WSO - February 2024 - 171

Hayward et al.
171
Methods
Stage 1: A working group with expertise in preclinical and
clinical trial design that spanned the domains of stroke
recovery including motor function, cognition, language,
mood, and adjuvants, as well as biostatistics and design
was established. Members were identified through Scopus
searches using keywords (e.g. rehabilitation, stroke, and
trial) and co-chair (KSH/CEL) knowledge of the field.
Stage 2: The core working group (monthly meetings, n = 13
participants) and consultants (involved as required by the
core group, n = 18 participants) defined the challenges and
enablers to optimal control comparator design. Various
methods were used including video-conference meetings
and web-based surveys. The challenges identified were
ranked on a scale from 1 (lowest) to 5 (highest) by core
members for both importance to address and ease of
addressing during design of an optimal control comparator.
A graph theory-based voting system was used to develop
an overall ranked list of challenges.21
Stage 3: The CONSIGN tool was developed through two
rounds of testing. All testers applied the working tool to a
preclinical or clinical trial in development (real or hypothetical).
In Round 1, a one-on-one approach between a
core member and early career consultant researcher (n = 12)
was used. In Round 2, a self-guided approach by international
expert consultant researchers (n = 6) was applied.
Feedback was captured using a structured form with openended
questions: what worked well, what did not work
well, what could be improved? Responses were collated
and reviewed by core members and guided changes to the
tool.
Stage 4: In a hybrid (in-person and virtual) meeting in
Vienna, Austria (December 2022), we systematically
addressed the challenges identified by working through the
CONSIGN tool design, developing exemplar preclinical
and clinical trials to demonstrate the utility of the tool and
establishing recommendations for the field. Inputs from
other SRRRIII taskforce group members (n > 40), as well
as via a seminar plenary session at the World Congress of
NeuroRehabilitation (2022, >100 attendees) were captured
and used to refine ideas and the language used to express
those ideas.
Stage 5: The CONSIGN tool was built in REDCap22 as a
survey instrument to enable users to complete the tool iteratively
for control comparator design. The tool and associated
decision logic were pilot tested by four core working
group members.
Stage 6: The core group developed four preclinical and
clinical trial exemplars using the tool to support future tool
users (Supplemental 1). Minor refinements were made to
the tool because of the varied exemplar trials designed.
Stage 7: The CONSIGN tool was piloted at a workshop
(n > 120 attendees from a variety of neurorehabilitation
domains and clinical training background, American
Society for NeuroRehabilitation
Annual Meeting,
Charleston, USA, April 2023) using a semi-supervised
approach to complete piloting and user testing of the final
version of the tool. There were 84 attempted REDCap
CONSIGN tool entries. Feedback provided by attendees
was used to further refine the tool for a broad audience.
Results
The aggregated ranking of five identified challenges to
control comparator design, according to ease (i.e. easy to
hard) and importance (i.e. low to high), are presented in
Figure 1. The challenge of " identifying appropriate type of
control " was ranked easy to address and very important.
This confirmed the need to develop a decision support tool.
Interestingly, the challenge of " variability in usual care "
was ranked hard to address and of low importance. This
likely reflects that it is near impossible to address usual care
globally from a clinical (e.g. different health care systems
and funding structures worldwide) and preclinical (e.g. different
veterinary guidelines and institutional husbandry
support) perspective. " Understanding the content of the
control and how it differs from the experimental intervention "
was ranked as very important but not easy to address
despite the availability of reporting checklists, for example,
TIDieR. As " feasibility of delivering, monitoring, and
recording control intervention content " was ranked easy to
address, it provided a possible solution to include in the
trial protocol that would ensure that variability in usual care
is captured.
CONSIGN tool
The CONSIGN tool was designed and implemented to provide
decision support for design and development of a control
comparator for a preclinical or clinical trial. We were
inclusive of both participant groups to address the standard
of control design across the discovery pipeline.14 The tool
is accessible at https://www.redcap.link/SRRR-CONSIGN
and the International Stroke Recovery and Rehabilitation
Alliance website https://www.strokerecoveryalliance.com/.
Box 2 provides an overview of the tool. The tool addresses
challenges identified including appropriate type of control
selection (Step 3), threats to internal validity (Step 4),
understanding the content of the control and how it differs
from the experimental intervention (Step 2&6), and feasibility
of the control intervention (Step 5). The tool also
draws upon the established TIDieR checklist.4 In developing
the CONSIGN tool, the core group was driven to make
the content and concepts accessible to all people involved
in designing a trial that explicitly compares an experimental
intervention(s) to a control comparator. While conceived
for stroke recovery and rehabilitation trials, we intentionally
developed the tool in a way that is agnostic to domain
International Journal of Stroke, 19(2)
https://www.redcap.link/SRRR-CONSIGN https://www.strokerecoveryalliance.com/
WSO - February 2024

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