Document Type
Article
Publication Date
2013
Abstract
In phase I clinical trials, the standard ‘3+3’ design has passed the test of time and survived various sample size adjustments, or other dose-escalation dynamics. The objective of this study is to provide a probabilistic support for analyzing the heuristic performance of the ‘3+3’ design. Our likelihood method is based on the evidential paradigm that uses the likelihood ratio to measure the strength of statistical evidence for one simple hypothesis over the other. We compute the operating characteristics and compare the behavior of the standard algorithm under different hypotheses, levels of evidence, and true (or best guessed) toxicity rates. Given observed toxicities per dose level, the likelihood-ratio is evaluated according to a certain k threshold (level of evidence). Under an assumed true toxicity scenario the following statistical characteristics are computed and compared: i) probability of weak evidence, ii) probability of favoring H1 under H1(analogous to 1-α), iii) probability of favoring H2 under H2 (analogous to 1-β). This likelihood method allows consistent inferences to be made and evidence to be quantified regardless of cohort size. Moreover, this approach can be extended and used in phase I designs for identifying the highest acceptably safe dose and is akin to the sequential probability ratio test.
Recommended Citation
Chiuzan, Cody; Garrett-Mayer, Elizabeth; and Yeatts, Sharon D., "A Likelihood-Based Approach for Computing the Operating Characteristics of the Standard Phase I Clinical Trial Design" (2013). MUSC Department of Public Health Sciences Working Papers. 7.
https://medica-musc.researchcommons.org/workingpapers/7
Comments
This work was supported by a National Institute of Health (NIH) grant, P01 CA 154778-01 and part by the Biostatistics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313).