Front Pediatr

. 2022 Apr 15;10:852843. doi: 10.3389/fped.2022.852843. eCollection 2022. https://pubmed.ncbi.nlm.nih.gov/35498783/

Challenges and Pitfalls: Performing Clinical Trials in Patients With Congenital Diaphragmatic Hernia

Suzan Cochius-den Otter ¹, Jan A Deprest ^2 3 4, Laurent Storme ^5 6 7, Anne Greenough ^8 9 10 11, Dick Tibboel ¹Affiliations expand

• PMID: 35498783
• PMCID: PMC9051320
• DOI: 10.3389/fped.2022.852843

Free PMC article

Abstract

Congenital diaphragmatic hernia (CDH) is a rare developmental defect of the lungs and diaphragm, with substantial morbidity and mortality. Although internationally established treatment guidelines have been developed, most recommendations are still expert opinions. Trials in patients with CDH, more in particular randomized controlled trials, are rare. Only three multicenter trials in patients with CDH have been completed, which focused on fetoscopic tracheal occlusion and ventilation mode. Another four are currently recruiting, two with a focus on perinatal transition and two on the treatment of pulmonary hypertension. Herein, we discuss major challenges and pitfalls when performing a clinical trial in infants with CDH. It is essential to select the correct intervention and dose, select the appropriate population of CDH patients, and also define a relevant endpoint that allows a realistic duration and sample size. New statistical approaches might increase the feasibility of randomized controlled trials in patients with CDH. One should also timely perform the trial when there is still equipoise. But above all, awareness of policymakers for the relevance of investigator-initiated trials is essential for future clinical research in this rare disease.

Keywords: clinical trials; congenital anomaly; congenital diaphragmatic hernia; postnatal therapy; prenatal therapy.

Copyright © 2022 Cochius – den Otter, Deprest, Storme, Greenough and Tibboel.