A review of available software for adaptive clinical trial design.

Graham Mark Wheeler,Michael John Grayling

doi:10.1177/1740774520906398

Graham Mark Wheeler, Michael John Grayling

Open Access

https://doi.org/10.1177/1740774520906398

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Abstract

Background/aims:The increasing cost of the drug development process has seen interest in the use of adaptive trial designs grow substantially. Accordingly, much research has been conducted to identify barriers to increasing the use of adaptive designs in practice. Several articles have argued that the availability of user-friendly software will be an important step in making adaptive designs easier to implement. Therefore, we present a review of the current state of software availability for adaptive trial design.Methods:We review articles from 31 journals published in 2013–2017 that relate to methodology for adaptive trials to assess how often code and software for implementing novel adaptive designs is made available at the time of publication. We contrast our findings against these journals’ policies on code distribution. We also search popular code repositories, such as Comprehensive R Archive Network and GitHub, to identify further existing user-contributed software for adaptive designs. From this, we are able to direct interested parties toward solutions for their problem of interest.Results:Only 30% 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 adaptive designs.Conclusions:There is much room for improvement in the provision of software alongside adaptive design publications. In addition, while progress has been made, well-established software for various types of trial adaptation remains sparsely available.

Highlights

Both the U.S Food and Drug Administration and the European Medicines Agency have recognized that adaptive designs (ADs) could become key in drug development.[3,4]
We review articles from a variety of journals that publish AD methodology, assessing how often code/software are provided alongside publications and how these results compare with the policies of these journals
In another six articles (2.4%), code was either released as a downloadable package/standalone software (4/6), or the functions were incorporated into an existing package (2/6)

Summary

Introduction

One suggestion that has received much attention is that adaptive designs (ADs), which permit data-dependent modifications to be made to a trial’s conduct through a series of prospectively planned interim analyses, should be used more often. Both the U.S Food and Drug Administration and the European Medicines Agency have recognized that ADs could become key in drug development.[3,4]. Overviews can be found in several recent monographs.[5,6,7] guidance is available on when and why ADs may be useful, as well as on how to run such studies.[8,9,10,11] Recommendations on how to report adaptively designed clinical trials are under development.[12]

Methods

Results

Conclusion