When referring physicians and researchers disagree on equipoise: the TOTAL trial experience

Abstract

In this article, we reflect on whether randomized controlled trials (RCTs) are adequate for the clinical evaluation of maternal-fetal surgery for congenital diaphragmatic hernia (CDH), focusing on the role of patients' preferences in the setting up of research protocols, on the requirement of equipoise and on the concept of therapeutic misconception (TM). We describe the conception and setting up of the tracheal occlusion (TO) to accelerate lung growth trial and analyze the ethical dilemmas faced by the research team during that time. Depending on the view adopted regarding the scope of equipoise, there are two ways of dealing with patient's preferences concerning fetoscopic endoluminal TO and expectant management during pregnancy for CDH. The solution adopted for fetoscopic endoluminal tracheal occlusion (FETO) is justified by the extended period of time it has been available to patients before the start of the RCT. Strong patient and referring physician preferences do not entail a right to have FETO, since it is a procedure of yet unproven efficacy and safety. In the future, to avoid the dilemmas posed by the TM and in name of the right of future generations of patients to have access to treatment of proven safety and efficacy, researchers must be able to plan RCT in due time.