|Grant Number:||5R01CA154517-03 Interpret this number|
|Primary Investigator:||Petersen, Gloria|
|Organization:||Mayo Clinic Rochester|
|Project Title:||Disclosing Genomic Incidental Findings in a Cancer Biobank: an ELSI Experiment|
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.
The First Amendment Right to Speak About the Human Genome.
Authors: Evans BJ
Source: Univ Pa J Const Law, 2014 Feb 1;16(3), p. 549-636.
The challenge of informed consent and return of results in translational genomics: empirical analysis and recommendations.
Authors: Henderson GE, Wolf SM, Kuczynski KJ, Joffe S, Sharp RR, Parsons DW, Knoppers BM, Yu JH, Appelbaum PS
Source: J Law Med Ethics, 2014 Fall;42(3), p. 344-55.
Have we asked too much of consent?
Authors: Koenig BA
Source: Hastings Cent Rep, 2014 Jul-Aug;44(4), p. 33-4.
Return of genomic results to research participants: the floor, the ceiling, and the choices in between.
Authors: Jarvik GP, Amendola LM, Berg JS, Brothers K, Clayton EW, Chung W, Evans BJ, Evans JP, Fullerton SM, Gallego CJ, Garrison NA, Gray SW, Holm IA, Kullo IJ, Lehmann LS, McCarty C, Prows CA, Rehm HL, Sharp RR, Salama J, Sanderson S, Van Driest SL, Williams MS, Wolf SM, Wolf WA, eMERGE Act-ROR Committee and CERC Committee, CSER Act-ROR Working Group, Burke W
Source: Am J Hum Genet, 2014 Jun 5;94(6), p. 818-26.
EPub date: 2014 May 8.
Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group.
Authors: Gray SW, Martins Y, Feuerman LZ, Bernhardt BA, Biesecker BB, Christensen KD, Joffe S, Rini C, Veenstra D, McGuire AL, CSER Consortium Outcomes and Measures Working Group
Source: Genet Med, 2014 Oct;16(10), p. 727-35.
EPub date: 2014 Mar 13.
Addressing the ethical challenges in genetic testing and sequencing of children.
Authors: Clayton EW, McCullough LB, Biesecker LG, Joffe S, Ross LF, Wolf SM, Clinical Sequencing Exploratory Research (CSER) Consortium Pediatrics Working Group
Source: Am J Bioeth, 2014 Mar;14(3), p. 3-9.
Clinical research. Divulging DNA secrets of dead stirs debate.
Authors: Couzin-Frankel J
Source: Science, 2014 Jan 24;343(6169), p. 356-7.
Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium.
Authors: Berg JS, Amendola LM, Eng C, Van Allen E, Gray SW, Wagle N, Rehm HL, DeChene ET, Dulik MC, Hisama FM, Burke W, Spinner NB, Garraway L, Green RC, Plon S, Evans JP, Jarvik GP, Members of the CSER Actionability and Return of Results Working Group
Source: Genet Med, 2013 Nov;15(11), p. 860-7.
EPub date: 2013 Oct 24.
Stakeholder engagement: a key component of integrating genomic information into electronic health records.
Authors: Hartzler A, McCarty CA, Rasmussen LV, Williams MS, Brilliant M, Bowton EA, Clayton EW, Faucett WA, Ferryman K, Field JR, Fullerton SM, Horowitz CR, Koenig BA, McCormick JB, Ralston JD, Sanderson SC, Smith ME, Trinidad SB
Source: Genet Med, 2013 Oct;15(10), p. 792-801.
EPub date: 2013 Sep 12.
Ethical, legal, and social implications of incorporating genomic information into electronic health records.
Authors: Hazin R, Brothers KB, Malin BA, Koenig BA, Sanderson SC, Rothstein MA, Williams MS, Clayton EW, Kullo IJ
Source: Genet Med, 2013 Oct;15(10), p. 810-6.
EPub date: 2013 Sep 12.
Reporting genomic sequencing results to ordering clinicians: incidental, but not exceptional.
Authors: Green RC, Lupski JR, Biesecker LG
Source: JAMA, 2013 Jul 24;310(4), p. 365-6.
Recommendations for returning genomic incidental findings? We need to talk!
Authors: Burke W, Antommaria AH, Bennett R, Botkin J, Clayton EW, Henderson GE, Holm IA, Jarvik GP, Khoury MJ, Knoppers BM, Press NA, Ross LF, Rothstein MA, Saal H, Uhlmann WR, Wilfond B, Wolf SM, Zimmern R
Source: Genet Med, 2013 Nov;15(11), p. 854-9.
EPub date: 2013 Aug 1.
Return of individual research results and incidental findings: facing the challenges of translational science.
Authors: Wolf SM
Source: Annu Rev Genomics Hum Genet, 2013;14, p. 557-77.
EPub date: 2013 Jul 15.
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.
Authors: Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG, American College of Medical Genetics and Genomics
Source: Genet Med, 2013 Jul;15(7), p. 565-74.
EPub date: 2013 Jun 20.
Point-counterpoint. Patient autonomy and incidental findings in clinical genomics.
Authors: Wolf SM, Annas GJ, Elias S
Source: Science, 2013 May 31;340(6136), p. 1049-50.
EPub date: 2013 May 16.
Point-counterpoint. Ethics and genomic incidental findings.
Authors: McGuire AL, Joffe S, Koenig BA, Biesecker BB, McCullough LB, Blumenthal-Barby JS, Caulfield T, Terry SF, Green RC
Source: Science, 2013 May 31;340(6136), p. 1047-8.
EPub date: 2013 May 16.
Management of incidental findings in clinical genomic sequencing.
Authors: Krier JB, Green RC
Source: Curr Protoc Hum Genet, 2013;Chapter 9, p. Unit9.23.
Return of results in genomic biobank research: ethics matters.
Authors: Wolf SM
Source: Genet Med, 2013 Feb;15(2), p. 157-9.
The Role of Law in the Debate over Return of Research Results and Incidental Findings: The Challenge of Developing Law for Translational Science.
Authors: Wolf SM
Source: Minn J Law Sci Technol, 2012;13(2), p. null.