title: How clinical trials of myasthenia gravis can inform pre-clinical drug development.
abstract: Pre-clinical evaluations often provide the rationale for therapeutic assessments in humans; however, in many diseases an agent found successful in animal models does not show efficacy in human subjects. Our contention is that the approach of rigorous, clinical trials can be used to inform how preclinical assessments should be performed. Clinical trials in humans are carefully designed investigations executed with consideration of critical methodological issues, such as pre-specified entrance criteria and validated, outcome measures coupled with power analysis to identify sample size. Blinding of evaluators of subjective measures and randomization of subjects are also critical aspects of trial performance. Investigative agents are also tested in subjects with active disease, rather than prior to disease induction as in some pre-clinical assessments. Application of standard procedures, including uniform reporting standards, would likely assist in reproducibility of pre-clinical experiments. Adapting methods of clinical trial performance will likely improve the success rate of therapeutics to ultimately achieve human use.
authors.affiliation: Institute of Neuroscience, Department of Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rostedt Punga
authors.affiliation: Department of Neurology, George Washington University, Washington DC, USA. Electronic address: HKaminski@mfa.gwu.edu.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaminski
authors.affiliation: Department of Neurology, University of California Davis School of Medicine, Davis, CA, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Richman
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Benatar
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D009157:Myasthenia Gravis; D012107:Research Design / Q000592:standards*
keywords: Animal models; Clinical trials; Myasthenia gravis; Preclinical assessment; Therapeutic development