Improved designs for dose escalation studies using pharmacokinetic measurements

Steven Piantadosi, Guanghan Liu

    Research output: Contribution to journalArticle

    Abstract

    We describe a method for incorporating pharmacokinetic (PK) data into dose escalation clinical trial designs. Doing so can improve the efficiency and accuracy of these studies. The method proposed uses a parametric dose response function that models the probability of response in each person with two effects: the dose of drug administered and an ancillary pharmacokinetic measurement. After treatment and observation of each subject (or group of subjects) for response, one calculates the dose to be administered to the next individual (or group) to yield the target probability of response from the current best estimate of the dose-response curve. This procedure is a variant of the continual reassesment method (CRM). Statistical simulations employing a logistic dose-response model (that is, we model the legit of the response probability as a linear combination of predictors), dose of drug, and the area under the time-concentration curve (AUC) demonstrate that the addition of pharmacokinetic information to the CRM is a practical and useful way to improve both dose-response modelling and the design of dose escalation studies.

    Original languageEnglish (US)
    Pages (from-to)1605-1618
    Number of pages14
    JournalStatistics in Medicine
    Volume15
    Issue number15
    DOIs
    StatePublished - Aug 15 1996

    Fingerprint

    Pharmacokinetics
    Dose
    Dose-response
    Drugs
    Statistical Simulation
    Dose-response Curve
    Response Function
    Pharmaceutical Preparations
    Clinical Trials
    Logistics
    Area Under Curve
    Linear Combination
    Predictors
    Person
    Observation
    Design
    Model
    Calculate
    Curve
    Target

    ASJC Scopus subject areas

    • Epidemiology

    Cite this

    Improved designs for dose escalation studies using pharmacokinetic measurements. / Piantadosi, Steven; Liu, Guanghan.

    In: Statistics in Medicine, Vol. 15, No. 15, 15.08.1996, p. 1605-1618.

    Research output: Contribution to journalArticle

    Piantadosi, Steven ; Liu, Guanghan. / Improved designs for dose escalation studies using pharmacokinetic measurements. In: Statistics in Medicine. 1996 ; Vol. 15, No. 15. pp. 1605-1618.
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