Abstract
Background and Objectives: Bayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional p-value-based binary cutoffs. We conducted an exploratory post-hoc Bayesian re-analysis of the minimally invasive surgery with thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE-3) trial and derived probabilities of potential intervention effect on functional and survival outcomes.
Methods: MISTIE-3 was a multicenter phase-3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. 506 adults (≥18 years) with spontaneous, non-traumatic, supratentorial ICH of ≥30mL 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 pre-specified thresholds. We used two 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.
Results: The 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.
Conclusions: 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 ICH patients is between 68% to 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist p-values, which indirectly evaluate treatment effects and only provide an arbitrary binary cut-off (such as 0.05), the Bayesian framework directly estimates probabilities of potential treatment effects.
Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01827046
Classification of Evidence This study provides Class II evidence that minimally invasive surgery (MIS) + rt-PA does not significantly improve functional outcome in patients with intracerebral hemorrhage. However, The study lacks the precision to exclude a potential benefit of MIS + rt-PA.
- Received September 9, 2022.
- Accepted in final form June 20, 2023.
- © 2023 American Academy of Neurology
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