Exploring the Ethical Dimensions of Peanut Allergy Immunotherapy Research

项目摘要 儿科研究和开发的一个重要领域是花生过敏免疫疗法。研究人员正在 追求口服，舌下，皮下和表皮产品，激活免疫系统，通过 过敏原暴露使个体对花生不敏感。一种这样的治疗方法现在已经被FDA批准，另一种 即将获得市场认可然而，免疫疗法给患者带来了显著的风险，例如高风险。 治疗引起的过敏反应的发生率。本项目的目标是以经验为依据确定当地的道德 儿科花生免疫疗法（PIT）临床试验中出现的挑战。迄今为止， 在食物过敏研究和实践的广泛领域内关注伦理。然而，PIT研究涉及到 许多值得伦理考虑的特征，包括招募儿童的临床试验，有些甚至只有 1岁，风险-受益特征与许多其他治疗领域不同。为了探讨这些伦理问题， 该项目有两个具体目标：（1）记录研究人员、照顾者、青少年、病人 倡导者、FDA官员和制药公司代表-定义和理解可接受的风险 从花生免疫疗法中受益，无论是在研究方案还是最终产品方面， 在临床实践中使用;（2）确定从这些利益相关者的立场出现的伦理挑战， 花生免疫疗法的风险和好处。对于目标1，该项目采用了人种学方法，包括 观察性研究和125个半结构化访谈，重点关注6个领先的美国PIT研究中心， 学术食物过敏会议，患者宣传活动，以及PIT产品的FDA听证会。完成 目标2，该项目采用分析方法，在生物伦理框架中为目标1的实证研究结果奠定基础， 包括原则主义和对脆弱或复杂人群的研究。所提出的研究是有意义的 因为它将为PIT临床试验的伦理行为制定一个初步框架， 推动生物医学研究的兴趣，包括寻找有意义地改善人类生活的疗法。 儿童和成人花生过敏，需要设计和进行临床试验，以满足监管 FDA批准产品所需的标准，以及研究者 公司有经济利益冲突，这促使新疗法的成功开发。 该项目具有创新性，因为它探索了社会科学和生物伦理学研究的新领域， 它调查了PIT研究的整个领域和广泛的利益相关者。该应用程序直接 响应国家卫生研究院的通知，在生物伦理，法律的和社会影响的高优先级研究的兴趣， 生物医学研究（NOT-LM-17-001），特别关注新技术和新兴技术的发展 和使用，儿科研究，以及当前和新兴的监管环境。

PROJECT SUMMARY An important area of pediatric research and development is peanut allergy immunotherapy. Researchers are pursuing oral, sublingual, subcutaneous, and epicutaneous products that activate the immune system through allergen exposure to desensitize individuals to peanuts. One such treatment is now FDA approved, and another is poised to receive market approval. However, immunotherapy conveys significant risk to patients, such as high rates of treatment-induced anaphylaxis. This project's objective is to identify empirically the on-the-ground ethical challenges that emerge in pediatric peanut immunotherapy (PIT) clinical trials. To date, there has been little attention to ethics within the broad domain of food allergy research and practice. Yet, PIT research involves many features that warrant ethical consideration, including clinical trials that enroll children, some as young as 1 year old, and risk-benefit profiles that differ from many other therapeutic areas. To explore these ethical issues, the project has 2 specific aims: (1) Document how stakeholders—investigators, caregivers, adolescents, patient advocates, FDA officers, and pharmaceutical company representatives—define and understand acceptable risks and benefits from peanut immunotherapy, both in terms of research protocols and the eventual products to be used in clinical practice; and (2) Identify the ethical challenges that emerge from these stakeholders' stances on peanut immunotherapy risks and benefits. For Aim 1, the project uses an ethnographic approach—consisting of observational studies and 125 semi-structured interviews—that focuses on 6 leading U.S. PIT research centers, academic food allergy conferences, patient advocacy events, and FDA hearings for PIT products. To accomplish Aim 2, the project employs analytic methods to ground the empirical findings from Aim 1 in bioethical frameworks, including principlism and research on vulnerable or complex populations. The proposed research is significant because it will develop an initial framework for the ethical conduct of PIT clinical trials that attends to the myriad interests that drive biomedical research, including the search for therapies that meaningfully improve the lives of children and adults with peanut allergy, the need to design and conduct clinical trials to meet the regulatory standards required by the FDA for the approval of products, and the commercial context in which investigators and companies have financial conflicts of interest that motivate the successful development of new therapies. This project is innovative because it explores a novel area of social science and bioethics research and because it investigates the entire sphere of PIT research and a wide array of stakeholders. This application is directly responsive to NIH's Notice of Interest in High Priority Research in Bioethical, Legal, and Societal Implications of Biomedical Research (NOT-LM-17-001), focusing in particular on new and emerging technology development and use, pediatric research, and the current and emerging regulatory environments.