Improving efficiency in stroke trials: an exploration of methods to improve the use of the modified Rankin Scale in acute stroke trials
In: McArthur, Kate S (2014) Improving efficiency in stroke trials: an exploration of methods to improve the use of the modified Rankin Scale in acute stroke trials. MD thesis, University of Glasgow.; (2014)
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Hochschulschrift
Zugriff:
The modified Rankin Scale (mRS) is the preferred outcome measure in stroke trials. Typically, mRS assessment is based on a clinician’s rating of a patient interview and interobserver variability is common. Meta-analysis suggests an overall reliability of k=0.46 but this may be less (k=0.25) in multi-centre studies. Mandatory training in mRS assessment is employed in most trials to mitigate this but the problem persists. Variability in assigning outcomes may lead to endpoint misclassification increasing the challenge of accurately demonstrating a treatment effect. We aimed to assess the impact of endpoint misclassification on trial power and explore methods to improve the use of the mRS in acute stroke trials. First we used the mRS outcome distributions of previous phase III randomised controlled trials (RCT) in stroke (NXY059 study and tPA NINDS study) to perform statistical simulations. We generated power estimates and sample sizes from simulated mRS studies under various combinations of sample size, mRS reliability and adjudication panel size. Simulations suggest that the potential benefit of improving mRS reliability from k 0.25 to k 0.5, k 0.7 or k 0.9 may allow a reduction in sample size of n= 386, n= 490 or n= 488 in a typical n=2000 RCT. We then developed a method for providing group adjudication of mRS endpoints and examined the feasibility, reliability and validity of its use in a multicentre clinical trial. We conducted a “virtual” acute stroke trial across 14 UK sites. Local mRS interviews were scored as normal but also recorded to digital video camera. Video clips were uploaded via secure web portal for scoring by adjudication committee reviewers. We demonstrated excellent technical success rates with acceptability to both participants and investigators. 370 participants were included in our “virtual” acute stroke trial and 563 mRS video assessments were uploaded for central review. 96% (538/563) of study visits resulted in an adjudicated mRS score. At 30 and 90 days respectively, 57.5% (161/280) and ...
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Improving efficiency in stroke trials: an exploration of methods to improve the use of the modified Rankin Scale in acute stroke trials
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Autor/in / Beteiligte Person: | McArthur, Kate S |
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Quelle: | McArthur, Kate S (2014) Improving efficiency in stroke trials: an exploration of methods to improve the use of the modified Rankin Scale in acute stroke trials. MD thesis, University of Glasgow.; (2014) |
Veröffentlichung: | 2014 |
Medientyp: | Hochschulschrift |
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