Bayesian adaptive designs in single ascending dose trials in healthy volunteers

• Published in: British journal of clinical pharmacology Vol. 78; no. 2; pp. 393 - 400
• Main Authors: Guédé, David, Reigner, Bruno, Vandenhende, Francois, Derks, Mike, Beyer, Ulrich, Jordan, Paul, Worth, Eric, Diack, Cheikh, Frey, Nicolas, Peck, Richard
• Format: Journal Article
• Language: English
• Published: England Blackwell Science Inc 01.08.2014
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Bayes Theorem; Bayesian adaptive design; Clinical Trials, Phase I as Topic - methods; Clinical Trials, Phase I as Topic - standards; Computer Simulation; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Maximum Tolerated Dose; Methods in Clinical Pharmacology Series; safety; Sample Size; single ascending dose trial; single ascending dose trial; safety; Bayesian adaptive design
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.12344

Aim Recent publications indicate a strong interest in applying Bayesian adaptive designs in first time in humans (FTIH) studies outside of oncology. The objective of the present work was to assess the performance of a new approach that includes Bayesian adaptive design in single ascending dose (SAD) trials conducted in healthy volunteers, in comparison with a more traditional approach. Methods A trial simulation approach was used and seven different scenarios of dose–response were tested. Results The new approach provided less biased estimates of maximum tolerated dose (MTD). In all scenarios, the number of subjects needed to define a MTD was lower with the new approach than with the traditional approach. With respect to duration of the trials, the two approaches were comparable. In all scenarios, the number of subjects exposed to a dose greater than the actual MTD was lower with the new approach than with the traditional approach. Conclusions The new approach with Bayesian adaptive design shows a very good performance in the estimation of MTD and in reducing the total number of healthy subjects. It also reduces the number of subjects exposed to doses greater than the actual MTD.