A review of available software for adaptive clinical trial design

TL;DR

This review assesses the availability of software for adaptive clinical trial design, highlighting limited code sharing in publications and identifying gaps in software for specific adaptive methods.

Contribution

The paper systematically reviews published articles and repositories to evaluate software availability for adaptive trial designs and highlights areas needing improvement.

Findings

Only 29% of articles shared code.

Mandatory code sharing policies are not always followed.

Limited software exists for biomarker-guided adaptive designs.

Abstract

Background/Aims: The increasing expense of the drug development process has seen interest in the use of adaptive designs (ADs) grow substantially in recent years. Accordingly, much research has been conducted to identify potential barriers to increasing the use of ADs in practice, and several articles have argued that the availability of user-friendly software will be an important step in making ADs easier to implement. Therefore, in this paper we present a review of the current state of software availability for AD. Methods: We first review articles from 31 journals published in 2013-17 that relate to methodology for adaptive trials, in order to assess how often code and software for implementing novel ADs is made available at the time of publication. We contrast our findings against these journals' current policies on code distribution. Secondly, we conduct additional searches of popular code repositories, such as CRAN and GitHub, to identify further existing user-contributed software for ADs. From this, we are able to direct interested parties towards solutions for their problem of interest by classifying available code by type of adaptation. Results: Only 29% of included articles made their code available in some form. In many instances, articles published in journals that had mandatory requirements on code provision still did not make code available. There are several areas in which available software is currently limited or saturated. In particular, many packages are available to address group sequential design, but comparatively little code is present in the public domain to determine biomarker-guided ADs. Conclusions: There is much room for improvement in the provision of software alongside AD publications. Additionally, whilst progress has been made, well-established software for various types of trial adaptation remains sparsely available.