@article { , title = {Key design elements of successful acute ischemic stroke treatment trials}, abstract = {Purpose: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. Method: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. Findings: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). Discussion: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. Conclusion: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.}, doi = {10.1186/s42466-022-00221-9}, eissn = {2524-3489}, issue = {1}, journal = {Neurological Research and Practice}, publicationstatus = {Published}, url = {https://nottingham-repository.worktribe.com/output/13179941}, volume = {5}, year = {2023}, author = {Yperzeele, L. and Shoamanesh, A. and Venugopalan, Y. V. and Chapman, S. and Mazya, M. V. and Charalambous, M. and Caso, V. and Hacke, W. and Bath, P. M. and Koltsov, I.} }