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Abstract:
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Approaches for identifying doses of a drug to carry forward in development usually address whether responses are related to doses, the doses whose responses differ from control responses, the functional form of the dose-response relationship, and the doses that should be carried forward. In fact, however, the actual functional form of a dose-response relationship may be unnecessary if a response distribution can be determined for any dose. The real objective is to determine if a dose-response relationship exists, regardless of its functional form, and, if so, to identify a range of doses to study further. We describe a Bayesian approach for addressing the issues using an estimation instead of a hypothesis-testing paradigm. Functions of realizations from the posterior distributions of the parameters of linear, generalized, and nonlinear regression models relating response to dose provide realizations from posterior and predictive distributions of quantities that address the key issues directly. Multiplicity adjustments are not required. A number of examples illustrate the application of the method.
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