Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

Kaesmacher, Johannes; Mujanovic, Adnan; Treurniet, Kilian; Kappelhof, Manon; Meinel, Thomas R; Yang, Pengfei; Liu, Jianmin; Zhang, Yongwei; Zi, Wenjie; Yang, Qingwu; Nogueira, Raul G; Kimura, Kazumi; Matsumaru, Yuji; Suzuki, Kentaro; Yan, Bernard; Mitchell, Peter J; Miao, Zhongrong; Roos, Yvo B W E M; Majoie, Charles B L M; Gralla, Jan; ... (2023). Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. Journal of neurointerventional surgery, 15(3), pp. 227-232. BMJ Publishing Group 10.1136/neurintsurg-2022-018665

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Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown.


To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers.


A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results.


There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67).


Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology

UniBE Contributor:

Kaesmacher, Johannes, Mujanovic, Adnan, Meinel, Thomas Raphael, Gralla, Jan, Fischer, Urs Martin


600 Technology > 610 Medicine & health




BMJ Publishing Group




Pubmed Import

Date Deposited:

03 Mar 2022 10:42

Last Modified:

02 Mar 2023 23:36

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Uncontrolled Keywords:

stroke thrombectomy thrombolysis




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