TY - JOUR
T1 - Minimally Invasive Surgery With Thrombolysis for Intracerebral Hemorrhage Evacuation
T2 - Bayesian Reanalysis of a Randomized Controlled Trial
AU - Potter, Thomas
AU - Bako, Abdulaziz T.
AU - Pan, Alan P.
AU - Tannous, Jonika
AU - Britz, Gavin
AU - Ziai, Wendy C.
AU - Awad, Issam
AU - Hanley, Daniel
AU - Vahidy, Farhaan S.
N1 - Funding Information:
MISTIE III trial was funded by a NIH National Institute of Neurological Disorders and Stroke grant (Grant No. 1U01NS080824-01A1; Trial Innovation Center Grant No. 1U24TR001609-01) and received material support from Genentech.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/10/17
Y1 - 2023/10/17
N2 - 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 reanalysis 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. 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.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.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
p values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects.
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.
AB - 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 reanalysis 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. 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.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.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
p values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects.
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.
KW - Adult
KW - Humans
KW - Cerebral Hemorrhage/drug therapy
KW - Minimally Invasive Surgical Procedures
KW - Probability
KW - Thrombolytic Therapy
KW - Tissue Plasminogen Activator/therapeutic use
KW - Treatment Outcome
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UR - http://www.scopus.com/inward/citedby.url?scp=85174641852&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000207735
DO - 10.1212/WNL.0000000000207735
M3 - Article
C2 - 37684058
AN - SCOPUS:85174641852
SN - 0028-3878
VL - 101
SP - E1614-E1622
JO - Neurology
JF - Neurology
IS - 16
ER -