Abstract
We propose a design strategy for single-arm clinical trials in which the goals are to find a dose of an experimental treatment satisfying both safety and efficacy requirements, treat a sufficiently large number of patients to estimate the rates of these events at the selected dose with a given reliability, and stop the trial early if it is likely that no dose is both safe and efficacious. Patient outcome is characterized by a trinary ordinal variable accounting for both efficacy and toxicity. Like Thall, Simon, and Estey (1995, Statistics in Medicine 14, 357-379), we use Bayesian criteria to generate decision rules while relying on frequentist criteria obtained via simulation to determine a design parameterization with good operating characteristics. The strategy is illustrated by application to a bone marrow transplantation trial for hematologic malignancies and a trial of a biologic agent for malignant melanoma.
Original language | English (US) |
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Pages (from-to) | 251-264 |
Number of pages | 14 |
Journal | Biometrics |
Volume | 54 |
Issue number | 1 |
DOIs | |
State | Published - Mar 1998 |
Keywords
- Bayesian inference
- Clinical trial
- Dose-finding studies
- Phase I trial
- Phase II trial
- Safety monitoring
ASJC Scopus subject areas
- Statistics and Probability
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences
- Applied Mathematics