Review article: Single subject trials as a research instrument in gastrointestinal pharmacology

Abstract

The single subject trial is a randomized controlled trial carried out in the individual patient, and the result obtained is specific to the individual patient and the drug being investigated. This type of trial offers a supplement to traditional parallel group trials, especially in patients with heterogeneous disorders, often characterized by varying treatment responses and/or high placebo response rates. Pooled results from several individual single subject trials could extend the conclusions beyond the individual patient, and help to characterize a subset of responders to a specific treatment or clarify the heterogeneity of the disease. The basic principles of the different single subject trial designs are described. Advantages and limitations are reviewed with a special focus on published trials in functional gastrointestinal disorders. The single subject trial may be a valuable supplement to traditional drug treatment trials, either used as isolated trials in individual patients to determine optimal therapy, or in groups of patients to identify those with a uniform response to treatment. However, the lack of validation and reliability studies limits the value of the single subject trials presented so far.