Therapeutic Misconception and the Ethics of Sham Surgery Controls in PD Research

描述（由申请人提供）：伦理学家提出了一个担忧，即患有逐渐衰弱性疾病（如帕金森病（PD））的老年患者可能太容易受到涉及使用有争议的掩蔽设计（即假神经外科控制）的新颖侵入性干预（如基因转移和细胞移植）的研究的影响。一个常见的伦理问题是，受试者对治疗益处的渴望可能会损害他们决策的质量。这些受试者是否存在治疗误解（TM），即受试者将研究与个体化治疗混为一谈的现象，或者存在一些相关现象，例如严重错误估计参与研究的风险和收益？有越来越多的PD临床试验提出假对照设计，因此这一重要的伦理问题将继续出现。本项目拟研究四个实际PD神经外科临床试验的入组者和退组者，其中包括假手术对照。因为评估TM没有标准的方法，而且确实因为它仍然是一个有争议和不断发展的问题，这个项目的主要目的是从受试者的角度深入描述他们决定是否参加这样的研究。一种半结构化的访谈方法（条件调查访谈）已经被开发出来，以提供对受试者动机、期望、理解和决策过程的深入描述——强调受试者对每一项的基本原理以及它们之间的关系。我们将进行前瞻性和回顾性访谈相结合；筛选面试后拒绝的受试者也将接受面试。试验的参与者也将被纵向跟踪，因此动机、态度或理解的任何变化都可以被评估。这个项目的一个独特之处在于，分析将强调主体叙事的整体，作为分析可能或可能不表明TM相关现象的具体陈述的背景。因此，在解释个别陈述时，主体成为分析的主要单位。将采用互补的定性和定量分析方法。通过提供一个深入的、上下文敏感的关于严重神经病患者如何在涉及假手术对照的研究中做出参与决策的描述，该项目将(1)为优化未来假手术对照试验的知情同意实践提供宝贵的见解；(2)厘清TM及其相关现象的关键争议点和复杂轮廓。公共卫生相关性：当患有严重疾病的受试者参加涉及假手术对照的临床试验时，该项目解决了人类受试者研究的伦理挑战。特别是，它将通过关注帕金森病神经外科试验中假手术控制的伦理来增强NINDS的使命，这种设计越来越多地用于测试PD的新型外科干预措施。具体而言，本研究的结果将为如何减少甚至消除参与者可能影响其同意质量的严重误解或误解提供重要见解。

DESCRIPTION (provided by applicant): Ethicists have raised concerns that elderly patients with a progressively debilitating disease such as Parkinson's disease (PD) may be too vulnerable for research that involves novel, invasive interventions (such as gene transfer and cell transplants) that use a controversial masking design, i.e., sham neurosurgical controls. A common ethical concern is that the subjects' desire for therapeutic benefit may compromise the quality of their decisions. Are these subjects laboring under a therapeutic misconception (TM), a phenomenon in which subjects conflate research with individualized treatment, or some related phenomena, e.g., seriously misestimating the risks and benefits of research participation? There is an increasing number of PD clinical trials proposing the sham control design, so this important ethical issue will continue to arise. This project proposes to study enrollees and decliners of four actual PD neurosurgical clinical trials that involve a sham surgery control. Because there is no standard method for assessing TM and indeed because it remains a controversial and evolving issue, this project's main aim is to describe in depth from the subjects' perspective their decision whether to participate in such studies. A semi-structured interview method (Conditional Probe Interview) has been developed to provide an in depth account of the subjects' motivations, expectations, understanding, and decision-making process-emphasizing the subjects' rationale for each and the relationship between them. We will conduct a combination of prospective and retrospective interviews; those subjects who decline after screening interviews will also be interviewed. Enrollees of the trials will also be followed longitudinally, so any changes in motivations, attitudes, or understanding can be assessed. A unique focus of this project is that the analysis will emphasize the entirety of the subject's narrative as the context for analyzing specific statements that may or may not indicate TM related phenomena. Thus, the subject becomes the primary unit of analysis in the interpretation of individual statements. A complementary qualitative and quantitative analytic approach will be used. By providing an in depth, context-sensitive account of how seriously ill neurological patients make participation decisions regarding research involving sham neurosurgery controls, this project will (1) provide invaluable insights for optimizing informed consent practices for future sham surgery controlled trials; and (2) clarify the key controversial aspects, and the complex contours of, TM and related phenomena. PUBLIC HEALTH RELEVANCE: This project addresses the ethical challenges of human subject research when subjects with serious illnesses are enrolled in clinical trials involving sham surgery controls. In particular, it will enhance the mission of NINDS by focusing on the ethics of sham surgery controls in Parkinson's disease neurosurgical trials-a design that is increasingly used in testing novel surgical interventions for PD. Specifically, the results of this study will provide important insights into how to minimize or even eliminate serious misconceptions or misunderstandings on the part of participants that may compromise the quality of their consent.