Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades.
Overview
abstract
UNLABELLED: Rigorous evidence generation with randomized controlled trials (RCTs) has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared to other forms of acute stroke. Besides its lower incidence compared to other stroke subtypes, the presentation and outcome of SAH patients also differ. This must be considered and adjusted for in designing pivotal RCTs of SAH patients. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons, WFNS, grade) on the outcome most used in pivotal stroke RCTs (modified Rankin Scale, mRS) and consequently on the sample size. Further, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of WFNS grades in addition to showing their effects on the sample size. Last, we offer methods that investigators can adapt to more precisely understand the effect of common mRS analysis methods and trial eligibility pertaining to the WFNS grade in designing their large-scale SAH RCTs. PURPOSE: The generation of rigorous evidence to inform the management of patients with aneurysmal subarachnoid hemorrhage (SAH) has lagged other types of acute strokes. The reason for this lag is multifactorial-one being that SAH has the lowest incidence of all forms of stroke. However, the paucity of SAH randomized controlled trials (RCTs) can also be self-exacerbating. Rather than adopting existing trial designs and biostatistical methods, it forces new investigators to craft these anew. Here, we provide a basic biostatistical guide for investigators to navigate two foundational dilemmas in designing large-scale SAH RCTs.
