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

Suzan Cochius - den Otter; Jan A. Deprest; Laurent Storme; Anne Greenough; Dick Tibboel

doi:10.3389/fped.2022.852843

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

Suzan Cochius - den Otter^*, Jan A. Deprest, Laurent Storme, Anne Greenough, Dick Tibboel

^*Corresponding author for this work

Women & Children's Health

Research output: Contribution to journal › Review article › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	852843
Journal	Frontiers in Pediatrics
Volume	10
DOIs	https://doi.org/10.3389/fped.2022.852843
Publication status	Published - 15 Apr 2022

Keywords

clinical trials
congenital anomaly
congenital diaphragmatic hernia
postnatal therapy
prenatal therapy

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10.3389/fped.2022.852843

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title = "Challenges and Pitfalls: Performing Clinical Trials in Patients With Congenital Diaphragmatic Hernia",

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",

author = "{Cochius - den Otter}, Suzan and Deprest, {Jan A.} and Laurent Storme and Anne Greenough and Dick Tibboel",

note = "Funding Information: SC-dO and DT were supported by a Grant from the Sophia Children's Hospital Foundation (SSWO 17-29) and CDH UK (16EM01). Funding Information: As to CDH, which is a rare disease, one would hope that the European Reference Networks, launched in 2017, would facilitate clinical research, which was amongst others one of the goals of ERNs. One of these networks is the European Reference Network for rare Inherited and Congenital (digestive and gastrointestinal) Anomalies (ERNICA). The CDH EURO Consortium, which has been existing longer and has a proven track record, is now affiliated with ERNICA, which may help to increase funding and resources. ERNs include patient organizations, but the latter did not wait and have been and still are involved in the funding and development of investigator-initiated trials. Their participation increases the clinical relevance of trials. For instance, the CoDiNOS trial is funded for an important part by CDH-UK, the CDH patient organization in the United Kingdom. Publisher Copyright: Copyright {\textcopyright} 2022 Cochius - den Otter, Deprest, Storme, Greenough and Tibboel.",

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doi = "10.3389/fped.2022.852843",

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T1 - Challenges and Pitfalls

T2 - Performing Clinical Trials in Patients With Congenital Diaphragmatic Hernia

AU - Cochius - den Otter, Suzan

AU - Deprest, Jan A.

AU - Storme, Laurent

AU - Greenough, Anne

AU - Tibboel, Dick

N1 - Funding Information: SC-dO and DT were supported by a Grant from the Sophia Children's Hospital Foundation (SSWO 17-29) and CDH UK (16EM01). Funding Information: As to CDH, which is a rare disease, one would hope that the European Reference Networks, launched in 2017, would facilitate clinical research, which was amongst others one of the goals of ERNs. One of these networks is the European Reference Network for rare Inherited and Congenital (digestive and gastrointestinal) Anomalies (ERNICA). The CDH EURO Consortium, which has been existing longer and has a proven track record, is now affiliated with ERNICA, which may help to increase funding and resources. ERNs include patient organizations, but the latter did not wait and have been and still are involved in the funding and development of investigator-initiated trials. Their participation increases the clinical relevance of trials. For instance, the CoDiNOS trial is funded for an important part by CDH-UK, the CDH patient organization in the United Kingdom. Publisher Copyright: Copyright © 2022 Cochius - den Otter, Deprest, Storme, Greenough and Tibboel.

PY - 2022/4/15

Y1 - 2022/4/15

N2 - 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.

AB - 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.

KW - clinical trials

KW - congenital anomaly

KW - congenital diaphragmatic hernia

KW - postnatal therapy

KW - prenatal therapy

UR - http://www.scopus.com/inward/record.url?scp=85129338977&partnerID=8YFLogxK

U2 - 10.3389/fped.2022.852843

DO - 10.3389/fped.2022.852843

M3 - Review article

AN - SCOPUS:85129338977

SN - 2296-2360

VL - 10

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

M1 - 852843

ER -

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

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