An approach to the assessment of therapeutic drug interactions with fixed combination drug products.

Journal Article (Journal Article;Review)

Several complex clinical and statistical issues are involved in the development of a combination drug product. The medical rationale for the combination, the intended clinical use, drug-drug interactions, and dose response are just a few of the considerations. The factorial design is a useful experimental model for evaluating combination therapies. This paper outlines some of the considerations involved in the use of this design in the study of combination drugs. Questions related to design and methods of analysis are discussed in general and through use of an example. Such a design was applied to study the combination of a vasodilator with a diuretic in the treatment of hypertension. The sample size derivation, the evaluation of "interaction," the use of ANOVA versus regression techniques, and methods of data display are reviewed. It is recognized that although these are complex issues, substantially more information per patient can be obtained than with standard parallel-design approaches. The design could be an especially powerful tool early in the development of a drug.

Full Text

Duke Authors

Cited Authors

  • Rockhold, FW; Goldberg, MR

Published Date

  • July 1996

Published In

Volume / Issue

  • 6 / 3

Start / End Page

  • 231 - 240

PubMed ID

  • 8854228

International Standard Serial Number (ISSN)

  • 1054-3406

Digital Object Identifier (DOI)

  • 10.1080/10543409608835139


  • eng

Conference Location

  • England