Assessing Non-Inferiority of Scalable eConsent for Genomics

评估基因组学可扩展电子同意的非劣效性

• 批准号: 9929394
• 负责人: Alanna K Rahm
• 金额: $ 16.29万
• 依托单位: GEISINGER CLINIC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9929394
• 关键词: Address; All of Us Research Program; Apple; Award; Behavior; Bioethics; Cancer Patient; Clinical Trials; Collaborations; Colorectal Cancer; Community Health; Comprehension; Consent; Data; Diagnosis; Economic Models; Effectiveness; Elements; Eligibility Determination; Employee; Endometrial Carcinoma; Enrollment; Ensure; Evaluation; Face; Failure; Future; Genetic; Genetic Privacy; Genetic screening method; Genomics; Geography; Goals; Grant; Health system; Hereditary Malignant Neoplasm; Hereditary Nonpolyposis Colorectal Neoplasms; Human; Immunohistochemistry; Individual; Informed Consent; Inherited; Institution; Knowledge; Lead; Learning; Literature; Logistics; Malignant Neoplasms; Mediating; Medical; Medically Underserved Area; Methods; Morbidity - disease rate; Outcome; Paper; Participant; Patients; Persons; Population; Privacy; Process; Program Effectiveness; Protocols documentation; Randomized; Randomized Controlled Trials; Research; Research Personnel; Rural; Sample Size; Security; Surveys; Syndrome; Time; United States National Institutes of Health; Work; actionable mutation; arm; biobank; cancer risk; clinically actionable; cost; cost effective; cost effectiveness; design; exome sequencing; genome sequencing; improved; indexing; medically underserved population; mortality; patient population; patient screening; preference; prevent; primary outcome; programs; response; screening; screening program; secondary outcome; socioeconomics; success; trial comparing; tumor; uptake

Identifying individuals with medically actionable, hereditary syndromes such as Lynch Syndrome (LS) can lead to reduced morbidity and mortality. However, prior evaluations of LS screening programs in the endometrial cancer context find that the biggest threat to their success, by orders of magnitude, is the high rate of non- consent for sequencing. Largely due to non-consent, protocols that call for sequencing following immunohistochemistry (IHC)–positive screens are estimated to miss 58% of LS index cases, while direct-to- sequencing screening protocols are expected to miss 30%. It is not known, however, why non-consent occurs: perhaps people misunderstand some important aspect of genetic sequencing, or perhaps they have concerns (e.g., genetic privacy) that could be better or more thoroughly addressed during the consent process. Traditional, in-person consent for sequencing faces two additional challenges: reaching patients in rural and other medically underserved areas and ensuring that screening protocols are cost-effective. Electronic consent (eConsent) shows promise in overcoming barriers of both access and cost and has begun to be used in important genomics projects, including the All of Us Research Program, yet has never been rigorously compared to traditional consent to ensure non-inferiority. Working with Sage Bionetworks, we adapted the eConsent framework they developed for All of Us to Geisinger's MyCode Community Health Initiative, which involves population screening for clinically actionable variants, including LS. We propose a pragmatic, non- inferiority RCT—which we have already piloted—of Sage eConsent compared to traditional consent. In addition to determining whether eConsent is non-inferior in ensuring patient comprehension (Aim 1), this study will help identify aspects of genomic screening that are difficult for patients to understand or that they express a preference to learn more about, which will inform both eConsent and traditional consent processes, and potentially improve screening uptake (Aim 2). Compared to conducting this study in a LS-only screening population, the large MyCode population will provide sufficient sample size to power a non-inferiority trial over a short period of time. Moreover, as the cost of sequencing continues to decline, population genomic screening will itself become a viable, cost-effective approach to identifying individuals with LS and other hereditary syndromes. Indeed, multiple health systems are already piloting such programs, which will require scalable, accessible, and cost-effective approaches to consent. The results of this study will greatly benefit the IMPULSS implementation toolkit that will be designed to help institutions implement, evaluate, and adapt LS screening programs over time, particularly as it becomes cost-effective for institutions to move their programs towards a direct-to-sequencing protocol in cancer patients or to population screening. Including data on the costs and effectiveness of scalable eConsent for sequencing will be a valuable addition to the IMPULSS toolkit that can help reduce barriers to identifying individuals with hereditary cancer risk in order to prevent cancer.

识别具有医学上可操作的遗传性综合征（如林奇综合征（LS））的个体可以导致 降低发病率和死亡率。然而，子宫内膜LS筛查项目的既往评价 癌症背景下发现，最大的威胁，他们的成功，由数量级，是高利率的非- 同意测序。由于未经同意而被解雇，要求测序的协议如下 免疫组化（IHC）阳性筛查估计会错过58%的LS指数病例，而直接免疫组化（IHC）阳性筛查可能会错过58%的LS指数病例。 测序筛选方案预计会错过30%。然而，不知道为什么会发生不同意： 也许人们误解了基因测序的一些重要方面，或者他们担心 (e.g.,遗传隐私权），这些问题在同意过程中可以得到更好或更彻底的解决。 传统的亲自同意测序面临两个额外的挑战：接触农村患者， 其他医疗服务不足的地区，并确保筛查方案具有成本效益。电子知情同意 （eConsent）在克服获取和费用方面的障碍方面显示出希望，并已开始用于 重要的基因组学项目，包括我们所有的研究计划，但从来没有严格 与传统的同意相比，以确保非劣效性。通过与Sage Bionetworks合作， 他们为我们所有人开发的eConsent框架适用于Geisinger的MyCode社区健康倡议， 涉及对临床上可行的变体进行群体筛查，包括LS。我们提出一个务实的，非- Sage eConsent与传统知情同意相比的劣效性RCT（我们已经进行了试点）。在 除了确定eConsent在确保患者理解方面是否具有非劣效性（目标1）外，本研究 将有助于确定基因组筛查的一些方面，这些方面对患者来说很难理解，或者他们表达了一种 优先了解更多信息，这将为电子同意和传统同意流程提供信息，以及 潜在地提高筛选摄取（目标2）。与在仅LS筛选中进行本研究相比， 人群，大的MyCode人群将提供足够的样本量，以支持非劣效性试验， 短时间此外，随着测序成本的不断下降， 本身将成为一个可行的，具有成本效益的方法，以确定个人与LS和其他遗传 综合征事实上，多个卫生系统已经在试点此类计划，这将需要可扩展的， 方便、成本效益高的同意方法。这项研究的结果将大大有利于 IMPULSS实施工具包，旨在帮助机构实施、评估和调整LS 随着时间的推移筛选项目，特别是当机构转移项目变得具有成本效益时 用于癌症患者或人群筛查的直接测序方案。包括关于 用于测序的可扩展eConsent的成本和有效性将是IMPULSS工具包的重要补充 这可以帮助减少识别具有遗传性癌症风险的个体的障碍，以预防癌症。