In November 2017, the Lancet Neurology Commission on Traumatic Brain Injury (TBI) highlighted existing deficiencies in epidemiology, patient characterization, identifying best practice, outcome assessment, and evidence generation. The Commission concluded that C needed to address deficiencies in prevention , and made a recommendation for large collaborative studies which could provide the framework for precision medicine and comparative effectiveness research (CER).
Background:
The 90-day modified Rankin Scale (mRS) is the most commonly used primary outcome measure in stroke treatment trials, but has drawbacks, including the potential loss of subjects due to prolonged follow-up. An alternative may be the NIH Stroke Scale (NIHSS) early after stroke, which is frequently used as a secondary outcome measure. The aim of this study was to evaluate whether the NIHSS assessed within one week after trial inclusion could serve as a primary outcome measure for trials of acute ischaemic stroke treatment.
Methods:
We used the Prentice criteria to evaluate NIHSS 1 day and 5-7 days after trial inclusion as primary outcome measures in two trials of endovascular treatment (EVT): the positive MR CLEAN and the neutral IMS III. The four Prentice criteria evaluate a surrogate endpoint against a true endpoint (Figure). We adjusted for age, baseline NIHSS, collateral score, and time of symptom onset to randomization.
Results:
The Prentice criteria were met for NIHSS at 1 day and 5-7 days in MR CLEAN (n=500). We found a significant treatment effect of EVT on the mRS and on the NIHSS at 1 day and 5-7 days. After adjustment for NIHSS at 1 day and 5-7 days, the effect of EVT on mRS decreased from common odds ratio 1·69 (95%CI: 1·22-2·33) to respectively 1·33 (95%CI: 0·95-1·85) and 1·21 (95%CI: 0·86-1·72). In IMS III (n=656) there was no treatment effect on NIHSS at 1 day (p=0.56) and 5-7 days (p=0.28), coinciding with the absence of a treatment effect on mRS.
Conclusion:
NIHSS is able to replace the mRS at 90 days as a measure of treatment effect. NIHSS within one week after trial inclusion may be used as a primary outcome measure in trials of acute ischemic stroke treatment, particularly in phase II(b) trials. This could minimize loss to follow-up, and reduce trial duration and costs.
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