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
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 pa...
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| Format: | Article |
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SAGE
2017
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| Online Access: | https://eprints.nottingham.ac.uk/46990/ |
| _version_ | 1848797443519414272 |
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| author | Makin, Stephen D.J. Doubal, Fergus Quinn, Terence J. Bath, Philip M.W. Dennis, Martin S. Wardlaw, Joanna M. |
| author_facet | Makin, Stephen D.J. Doubal, Fergus Quinn, Terence J. Bath, Philip M.W. Dennis, Martin S. Wardlaw, Joanna M. |
| author_sort | Makin, Stephen D.J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 ≤ 7) and assessed recurrent vascular events (stroke, transient ischaemic attack (TIA), ischemic heart disease (IHD)), modified Rankin Score (mRS) and cognitive testing with the Addenbrooke’s Cognitive Examination (ACE-R) one year post-stroke. For a potential secondary prevention randomised controlled trial (RCT), we estimated sample sizes using individual or combined outcomes, at power 80% (and 90%), alpha 5%, required to detect a relative 10% risk reduction.
Results
Amongst 264 patients (118 lacunar, 146 non-lacunar), at one year, 30/264 (11%) patients had a recurrent vascular event, 5 (2%) had died, 3 (1%) had clinically-diagnosed dementia, 53/264 (20%) had mRS ≥ 3 and 29/158 (19%) had ACE-R ≤ 82 (57 could not attend for cognitive testing). For a potential trial, at 80% power, using mRS ≥ 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R ≤ 82, dementia or mRS ≥ 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. |
| first_indexed | 2025-11-14T20:03:58Z |
| format | Article |
| id | nottingham-46990 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:03:58Z |
| publishDate | 2017 |
| publisher | SAGE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-469902020-05-04T19:04:28Z https://eprints.nottingham.ac.uk/46990/ 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 D.J. Doubal, Fergus Quinn, Terence J. Bath, Philip M.W. Dennis, Martin S. Wardlaw, Joanna M. 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 ≤ 7) and assessed recurrent vascular events (stroke, transient ischaemic attack (TIA), ischemic heart disease (IHD)), modified Rankin Score (mRS) and cognitive testing with the Addenbrooke’s Cognitive Examination (ACE-R) one year post-stroke. For a potential secondary prevention randomised controlled trial (RCT), we estimated sample sizes using individual or combined outcomes, at power 80% (and 90%), alpha 5%, required to detect a relative 10% risk reduction. Results Amongst 264 patients (118 lacunar, 146 non-lacunar), at one year, 30/264 (11%) patients had a recurrent vascular event, 5 (2%) had died, 3 (1%) had clinically-diagnosed dementia, 53/264 (20%) had mRS ≥ 3 and 29/158 (19%) had ACE-R ≤ 82 (57 could not attend for cognitive testing). For a potential trial, at 80% power, using mRS ≥ 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R ≤ 82, dementia or mRS ≥ 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. SAGE 2017-09-05 Article PeerReviewed Makin, Stephen D.J., Doubal, Fergus, Quinn, Terence J., Bath, Philip M.W., Dennis, Martin S. and Wardlaw, Joanna M. (2017) 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). pp. 66-73. ISSN 2396-9881 Stroke Randomised trial Sample size Power calculation Lacunar Cognition Dependency Outcome http://journals.sagepub.com/doi/10.1177/2396987317728854 doi:10.1177/2396987317728854 doi:10.1177/2396987317728854 |
| spellingShingle | Stroke Randomised trial Sample size Power calculation Lacunar Cognition Dependency Outcome Makin, Stephen D.J. Doubal, Fergus Quinn, Terence J. Bath, Philip M.W. Dennis, Martin S. Wardlaw, Joanna M. 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Stroke Randomised trial Sample size Power calculation Lacunar Cognition Dependency Outcome |
| url | https://eprints.nottingham.ac.uk/46990/ https://eprints.nottingham.ac.uk/46990/ https://eprints.nottingham.ac.uk/46990/ |