In systematic reviews of research on neuraminidase inhibitors for either prevention or treatment of influenza, authors who had ties to drug manufacturers were much more likely to present the evidence as favorable and to recommend the drugs than were authors who had no such conflicts of interest, according to a report published online Oct. 6 in Annals of Internal Medicine.
“Reviewers with such conflicts of interest were also less likely to address issues with the underlying primary clinical evidence, such as publication bias and the lack of access to comprehensive study data,” said Adam G. Dunn, Ph.D., of the Centre for Health Informatics, University of New South Wales, Sydney, and his associates (Ann. Intern. Med. 2014 Oct.6 [doi:10.7326/M14-0933]).
The findings suggest that “further measures may be necessary to ensure that industry collaborations do not compromise the scientific evidence,” the investigators noted.
“If the benefits of neuraminidase inhibitors are eventually found to have been inflated, millions of patients will have been unnecessarily exposed to drugs that may be of little or no benefit,” the researchers added.
Dr. Dunn and his colleagues observed that reviews of neuraminidase inhibitors had widely divergent conclusions, with some strongly endorsing the agents as influenza prophylaxis or treatment, while others questioned the drugs’ safety and efficacy.
To examine whether industry influence may have contributed to these inconsistent conclusions, the investigators analyzed 26 systematic reviews. Thirteen assessed prophylaxis, and 24 assessed treatment; so, there were 37 distinct assessments. Seven of those were Cochrane analyses.
Two of the investigators read redacted copies of the reviews and rated them as favorable or unfavorable toward the use of neuraminidase inhibitors. Those copies showed no identifying information for the authors and no journal name or formatting clues. The agreement between the two investigators was “strong,” at 86%.
At the same time, Dr. Dunn and his associates searched for all the financial conflicts of interest for all the authors of these reviews, paying special attention to ties to the pharmaceutical companies that made the neuraminidase inhibitors under review. To do so, they went beyond the affiliations and funding listed in the systematic reviews, examining the authors’ personal and institutional websites, as well as disclosure lists provided by GlaxoSmithKline and Roche. They also performed Web searches combining the authors’ names, drug names, and manufacturers’ names.
Reviewers who had ties to the pharmaceutical industry rated neuraminidase inhibitors favorably in 88% (seven of eight) systematic reviews. In contrast, reviewers who had no such ties rated the drugs favorably in only 17% (5 of 29) of systematic reviews. That pattern persisted when prophylaxis and treatment were assessed separately.
Regarding prophylaxis, 100% (2 of 2) of the reviews with financial conflicts of interest were favorable, compared with only 9% (1 of 11) of those without conflicts of interest. Regarding treatment, 83% (5 of 6) of the reviews with financial conflicts of interest were favorable, compared with only 22% (4 of 18) of those without conflicts of interest.
In addition, reviewers who had ties to the pharmaceutical industry were less likely to include information about publication bias in their reports (14%, or only 1 of 7), compared with reviewers who had no such ties (79%, or 15 of 19), Dr. Dunn and his associates said.
The study findings indicate that financial conflicts of interest “are associated with product assessments favorable to the sponsors involved,” the authors asserted.
Factors that may contribute to biased conclusions include “the design of the review, the patient populations and outcomes assessed, the selective inclusion of primary evidence, [and] the critical appraisal of evidence quality and provenance,” the investigators noted. In addition, “the tone, emphasis, and interpretation provided by the authors may also influence the message that is conveyed,” they said.
The Australian National Health and Medical Research Council funded the study. Dr. Dunn and his associates reported having no financial conflicts of interest.