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. 2024 Feb;19(2):169-179.
doi: 10.1177/17474930231199336. Epub 2023 Oct 12.

Control intervention design for preclinical and clinical trials: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

Kathryn S Hayward  1 , Emily J Dalton  1 , Jessica Barth  2 , Marian Brady  3 , Leora R Cherney  4 , Leonid Churilov  1 , Andrew N Clarkson  5 , Jesse Dawson  6 , Sean P Dukelow  7 , Peter Feys  8 , Maree Hackett  9 , Steve R Zeiler  10 , Catherine E Lang  11
Affiliations

Control intervention design for preclinical and clinical trials: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

Kathryn S Hayward et al. Int J Stroke. 2024 Feb.

Abstract

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.

Keywords: Clinical trial; consensus; control; preclinical; recovery; rehabilitation; stroke.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Scatter plot of aggregated rankings of identified control comparator challenges. 0 = low importance/very hard. 5 = low importance/very easy.
Figure 2.
Figure 2.
Demonstration of how threats may impact control comparator selection and potential mitigation strategies.
See this image and copyright information in PMC

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