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A utility‐based design for randomized comparative trials with ordinal outcomes and prognostic subgroups
Author(s) -
Murray Thomas A.,
Yuan Ying,
Thall Peter F.,
Elizondo Joan H.,
Hofstetter Wayne L.
Publication year - 2018
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/biom.12842
Subject(s) - randomized controlled trial , ordinal data , statistics , medicine , ordinal regression , research design , medline , mathematics , computer science , oncology , econometrics , biology , biochemistry
Summary A design is proposed for randomized comparative trials with ordinal outcomes and prognostic subgroups. The design accounts for patient heterogeneity by allowing possibly different comparative conclusions within subgroups. The comparative testing criterion is based on utilities for the levels of the ordinal outcome and a Bayesian probability model. Designs based on two alternative models that include treatment‐subgroup interactions are considered, the proportional odds model and a non‐proportional odds model with a hierarchical prior that shrinks toward the proportional odds model. A third design that assumes homogeneity and ignores possible treatment‐subgroup interactions also is considered. The three approaches are applied to construct group sequential designs for a trial of nutritional prehabilitation versus standard of care for esophageal cancer patients undergoing chemoradiation and surgery, including both untreated patients and salvage patients whose disease has recurred following previous therapy. A simulation study is presented that compares the three designs, including evaluation of within‐subgroup type I and II error probabilities under a variety of scenarios including different combinations of treatment‐subgroup interactions.