Disclosing Genomic Incidental Findings in a Cancer Biobank: An ELSI Experiment

披露癌症生物库中的基因组偶然发现：ELSI 实验

• 批准号: 8521164
• 负责人: Barbara A. Koenig
• 金额: $ 54.65万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-12 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521164
• 关键词: Address; Advocate; Archives; Authorization documentation; BRCA2 gene; Bioethics; Biological; CDKN2A gene; Cancer Family; Cancer Patient; Cancer-Predisposing Gene; Clinic; Communication; Consensus; Consent; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA; Data; Decision Making; Disclosure; Disease; Epidemiologist; Ethical Issues; Ethics; Face; Family; Family member; Funding; Genes; Genetic; Genetic Research; Genome; Genomics; Germ-Line Mutation; Goals; Grant; Health; Incidental Findings; Individual; Informed Consent; Institutional Review Boards; Interview; Laws; Legal; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Methods; Minnesota; Mutation; National Human Genome Research Institute; Notification; Online Systems; Paper; Participant; Patients; Policies; Practice Guidelines; Procedures; Process; Recommendation; Recording of previous events; Relative (related person); Research; Research Ethics; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Risk; Role; Siblings; Spouses; Structure; Surveys; Testing; Universities; Variant; Wolves; Work; base; biobank; cancer genetics; clinical practice; clinically relevant; clinically significant; design; disorder risk; gene discovery; genome wide association study; malignant breast neoplasm; meetings; melanoma; multidisciplinary; mutation carrier; novel; offspring; preference; proband; prototype; reproductive; research study; response; sound; symposium; working group

DESCRIPTION (provided by applicant): This empirical and normative bioethics research project will guide policy and practice about the disclosure of genomic incidental findings (GIFD), a much-debated topic. With ethical guidance from a multidisciplinary ELSI Working Group, we will conduct an experiment designed to develop strategies for offering incidental findings to family members of probands in a biobank for pancreatic cancer. Our approach will be informed by studying the preferences of biobank research participants (including kin).To our knowledge, no previous research has addressed the return of incidental findings to families. Yet biobanks face this question. Recommendations to guide practice are sorely needed. Mayo Clinic has collected germline DNA of pancreatic cancer probands in an NCI-funded SPORE biobank created for gene discovery. While seeking novel pancreatic cancer variants, we have identified 73 probands who are germline carriers of mutations in genes known to confer increased risk of diseases other than pancreatic cancer: BRCA2 (breast & ovarian cancer), CDKN2A/p16 (malignant melanoma), and CFTR (cystic fibrosis in offspring). Because these mutations are routinely disclosed in clinical practice and have serious health and/or reproductive implications, consideration of GIFD is justified. Given that the majority of the pancreatic cancer probands are deceased, many concerns arise: Who should be offered the findings, given that notification of the proband's legal next of kin may not assure that biologically at-risk family members are informed? Since relatives were not involved in the original biobank informed consent process, how should re-contact be managed? What disclosure proce- dures best meet family members' concerns? Is there an ethical threshold for determining when the researcher is obligated to offer GIFD? A partnership among 3 PIs-a genetic epidemiologist who directs the SPORE biobank (Gloria Petersen), an empirical researcher (Barbara Koenig), and a bioethics and law scholar (Susan Wolf)-combines the strengths of Mayo Clinic and the University of Minnesota (UMN). This project leverages the infrastructure of the SPORE biobank at Mayo Clinic and UMN's Consortium on Law and Values' history of NHGRI-funded work on incidental findings. This project addresses a critical problem in translational genomics research ethics. The Specific Aims-which combine descriptive and normative objectives-are: (1) to assess preferences of pancreatic cancer probands and their family members using a) interviews and b) a survey; (2) to conduct an in-depth ELSI analysis with an expert law and bioethics Working Group, leading to consensus recommendations; (3) based on the findings from Aims 1 and 2, to prototype and evaluate a procedure for offering findings to family members of probands who carry germline mutations; and (4) to develop "best practice" guidelines. This project will generate much-needed data on proband and family preferences, produce detailed analyses of the legal and ethical issues raised, create consensus recommendations, devise methods for honoring preferences, and advance sound biobank governance.

描述（由申请人提供）：这个经验和规范性生物伦理学研究项目将指导有关披露基因组偶然发现（GIFD）的政策和实践，这是一个备受推测的主题。在跨学科ELSI工作组的道德指导下，我们将进行一项实验，旨在制定策略，以向胰腺癌生物群中的探险家族成员提供偶然发现。我们的方法将通过研究生物库研究参与者（包括亲戚）的偏好来告知我们的方法。在我们的知识中，以前没有研究涉及偶然发现向家庭的回报。然而，生物银行面临这个问题。非常需要指导实践的建议。梅奥诊所已在用于基因发现的NCI资助的孢子生物库中收集了胰腺癌概率的种系DNA。在寻求新颖的胰腺癌变体的同时，我们已经确定了73个概率，它们是已知的基因突变的种系突变携带者，这些突变载体可赋予胰腺癌以外的疾病风险增加：BRCA2（乳腺癌和卵巢癌），CDKN2A/P16（恶性菌群）（恶性黑色素瘤）和CFTR（CFTR（CFTR）（CYSTIC纤维化）。由于这些突变在临床实践中常规披露并具有严重的健康和/或生殖意义，因此对GIFD的考虑是合理的。鉴于大多数胰腺癌的概率都已经死亡，因此出现了许多担忧：应该向谁提出发现，因为有关概率的近代合法的通知可能无法确保告知生物危险的家庭成员？由于亲戚不参与原始的生物银行知情同意过程，因此应该如何管理重新接触？哪些披露过程最能满足家庭成员的关注？确定研究人员何时有义务提供GIFD有道德阈值吗？指导孢子生物库（Gloria Petersen），经验研究员（Barbara Koenig）的3位PIS-A遗传流行病学家以及一位Mayo Clinic和Minnesota University（UMN）的实力。该项目利用梅奥诊所的孢子生物库的基础设施以及UMN关于法律与价值观的财团在NHGRI资助的偶然发现中的历史。该项目解决了转化基因组学研究伦理中的一个关键问题。具体目的 - 结合了描述性和规范性目标 - （1）使用a）访谈和b）调查来评估胰腺癌概率及其家人的偏好； （2）与专家法和生物伦理学工作组进行深入的ELSI分析，从而提出共识； （3）基于AIM 1和2的发现，原型和评估一种为携带种系突变的概率的家庭成员提供发现的程序； （4）制定“最佳实践”准则。该项目将生成有关概率和家庭偏好的急需数据，对提出的法律和道德问题进行详细分析，创建共识建议，设计尊重偏好的方法以及提高声音生物库的治理。