What's New in Stroke? Phase III Randomized Clinical Trials of 2012–2014

Hart, Robert G.; Ng, Kuan H.; Perera, Kanjana; Shoamanesh, Ashkan

doi:10.1111/ijs.12570

Cited by 1 publication

(2 citation statements)

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“…In this systematic review of 96 acute stroke therapeutic trials published between 2013 and 2020 in 9 high-impact journals, we found that a large proportion (41%) of trials were terminated before enrollment of their maximum planned sample size. This prevalence is similar to the estimate of 38% reported in a review of 34 phase 3 stroke RCTs published between 2012 and 2014 11 but higher than those reported in previous analyses of the general medical literature and cardiovascular-related RCTs, which ranged from 11% to 25%. 14,19–21 We also found higher utilization of prespecified stopping rules (59%), formal interim analyses (57%), and DSMBs (88%) than in previous reports conducted among a broader array of clinical trials.…”

Section: Discussionsupporting

confidence: 85%

“…3,4 Other studies have described the underutilization and underreporting of design features intended to minimize bias and ensure early termination is appropriate, which include the use of prespecified interim statistical analyses, prespecified statistical stopping rules, and the actions and responsibilities of data and safety monitoring boards (DSMBs). 9,10 Although a 2015 study of stroke RCTs reported on the frequency of early termination, 11 a detailed assessment of the reasons for, reporting on, and impact of early termination among stroke trials is lacking. Thus, the primary objectives of this systematic review were to determine the prevalence of early termination among recently published acute stroke trials, document reasons for early termination, describe the use of DSMBs, prespecified interim analyses and stopping rules, and evaluate the quality of reporting on early termination and relevant trial features.…”

mentioning

confidence: 99%

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Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2020: A Systematic Review

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Oostema

Nikroo

et al. 2021

Circ: Cardiovascular Quality and Outcomes

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Background: Termination of a clinical trial before the maximum planned sample size is accrued can occur for multiple valid reasons but has implications for the interpretation of results. We undertook a systematic review of contemporary acute stroke trials to document the prevalence of and reasons for early termination. Methods: We searched MEDLINE for randomized controlled trials of acute stroke therapies published between 2013 and 2020 in 9 major clinical journals. Manuscripts describing the primary results of phase 2 and phase 3 trials of acute stroke care were included. Data on study characteristics and adherence to CONSORT reporting guidelines were abstracted and summarized using descriptive statistics. Where feasible, we compared treatment effect sizes between trials terminated early and those not terminated early. Results: Of 96 randomized controlled trials, 39 (41%) were terminated early, 84 (88%) had a data and safety monitoring board, and 57 (59%) reported a prespecified statistical stopping rule. Among the 39 trials terminated early, 10 were discontinued for benefit, 10 due to logistical issues, 8 for futility, 6 because of newly available evidence, 1 for harm, and 4 for other or a combination of reasons. The median percentage of the maximum planned sample size accrued among trials terminated early was 63% (range, 8%–89%). Only 55% of trials (53 of 96) reported whether interim efficacy analyses were conducted, as recommended by the CONSORT guidelines. When 10 endovascular therapy trials were compared according to early termination status, the effect sizes of trials terminated early for benefit were only modestly larger than those not terminated early. Conclusions: The high prevalence of early termination in combination with the wide variety of reasons underscores the necessity of meticulous trial planning and adherence to methodological and reporting guidelines for early termination. Registration: URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42019128727.

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%