A utility-based design for randomized comparative trials with ordinal outcomes and prognostic subgroups.
Thomas A MurrayYing YuanPeter F ThallJoan H ElizondoWayne L HofstetterPublished in: Biometrics (2018)
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.
Keyphrases
- phase iii
- end stage renal disease
- ejection fraction
- newly diagnosed
- patients undergoing
- open label
- chronic kidney disease
- clinical trial
- double blind
- healthcare
- minimally invasive
- prognostic factors
- placebo controlled
- stem cells
- randomized controlled trial
- squamous cell carcinoma
- type diabetes
- adipose tissue
- coronary artery disease
- percutaneous coronary intervention
- single cell
- quality improvement
- coronary artery bypass
- resting state
- glycemic control
- surgical site infection