title: On improving human clinical trials to the level of animal ischemic stroke studies.
abstract: This is a response to Jickling and Sharp's paper discussing the near-complete failure of clinical trials for stroke interventions. While they propose a paradigm shift in the way preclinical research is conducted, I propose that it is clinical trial design that needs an overhaul. Clinical trials could be designed to reduce variance, prevent data entry errors, and encompass less ambitious enrollment criteria limited to fewer centers which have demonstrated expertise in the treatment of stroke (and TBI). Statistical fundamentalism is another soluble problem: clinical trial designs tend to address what is medically significant as opposed to what is primarily statistically significant. Adaptive Design is an alternative to current protocols that needs urgent consideration if we are to get through the Valley of Death between bench and bedside. Maybe it is time to change the clinical trial paradigm to adopt the precise modeling used in good laboratory research rather than asking scientists to give up well-established procedures for producing reliable and reproducible results.
authors.affiliation: Department of Emergency Medicine, Emory University, Atlanta, GA, 30322, USA, dstei04@emory.edu.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D012107:Research Design; D020521:Stroke / Q000188:drug therapy*