Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

Evaluating dose response from flexible dose clinical trials

BACKGROUND The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. METHODS To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5-20 mg/day), or patients with schizophrenia who received olanzapine...

Dose-finding Designs for Phase Ii Clinical Trials

Dose--schedule finding in phase I/II clinical trials using a Bayesian isotonic transformation.

A dose-schedule-finding trial is a new type of oncology trial in which investigators aim to find a combination of dose and treatment schedule that has a large probability of efficacy yet a relatively small probability of toxicity. We demonstrate that a major difference between traditional dose-finding and dose-schedule-finding trials is that while the toxicity probabilities follow a simple nond...

Dose‐finding methods for Phase I clinical trials using pharmacokinetics in small populations

The aim of phase I clinical trials is to obtain reliable information on safety, tolerability, pharmacokinetics (PK), and mechanism of action of drugs with the objective of determining the maximum tolerated dose (MTD). In most phase I studies, dose-finding and PK analysis are done separately and no attempt is made to combine them during dose allocation. In cases such as rare diseases, paediatric...

Bayesian dose-finding in phase I/II clinical trials using toxicity and efficacy odds ratios.

A Bayesian adaptive design is proposed for dose-finding in phase I/II clinical trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new treatment. Without specifying any parametric functional form for the drug dose-response curve, we jointly model the bivariate binary data to account for the correlation between toxicity and efficacy. After observing all the responses of eac...