Clinical trials supported by the pharmaceutical industry are more likely to
report positive outcomes than those backed by other sources, and the same
pattern appears to hold for meta-analyses, concluded a review in the October
14 British Medical Journal.
The analysis by Anders Jørgensen, M.D., and Peter Gøtzsche of
the Nordic Cochrane Center in Denmark, and Jørgen Hilden, an associate
professor of biostatistics at the University of Copenhagen, compared pairs of
meta-analyses or reviews that studied the same two drugs used to treat the
One set of these reviews was produced by the Cochrane Collaboration, an
independent international organization that produces and disseminates
systematic reviews of health care interventions. Twenty-four Cochrane reviews
were matched with meta-analysis papers published within two years before or
after the online Cochrane review and with no author in common. The paper
reviews were divided into those supported by industry, those with undeclared
support, and those with nonprofit or no support. Support from the
pharmaceutical industry meant grants, authorship, or major assistance such as
help with statistical analysis.
The authors assessed the methodological quality of the reviews and examined
their conclusions and recommendations.
They found no significant differences when comparing seven Cochrane reviews
paired with those having nonprofit or no outside support, although three pairs
of reviews came to different conclusions about the drugs being evaluated.
Eight industry-supported reviews, however, "should be read with
caution," they said.
"The estimated treatment effects in industry-supported reviews were
similar to those of Cochrane reviews, but the former had uniformly positive
recommendations for the experimental drug, without reservations about
methodological limitations of the trials or costs, in contrast to none of the
Cochrane reviews," wrote Jørgensen, Hilden, and Gøtzsche."
This suggests that the main problem with industry-supported reviews
lies in how conclusions are formulated."
The Cochrane reviews more often avoided bias in selecting studies,
described methods of concealing the patients' allocation to a treatment arm,
described patients who were excluded from a study, used appropriate criteria
for assessing validity, and used more sources to come up with studies to
include in the review.
Reviews with undeclared financial support "were often biased and
poorly done," said the authors. Such studies produced results similar to
industry-supported reviews but were more cautious in their conclusions.
The authors included several pairs of reviews of psychotropic drugs in
their analysis. For instance, a pairing of antidepressant studies found that
the industry-supported review failed to include 12 trials that appeared in the
Cochrane review yet did include 20 unpublished trials with "data on
file." An industry-backed review comparing risperidone and haloperidol
had problems with sample sizes and patient selection.
The Cochrane Collaboration forbids industry support of Cochrane reviews,
although a pharmaceutical company funded secondary analyses of a review
author's own work was included in a review before that policy was
The authors noted that they could not be blinded as to the source of the
articles and that they are all affiliated with the Cochrane Collaboration.
However, they provided details on their working methods to allow readers to
form their own judgments, a practice they believe should extend to all
systematic reviews or meta-analyses.
"Cochrane Reviews Compared With Industry-Supported
Meta-Analyses and Other Meta-Analyses of the Same Drugs: Systematic
Review" is posted at<http://bmj.bmjjournals.com/cgi/content/full/333/7572/782>.▪