University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands.
Clin Trials. 2011 Aug;8(4):408-16. doi: 10.1177/1740774511409600. Epub 2011 Jul 11.
Benjamin Freedman has argued in 1987 that before a controlled trial is started, there should be 'genuine uncertainty in the expert medical community about the preferred treatment'. Freedman's definition of the concept is widespread in clinical research, but has been controversial since its start. Over the past decade, the equipoise controversy has become increasingly complex.
This article aims: (1) to identify and clarify the main points of contention in the equipoise controversy, and (2) to reconcile the opposing views by pointing at areas of overlap between proponents and opponents in the equipoise debate.
We analyze the positions of the leading authors in the equipoise debate in the past decade.
There is substantial overlap between the opponents and proponents of equipoise. Both should be able to accept the following answers to points of contention in the debate: (1) the therapeutic obligation can remain the basis for equipoise as long as it is conceived as an obligation to provide participants with competent care, (2) equipoise is grounded in a competent care and an epistemological dilemma, (3) equipoise does not as a rule prohibit placebo-controlled trials when proven effective treatment exists, (4) patient equipoise and individual physician equipoise are irrelevant, and (5) having to stop a trial is not always equivalent to disturbing equipoise. Clarification of these points of contention leads to a sharpened definition of equipoise: 'a state of genuine agnosticism or conflict in the expert medical community about the net preferred medically established procedure for the condition under study'. This definition asks of physician-researchers and members of IRBs to meet two conditions: (1) to genuinely evaluate to what extent a proposed randomized clinical trial solves a state of agnosticism or a knowledge conflict in the expert medical community and (2) to respect the standard of competent care, meaning that they consider whether the regular clinical standard from an all-things considered perspective is also the preferred standard in the research context. Equipoise is a specification of two general ethical principles for clinical research: scientific validity and a favorable risk benefit ratio. As a specification equipoise adds substance to these principles since they do not explicitly ask for the two conditions. Equipoise is a prima facie obligation rather than a morally authoritative principle for determining the acceptability of clinical trials. It needs to be balanced against other norms for clinical research. Violation of equipoise is therefore not always unethical.
This study is limited to the context of randomized clinical trials.
There is no decisive reason to give up on the equipoise requirement.
本杰明·弗里德曼（Benjamin Freedman）曾在 1987 年指出，在进行对照试验之前，“医学专家对首选治疗方法存在真正的不确定性”。弗里德曼对这一概念的定义在临床研究中被广泛应用，但自提出以来一直存在争议。在过去的十年中，均衡争议变得越来越复杂。
本文旨在：（1）确定并阐明均衡争议的主要争议点；（2）通过指出均衡辩论的支持者和反对者之间的重叠领域，调和对立观点。
我们分析了过去十年中均衡辩论的主要作者的立场。
均衡的反对者和支持者之间存在很大的重叠。双方都应该能够接受以下对辩论中争议点的回答：（1）只要治疗义务被理解为提供参与者有能力的护理的义务，它就可以仍然是均衡的基础；（2）均衡是基于有能力的护理和认识论困境；（3）当存在已证明有效的治疗方法时，均衡并不总是禁止安慰剂对照试验；（4）患者均衡和个别医生均衡是无关紧要的；（5）不得不停止试验并不总是等同于扰乱均衡。对这些争议点的澄清导致了对均衡的定义的精细化：“研究人员对所研究疾病的最佳既定医学程序存在真正的怀疑或冲突”。这个定义要求医师研究员和 IRB 成员满足两个条件：（1）真正评估拟议的随机临床试验在多大程度上解决了医学专家社区的不确定状态或知识冲突；（2）尊重有能力的护理标准，这意味着他们考虑从全面角度来看，常规的临床标准是否也是研究背景下的首选标准。均衡是对临床研究的两个一般伦理原则的具体规定：科学有效性和有利的风险效益比。作为具体规定，均衡为这些原则增添了实质内容，因为它们没有明确要求这两个条件。均衡是确定临床试验可接受性的表面义务，而不是道德权威原则。它需要与其他临床研究规范相平衡。因此，违反均衡并不总是不道德的。
本研究仅限于随机临床试验的背景。
没有决定性的理由放弃均衡要求。
