Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review

Abstract

Objective To assess the eligibility criteria and trial characteristics among contemporary (2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation).Study design PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28 weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale.Results Among RCTs (n = 201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n = 301) of criteria. Fifty-five RCTs (27.4%) included infants <24 weeks of gestation; 454 (1.4%) infants were identified as <24 weeks of gestation.Conclusions The present study identifies sources of variability across RCTs that included infants born extremely preterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.

The challenges of heterogeneity in gestational age and birthweight inclusion criteria for research synthesis on very preterm birth and childhood cognition: An umbrella review and meta‐regression analysis

“…The problems for systematic reviews posed by methodological heterogeneity in primary studies are the justification for initiatives such as COMET 34 to define common data sets for clinical trials, 35,36 and several of these have focused on pregnancy outcomes and neonates. [37][38][39] Similar initiatives would be helpful for establishing guidelines for inclusion criteria for very preterm or very low birthweight longitudinal cohorts.…”

“…The WHO terminology based on GA 15 may need to be expanded to include higher risk sub-groups used for some studies, such as births <27 weeks, or births close to the limits of viability at <24 weeks (sometimes termed periviable). 36 Furthermore, while GA may be the preferred inclusion criteria, investigators in low-and middle-income countries may continue to opt for BW criteria because of availability and quality of GA measurement. 14,40 Our results also suggest that specific guidelines for reviews with meta-analyses of VPT birth are needed.…”

“…Similar initiatives would be helpful for establishing guidelines for inclusion criteria for very preterm or very low birthweight longitudinal cohorts. The WHO terminology based on GA 14 may need to be expanded to include higher risk sub‐groups used for some studies, such as births <27 weeks, or births close to the limits of viability at <24 weeks (periviable gestation) 35 . Furthermore, while GA may be the preferred inclusion criteria, investigators in low‐ and middle‐income countries may continue to opt for BW criteria because of availability and quality of GA measurement 13,39 …”

“…The problems for systematic reviews posed by methodological heterogeneity in primary studies are the justification for initiatives such as COMET 33 to define common data sets for clinical trials, 34,35 and several of these have focussed on pregnancy outcomes and neonates. [36][37][38] Similar initiatives would be helpful for establishing guidelines for inclusion criteria for very preterm or very low birthweight longitudinal cohorts. The WHO terminology based on GA 14 may need to be expanded to include higher risk sub-groups used for some studies, such as births <27 weeks, or births close to the limits of viability at <24 weeks (periviable gestation).…”