Global test statistics for treatment effect of stroke and traumatic brain injury in rats with administration of bone marrow stromal cells

Abstract

Because no single test measures disability in rats with middle cerebral artery occlusion/traumatic brain injury (MCAo/TBI), multiple tests are needed to assess the effect of bone marrow stromal cell (MSC) on functional recovery. Testing the treatment effect on each outcome at the 0.05 level without adjusting for multiple outcomes can increase type I error. Therefore, we applied the global test to evaluate a common MSC dose effect on multiple outcomes in two applications: (i) MCAo rats with the MSC dose of zero (BPS), 1×10 6 and 3×10 6, and (ii) TBI rats with the MSC dose of zero, 1×10 6, 2×10 6 and 4×10 6, administered intravenously at 1 day after injury. For the MCAo rats, 3×10 6 MSCs improved the 14 day functional recovery ( P<0.05) compared to the controls. TBI rats with the MSC dose 4×10 6 were improved significantly at 1 month compared to controls, rats with 1×10 6 or 2×10 6 MSCs ( P<0.05). The global test on multiple outcomes is more efficient than a single outcome when treatment effects are consistent. The less correlation among the outcomes, the more power and, therefore, the higher efficiency of the global test. We demonstrated that the global test for continuous outcomes could be implemented under careful statistical modeling and proper data transformation.