Treatment Success in Cancer: Industry Compared to Publicly Sponsored Randomized Controlled Trials

Abstract

ObjectiveTo assess if commercially sponsored trials are associated with higher success rates than publicly-sponsored trials.Study Design and SettingsWe undertook a systematic review of all consecutive, published and unpublished phase III cancer randomized controlled trials (RCTs) conducted by GlaxoSmithKline (GSK) and the NCIC Clinical Trials Group (CTG). We included all phase III cancer RCTs assessing treatment superiority from 1980 to 2010. Three metrics were assessed to determine treatment successes: (1) the proportion of statistically significant trials favouring the experimental treatment, (2) the proportion of the trials in which new treatments were considered superior according to the investigators, and (3) quantitative synthesis of data for primary outcomes as defined in each trial.ResultsGSK conducted 40 cancer RCTs accruing 19,889 patients and CTG conducted 77 trials enrolling 33,260 patients. 42% (99%CI 24 to 60) of the results were statistically significant favouring experimental treatments in GSK compared to 25% (99%CI 13 to 37) in the CTG cohort (RR = 1.68; p = 0.04). Investigators concluded that new treatments were superior to standard treatments in 80% of GSK compared to 44% of CTG trials (RR = 1.81; p<0.001). Meta-analysis of the primary outcome indicated larger effects in GSK trials (odds ratio = 0.61 [99%CI 0.47–0.78] compared to 0.86 [0.74–1.00]; p = 0.003). However, testing for the effect of treatment over time indicated that treatment success has become comparable in the last decade.ConclusionsWhile overall industry sponsorship is associated with higher success rates than publicly-sponsored trials, the difference seems to have disappeared over time.

Impact of industry collaboration on randomised controlled trials in oncology

“…15,36 These relationships are likely relevant in studies with industry collaboration as well as in those that are not industry funded, which may blunt the impact of collaboration itself. However, simple industry funding has been associated with positive results in oncology trials, 18 with a similar effect size as in the literature overall, 5 so a fundamental difference between oncology and other areas is unlikely.…”

“…First, it may reflect a general evolution over time with the impact of industry involvement on study results waning in recent years. 18 Most prior studies of the association between funder and outcome reflected older publications 3,4,27 and the single study demonstrating higher rates of positive results among trials with industry collaboration included trials published in 2011– 2012, whereas our study included trials published between 2013 and 2015. A possible shift in recent years may be related to a number of interventions to increase transparency and reduce bias.…”

“…A 2013 systematic review of the relationship between funder and outcome in cancer clinical trials similarly noted that industry funded studies were more likely than those without funding to have adequate allocation concealment and to describe blinding and patient withdrawals. 18 However, other studies have found that funded trials are more likely than those without industry funding to use a modified ITT compared with an ITT analytic approach, 23 though whether this results in bias is controversial. 19,24 While prior authors did not differentiate studies with industry collaboration from those with simple funding, we found higher rates of blinding and modified ITT only in collaborative studies; there was no difference between studies with industry funding alone and unfunded trials.…”

“…9,18 Further, funded trials have similar quality of study design 6 and perhaps higher rates of appropriate blinding 18 compared to unfunded trials. However, studies have not differentiated trials with industry funding alone from funded trials in which industry collaborated in the design, analysis, or reporting.…”

Network meta-analyses performed by contracting companies and commissioned by industry

“…Low publication rates have been found for randomized clinical trials in many fields, [9–13] and specifically in industry-sponsored trials [9, 10, 12]. Industry-sponsored trials that did get published have been shown to more often find a treatment effect in benefit of the sponsor’s treatment [14, 15]. Additionally, examples exist of intentional withholding of trial reports from publication due to results not in favor of the sponsor’s drug [16].…”