کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
466674 697867 2012 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bayesian population approaches to the analysis of dose escalation studies
موضوعات مرتبط
مهندسی و علوم پایه مهندسی کامپیوتر علوم کامپیوتر (عمومی)
پیش نمایش صفحه اول مقاله
Bayesian population approaches to the analysis of dose escalation studies
چکیده انگلیسی

In dose escalation studies cohorts of subjects are given increasing doses of a candidate drug to assess safety and tolerability, pharmacokinetics and pharmacological response. The escalation is carried on until a predefined stopping limit is achieved, often identified by a pharmacokinetic endpoint such as peak plasma concentration or area under the plasma concentration–time profile. In the present work, the application of Bayesian methodologies to Phase I dose escalation studies is explored. A Bayesian population model is devised, which provides predictions of dose–response and dose–risk curves, both for individuals already enrolled in the trial and for a new, previously untested subject. Empirical and fully Bayesian estimation algorithms are worked out. Such methods provide equivalent performances on both experimental and simulated datasets. With respect to previous work, it is quantitatively proven not only that a more general and flexible model is identifiable, but also that such flexibility is needed in real scenarios.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Computer Methods and Programs in Biomedicine - Volume 107, Issue 2, August 2012, Pages 189–201
نویسندگان
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