to prescribe drugs studied in industry-sponsored trials was greater regardless of whether the study design was high versus medium in rigor (P=0.87) or medium versus low rigor (P=0.83).

Conversely, they were more likely to prescribe a drug evaluated in a trial sponsored by NIH regardless of whether the study design was high versus medium rigor (P=0.81) or medium versus low rigor (P=0.56).

And regardless of sponsorship disclosure or the degree of methodologic rigor, physicians who felt strongly that drug company funding had an influence on trial results were less likely to prescribe a drug than were physicians who disagreed that funding played a role in study outcomes (OR 0.58, 95% CI 0.37 to 0.91, P=0.02).

The findings that the surveyed physicians held negative views of industry-sponsored clinical trials had "important implications," according to the researchers.

"Despite the occasional scientific and ethical lapses in trials funded by pharmaceutical companies, it is also true that the pharmaceutical industry has supported many major drug trials that have been of particular clinical importance," they observed.

The researchers commented that they found it "reassuring" that participants in their survey clearly were interested in the methodologic quality of the hypothetical studies.

However, they noted that if clinicians are overly skeptical about all industry-sponsored studies, major advances in drug treatment could be undervalued.

"Pharmaceutical companies seeking to enhance the appropriate use of important new products or to expand the appropriate uses of existing products must address the attitudes that our survey revealed, so that the credibility of the results of industry-supported trials is more likely to be based on methodologic rigor than on funding sources," Kesselheim and colleagues stated.

Among the strategies his group recommended were avoidance of "selective reporting" of trial results, ensuring the transparency of data, and allowing independent oversight of study endpoints.

In addition, because the physicians surveyed in this analysis rated NIH sponsorship highly, joint funding with industry might encourage trust in results.

"The methodologic rigor of a trial, not its funding disclosure, should be a primary determinant of its credibility," the researchers argued.

The study was supported by the Edmond J. Safra Center for Ethics at Harvard; the Agency for Healthcare Research and Quality; the Robert Wood Johnson Foundation; the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School; and the National Cancer Institute.

One author reported receiving grants from AstraZeneca and Novartis for data monitoring and trial analysis, and two others reported consulting for Merck and Genzyme/Sanofi.

Primary source: New England Journal of Medicine
Source reference:
Kesselheim A, et al "A randomized study of how physicians interpret research funding disclosures" N Engl J Med 2012; 367: 1119-1127.


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