The only proven acute stroke treatments act by restoring blood flow to the ischemic brain region. Numerous neuroprotective drugs are effective in animal models but have failed in clinical trials. A reason for many of these failures is that preclinical investigations optimize the treatment conditions and such protocols often differ substantially from methods that are feasible for patient management. Identification of the critical treatment variables is essential to improve the trial designs and clinical rating scales, but they are rather inefficient for this purpose. Specifically, we would like to identify surrogate end points that can be used in phase 2 trials to facilitate protocol designs for phase 3 studies. An important advantage for investigations of possible stroke treatments is that the cause of the disorder is well understood—it is simply a mechanical disruption of blood supply. Detailed mechanistic understanding at the molecular level is not required to generate useful therapies, although that would be helpful. No single abnormality has been identified that is responsible for irreversible ischemic nervous system damage.
Clinical investigation can employ empiric methods for developing valid biomarkers. Imaging techniques show some promise for providing useable surrogate end points to identify salvageable tissue. However, no such methods have been proven to be useful for clinical trials. The general problems with current imaging technology for assessment of stroke treatments were discussed as well as feasible objectives for future studies.
Zivin JA. Clinical End Points for Stroke Trials. Arch Neurol. 2000;57(8):1235. doi: