Are Neonatal Trials Better Conducted and Reported over the Last 6 Decades? An Analysis on Their Risk-of-Bias Status in Cochrane Reviews

Background: The introduction of Neonatology as a subspecialty in 1960 has stimulated an enormous amount of neonatal research. A large proportion of neonatal randomizedcontrolled trials (RCTs) have been included in the Cochrane reviews, within which methodological quality or risk-of-bias (ROB) assessment is an integral feature. Objectives: We described the ROB profile of neonatal RCTs published since the 1950s. Methods: We analyzed individual studies within the Cochrane Neonatal reviews published up to December 2016. We extracted the reviewers' judgments on the ROB domains including random sequence generation, allocation concealment, blinding, incomplete outcome data, and selective reporting. We evaluated blinding of personnel in trials in which blinding was considered feasible. Results: We assessed 1980 RCTs published between 1952 and 2016 from 294 Cochrane Neonatal systematic reviews, with full ROB assessments performed in 848 trials (42.8%). Among the ROB domains, the highest proportion of trials (73%) were judged as satisfactory ("low risk") in handling incomplete outcome data, while fewest trials achieved blinding of outcome assessor (38.4%). In the last 6 decades, a progressive increase has been observed in the proportion of trials that were rated as low risk in random sequence generation, allocation concealment, and selective reporting. However, blinding was achieved in less than half of the trials with no clear improvement across decades (23-44% since the 1980s). Conclusions: Despite steady improvement in the overall quality of neonatal RCTs over the last 6 decades, blinding remained unsatisfactory in the majority of the trials.