Continual reassessment method

J. O Quigley, M. Pepe, and L. Fisher, Continual reassessment method a practical design for phase 1 clinical trials in cancer. Biometrics 46 33 8 (1990). 

The continual reassessment method (CRM) introduced by O Quigley et al. (22) is the best known Bayesian approach and has been widely presented in the literature, either in its original form or with several modifications and extensions such as the bivariate approach. 

S. Chevret, The continual reassessment method in cancer phase I clinical trials a simulation study. Stat Med 12 1093-1108 (1993). 

S. N. Goodman, M. L. Zahurak, and S. Piantadosi, Some practical improvements in the continual reassessment method for phase I studies. Stat Med 14 1149-1161 (1995). 

N. Ishizuka and Y. Ohashi, The continual reassessment method and its applications a Bayesian methodology for phase I cancer clinical trials. Stat Med 20 2661-2681 (2001). 

J. O Quigley and E. Reiner, A stopping rule for the continual reassessment method. Biometrika 85 741-748 (1998). 

J. Q Quigley and L. Z. Shen, Continual reassessment method a likelihood approach. Biometrics 52 673-684 (1996). 

T. M. Braun, The bivariate continual reassessment method extending the CRM to phase I trials of two competing outcomes. Control Clin Trials 23 240-256 (2002). 

J. O Quigley, L. Z. Shen, and A. Gamst, Two-sample continual reassessment method. JBiopharm Stat 9 17-44 (1999). 

A. Kramar, A. Lebecq, and E. Candalh, Continual reassessment methods in phase I trials of the combination of two drugs in oncology. Stat Med 18 1849-1864 (1999). 

S. Morita, M. Toi, T. Kobayashi, Y. Ito, Y. Hozumi, S. Ohno, H. Iwata, and J. Sakamoto, Application of a continual reassessment method to a phase I clinical trial of capecitabine in combination with cyclophosphamide and epirubicin (CEX) for inoperable or recurrent breast cancer. Ipn I Clin Oncol 34 104-106 (2004). 

Working-dose models for the continual reassessment method... 

Chevret S, Zohar S (2006) The continual reassessment method. In Chevret S (ed.). Statistical Methods for Dose-Finding Experiments. John Wiley and Sons, Inc., Hoboken, pp. 133-148. 

Continuous reassessment method (O Quigley design.) An approach used in phase I trials in cancer for choosing the dose of the next patient, using results from the patients treated to date, in such a way that the probability of toxicity is at some pre-specified target level. 

In addition, non-pharmacokinetic statistical modeling approaches have been recommended to guide the dose escalation. These statistical approaches model the dose-toxicity relationship as a sigmoidal curve to predict the MTD. The predicted value of the MTD is adjusted as data on the occurrence or the absence of toxicity accumulate from the clinical trial. Thus, the statistical prediction of the MTD is higher when low toxicity is observed, allowing rapid dose escalation, and the predicted MTD is low when dose-related toxicity is observed, calling for conservative dose escalation steps. This approach of dose escalation has been termed the continual reassessment method (CRM) [54]. 

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