Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades

Abstract

Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials.

Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

“…We will estimate the marginal effects to obtain RRs and confidence intervals of the RRs (based on ‘nlcom’ from Stata (StataCorp LLC, Texas, USA)) or G-computation in R. We have chosen to—as a primary analysis—investigate our count outcomes without dichotomisation. Inappropriate dichotomisation—even though widely used—results in lower power and possibly also faulty results [ 28 , 30 , 31 ].…”