Meaningful clinical outcomes: perspectives of primary caregivers with lived experience of spontaneous preterm birth following spontaneous preterm labor

Abstract

Background: Patient-centered research is foundational to informing the measurement of clinical benefit in interventional studies. Understanding caregivers' lived experience of spontaneous preterm birth (sPTB) resulting from spontaneous preterm labor (sPTL) and characterizing their perspectives on the clinical outcomes of greatest importance and relevance are essential for advancing the development of interventions for the delay or prevention of sPTB.

Objective: This mixed methods study aimed to identify which clinical outcomes deriving from a (hypothetical) successful sPTL intervention are most important and relevant from the caregiver perspective to advance the therapeutic landscape for sPTB resulting from sPTL.

Study design: A targeted literature review was conducted to obtain preliminary insights, which informed the content of semi-structured, qualitative, concept elicitation telephone interviews with primary caregivers in the United States who had a live, singleton sPTB between 23 and 36 weeks' gestational age resulting from sPTL. Primary caregivers were those who self-identified as the parent who gave birth to the child preterm, had assumed the primary caring and parenting responsibility since birth, and understood the child's health-related needs since birth. Interview transcripts were thematically analyzed.

Results: Twenty-four primary caregivers were interviewed. Delaying delivery from sPTL onset was the clinical outcome most associated with a successful intervention for sPTL and considered most important by caregivers due to anticipated subsequent fetal, neonatal, and maternal benefits (which were also perceived as distinct benefits of an intervention). One to 2 days was typically considered the threshold defining a meaningful delay to delivery from sPTL onset. Additionally, caregivers did not view the individual components of the neonatal morbidity and mortality composite endpoint (historically used to measure clinical benefit in trials of sPTB interventions) as equally relevant to their children's experiences, or as equally important due to perceived differences in their severity and potential for causing further health complications.

Conclusions: This study centralizes the primary caregiver's voice regarding which clinical outcomes are most important and appropriate to measure for the demonstration of meaningful clinical benefit in interventional studies assessing the delay or prevention of sPTB. Specifically, caregivers perceived delaying delivery from sPTL onset, typically by a minimum of 1 or 2 days, as the most important clinical outcome. The findings confirm an unmet need for such interventions, provide a benchmark for defining a patient-perceived clinically meaningful time to delivery from sPTL onset, and establish the inadequacy of the traditional neonatal morbidity and mortality composite endpoint from the caregiver perspective. Specifically, caregivers perceived delaying delivery from sPTL onset, typically by a minimum of 1 or 2 days, as the most important clinical outcome. These insights are critical to evolving the therapeutic landscape for maternal and neonatal health, and informing regulatory decision-making on the selection of endpoints to demonstrate meaningful, patient-centered clinical benefit. Further research is necessary to incorporate weighting of the components of the neonatal morbidity and mortality composite endpoint that are most relevant to caregivers' experiences and to establish if, and to what extent, the surrogate endpoint of time to delivery from sPTL onset is reflective of neonatal clinical outcome.

Keywords: clinical benefit; composite endpoint; delay to delivery; endpoint selection; patient-centered; qualitative; treatment outcomes.