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Generalizability of the necrotizing enterocolitis surgery trial (NEST) to the target population of eligible infants
Rysavy, M. A., Eggleston, B., Dahabreh, I., Tyson, J. E., Patel, R. M., Watterberg, K. L., Greenberg, R. G., Pedroza, C., Trotta, M., Stevenson, D. K., Stoll, B. J., Lally, K. P., Das, A., Blakely, M. L., & Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (2023). Generalizability of the necrotizing enterocolitis surgery trial (NEST) to the target population of eligible infants. The Journal of Pediatrics, 262, Article 113453. https://doi.org/10.1016/j.jpeds.2023.113453
OBJECTIVE: To evaluate whether infants randomized in the NICHD Neonatal Research Network Necrotizing Enterocolitis Surgery Trial (NEST) differed from eligible infants and whether differences affected the generalizability of trial results.
STUDY DESIGN: Secondary analysis of infants enrolled in NEST (born 2010-2017, with follow-up through 2019) at 20 U.S. academic medical centers and an observational dataset of eligible infants through 2013. Infants born ≤1000 g and diagnosed with necrotizing enterocolitis or spontaneous intestinal perforation requiring surgical intervention at ≤8 weeks were eligible. The target population included trial-eligible infants (randomized and non-randomized) born during the first half of the study with available detailed pre-operative data. Using model-based weighting methods, we estimated the effect of initial laparotomy versus peritoneal drain had the target population been randomized.
RESULTS: The trial included 308 randomized infants. The target population included 382 (156 randomized and 226 eligible, non-randomized) infants. Compared with the target population, fewer randomized infants had necrotizing enterocolitis (31% vs 47%) or died before discharge (27% vs 41%). Rates of the primary composite outcome, death or neurodevelopmental impairment, were similar (69% vs 72%). Effect estimates for initial laparotomy versus drain weighted to the target population were largely unchanged from the original trial after accounting for pre-operative diagnosis of necrotizing enterocolitis (aRR [95% CI]: 0.85 [0.71-1.03] in target population vs 0.81 [0.64-1.04] in trial) or spontaneous intestinal perforation (1.02 [0.79-1.30] vs 1.11 [0.95-1.31]).
CONCLUSION: Despite differences between randomized and eligible infants, estimated treatment effects in the trial and target population were similar, supporting the generalizability of trial results.
