From the Michael E. DeBakey VA Medical Center Stroke Program (P.M., N.S.) and Analytical Software and Engineering Research Laboratory, Department of Neurology (P.M., N.S., T.A.K.), Baylor College of Medicine, Houston, TX; Department of Neurology (S.B.M.) and Clinical and Translational Neuroscience Unit (S.B.M.), Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY; APHP (Y.S.), Urgences Cerebro-Vasculaire, Pitié-Salpêtrière, and UPMC Paris Sorbonne Universités (Y.S.), Paris, France; Departments of Statistics and Bioengineering (M.K.) and Chemistry (T.A.K.), Rice University, Houston; Institute of Biosciences and Technology (IBT) (T.A.K.), Texas A&M Health Science Center-Houston Campus; and Department of Neurology (T.A.K.), Houston Methodist Hospital and Research Institute, TX.
Neurology. 2019 Apr 9;92(15):e1688-e1697. doi: 10.1212/WNL.0000000000007269. Epub 2019 Mar 20.
To develop models of outcome for intracerebral hemorrhage (ICH) to identify promising and futile interventions based on their early phase results without need for correction for baseline imbalances.
We developed a pooled outcome model from the control arms of randomized control trials and tested different interventions against the model at comparable baseline conditions. Eligible clinical trials and large case series were identified from multiple library databases. Models based on baseline factors reported in the control arms were tested for the ability to predict functional outcome (modified Rankin Scale score) and mortality. Interventions were grouped into blood pressure control, fibrinolytic-assisted hematoma evacuation, hemostatic medications, and neuroprotective agents. Statistical intervals around the model were generated at the = 0.1 level to screen how each trial's outcome compared to expected outcome.
Fourteen control arms with 3,386 patients were used to develop 7 alternate models for functional outcome. The model incorporating baseline NIH Stroke Scale, age, and hematoma volume yielded the best fit (adjusted = 0.89). All early phase treatments that eventually resulted in negative late phase trials were identified as negative by this method. Early phase fibrinolytic-assisted hematoma evacuation studies showed the most promise trending toward improved functional outcome with no suggestion of an increase in mortality, supporting its further study.
We successfully developed an outcome model for ICH that identified interventions destined to be negative while identifying a promising one. Such an approach may assist in prioritizing resources prior to multicenter trial.
建立脑出血（ICH）的结局模型，以便根据早期结果识别有前途和无前途的干预措施，而无需对基线不平衡进行校正。
我们从随机对照试验的对照组中建立了一个汇总结局模型，并在可比的基线条件下用该模型检验不同的干预措施。从多个库数据库中确定了符合条件的临床试验和大型病例系列。检验了基于对照组报告的基线因素的模型预测功能结局（改良 Rankin 量表评分）和死亡率的能力。将干预措施分为血压控制、纤维蛋白溶解辅助血肿清除、止血药物和神经保护剂。在 = 0.1 的水平生成模型周围的统计区间，以筛选每个试验的结果与预期结果的比较。
使用 14 个对照组（共 3386 例患者）来开发 7 个替代的功能结局模型。纳入基线 NIH 卒中量表、年龄和血肿量的模型拟合效果最佳（调整后的 = 0.89）。通过这种方法，所有最终导致负面后期试验的早期阶段治疗都被确定为负面。早期阶段纤维蛋白溶解辅助血肿清除研究显示出最有前途的趋势，改善功能结局，没有增加死亡率的迹象，支持进一步研究。
我们成功地建立了脑出血的结局模型，该模型可以识别注定为负面的干预措施，同时识别出有前途的干预措施。这种方法可以在多中心试验之前帮助优先分配资源。
