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A Reflection of Treatment Effect or Adverse Events?

Bodil Als-Nielsen, MD; Wendong Chen, MD; Christian Gluud, MD, DMSc; Lise L. Kjaergard, MD

JAMA. 2003;290:921-928.

Context  Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.

Objective  To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.

Design  Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).

Main Outcome Measure  Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.

Results  The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; ² test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.

Conclusions  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 data.

Author Affiliations: The Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark.

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