A methodological review of pragmatic designs in acute stroke trials

Randomized controlled trials (RCTs) have traditionally been designed with an explanatory approach, in contrast to incorporating real-world, pragmatic considerations.

This methodological review assesses the uptake of pragmatic designs in Phase III acute stroke RCTs.

We conducted a comprehensive literature search of the MEDLINE, Embase, and Cochrane Library databases from inception to 1 July 2024. Eligible articles included English-language published Phase III RCTs of acute ischemic stroke and intracerebral hemorrhage interventions. Using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) tool, each trial was rated on nine key domains, and relevant study characteristics were extracted. Trials with an average rating of 3 or higher, or a total score (sum of ratings) of 27 or higher (given that all domains were assessed), were considered to adopt an overall pragmatic approach to their design. Risk of bias was evaluated using the Cochrane risk of bias tool.

Of the 5663 unique articles obtained after deduplication, 136 trials were included, and 71 (52%) trials were classified as pragmatic using the PRECIS-2 tool. A majority had a low risk of bias (63.2%). Pragmatic trials were more likely to be large sample, multicenter, multinational trials with broad inclusion criteria that cover multiple types of strokes.

There has been an increased uptake of pragmatic designs in acute stroke over the last decade, reflecting improvements in acute stroke care and a greater consideration of real-world applicability by trialists.