Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

BMC Medical Research Methodology

Lucinda Billingham²  Andrew Pettitt¹  Christina Yap³ 

[1] Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK;Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK;MRC Midland Hub for Trials Methodology Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK

关键词: Moderate Sample Sizes;    Oncology;    Play-the-Winner;    Screening Design;    Selection Design;    Randomised Phase II;   

Others  :  1092343
DOI  :  10.1186/1471-2288-13-87

 received in 2013-03-21, accepted in 2013-06-26,  发布年份 2013

【 摘 要 】

Background

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials.

Methods

We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach.

Results

Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm.

Conclusions

SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

【 授权许可】

   
2013 Yap et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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