A Guide to the Design and Analysis of Small Clinical Studies

• Activity Number: 412
• Type: Contributed
• Date/Time: Tuesday, August 2, 2011 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistical Consulting
• Author(s): Farid Kianifard*+ and M. Zahur Islam
• Companies: Novartis and Novartis
• Keywords: exploratory study ; pilot study ; proof of concept ; sample size ; clinical trial

Abstract

Clinical studies which have a small number of patients are conducted by pharmaceutical companies and research institutions. Examples of constraints which 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. (To appear in Pharmaceutical Statistics, 2011)