Comparison of Isotonic Designs for Dose-Finding.
نویسندگان
چکیده
We compare several decision rules for allocating subjects to dosages that are based on sequential isotonic estimates of a monotone dose-toxicity curve. We conclude that the decision rule in which the next assignment is to the dose having probability of toxicity closest to target does not work well. The best rule in our comparison is given by the cumulative cohort design. According to this design, the dose for the next subject is decreased, increased, or repeated depending on the distance between the estimated toxicity rate at the current dose and the target quantile.
منابع مشابه
Bayesian dose-finding designs for combination of molecularly targeted agents assuming partial stochastic ordering
Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose-finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as t...
متن کاملAdaptive designs for identifying optimal biological dose for molecularly targeted agents.
Background Traditionally, the purpose of a dose-finding design in cancer is to find the maximum tolerated dose based solely on toxicity. However, for molecularly targeted agents, little toxicity may arise within the therapeutic dose range and the dose-response curves may not be monotonic. This challenges the principle that more is better, which is widely accepted for conventional chemotherapy. ...
متن کاملDose finding using the biased coin up-and-down design and isotonic regression.
We are interested in finding a dose that has a prespecified toxicity rate in the target population. In this article, we investigate five estimators of the target dose to be used with the up-and-down biased coin design (BCD) introduced by Durham and Flournoy (1994, Statistical Decision Theory and Related Topics). These estimators are derived using maximum likelihood, weighted least squares, samp...
متن کاملClinical Outcomes of Total Hip Arthroplasty in Patients with Ankylosed Hip
Background: Various drugs are administered intra-articularly to provide postoperative analgesia after arthroscopic knee surgery. The purpose of this study was to assess the analgesic effects of intra-articular injection of a dexmedetomidine following knee arthroscopy. Methods: Forty six patients schadualed for arthroscopic knee surgery under general anaesthesia, were randomly devided ...
متن کاملEffect of Dexmedetomidine on Postoperative Pain in Knee Arthroscopic Surgery; a Randomized Controlled Clinical Trial
knee surgery. The purpose of this study was to assess the analgesic effects of intra-articular injection of a dexmedetomidine following knee arthroscopy. Methods: Forty six patients schadualed for arthroscopic knee surgery under general anaesthesia, were randomly devided into two groups. Intervention group received 1μg/kg dexmedetomidine (D) and isotonic saline. Control group received 25ml is...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Statistics in biopharmaceutical research
دوره 1 1 شماره
صفحات -
تاریخ انتشار 2009