Front. Psychiatry, 22 November 2012 |

Obtaining the optimal dose in alcohol dependence studies

Nolan A. Wages1*, Lei Liu2, John O’Quigley3 and Bankole A. Johnson4
  • 1Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
  • 2Division of Biostatistics, Department of Preventive Medicine, Northwestern University, Chicago, IL, USA
  • 3Université Paris VI, Paris, France
  • 4Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated.

Keywords: alcohol research, dose-finding, maximum tolerated dose, most successful dose, continual reassessment method

Citation: Wages NA, Liu L, O’Quigley J and Johnson BA (2012) Obtaining the optimal dose in alcohol dependence studies. Front. Psychiatry 3:100. doi: 10.3389/fpsyt.2012.00100

Received: 06 July 2012; Paper pending published: 08 August 2012;
Accepted: 01 November 2012; Published online: 22 November 2012.

Edited by:

Wendy J. Lynch, University of Virginia, USA

Reviewed by:

Zachary A. Rodd, Indiana University School of Medicine, USA
Ludovico Abenavoli, University Magna Graecia, Italy

Copyright: © 2012 Wages, Liu, O’Quigley and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Nolan A. Wages, Department of Public Health Sciences, University of Virginia, P.O. Box 800717, Charlottesville, VA 22908, USA. e-mail: