Use of Real-World Data and Real-World Evidence in Rare Disease Drug Development: A Statistical Perspective

TL;DR

This paper reviews how real-world data and evidence are increasingly used in rare disease drug development, highlighting regulatory guidance, current practices, and case studies to support clinical trials and natural history studies.

Contribution

It provides a comprehensive overview of the role of RWD and RWE in rare disease clinical trials, including guidance, current practices, and practical case studies.

Findings

Regulatory guidance documents support RWE use in rare diseases.

RWD and RWE are used in natural history studies and clinical trial design.

Case studies demonstrate successful application of RWD and RWE.

Abstract

Real-world data (RWD) and real-world evidence (RWE) have been increasingly used in medical product development and regulatory decision-making, especially for rare diseases. After outlining the challenges and possible strategies to address the challenges in rare disease drug development (see the accompanying paper), the Real-World Evidence (RWE) Scientific Working Group of the American Statistical Association Biopharmaceutical Section reviews the roles of RWD and RWE in clinical trials for drugs treating rare diseases. This paper summarizes relevant guidance documents and frameworks by selected regulatory agencies and the current practice on the use of RWD and RWE in natural history studies and the design, conduct, and analysis of rare disease clinical trials. A targeted learning roadmap for rare disease trials is described, followed by case studies on the use of RWD and RWE to support a natural history study and marketing applications in various settings.