Key result
US-based RCTs in stroke guidelines drop ~54%, while China-based trials triple.
Why the study?
Despite the rapid growth of clinical trial programs in Europe and Asia outpacing the United States, limited data exist quantifying their relative influence on practice-defining results.
Observational (n=136)
Absolute Event Rate: 14.6% vs 31.9%
p-value: p=<0.01
There has been a significant shift in practice-changing acute ischemic stroke research over the past decade, with decreasing reliance on US-based and NIH-funded trials and increasing contributions from Europe and China.
Clinicians should monitor the shifting geographic sources of stroke evidence; this analysis extends global RCT trends while leaving applicability questions open.
BACKGROUND: The past decade has witnessed rapid growth of clinical trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the United States. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing the geographic origin, funding source, and clinical impact of practice-changing RCTs. METHODS: From the 2018 and 2026 American Heart Association/American Stroke Association Acute Ischemic Stroke guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/United States/Other), funding source (government/academic/nonprofit versus industry (private/mixed); National Institutes of Health versus non-National Institutes of Health), and research topic (endovascular therapy, thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the χ 2 /Fisher exact tests, with the Rao-Scott adjusted χ 2 tests accounting for weighting. RESULTS: We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the United States (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the United States declined to the smallest share (14.6%), across all weighted analyses ( P <0.01). National Institutes of Health–funded trials declined significantly from 21.3% (unweighted), 27.4% (reference-density-weighted), and 27.3% (clinical-impact-weighted) in 2018 to 4.5%, 4.8%, and 3.5% respectively in 2026 ( P <0.01 across all weighted strategies). CONCLUSIONS: In this analysis, we identify a shift in practice-guiding research away from United States–based clinical trials and increasingly towards Europe and China. United States–based RCTs fell from the second most cited to the least cited sources of recommendations. National Institutes of Health–funded RCTs fell from nearly one-quarter of guideline-cited RCTs in 2018 to <5% in 2026, highlighting increasing reliance on non-US studies to inform US clinical care.
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Khalid et al. (2026) conducted an observational in Acute Ischemic Stroke (n=136). 2026 guideline era vs. 2018 guideline era was evaluated on Proportion of United States-based RCTs cited for new recommendations (p=<0.01). Between the 2018 and 2026 AHA/ASA Acute Ischemic Stroke guidelines, the proportion of cited United States-based RCTs declined from 31.9% to 14.6%, while China-based RCTs increased from 8.5% to 29.2%.
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