title: Spinal cord injury neuroprotection and the promise of flexible adaptive clinical trials.
abstract: Effective treatments for acute neurologic illness and injury are lacking, particularly for spinal cord injury (SCI). The very structure of clinical trials may be contributing to this because assumptions made during trial planning preclude additional learning within residual important areas of uncertainty, such as dose, timing, and duration of treatment. Adaptive clinical trials offer potential solutions to some of the factors that may be slowing the pace of discovery. Broadly defined, one can consider an adaptive clinical trial as any sort of clinical trial that makes use of information from within the trial to make decisions about how the trial is conducted going forward; however, it is important to emphasize that regardless of the degree of flexibility or complexity of an adaptive clinical trial design, the types of designs being described are only those in which all potential changes to the conduct of the trial are prospectively defined before the first patient is enrolled. Within this review, we describe the structure of flexible adaptive clinical trial designs, the process by which they are developed and conducted, and potential opportunities and drawbacks of these approaches. We must accept that there are some uncertainties that remain when both exploratory and confirmatory trials are designed. The process by which teams carefully consider which uncertainties are most important and most likely to potentially compromise the ability to detect an effective treatment can lead to trial designs that are more likely to find the right treatment for the right population of patients.
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: wmeurer@umich.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Meurer
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Barsan
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007036:Hypothermia, Induced; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012107:Research Design; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000601:surgery* / Q000628:therapy*
chemical_list: D018696:Neuroprotective Agents
keywords: Adaptive clinical trials; Clinical trial design; Phase 2 clinical trials; Phase 3 clinical trials; Spinal cord trauma