A re-randomisation design for clinical trials

BMC Medical Research Methodology

Tim P Morris²  Caroline J Doré³  Andrew B Forbes¹  Brennan C Kahan⁴ 

[1] School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, VIC, Australia;Hub for Trials Methodology Research, MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK;Comprehensive Clinical Trials Unit, University College London, London WC1E 6BT, UK;Pragmatic Clinical Trials Unit, Queen Mary University of London, London E1 2AB, UK

关键词: Poor recruitment;    Re-enrolment;    Re-randomisation design;    Randomised controlled trial;    Clinical trial;   

Others  :  1230324
DOI  :  10.1186/s12874-015-0082-2

 received in 2015-02-03, accepted in 2015-10-07,  发布年份 2015

【 摘 要 】

Background

Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies.

Methods

For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used.

Results

The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations.

Conclusions

If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations.

【 授权许可】

   
2015 Kahan et al.

【 图 表 】

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