RESPECT3: A Randomized type 1 hybrid Effectiveness-implementation Study of returning actionable genetic PanEl researCh resulTs

利用储存的DNA进行的大型前瞻性队列研究越来越多地利用下一代测序 (NGS)评估基因、环境和生活方式对健康结果的影响，但NGS也可以 确定可能显著影响研究参与者未来健康的可操作的基因变异 和/或他们的亲属。如何最好地教育参与者他们可以选择拒绝或接受研究 结果，如何尊重接收结果的首选项，以及如何最好地传达结果，尤其是在 目前尚不清楚是否有大量病例。在这方面的研究(R01 CA190871：Bradbury)中，我们开发了 建立了使用电子健康教育的可行性和患者报告的良好结果 同意干预作为传统披露前遗传咨询的替代方案。的目标是 建议的竞争更新是进行混合类型1有效性-实施研究，以评估 电子健康提供替代方案，用于预先披露教育和返回可操作的基因研究结果。 在尊重研究的基础上(R01 CA190871：Bradbury)，我们将调整我们的尊重eHealth Pre 向1250名宾夕法尼亚州立大学生物库参与者(625名具有可操作结果和625名对照)提供披露干预 Chatbot支持的电子健康教育干预(EHealthED)，提供有关好处和 接收研究结果的限制、返回结果的方式及其拒绝接收的选择 结果(目标1)。在目标2中，我们将随机选择具有可操作研究结果的参与者，以获得他们的结果 通过电话与GC(日常护理)或利益相关者通知和用户测试的聊天机器人启用eHealth 结果返回干预(EHealthROR)。所有参与者被随机分配到eHealthROR(例如干预组) 将提供在收到结果之前或之后选择与GC交谈的选项。同时， 我们将进行CFIR(实施研究综合框架)知情的过程评估 了解电子健康干预措施使用的主持人、患者结果、成本以及促进者和障碍 使用电子健康干预措施返还可操作基因的未来实施和可持续性 在大规模和社会人口学不同的研究队列中的研究结果(目标3)。我们假设 大多数参与者将获得补充的电子健康和聊天机器人支持的教育，并披露 我们的电子健康干预的可操作性研究结果将导致非劣质的短期和纵向 患者的认知、情感和行为结果以及更低的成本，提供了一个可扩展的回归模式 对大型生物库中的研究参与者具有可操作性的结果。因此，我们希望这项研究能提供证据- 以实践指南为基础，向参与者返还可操作的基因研究成果。

Large prospective cohort studies with banked DNA have increasingly utilized next generation sequencing (NGS) to evaluate the effects of genes, the environment and lifestyle on health outcomes, but NGS can also identify actionable genetic variants that may significantly impact the future health of the research participant and/or their relatives. How best to educate participants about their options to decline or receive research results, how to honor preferences for receipt of results, and how to best communicate results, particularly in large cohorts remains unknown. In the RESPECT studies (R01 CA190871:Bradbury), we have developed and established the feasibility and favorable patient-reported outcomes with using an eHealth education and consent intervention as an alternative to traditional pre-disclosure genetic counseling. The goal of the proposed competitive renewal is to conduct a Hybrid Type 1 effectiveness-implementation study to evaluate eHealth delivery alternatives for pre-disclosure education and return of actionable genetic research results. Building upon the RESPECT studies (R01 CA190871: Bradbury), we will adapt our RESPECT eHealth pre- disclosure intervention to offer 1250 Penn Biobank participants (625 with actionable results and 625 controls) a chatbot enabled eHealth education intervention (eHealthED) that provides information about the benefits and limitations of receiving research results, how results will be returned and their options for declining receipt of results (Aim 1). In Aim 2, we will randomize participants with actionable research results to receive their results via telephone with a GC (usual care) or a stakeholder-informed and user-tested chat-bot enabled eHealth return of results intervention (eHealthROR). All participants randomized to eHealthROR (e.g. intervention arm) will be provided the option to speak with a GC as an alternative, before or after receiving results. Concurrently, we will conduct a CFIR (Consolidated Framework for Implementation Research)-informed process evaluation to understand moderators of eHealth intervention usage, patient outcomes, costs and facilitators and barriers to future implementation and sustainability of using eHealth interventions for return of actionable genetic research results in large and sociodemographically diverse research cohorts (Aim 3). We hypothesize that the majority of participants will access supplemental eHealth and chatbot enabled education and that disclosure of actionable research results by our eHealth intervention will result in non-inferior short-term and longitudinal patient cognitive, affective and behavioral outcomes and lower costs, providing a scalable model for returning actionable results to research participants in large biobanks. Thus, we expect this study to inform evidence- based practice guidelines for return of actionable genetic research results to participants.