HIV cure studies: risk, risk perception, and ethics

 描述(由申请人提供)：许多艾滋病毒治愈研究是计划或预期的。这些研究往往涉及高风险或未知风险，在(I)风险/收益比率、(Ii)知情同意和(Iii)对调查人员的信任方面提出了严重的道德挑战。对这些挑战的实证或哲学研究很少。拟议的研究将使用建模来评估各种艾滋病毒治愈干预措施的客观风险，使用调查来评估患者和研究人员的风险伦理认可和参与这些研究的意愿，并使用哲学分析对艾滋病毒治愈研究的伦理行为提出相关建议。创新：拟议的研究在几个方面是创新的：(A)它将应用已在其他情况下得到验证的CEPAC模型，以调查艾滋病毒治疗干预的新领域；(B)它将利用我们已成功支持其他调查的大型ACTG网络，对患者和临床医生进行一项关于目前尚不存在调查的东西--道德和参与高风险艾滋病毒治疗研究的意愿--的大型调查；(C)这是第一次彻底检查艾滋病毒治疗研究中这些哲学挑战的大型研究；(D)它将把来自早期癌症研究、其他首个人类研究和其他地方的伦理见解转化为针对艾滋病毒治疗伦理研究的实用建议，以指导调查人员、资助者和IRBs，并与关键利益攸关方一起磨练。方法：我们将首先对艾滋病毒治疗研究的伦理挑战进行汇编和编目。一些回复将立即被筛选出明显的逻辑、实践或道德缺陷(“Filte A”)。在其余的应对措施中，我们将评估包括这些措施在内的治疗干预措施的风险(目标1)。我们还将进行调查，以检查34个美国ACTG地点的艾滋病毒患者和临床医生愿意参与涉及类似风险水平的研究的程度，以及他们在道德上对此类研究的接受程度(目标2)。综合起来，目标1和目标2将排除对挑战的一些反应，认为这是不可行的(“过滤器B”)。然后，我们将评估应对挑战的其余应对措施的伦理(“过滤器C”)，并就如何从伦理角度开展艾滋病毒治愈研究(目标3)提出建议。我们的建议草案将提交给艾滋病毒治疗决策者、IRB成员和其他关键利益攸关方，以获得反馈并完善建议。(“过滤器D”)。我们提出了以下目标：1.通过建模评估不同患者群体参与HIV治愈研究的风险。2.经验性地评估HIV研究者和HIV患者的伦理评价以及参与涉及给定风险水平的HIV治疗研究的意愿。3.使用这些结果，以及哲学分析、出版的伦理文献、我们顾问委员会的反馈以及主要利益相关者的反馈，形成艾滋病毒治疗研究的伦理建议范本。

 DESCRIPTION (provided by applicant): Many HIV cure studies are planned or expected. These studies often involve high or unknown risks, raising serious ethical challenges concerning (I) risk/benefit ratios, (II) informed consent, and (III) trust in investigators. Little empirical r philosophical research into these challenges is available. The proposed study will use modeling to assess objective risks from various HIV cure interventions, use surveys to assess patients' and investigators' risk ethical approval and willingness to partake in those studies, and use philosophical analysis to make related recommendations on the ethical conduct of HIV cure studies. Innovation: The proposed study is innovative in several ways: (a) It will apply CEPAC modeling, which has been validated in other contexts, to investigate the new area of HIV cure interventions; (b) It will use our ready access to the large ACTG network, which has successfully supported other surveys, for a large survey of patients and clinicians on something for which no survey currently exists-ethics and willingness to participate in risky HIV cure studies; (c) It is the first large study to thoroughly examine these philosophical challenges in HIV cure studies; (d) It will translate ethics insights from early phase cancer studies, other first-in-human studies and elsewhere into practical recommendations for ethical HIV cure research, to guide investigators, funders, and IRBs, honed with key stakeholders. Approach: We will first compile and catalogue conceivable responses to the ethical challenge of HIV cure studies. Some responses will be immediately screened out for obvious logical, practical, or ethical flaws ("Filte A"). Among remaining responses, we shall assess the risks of cure interventions comprising them (Aim 1). We shall also conduct surveys to check how much HIV patients and clinicians in 34 US-based ACTG sites are willing to partake in studies that involve similar risk levels, and how morally acceptable they would find such studies (Aim 2). Combined, Aims 1 and 2 will rule out some responses to the challenge as infeasible ("Filter B"). Then, we shall assess the ethics of remaining responses to the challenge ("Filter C") and make recommendations on how to conduct HIV cure studies ethically (Aim 3). Our draft recommendations will be presented to HIV cure decision makers, IRB members, and other key stakeholders to obtain feedback and hone the recommendations. ("Filter D"). We propose the following aims: 1. Assess through modeling the risk from HIV cure study participation for various patient populations. 2. Empirically assess HIV investigators' and HIV patients' ethical evaluation and willingness to partake in HIV cure studies involving given risk levels. 3. Use these results, along with philosophical analysis, published ethics literature, feedback from our Board of Advisors, and feedback from key stakeholders, to form model ethical recommendations for HIV cure research.