Decentralized Clinical Trials in the Era of Real-World Evidence: A Statistical Perspective

TL;DR

This paper discusses the statistical considerations and challenges of decentralized clinical trials, emphasizing design, analysis, and regulatory aspects to support their use in real-world evidence generation.

Contribution

It provides a comprehensive statistical perspective on decentralized clinical trials, including design, analysis, and regulatory considerations, which is a novel synthesis in this emerging field.

Findings

Highlights key statistical implications of decentralized elements

Summarizes regulatory guidance and initiatives on DCTs

Provides considerations for design, analysis, and reporting in DCTs

Abstract

There has been a growing trend that activities relating to clinical trials take place at locations other than traditional trial sites (hence decentralized clinical trials or DCTs), some of which are at settings of real-world clinical practice. Although there are numerous benefits of DCTs, this also brings some implications on a number of issues relating to the design, conduct, and analysis of DCTs. The Real-World Evidence Scientific Working Group of the American Statistical Association Biopharmaceutical Section has been reviewing the field of DCTs and provides in this paper considerations for decentralized trials from a statistical perspective. This paper first discusses selected critical decentralized elements that may have statistical implications on the trial and then summarizes regulatory guidance, framework, and initiatives on DCTs. More discussions are presented by focusing on the design (including construction of estimand), implementation, statistical analysis plan (including missing data handling), and reporting of safety events. Some additional considerations (e.g., ethical considerations, technology infrastructure, study oversight, data security and privacy, and regulatory compliance) are also briefly discussed. This paper is intended to provide statistical considerations for decentralized trials of medical products to support regulatory decision-making.