The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke

Stephen DJ Makin; Fergus N Doubal; Terence J Quinn; Philip MW Bath; Martin S Dennis; Joanna M Wardlaw

doi:10.1177/2396987317728854

The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke

Stephen DJ Makin, Fergus N Doubal, Terence J Quinn, Philip MW Bath, Martin S Dennis, Joanna M Wardlaw (Corresponding Author)

Applied Health Sciences

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

3 Downloads (Pure)

Abstract

Background: Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints. Methods: We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS /= 3 and 29/158 (19%) had ACE-R /= 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R /= 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke. Conclusions: Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.

Original language	English
Pages (from-to)	66-73
Number of pages	8
Journal	European Stroke Journal
Volume	3
Issue number	1
Early online date	5 Sept 2017
DOIs	https://doi.org/10.1177/2396987317728854
Publication status	Published - 2018

Bibliographical note

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Wellcome Trust (grant 088134/Z/09/A), the Scottish Funding Council and the Chief Scientist Office, Scotland, through the Scottish Imaging Network: A Platform for Scientific Excellence (‘SINAPSE’) and the European Union Horizon 2020 research and innovation programme SVDs@Target under grant agreement 666881. FD and TQ are funded by the Stroke Association/Garfield Weston Foundation and Stroke Association/Chief Scientist Office Senior Lectureships respectively. PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Senior Investigator. The work was supported by the Fondation Leducq Transatlantic Network of Excellence in Small Vessel Disease ref no. 16 CVD 05, and the Horizon 2020 Programme PHC-03-15, project No 666881, ‘SVDs @Target.’ The work was conducted independently of the funders.

Keywords

Stroke cognition dependency
lacunar outcome
power calculation
randomised trial sample size

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Stephen Makin
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Makin, S. DJ., Doubal, F. N., Quinn, T. J., Bath, P. MW., Dennis, M. S., & Wardlaw, J. M. (2018). The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke. European Stroke Journal , 3(1), 66-73. https://doi.org/10.1177/2396987317728854

The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke. / Makin, Stephen DJ; Doubal, Fergus N; Quinn, Terence J et al.
In: European Stroke Journal , Vol. 3, No. 1, 2018, p. 66-73.

Research output: Contribution to journal › Article › peer-review

Makin, SDJ, Doubal, FN, Quinn, TJ, Bath, PMW, Dennis, MS & Wardlaw, JM 2018, 'The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke', European Stroke Journal , vol. 3, no. 1, pp. 66-73. https://doi.org/10.1177/2396987317728854

Makin SDJ, Doubal FN, Quinn TJ, Bath PMW, Dennis MS, Wardlaw JM. The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke. European Stroke Journal . 2018;3(1):66-73. Epub 2017 Sept 5. doi: 10.1177/2396987317728854

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abstract = "Background: Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints. Methods: We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS /= 3 and 29/158 (19%) had ACE-R /= 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R /= 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke. Conclusions: Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.",

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note = "The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Wellcome Trust (grant 088134/Z/09/A), the Scottish Funding Council and the Chief Scientist Office, Scotland, through the Scottish Imaging Network: A Platform for Scientific Excellence ({\textquoteleft}SINAPSE{\textquoteright}) and the European Union Horizon 2020 research and innovation programme SVDs@Target under grant agreement 666881. FD and TQ are funded by the Stroke Association/Garfield Weston Foundation and Stroke Association/Chief Scientist Office Senior Lectureships respectively. PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Senior Investigator. The work was supported by the Fondation Leducq Transatlantic Network of Excellence in Small Vessel Disease ref no. 16 CVD 05, and the Horizon 2020 Programme PHC-03-15, project No 666881, {\textquoteleft}SVDs @Target.{\textquoteright} The work was conducted independently of the funders.",

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AU - Doubal, Fergus N

AU - Quinn, Terence J

AU - Bath, Philip MW

AU - Dennis, Martin S

AU - Wardlaw, Joanna M

N1 - The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Wellcome Trust (grant 088134/Z/09/A), the Scottish Funding Council and the Chief Scientist Office, Scotland, through the Scottish Imaging Network: A Platform for Scientific Excellence (‘SINAPSE’) and the European Union Horizon 2020 research and innovation programme SVDs@Target under grant agreement 666881. FD and TQ are funded by the Stroke Association/Garfield Weston Foundation and Stroke Association/Chief Scientist Office Senior Lectureships respectively. PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Senior Investigator. The work was supported by the Fondation Leducq Transatlantic Network of Excellence in Small Vessel Disease ref no. 16 CVD 05, and the Horizon 2020 Programme PHC-03-15, project No 666881, ‘SVDs @Target.’ The work was conducted independently of the funders.

PY - 2018

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N2 - Background: Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints. Methods: We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS /= 3 and 29/158 (19%) had ACE-R /= 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R /= 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke. Conclusions: Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.

AB - Background: Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints. Methods: We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS /= 3 and 29/158 (19%) had ACE-R /= 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R /= 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke. Conclusions: Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.

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KW - lacunar outcome

KW - power calculation

KW - randomised trial sample size

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DO - 10.1177/2396987317728854

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The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke

Abstract

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Keywords

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