scholarly journals Adaptive prior variance calibration in the Bayesian continual reassessment method

2012 ◽  
Vol 32 (13) ◽  
pp. 2221-2234 ◽  
Author(s):  
Jin Zhang ◽  
Thomas M. Braun ◽  
Jeremy M.G. Taylor
Keyword(s):  
Continual Reassessment Method ◽  
Prior Variance ◽  
Continual Reassessment

scholarly journals A Bayesian dose-finding design for outcomes evaluated with uncertainty

2021 ◽  
pp. 174077452110015
Author(s):  
Matthew J Schipper ◽  
Ying Yuan ◽  
Jeremy MG Taylor ◽  
Randall K Ten Haken ◽  
Christina Tsien ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Data Augmentation ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Continual Reassessment Method ◽  
Number Of Patients ◽  
Continual Reassessment ◽  
Partially Observed ◽  
Dose Limiting Toxicity

Introduction: In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity. Methods: We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity. We assume that for some patients, instead of the usual binary dose-limiting toxicity outcome, we observe a physician-assessed probability of dose-limiting toxicity specific to a given patient. Data augmentation is used to estimate the posterior probabilities of dose-limiting toxicity at each dose level based on both the fully observed and partially observed patient outcomes. A simulation study is used to assess the performance of the design relative to using the continual reassessment method on the true dose-limiting toxicity outcomes (available in simulation setting only) and relative to simple thresholding approaches. Results: Among the designs utilizing the partially observed outcomes, our proposed design has the best overall performance in terms of probability of selecting correct maximum tolerated dose and number of patients treated at the maximum tolerated dose. Conclusion: Incorporating uncertainty in dose-limiting toxicity assessment can improve the performance of the continual reassessment method design.

Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation.

1995 ◽  
Vol 13 (11) ◽  
pp. 2842-2850 ◽  
Author(s):  
D A Rinaldi ◽  
H A Burris ◽  
F A Dorr ◽  
J R Woodworth ◽  
J G Kuhn ◽  
...  
Keyword(s):  
Dose Level ◽  
Thymidylate Synthase ◽  
Dose Escalation ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Treatment Schedule ◽  
Continual Reassessment Method ◽  
Toxic Dose ◽  
Continual Reassessment ◽  
Dose Limiting Toxicity

PURPOSE To determine the toxicities, maximal-tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of LY231514, a novel thymidylate synthase (TS) inhibitor. PATIENTS AND METHODS Patients with advanced solid tumors were administered LY231514 intravenously over 10 minutes, weekly for 4 weeks, every 42 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS Twenty-five patients were administered 58 courses of LY231514 at doses that ranged from 10 to 40 mg/m2/wk. Reversible neutropenia was the dose-limiting toxicity. Inability to maintain the weekly treatment schedule due to neutropenia limited dose escalation on this schedule. Nonhematologic toxicities observed included mild fatigue, anorexia, and nausea. At the 40-mg/m2/wk dose level, the mean harmonic half-life, maximum plasma concentration, clearance, and apparent volume of distribution at steady-state were 2.02 hours, 11.20 micrograms/mL, 52.3 mL/min/m2, and 6.64 L/m2, respectively. No major antitumor responses were observed; however, minor responses were achieved in two patients with advanced colorectal cancer. CONCLUSION The dose-limiting toxicity, MTD, and recommended phase II dose of LY231514 when administered weekly for 4 weeks every 42 days are neutropenia, 40 mg/m2, and 30 mg/m2, respectively.

Characterization of the likelihood continual reassessment method

Biometrika ◽  
2014 ◽  
Vol 101 (3) ◽  
pp. 599-612 ◽  
Author(s):  
X. Jia ◽  
S. M. Lee ◽  
Y. K. Cheung
Keyword(s):  
Continual Reassessment Method ◽  
Continual Reassessment

Bridging continual reassessment method for phase I clinical trials in different ethnic populations

2015 ◽  
Vol 34 (10) ◽  
pp. 1681-1694 ◽  
Author(s):  
Suyu Liu ◽  
Haitao Pan ◽  
Jielai Xia ◽  
Qin Huang ◽  
Ying Yuan
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase I Clinical Trials ◽  
Continual Reassessment Method ◽  
Ethnic Populations ◽  
Continual Reassessment
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