Systematic review of industry-led versus investigator-led randomized controlled trials

Introduction

Funding sources may influence the focus and conduct of randomized controlled trials (RCTs). We undertook a systematic review to examine differences between industry-funded and non-industry-funded (including mixed funding) RCTs.

Methods

We searched MEDLINE for RCTs that enrolled at least 100 subjects and were published between 1990 and 2009 in five critical care journals (AJRCCM, CCM, ICM, Chest, Shock), two pediatric journals (Pediatric CCM and J Pediatrics), and five general medical journals (NEJM, Lancet, JAMA, BMJ, Ann Intern Med). We screened 1,094 abstracts to identify potentially eligible trials independently, and two investigators abstracted data independently and in duplicate. Statistical analysis was by the Mann-Whitney U test, t test or Fisher's exact test; the α level for significance was set at P < 0.05.

Results

We identified 313 RCTs for which the funding source could be ascertained; 83 (26.5%) were fully industry-funded, 78 (24.9%) had mixed funding, and 152 (48.6%) received no industry funding. RCTs fully funded by industry randomized more patients (median 385 vs. 255 patients, P = 0.0006), used more hospital sites (63.3 ± 92.9 vs. 10.3 ± 14.8, P < 0.0001) and were more likely to originate from North America (51/83; 61.4% vs. 84/231; 36.4%, P < 0.0001). Studies investigating drugs and devices accounted for over 90% of industry-funded RCTS. Non-industry-funded trials were more likely to investigate weaning/ventilation and feeds/nutrition. A higher proportion of industry-funded RCTs recruited sepsis patients (35/83, 42.2% vs. 28/230, 12.1%, P < 0.0001), whereas non-industry-funded RCTs were more likely to randomize neonatal or pediatric patients (22.2% vs. 10.8%, P = 0.02). The number of published critical care RCTs has increased over time, from 34 from 1990 through 1994 to 116 from 2005 through 2009. The proportion of fully industry-funded trials has been constant over time. Reporting of Data and Safety Monitoring Board involvement also increased over time for both industry-funded and non-industry-funded RCTs. Studies investigating drug interventions increased over time for industry-funded RCTs, but has remained relatively constant for non-industry-funded trials.

Conclusions

The total number of critical care RCTs has increased over time; a minority of these is fully funded by industry. Industry-funded trials are larger, more frequently originate from North America, and more frequently target patients with sepsis.