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CC BY-NC-ND 4.0 · AJP Rep 2018; 08(01): e25-e32
DOI: 10.1055/s-0038-1635097
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials

Jeanne M. Pimenta
1   Real World Evidence (Epidemiology), GSK, Uxbridge, Middlesex, United Kingdom
,
Myla Ebeling
2   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
,
Timothy H. Montague
3   Clinical Statistics, GSK, Philadelphia, Pennsylvania
,
Kathleen J. Beach
4   Maternal Neonatal Health Unit, GSK, Research Triangle Park, North Carolina
,
Jill Abell
5   Clinical Effectiveness and Safety Clinical Evaluation Science, GSK, Philadelphia, Pennsylvania
6   Janssen Scientific Affairs, Real World Evidence, Philadelphia, Pennsylvania
,
Michael T. O'Shea
7   Department of Pediatrics (Neonatology Section), University of North Carolina, Chapel Hill, North Carolina
,
Marcy Powell
8   Safety Evaluation and Risk Mitigation, GSK, Research Triangle Park, North Carolina
,
Thomas C. Hulsey
2   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
9   Department of Epidemiology, West Virginia University, Morgantown, West Virginia
› Author Affiliations Funding This study was funded by GSK R&D (study number WEUSRTP4174/EPI40607).
Further Information

Publication History

02 May 2017

06 January 2018

Publication Date:
07 March 2018 (online)

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Abstract

Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials.

Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother–neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks' GA.

Results Among 17,912 mother–neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at <31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without.

Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately.

Keywords

neonatal benefit - composite endpoint - preterm birth - preterm labor - gestational age - tocolytics

Supplementary Material

 

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