Do we measure the right end points? A systematic review of primary outcomes in recent neonatal randomized clinical trials

Abstract

Objectives: We performed a systematic review of primary outcomes in recently published neonatal randomized clinical trials to determine what end points are chosen for the evaluation of therapies in newborn infants. Methods: MEDLINE was searched in May 1998 for neonatal RCTs that had been published since 1993 in the British Medical Journal , The Journal of Pediatrics , Lancet , The New England Journal of Medicine , and Pediatrics. The primary outcome was identified wherever possible. Continuous measures were distinguished from discrete outcome events. The latter were classified as “long-term” if they were ascertained at least 6 months after birth. The hypothesized relative risk reduction for primary outcome event rates was calculated, where possible. Results: Of 119 eligible reports, 91 had an identifiable primary outcome that was a continuous measure in 46 trials and a discrete event in 45 trials. The median relative risk reduction was 50% for 28 of 40 short-term trials and 40% for 3 of 5 long-term trials. Conclusions: Most authors of recently published neonatal RCTs in 5 high-profile journals either failed to specify a primary end point or chose a continuous outcome measure. Trials with a discrete primary outcome were often short-term and designed to detect large risk reductions. Therefore modest but important treatment effects were likely missed by many of these trials. (J Pediatr 2001;138:76-80)