Improving the efficiency of stroke trials: feasibility and efficacy of group adjudication of functional end points.

BACKGROUND AND PURPOSE: Use of the modified Rankin scale (mRS) in multicenter trials may be limited by interobserver variability. We assessed the effect of this on trial power and developed a novel group adjudication approach. METHODS: We generated power and sample size estimates from simulated trials modeled with varying mRS reliability. We conducted a virtual acute stroke trial across 14 UK sites to develop a group adjudication approach. Traditional mRS interviews, performed at local sites, were digitally recorded and scored by adjudication committee. We assessed the effect of translation by comparing scores in translated mRS interviews, originally conducted in English and Mandarin. Agreement was measured using κ and weighted κ (κw) statistics and intraclass correlation coefficient. RESULTS: Statistical simulations suggest that improving mRS reliability from κ=0.25 to κ=0.5 or 0.7 may allow reductions in sample size of n=386 or 490 in a typical n=2000 study. Our virtual acute stroke trial included 370 participants and 563 mRS video assessments. We adjudicated mRS in 538 of 563 (96%) study visits. At 30 and 90 days, 161 of 280 (57.5%) and 131 of 258 (50.8%) clips showed interobserver disagreement. Agreement within the adjudication committee was good (30-day κw=0.85 [95% confidence interval, 0.81-0.86]; 90-day κw=0.86 [95% confidence interval, 0.82-0.88]) without significant or systematic bias in mRS scoring compared with the local mRS. Interobserver reliability of translated mRS assessments was similar to native language clips (native [n=69] κw=0.91 [95% confidence interval, 0.94-0.99]; translated [n=89] κw=0.90 [95% confidence interval, 0.83-0.96]). CONCLUSIONS: Achievable improvements in interobserver reliability may substantially reduce study sample size, with associated financial benefits. Central adjudication of mRS assessments is feasible (including across international centers), valid and reliable despite the challenges of mRS assessment in large clinical trials.

Prestroke modified rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting.

BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is the recommended functional outcome assessment in stroke trials. Utility of mRS may be limited by interobserver variability. prestroke function, described using mRS, is often used as trial entry criterion. We assessed the reliability and validity of prestroke mRS in acute stroke. METHODS: We present two complementary analyses of the properties of prestroke mRS: (1) Paired interviewers (trained in mRS) performed independently a blinded assessment of mRS and prestroke mRS. Interobserver variability was described using percentage agreement and weighted (kw) κ statistics with 95% confidence interval (95% CI). Validity was assessed by comparing prestroke mRS with other markers of function (comorbidity; medication count; need for carers). (2) We further assessed validity using a larger retrospective dataset. We compared prestroke mRS with Charlson comorbidity index (CCI) and the Rockwood frailty index. Rank correlation coefficient or Fisher exact test were used as appropriate. RESULTS: Paired interviewers assessed 74 stroke survivors. Median standard mRS was 4 (interquartile range [IQR], 2-4), median prestroke mRS was 1 (IQR, 0-3; range, 0-4). Reliability for standard mRS interview was 56% agreement, kw=0.55 (95% CI, 0.39-0.71). Reliability for prestroke mRS was 70%, kw=0.70 (95% CI, 0.53-0.87). The retrospective dataset described 231 subjects. In this data set, Spearman Rho for prestroke mRS and frailty index was J. 0.82 (95% CI, 0.78-0.86); CCI 0.50 (95% CI, 0.40-0.59); patient age 0.45 (95% CI, 0.34-0.54); medication count 0.28 (95% CI, 0.15-0.40). There was no association between need for carers and prestroke mRS (p=0.10). CONCLUSIONS: Interobserver reliability of prestroke mRS is limited but comparable with standard mRS. Poor correlation of prestroke mRS with certain markers of function suggests limited validity. Our data would suggest that relying on mRS alone may be a suboptimal measure of prestroke function and could potentially bias trial samples.