HIV cure studies: risk, risk perception, and ethics

描述（由申请人提供）：计划或预期进行许多HIV治愈研究。这些研究通常涉及高风险或未知风险，在（I）风险/获益比，（II）知情同意和（III）对研究者的信任方面提出了严重的伦理挑战。对这些挑战的经验或哲学研究很少。这项拟议的研究将使用建模来评估各种艾滋病毒治疗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批准和参与这些研究的意愿，并使用哲学分析对艾滋病毒治疗研究的道德行为提出建议。创新：拟议的研究在几个方面具有创新性：（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）它将利用我们随时可以进入的大型ACTG网络，该网络已成功地支持了其他调查，对患者和临床医生进行一项大规模的调查，调查内容是目前还没有调查的内容--道德和参与有风险的艾滋病治疗研究的意愿;（c）这是第一个彻底审查艾滋病毒治疗研究中的哲学挑战的大型研究;（d）它将把早期癌症研究、其他首次人体研究和其他研究中的伦理见解转化为艾滋病毒治疗研究伦理的实际建议，以指导研究人员、资助者和IRB。方法：我们将首先汇编和编目可以想象的艾滋病毒治疗研究的伦理挑战的反应。有些回答会被立即筛选出明显的逻辑、实践或道德缺陷（“过滤器A”）。在其余的反应中，我们将评估包括它们的治愈干预措施的风险（目标1）。我们还将进行调查，以检查有多少艾滋病毒患者和临床医生在34个美国的ACTG网站愿意参加研究，涉及类似的风险水平，以及道德上如何接受他们会发现这样的研究（目标2）。结合目标1和目标2，将排除对挑战的一些不可行响应（“过滤器B”）。然后，我们将评估挑战的剩余反应的伦理（“过滤器C”），并就如何在伦理上进行HIV治愈研究提出建议（目标3）。我们提出以下目标：1.通过对不同患者人群参与HIV治愈研究的风险建模进行评估。 2.实证评估HIV研究者和HIV患者的伦理评价和参与涉及特定风险水平的HIV治疗研究的意愿。 3.使用这些结果，沿着哲学分析，出版的伦理文献，并从我们的顾问委员会的反馈意见，形成模式的艾滋病毒治疗研究的伦理建议。

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 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 he first large study to thoroughly examine 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. 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 ("Filter 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). 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, and feedback from our Board of Advisors, to form model ethical recommendations for HIV cure research.