Minimally Invasive Surgery With Thrombolysis for Intracerebral Hemorrhage Evacuation: Bayesian Reanalysis of a Randomized Controlled Trial.

BACKGROUND AND

objectivesBayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional

methodsMISTIE-3 was a multicenter phase 3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. Five hundred and six adults (18 years or older) with spontaneous, nontraumatic, supratentorial ICH of ≥30 mL were randomized to receive either the MISTIE intervention (n = 255) or standard medical care (n = 251). We provide Bayesian-derived estimates of the effect of the MISTIE intervention on achieving a good 365-day modified Rankin Scale score (mRS score 0-3) as relative risk (RR) and absolute risk difference (ARD), and the probabilities that these treatment effects are greater than prespecified thresholds. We used 2 sets of prior distributions: (1) reference priors, including minimally informative, enthusiastic, and skeptical priors, and (2) data-derived prior distribution, using a hierarchical random effects model. We additionally evaluated the potential effects of the MISTIE intervention on 180-day and 30-day mRS and 365-, 180-, and 30-day mortality using data-derived priors.

resultsThe Bayesian-derived probability that MISTIE intervention has any beneficial effect (RR >1) on achieving a good 365-day mRS score was 70% using minimally informative prior, 87% with enthusiastic prior, 68% with skeptical prior, and 73% with data-derived prior. However, these probabilities were ≤55% for RR >1.10 and 0% for RR >1.52 across a range of priors. The probabilities of achieving RR >1 for 180- and 30-day mRS scores are 65% and 80%, respectively. Furthermore, the probabilities of achieving RR <1 for 365-, 180-, and 30-day mortality are 93%, 98%, and 99%, respectively. DISCUSSION: Our exploratory analyses indicate that across a range of priors, the Bayesian-derived probability of MISTIE intervention having any beneficial effect on 365-day mRS for patients with ICH is between 68% and 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov/ct2/show/NCT01827046. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that minimally invasive surgery (MIS) + recombinant tissue plasminogen activator (rt-PA) does not significantly improve functional outcome in patients with ICH. However, this study lacks the precision to exclude a potential benefit of MIS + rt-PA.