Adaptive optimal designs for dose-finding studies based on sigmoid Emax models

نویسندگان

  • Tianhua Wang
  • Min Yang
چکیده

The adaptive design strategy is a feasible approach for optimal designs in dose-finding studies, where the information matrices usually depend on the unknown parameters. Focusing on three pharmacodynamics sigmoid Emax models, we derive the corresponding simple formats of the adaptive optimal designs regardless of the optimality criteria or parameters of interest. An algorithm for deriving a specific adaptive optimal design is developed. A simulation study comparing the adaptive optimal designs and the uniform designs is also performed. & 2013 Elsevier B.V. All rights reserved.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

On the efficiency of two-stage response-adaptive designs.

In this paper, we investigate the efficiency of response-adaptive locally optimum designs. We focus on two-stage adaptive designs, where after the first stage the accrued data are used to determine a locally optimum design for the second stage. On the basis of an explicit expansion of the information matrix, we compare the variance of the maximum likelihood estimates obtained from a two-stage a...

متن کامل

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity

BACKGROUND It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design ...

متن کامل

Adaptive 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 کامل

Best Intention Designs in Dose–finding Studies

In the dose–finding setting, we discuss and compare adaptive designs, including those which allocate each new patient (or a cohort of patients) to the dose currently viewed as the best one, for example, the seemingly most efficacious. We call this type of allocation “best intention” designs and found that, similar to other areas of life, the best intention may pave the road to rather disastrous...

متن کامل

Designing dose finding studies with an active control for exponential families.

In a recent paper Dette et al. (2014) introduced optimal design problems for dose finding studies with an active control. These authors concentrated on regression models with normal distributed errors (with known variance) and the problem of determining optimal designs for estimating the smallest dose, which achieves the same treatment effect as the active control. This paper discusses the prob...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2013