Honoraria, Consulting Linked to Positive RA Trial Results

Janis C. Kelly

January 03, 2019

The first study to document the prevalence and structure of financial conflicts of interest (FCOI) among authors of rheumatoid arthritis (RA) randomized clinical trials (RCTs) found no overall impact of authors' FCOI or of funding source on study outcomes. The study did find, however, that trials were more likely to be positive if an author had received honoraria or consulting fees from the sponsoring drug company.

In a study published online December 10 in the journal Rheumatology, Nasim Ahmed Khan, MD, and colleagues report that the prevalence of FCOI among RA drug trial authors increased from 54.2% of RCTs in 2002-03 to 60.5% of RCTs in 2010-11, and 64.4% of RA RCTs had complete or partial industry funding.

The analysis included 146 non-phase 1, parallel-group, drug therapy RA RCTs published during 2002-03, 2006-07, or 2010-11. Interventions tested included traditional disease-modifying antirheumatic drugs (DMARDs), biologics, small molecules, and others. The researchers considered the outcome positive if statistically significant results favored the experimental intervention.

Slightly more than half of the trials (56.8%) had at least one author with an FCOI related to the industry sponsor. Of these authors, 43.2% were employees of the sponsoring company, 33.6% had received honoraria or consultation fees, 20.5% had received research grants, and 19.2% owned stock in the company.

Positive study outcomes were not associated with reporting of FCOI in general or with author FCOI, but the trials in which an author had received honoraria or consulting fees were three times more likely to have a positive outcome (adjusted odds ratio, 3.24; 95% confidence interval, 1.06 - 9.88).

Clinical Implications of Findings Uncertain

The clinical implications of these findings are uncertain. Although a Cochrane review found that industry funding of RCTs was associated with increased likelihood of pro-industry results, no such association was observed for the RA RCTs. Furthermore, RCTs with an author FCOI did not have a higher likelihood of positive outcome than those without an author FCOI.

Clifford Perlis, MD, Keystone Dermatology Partners, King of Prussia, Pennsylvania, who coauthored an analysis of the extent and impact of industry sponsorship COI in dermatology but was not involved in this study, told Medscape Medical News, "Unfortunately, like most other studies about financial conflicts of interest, this study doesn't do much to help clinicians. We know that financial conflicts of interest introduce conscious and unconscious bias. This study seems to document this with respect to positive study outcomes.

"However, we still can't quantify the degree of this influence (which is likely to vary depending on the conflict, study, and individual) and we have no tools for recognizing how to address this bias. So, the study highlights (again) that there is a problem, but offers no real insights into how clinicians should address this problem," Perlis continued.

Receipt of Honoraria, Consulting Fees May Reflect Researchers' Skill

Khan and colleagues suggest the association with authors receiving honoraria or consulting fees might reflect the fact that such authors are often respected experts in their fields and "may contribute to better study questions and design, and patient population or study outcome selection, in a way that enables more precise assessment of the efficacy and safety of an intervention."

"The trials with FCOIs were larger and more likely to test newer therapies, which may be more effective and thus likely to contribute to more

positive outcomes," they continue. The researchers point out that RCTs with authors who received honoraria/consulting fees had an 83% probability of positive outcomes, independent of trial characteristics."

Perlis explained, "There have been earlier studies showing that industry funding of studies actually improves study quality — based on accepted measures of quality such as blinded, randomized, etc. This would make sense given that industry is generally funding studies that will be scrutinized in FDA applications. As far as why honoraria/consulting fees influence outcome, I don't have any real insights."

The researchers found a temporal increase in RA clinical trial author FOIs from 54.2% in 2002-03 and 52.7% in 2006-07 to 65.1% in 2010-11 (P = .423 for all), but this might be an artifact of more thorough disclosure. "Nearly two-thirds of the RCTs published in 2010-11 had an author FCOI. This is more likely due to better reporting transparency rather than higher FCOI prevalence, because the funding pattern remained unchanged," the authors write.

Unanswered Questions Remain

"I don't see any major gaps in their analysis. If I had a concern, it would be that the primary study outcome — whether or not a clinical trial had a positive outcome or not — may not be the most valuable question to ask. As the authors note in the introduction, this finding has already been fairly well-described in other medical fields, and it's not clear why one would expect a difference in rheumatoid arthritis, specifically," Perlis told Medscape Medical News.

He suggested that more interesting questions might be: Have requirements for disclosure of financial conflicts of interest adversely impacted innovation or patient care? How clinically valuable are studies with financial conflicts of interest vs other studies? How methodologically sound are studies with financial conflicts of interest vs other studies? Do FCOIs inappropriately influence study design?

Perlis added, "In fact, the authors fail to mention at least one study from the oncology literature showing that patients were more likely to participate in a clinical trial if they knew their oncologist had a financial interest in the trial. The reasoning was that this conflict of interest indicates that the doctor is well-known or well-connected in the field."

Dr Khan, study coauthors, and Dr Perlis have disclosed no relevant financial relationships.

Rheumatology. Published online December 10, 2018.  Full text   

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