Clifton Lei, Clifton David A
Nuffield Department of Population Health (NDPH), University of Oxford, UK.
Institute of Biomedical Engineering (IBME), Department of Engineering Science, University of Oxford, UK.
Contemp Clin Trials Commun. 2019 Apr 9;14:100356. doi: 10.1016/j.conctc.2019.100356. eCollection 2019 Jun.
We illustrate the approach of randomising treatments and compare it with the traditional approach of randomising patients, using a case study drawn from the authors' experience in clinical trials. The setting is a double-blind parallel two-arm randomised controlled trial (RCT), but the method in this paper can be extended to single-blind, cross-over, or multi-arm RCTs. We propose the concept of two different levels of blinding: full blinding and partial blinding. We subsequently show how to maintain the maximal level of blinding. Using an example, we show that a pharmacist can be fully blinded if the investigational medical products (IMPs) that they prescribe (instead of patients) are randomised, and they can be partially blinded if they need to dispense replacement (i.e., surplus) IMPs. A small number of surplus IMPs is commonly required in a clinical trial to replace lost or damaged IMPs. We note that the concept of full blinding and partial blinding is different from double-blind trial, and the level of blinding is relevant in both single-blind and double-blind trials. A trial statistician needs to work closely with all parties in the design of the randomisation, including the pharmacist, the trial manager, and the manufacturer. We detail what should and should not be shown in the various documents that the trial statistician need to provide to the pharmacist and to the manufacturer. We provide template tables for these documents.
我们通过一个来自作者临床试验经验的案例研究,阐述随机分配治疗方法,并将其与传统的随机分配患者的方法进行比较。该案例为双盲平行双臂随机对照试验(RCT),但本文中的方法可扩展到单盲、交叉或多臂RCT。我们提出了两种不同程度设盲的概念:完全设盲和部分设盲。随后,我们展示了如何维持最大程度的设盲。通过一个例子,我们表明,如果随机分配的是药剂师所开具的研究用医疗产品(IMP,而非患者),那么药剂师可以实现完全设盲;而如果他们需要分发替代(即多余)的IMP,则可以实现部分设盲。在临床试验中,通常需要少量多余的IMP来替换丢失或损坏的IMP。我们注意到,完全设盲和部分设盲的概念与双盲试验不同,设盲程度在单盲和双盲试验中均具有相关性。试验统计学家在随机化设计过程中需要与各方密切合作,包括药剂师、试验管理者和制造商。我们详细说明了试验统计学家需要向药剂师和制造商提供的各种文件中应包含和不应包含的内容。我们为这些文件提供了模板表格。