1 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
2 Department of Family and Social Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Stat Methods Med Res. 2019 Feb;28(2):626-640. doi: 10.1177/0962280217734584. Epub 2017 Nov 9.
Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants' preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants' preference after randomization, which we call a "preference option randomized design (PORD)". In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters-comparative, preference, selection, intent-to-treat, and overall/as-treated-to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.
在真实环境中进行的比较疗效研究试验可能需要参与者在偏好的干预措施之间做出选择。随机临床试验具有平行的实验组和对照组，这是一种简单直接且被认为是黄金标准的设计，但它通过设计强制参与者无论其偏好如何都要遵守随机分配的干预措施。因此，当计划进行比较疗效研究试验时，随机临床试验可能会施加不切实际的限制。为了在参与者表达偏好时予以考虑，并保持随机化，我们提出了一种替代设计，允许参与者在随机化后选择偏好，我们称之为“偏好选择随机设计（PORD）”。与其他询问参与者在随机化后是否同意分配的干预措施的偏好设计不同，偏好选择随机设计的关键特征是其独特的随机化前知情同意过程。具体而言，偏好选择随机设计的知情同意过程告知参与者，如果他们在随机化后积极表达这样的愿望，他们可以选择退出并切换到另一种干预措施。如果参与者没有独立表达明确的替代偏好或同意随机分配的干预措施，则认为他们没有替代偏好。总之，偏好选择随机设计旨在最大限度地保留参与者，最大程度地减少任何参与者被迫分配的可能性，并通过允许没有偏好或偏好相等的参与者代表随机分配来保持随机化。该设计方案可以定义五个相互关联的效果，这些效果通过共同的设计参数——比较、偏好、选择、意向治疗和总体/实际治疗——来共同指导干预措施之间的决策。推导了用于测试所有这些效果的统计功效函数，并通过模拟验证了在正态和二项分布下功效函数的有效性。
