A curve-free method for phase I clinical trials.

*(English)*Zbl 1060.62611Summary: Consider the problem of finding the dose that is as high as possible subject to having a controlled rate of toxicity. The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity. The continual reassessment method (CRM) is an improvement over traditional up-and-down schemes for estimating the MTD. It is based on a Bayesian approach and on the assumption that the dose-toxicity relationship follows a specific response curve, e.g., the logistic or power curve. The purpose of this paper is to illustrate how the assumption of a specific curve used in the CRM is not necessary and can actually hinder the efficient use of prior inputs. An alternative curve-free method in which the probabilities of toxicity are modeled directly as an unknown multidimensional parameter is presented. To that purpose, a product-of-beta prior (PBP) is introduced and shown to bring about logical improvements. Practical improvements are illustrated by simulation results.

##### MSC:

62P10 | Applications of statistics to biology and medical sciences; meta analysis |

62F15 | Bayesian inference |

##### Keywords:

continual reassessment method; dose-finding studies; maximum tolerated dose; neutral to the right process; phase I clinical trial; product-of-beta priors; toxicity
PDF
BibTeX
XML
Cite

\textit{M. Gasparini} and \textit{J. Eisele}, Biometrics 56, No. 2, 609--615 (2000; Zbl 1060.62611)

Full Text:
DOI

**OpenURL**

##### References:

[1] | Berger, Statistical Decision Theory and Bayesian Analysis (1985) |

[2] | Doksum, Tailfree and neutral random probabilities and their posterior distributions, Annals of Probability 2 pp 183– (1974) · Zbl 0279.60097 |

[3] | Fan, The distribution of the product of independent beta variables, Communications in Statistics, Series A 20 pp 4043– (1991) · Zbl 04506212 |

[4] | Faries, Practical modifications of the continual reassessment method for Phase I cancer clinical trials, Journal of Biopharmaceutical Statistics 4 pp 147– (1994) |

[5] | Goodman, Some practical improvements in the continual reassessment method for phase I studies, Statistics in Medicine 14 pp 1149– (1995) |

[6] | Korn, A comparison of two Phase I trial designs, Statistics in Medicine 13 pp 1799– (1994) |

[7] | Muliere, A Bayesian nonparametric approach to determining a maximum tolerated dose, Journal of Statistical Planning and Inference 61 pp 339– (1997) · Zbl 0873.62120 |

[8] | O’Quigley, Continual reassessment method: A likelihood approach, Biometrics 52 pp 673– (1996) · Zbl 0925.62454 |

[9] | O’Quigley, Continual reassessment method: A practical design for Phase I clinical trials in cancer, Biometrics 46 pp 33– (1990) · Zbl 0715.62242 |

[10] | Tang, On the distribution of the product of independent beta variables, Statistics and Probability Letters 2 pp 165– (1984) · Zbl 0543.62040 |

[11] | Whitehead, Bayesian decision procedures with application to dose-finding studies, International Journal of Pharmaceutical Medicine 11 pp 201– (1997) |

This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. It attempts to reflect the references listed in the original paper as accurately as possible without claiming the completeness or perfect precision of the matching.