Designing a series of clinical trials
Hee, Siew Wan (2012) Designing a series of clinical trials. PhD thesis, University of Warwick.
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This thesis presents designs for a series of clinical trials where instead of designing clinical trials individually, each of the trials is designed as part of a series of trials. The framework of the design is based on a combination of classical frequentist and Bayesian approaches which is sometimes known as the hybrid approach. The unknown parameter of the treatment efficacy is assumed to be random and follows a prior distribution in the design stage but at the end of the trial a frequentist test statistic is used on the observed data to infer the parameter. The design introduced in Chapter 5 aims to determine an optimum sample size for each trial by optimizing the average power of each trial and the overall resources while fixing the conventional type I error. The design has the exibility to either run sequentially or concurrently. The design is then extended to allow interim analyses in each trial (Chapter 6). The focus of the extended design is on a series of Bayesian decision-theoretic phase II trials and one frequentist phase III trial. At each interim stage, a decision is made based on the expected utilities of subsequent actions. There are four possible actions to choose from, namely, to continue the current trial by recruiting more patients, to initiate a new phase II trial, to abandon the development plan or to proceed to a phase III trial with this treatment against a control arm. For the last action, the phase III trial is designed with the hybrid methodology as described above. Finally, the prior distributions for each treatments are assumed to be correlated and as information is gathered from the previous and current trials, the current and following prior distributions are updated (Chapter 7).
|Item Type:||Thesis or Dissertation (PhD)|
|Subjects:||R Medicine > R Medicine (General)|
|Library of Congress Subject Headings (LCSH):||Clinical trials -- Design, Bayesian statistical decision theory|
|Institution:||University of Warwick|
|Theses Department:||Warwick Medical School|
|Sponsors:||Roche Products Limited ; Warwick Medical School|
|Extent:||ix, 221 leaves : charts|
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