Analysis of trichotomous pharmaceutical endpoints.

Many important clinical trial endpoints are measured on an ordered categorical scale. These include objective tumor response in oncology trials, the Thombolysis in Myocardial Infarction (TIMI) flow in cardiovascular trials, and the American College of Radiology (A CR) criterion in rheumatology trials. A common tendency among researchers is to simplify the ordered outcomes and collapse the data into a 2 x 2 contingency table in order to perform simpler statistical tests, such as the chi-square test or Fisher's exact test. Recently, more appropriate approaches, such as adaptive tests, have been developed for the analysis of ordered categorical endpoints. Each test in the adaptive class of tests is exact and balances good global power with nearly optimal power to detect a specific alternative of most interest. Prior knowledge of the direction of the treatment effect and the level of confidence in this prior information can be used to select a specific test from this class. However, little guidance has been offered regarding the selection of adaptive parameters when prior information is available. The purpose of this paper is to fill this gap by offering an objective approach for parameter selection, and to provide real data examples to illustrate the use of this objective approach.