Methods for clinical research in rare diseases

Music City Center 

In rare diseases limited numbers of patients present several challenges to clinical research, including statistical issues. In this presentation, we start by providing an overview of previous initiatives resulting in a range of statistical approaches to clinical research in rare diseases. These include adaptive designs and evidence synthesis, both in frequentist and Bayesian frameworks (Friede et al 2018 Orphanet). To provide perspectives on the current practice, these concepts will be introduced using clinical trial examples including paediatric settings (Gross et al 2020 Kidney International; Papchristofi et al 2024 Pharmaceutical Statistics). Particular emphasis will be given to the integration of randomized controlled trials with clinical registries, also referred to as real world data (Friede et al 2023 Prävention und Gesundheitsförderung). Finally, an outlook for future research methods in rare diseases is provided. Specifically, we will comment on the role in-silico clinical trials might play in small populations including rare diseases and paediatrics.

Adaptive designs

Evidence synthesis

Bayesian statistics

Clinical trials

Model-based drug development

In-silico clinical trials 

Biopharmaceutical Section