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

描述(由申请人提供)：伦理学家担心，患有帕金森氏病(PD)等渐进性衰弱疾病的老年患者可能过于脆弱，无法进行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。一个共同的伦理问题是，受试者对治疗益处的渴望可能会损害他们的决策质量。这些受试者是在治疗误解(TM)下工作，这是一种受试者将研究与个体化治疗混为一谈的现象，还是一些相关的现象，例如，严重错误地估计了参与研究的风险和好处？有越来越多的PD临床试验提出了假对照设计，因此这一重要的伦理问题将继续出现。该项目建议研究四个实际帕金森病神经外科临床试验的参与者和衰退者，这些试验涉及假手术对照。由于没有评估TM的标准方法，而且它仍然是一个有争议的和不断发展的问题，本项目的主要目的是从受试者的角度深入描述他们是否参与此类研究的决定。一种半结构化访谈方法(条件探索式访谈)被用来深入描述受试者的动机、期望、理解和决策过程--强调受试者各自的理由以及他们之间的关系。我们将进行前瞻性和回溯性采访相结合；那些在筛选面试后拒绝的受试者也将接受采访。试验的参与者也将被纵向跟踪，因此可以评估动机、态度或理解的任何变化。这个项目的一个独特的重点是，分析将强调主体叙述的完整性，作为分析特定陈述的背景，这些陈述可能表明或可能不表明与TM相关的现象。因此，主体成为解释个别陈述的主要分析单位。将采用定性和定量相结合的分析方法。通过提供一个深入的、上下文敏感的关于神经科重症患者如何做出涉及假神经外科控制的研究的参与决策的描述，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；以及(2)澄清关键的争议方面以及TM和相关现象的复杂轮廓。公共卫生相关性：当患有严重疾病的受试者被纳入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氏病神经外科试验中假手术控制的伦理问题来加强NINDS的使命--这种设计越来越多地被用于测试治疗帕金森氏病的新型手术干预措施。具体地说，这项研究的结果将为如何最大限度地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的见解。

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.