Drug effectiveness trials authored by principal investigators who have financial ties to drug makers are more likely than other trials to report favorable results, according to a study published online January 17 in the BMJ.

Prior studies have shown that industry-funded trials are more likely to be positive than those without industry funding, but these new data suggest that the likelihood of positive results increases when a principal investigator has industry ties, even after controlling for funding sources.

Specifically, trials run by primary investigators with industry ties were more than three times more likely to report positive results than trials led by investigators without such ties, after adjusting for funding source, sample size, study phase, and design and outcome measures (odds ratio, 3.37; 95% confidence interval, 1.4 - 7.9), according to the study by Rosa Ahn, an MD/MPH student at Oregon Health and Science University in Portland, and colleagues.

The authors reviewed 195 randomized controlled trials published in 2013. They focused on drug effectiveness trials because of their direct effect on practices and healthcare costs.

More Than Half Had Financial Ties

Overall, 58% of principal investigators had financial ties to the drug industry in the form of travel expenses, honorariums, consultant fees, or stock ownership.

Among positive studies, the prevalence of a financial relationship between the principal investigators and the funder was 76% (103/136). Among negative studies, the prevalence was 49% (29/59).

US authors were more likely to have financial ties than authors from other countries (70% vs 49%; P < .001).

Of the categories of ties principal investigators reported, the most common was adviser/consultant fees, reported by 39% of principal investigators, followed by speakers' fees and unspecified ties (both 20%) and honorariums and employee relationships (13% each).

"These findings may be suggestive of bias in the evidence base," the authors write.

One strategy for reducing the potential bias is to require publishing of data sets, the authors write. The International Committee of Medical Journal Editors recently proposed that publication of data sets should be a requirement for journal publication, as reported by Medscape Medical News.

"This requirement is increasingly common in other fields of inquiry such as economics," Ahn and colleagues note.

They also suggest it may be time to bring back independent statistical analysis of major randomized controlled trials, a practice largely replaced by transparency measures.

The authors say that among the reasons for the association between financial ties and positive outcomes may be that negative industry-funded studies may be less likely to get published than the positive ones. Also, single-site randomized controlled trials may not draw the interest of journals.

It could also be that the relationship affects the design of the study and its analytical approach, they say.

The authors acknowledge that the study is observational and cannot prove causation; however, they say, "more thought needs to be given to the roles that investigators, policy makers, and journal editors can play in ensuring the credibility of the evidence base."

Company's True Role Key

In an accompanying editorial, Andreas Lundh, MD, from the Center for Evidence-based Medicine at Odense University Hospital in Denmark and University of Southern Denmark in Odense, and Lisa Bero, PhD, professor in the Charles Perkins Centre and Faculty of Pharmacy at the University of Sydney in Australia, said it is important to know the company's true role in the study.

Some industry-linked trials are authored by opinion leaders "who act as window dressing" to add scientific credibility, but such trials are usually influenced by companies with little author input, they say.

They include as a possible reason for more positive results that companies may have a role in the design, such as the population used and comparators. Using an inferior dose of a comparison drug or changing the way outcomes are coded could favor the company's drug, for instance, they write.

"Although journals increasingly require authors to disclose what role a sponsor had in the design, conduct, or publication of a trial, to our knowledge no journals ask authors whether their financial relationships influenced the design, conduct, or publication of a trial," the editorialists write.

Journal editors could also reject work by authors who will not share data and penalize those who do not fully disclose financial relationships.

"Trials with industry funding or authors with financial ties should be interpreted with caution until all relevant information is fully disclosed and easily accessible," they conclude.

This project was not directly supported by any research funds. One coauthor received support from the National Institutes of Health and Veterans Affairs. Another coauthor's work on this article was supported by a Cancer Center Support Grant from the National Cancer Institute to Memorial Sloan Kettering Cancer Center. Dr Lundh is a member of the Danish organization Physicians without Sponsor, which seeks to promote independence from commercial influence in clinical work, research, and education. The other authors and editorialist have disclosed no relevant financial relationships.

BMJ. Published online January 17, 2017. Article full text, Editorial full text

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