Navigating challenges in pediatric trial conduct: integrating bayesian sequential design with semiparametric elicitation for handling primary and secondary endpoints

TL;DR

This paper introduces a Bayesian adaptive method for pediatric trials that improves handling of treatment effects with limited or conflicting data.

Contribution

The novel approach combines Bayesian sequential design with semiparametric priors to better manage primary and secondary endpoints in pediatric trials.

Findings

Semiparametric priors improve correct treatment effect declarations despite recruitment challenges and prior-data conflicts.

The method shows better stopping for futility compared to parametric priors, especially with smaller sample sizes.

The approach is effective in pediatric trials with limited or contradictory prior data.

Abstract

This study presents a Bayesian Adaptive Semiparametric approach designed to address the challenges of pediatric randomized controlled trials (RCTs). The study focuses on efficiently handling primary and secondary endpoints, a critical aspect often overlooked in pediatric trials. This methodology is particularly pertinent in scenarios where sparse or conflicting prior data are present, a common occurrence in pediatric research, particularly for rare diseases or conditions.

Our approach considers Bayesian adaptive design, enhanced with B-Spline Semiparametric priors, allowing for the dynamic updating of priors with ongoing data. This improves the efficiency and accuracy of the treatment effect estimation. The Semiparametric prior inherent flexibility makes it suitable for pediatric populations, where responses to treatment can be highly variable. The design operative characteristics were assessed through a simulation study, motivated by the real-world case of the REnal SCarring Urinary infEction Trial (RESCUE).

We demonstrate that Semiparametric prior parametrization exhibits an improved tendency to correctly declare the treatment effect at the study conclusion, even if recruitment challenges, uncertainty, and prior-data conflict arise. Moreover, the Semiparametric prior design demonstrates an improved ability in truly stopping for futility, with this tendency varying with the sample size and discontinuation rates. Approaches based on Parametric priors are more effective in detecting treatment efficacy during interim assessments, particularly with larger sample sizes.

Our findings indicate that these methods are especially effective in managing the complexities of pediatric trials, where prior data may be limited or contradictory. The flexibility of Semiparametric prior design in incorporating new evidence proves advantageous in addressing recruitment challenges and making informed decisions with restricted data.

The online version contains supplementary material available at 10.1186/s12874-025-02484-7.

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