title: A guide to the design and analysis of small clinical studies.
abstract: Clinical studies, which have a small number of patients, are conducted by pharmaceutical companies and research institutions. Examples of constraints that lead to a small clinical study include a single investigative site with a highly specialized expertise or equipment, rare diseases, and limited time and budget. We consider the following topics, which we believe will be helpful for the investigator and statistician working together on the design and analysis of small clinical studies: definitions of various types of small studies (exploratory, pilot, proof of concept); bias and ways to mitigate the bias; commonly used study designs for randomized and nonrandomized studies, and some less commonly used designs; potential ethical issues associated with small underpowered clinical studies; sample size for small studies; statistical analysis methods for different types of variables and multiplicity issues. We conclude the paper with recommendations made by an Institute of Medicine committee, which was asked to assess the current methodologies and appropriate situations for conducting small clinical studies.
authors.affiliation: Biometrics, US Medical and Drug Regulatory Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA. farid.kianifard@novartis.com
authors.forename: Farid
authors.initials: F
authors.lastname: Kianifard
authors.forename: M Zahur
authors.initials: MZ
authors.lastname: Islam
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods*; D003627:Data Interpretation, Statistical; D004345:Drug Industry / Q000379:methods; D006801:Humans; D015233:Models, Statistical; D015969:National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D014481:United States