A recent study published in the Journal of Arthritis & Rheumatism assessed the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA).
RA is a chronic systemic autoimmune disease that chiefly manifests as inflammatory destructive arthritis, and affects 0.5-1% of adults. Drug therapy options for RA treatment have “remarkably improved over the past fifteen years.” In particular, the discovery and availability of biologics as therapeutic agents for RA treatment was facilitated by the funding of clinical trials from pharmaceutical companies.
The study found that the funding source of RCT’s was not associated with higher likelihood of positive outcomes favoring the sponsored experimental drug. As a result, the authors concluded that “Industry funding was not associated with higher likelihood of positive outcomes of published drug therapy RCTs for RA, and reported better on some key RCT quality measures.
Background
As the article explains, “a dramatic increase in pharmaceutical industry funding and support of biomedical research” over the past few decades,” has “led to strong concerns regarding inappropriate influence of industry funding on the biomedical research. Some studies have shown that industry funded research is associated with an increased likelihood of pro-industry results and conclusions.
RCTs are considered the “gold standard” means to assess healthcare interventions. They are designed to eliminate bias by randomly distributing known and unknown confounding factors. RCTs need to be methodologically sound to eliminate sources of bias that may appear at various stages.
A previous study assessing secular changes in the methodological quality of published RCTs in rheumatology found no differences between industry and non-profit funded RCTs. However, the authors acknowledged that there are no data on the influence of industry funding on outcome of RA drug therapy RCTs. As a result, the objective of their study was to determine the association of industry funding with the characteristics, outcome and the reported methodological quality of drug therapy RCTs for RA.
Methods
Two reviewers independently assessed RCTs conducted in 2002-3 and 2006-7 for the funding source, characteristics, outcome (positive or not positive), and reporting of methodological measures whose inadequate performance may bias treatment effect assessment.
103 eligible RCTs were identified with the following funding sources: 56.3% industry; 18.4% non-profit; 5.8% mixed; and 19.4% unspecified. Outcome could be assessed for 86 (83.5%) of RCT’s.
In assessing the methodological quality of RCT’s, the authors looked at randomization; allocation concealment; blinding; participant flow description; and intention-to-treat analysis. The authors also used an approach to assess publication bias.
Findings
Industry funded RCT’s had a trend towards higher likelihood of non-publication and reported more frequent performance of double-blinding, adequate participant flow description, and performance of intention-to-treat analysis. However, non-profit studies were likely to last longer. Industry-funded RCTs had larger number of study subjects, and were more likely to be conducted in multiple centers and countries. Non-profit funded RCT’s tended to evaluate established drugs and different strategies to use drugs for RA treatment, while industry-funded RCTs focused on assessment of efficacy and safety of newere therapeutic drugs.
These differences, the authors asserted, “clearly highlight the importance of both industry and non-profit sources for funding of RCT’s to generate efficacy and safety evidence for newer as well as established drugs and strategies for their use in clinical care.
The authors acknowledged several advantages to industry funded RCT’s, such as the availability of greater financial resources allows performance of more expensive measures such as double-blinding and more vigorous tracking and follow-up of study subjects. The higher quality of RCTs from industry also may be a product of rigorous requirements set by the Food and Drug Administration (FDA).
There was some concern, however, that the study did not address whether trials asked questions that are relevant to doctors and patients. In other words, the studies were only compared to an inactive placebo pill instead of currently used medications, and therefore, some argue that the study is not practical because it leaves doctors and patients unable to judge whether they would be better off by switching to the new drug.
Conclusion
Ultimately, the study concluded that industry funding of RCTs was not associated with a higher likelihood of positive outcomes favoring the RA experimental drug. An association between industry funding and study outcome was not found when comparing RCTs with any industry funding with those that had no declared industry funding; or when comparing only RCTs that were exclusively industry funded with those exclusively non-profit source funded.
Moreover, no association between funding source and the study outcome was found after adjustment for the type of study drug used, number of study center, study phase, number of study subject or journal IF. Hence, among “published” RA drug therapy RCT’s, the authors found that relatively small differences exist in the study outcomes between those with industry and non-profit funding source.
The lack of industry influence on positive outcomes coupled with the significantly better performance of certain methodological quality measures in industry funded RCTs should dispel the concerns of many about any alleged inappropriate influence of industry funded trials. Studies like this should be replicated in other disease areas to further demonstrate and address concerns about the alleged bias industry funding creates.
Of course the media had to include a critic who discarded the evidence David J. Rothman, who heads the Center for the Study of Society and Medicine at Columbia University in New York, called the findings “interesting” and told Reuters Health that, “It would be nice if industry studies were not biased as the literature suggests … [because] Nobody wants to demonize the industry.”
The more transparent research we have, the more we can address any concerns patients or physicians may have, so that industry can continue to fund these important breakthrough RCTs.