School of Medicine, Keele University, Staffordshire, UK.
J Eval Clin Pract. 2021 Jun;27(3):657-664. doi: 10.1111/jep.13556. Epub 2021 Mar 18.
Prior to a main randomized clinical trial, investigators often carry out a pilot or feasibility study in order to test certain trial processes or estimate key statistical parameters, so as to optimize the design of the main trial and/or determine whether it can feasibly be run. Pilot studies reflect the design of the intended main trial, whereas feasibility studies may not do so, and may not involve allocation to different treatments. Testing relative clinical effectiveness is not considered an appropriate aim of pilot or feasibility studies. However, consent is no less important than in a main trial as a means of morally legitimizing the investigator's actions. Two misperceptions are central to consent in clinical studies-therapeutic misconception (a tendency to conflate research and therapy) and therapeutic misestimation (a tendency to overestimate possible benefits and/or underestimate possible harms associated with participation). These phenomena may take a distinctive form in pilot and feasibility studies, owing to potential participants' likely prior unfamiliarity with the nature and purposes of such studies. Thus, participants may confuse the aims of a pilot or feasibility study (developing or optimizing trial design and processes) with those of a main trial (testing treatment effectiveness) and base consent on this misconstrual. Similarly, a misunderstanding of the ability of pilot and feasibility studies to provide information that will inform clinical care, or the underdeveloped nature of interventions included in such studies, may lead to inaccurate assessments of the objective possibility of benefit, and weaken the epistemic basis of consent accordingly. Equipoise may also be particularly challenging to grasp in the context of a pilot study. The consent process in pilot and feasibility studies requires a particular focus, and careful communication, if it is to carry the appropriate moral weight. There are corresponding implications for the process of ethical approval.
在进行主要的随机临床试验之前，研究人员通常会进行试点或可行性研究，以测试某些试验过程或估计关键统计参数，从而优化主要试验的设计和/或确定是否可以实际进行。试点研究反映了预期的主要试验设计，而可行性研究可能不会这样做，并且可能不涉及分配给不同的治疗方法。测试相对临床效果不被认为是试点或可行性研究的适当目标。然而，同意与主要试验一样重要，是使研究者的行为在道德上合法化的一种手段。在临床试验中，有两个误解是同意的核心问题——治疗误解（将研究和治疗混淆的倾向）和治疗估计错误（高估参与可能带来的益处和/或低估可能带来的危害的倾向）。由于潜在参与者可能对这些研究的性质和目的不太熟悉，这些现象在试点和可行性研究中可能会呈现出独特的形式。因此，参与者可能会将试点或可行性研究的目的（开发或优化试验设计和过程）与主要试验的目的（测试治疗效果）混淆，并基于这种误解来同意。同样，对试点和可行性研究提供信息以告知临床护理的能力的误解，或者此类研究中包含的干预措施的不发达性质，可能导致对客观获益可能性的不准确评估，并相应削弱同意的认知基础。在试点研究的背景下，平衡也可能特别难以理解。如果要赋予适当的道德权重，则需要特别关注和仔细沟通试点和可行性研究中的同意过程。这对伦理审查过程也有相应的影响。
