Stroke
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Introduction
Berry has designed many impactful trials in stroke. Many of these trials contain innovative and/or adaptive elements to gain efficiency. These features include endpoints such as utility weighted mRS, which often produces higher power than trials utilizing a dichotomized endpoint or an ordinal shift analysis. Adaptive stopping of trials for futility or success can save 30-50% of resources compared to a fixed, nonadaptive trial. In addition, Berry has designed many trials employing enrichment strategies, allowing patient populations to be refined along such dimensions as location of the stroke, time since last seen well, or amount of brain that is expected to be saved. These enrichment strategies may begin by enrolling a broader patient population and then narrowing that population, or by beginning with a smaller patient population and then expanding.
Berry Examples and Case Studies
The DAWN trial, currently cited over 5000 times, investigated thrombectomy for the treatment of ischemic stroke in patients 6-24 hours since last seen well. DAWN incorporated adaptive stopping for futility and success as well as enrichment across both time since last seen well and the mismatch between clinical deficit and infarct (essentially a measure of how much of the brain could be saved by the treatment). Thrombectomy proved highly effective across the entire enrolled patient population, resulting in an early stop for success for all patients at the earliest possible interim analysis (N=200 of a planned maximal sample size of N=500). Thrombectomy continues to be one of the great clinical advances of the 21st century.
ENRICH investigated minimally invasive surgical removal of intracerebral hemorrhage in both the lobar and anterior basal ganglia. The trial design included interim analyses that analyzed both regions of the brain and allowed for either of the regions to be discontinued if the treatment appeared ineffective. At the second interim analysis, futility was declared for the anterior basal ganglia region. Enrollment ceased in the anterior basal ganglia, but continued in the lobar region, eventually declaring success in the lobar region (mean utility weighted mRS within the lobar region was 0.513 for the treated group and 0.371 in the control group).
Both DAWN and ENRICH were published in the New England Journal of Medicine.
