618 - Evaluation of Primary Outcome Reporting in Neonatal Clinical Trials

Publication Number: 2603.618

Grace E. Fuller, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States; John Zupancic, Harvard Medical School, Boston, MA, United States; Susanne Hay, Harvard Medical School, Boston, MA, United States; Kim Ruiz-Arellanos, Beth Israel Deaconess Medical Center, Boston, MA, United States; Maria Laura Mourão, Beth Israel Deaconess Medical Center, Boston, MA, United States; Luna Hurtado-A, Beth Israel Deaconess Medical Center, Brighton, MA, United States; Sofia Gnecco, Beth Israel Deaconess Medical Center, Brookline, MA, United States; Santiago Reyes, Beth Israel Deaconess Medical Center, Boston, MA, United States; Marianna B. Castellanos, The Children's Hospital at Montefiore, Bronx, NY, United States; Kristyn S. Beam, Beth Israel Deaconess Medical Center, Needham, MA, United States; Haresh Kirpalani, McMaster University Michael G. DeGroote School of Medicine, Burlington, ON, Canada; Roger F. Soll, University of VT, Burlington, VT, United States; Brian King, Harvard Medical School, Boston, MA, United States

Background: Making the primary outcome and its associated analysis explicit in randomized controlled trials (RCTs) is essential to properly interpret and synthesize study findings. Inconsistent reporting practices may limit comparability across studies.

Objective: To characterize variability in primary outcome reporting, terminology, and classification in neonatal RCTs published between 2018 and 2022.

Design/Methods: A 20% random sample of manuscripts, stratified by publication year (2018-2022), was reviewed from the NeoCanon database, a comprehensive repository of neonatal RCTs. A trained reviewer coded each study for clarity of primary outcome reporting. Studies were coded as Explicit when a primary outcome was clearly labeled by the authors, Implicit when an outcome was emphasized without explicit labeling, and Unclear when no primary outcome was obvious. The reviewer also recorded thematic outcome category, physiologic system, and timepoint classification. Thematic categories encompassed broad groupings such as Physiologic Surrogates (e.g., oxygen saturation or heart rate), Laboratory Parameters (e.g., hemoglobin or bilirubin), Respiratory Support, and Neurodevelopment. Regression analyses assessed changes in reporting over time and evaluated distributions across outcome themes, physiologic systems, and timepoints.

Results: In 304 RCTs, 50.7% explicitly identified a primary outcome, 24.7% implicitly conveyed one, and 24.7% failed to clearly report a primary outcome. However, the proportion of RCTs explicitly identifying a primary outcome increased from 2018 to 2022 (50% vs 62.2%, p = 0.04, Figure 1). The most frequently studied outcome themes were Physiologic Surrogates (15.1%), Feeding & Breastfeeding (12.8%), and Laboratory Parameters (12.8%). Physiologic systems most represented were Respiratory (17.1%), Growth/Nutrition (11.2%), and Gastrointestinal (10.2%). Outcome assessment timepoints were most often Immediate ( < 24 hours, 33.9%) and Short-term ( < 28 days or until discharge, 25.7%). Except for neurodevelopmental outcomes, long-term outcomes were infrequently reported as the primary outcome (>6 months, 7.9%).

Conclusion(s): Nearly half of neonatal trials failed to explicitly identify a primary outcome, and most prioritized short-term physiologic measures over long-term, patient-centered endpoints. These patterns underscore inadequate outcome reporting and highlight the need for standardized reporting practices to improve the interpretability, comparability, and clinical relevance of neonatal trial evidence.

Characteristics of Included Neonatal Randomized Controlled Trials (2018-2022)


Trends in Outcome Reporting Clarity (2018 - 2022)
Studies were coded as Explicit when a primary outcome was clearly labeled by the authors, Implicit when an outcome was emphasized without explicit labeling, and Unclear when no clear primary outcome was obvious.

Distribution of Top Outcome Themes by Timepoint Classification (2018-2022)
The Acute timepoint captures Immediate ( < 24 hours), Early (1-7 days), and Short-term ( < 30 days or until discharge) outcomes. Intermediate outcomes were assessed at < 6 months, while long-term outcomes were > 6 months.