Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor

Objective: To map the current status of head-to-head comparative randomized evidence, and to assess whether funding may impact on trial design and results. Study design and Setting: In this cross-sectional survey, we selected the trials with ≥100 participants, evaluating the efficacy and safety of drugs, biologics and medical devices through a head-to-head comparison, from a 50% random sample of the RCTs published in journals indexed in PubMed during 2011. Results: We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only 3 involved truly antagonistic comparisons. Industry sponsored trials were larger, more commonly registered, used more frequently non-inferiority/equivalence designs, had higher citation impact and were more likely to have “favourable” results (superiority or non-inferiority/equivalence for the experimental treatment) than non-industry sponsored trials. Industry funding (odds ratio 2.8, 95%CI: 1.6-4.7) and non-inferiority/equivalence designs (OR 3.2, 95%CI: 1.5-6.6), but not sample size, were strongly associated with “favourable” findings. Fifty-five of the 57 (96.5%) industry-funded non-inferiority/equivalence trials got desirable “favourable” results. Conclusions: The literature of head-to-head RCTs is dominated by the industry. Industry sponsored comparative assessments systematically yield favourable results for the sponsors, even more so when non-inferiority designs are involved.