lunes, 5 de agosto de 2013

Genome Sequencing Return of Findings: We Need to Talk!

Features of the Week


Genome Sequencing Return of Findings: We Need to Talk!


whole genome sequencing
CDC paper: Recommendations for returning genomic incidental findings?  We need to talk!External Web Site Icon
Wylie Burke et al. Genetics in Medicine 2013 Aug 1
CDC blog post:  On the importance of a policy framework to guide an evidence-based approach to incorporate genome sequencing technology into health care and public health
Reporting genomic sequencing results to ordering clinicians: Incidental, but not exceptionalExternal Web Site Icon
Robert C. Green, et al. JAMA. 2013;310(4):365-366.
Mandatory extended searches in all genome sequencing: “incidental findings,” patient autonomy, and shared decision makingExternal Web Site Icon
Lainie Friedman Ross, et al. JAMA. 2013;310(4):367-368.

Return of secondary genomic findings vs patient autonomy: Implications for medical careExternal Web Site Icon
Robert Klitzman, et al. JAMA. 2013;310(4):369-370.
Incidental swimming with millstones.External Web Site Icon
Stephen F. Kingsmore Sci Transl Med 17 July 2013


Recommendations for returning genomic incidental findings? We need to talk!

Genetics in Medicine
(2013)
doi:10.1038/gim.2013.113
Received
Accepted
Published online

Abstract

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines.
Genet Med advance online publication 1 August 2013

References

  1. Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 2013;15:565574.
  2. Jarvik G, Turner E, Robertson P, et al. Actionable, known pathogenic incidental findings in 1000 subjects’ exomes. American College of Medical Genetics Annual Meeting, Phoenix, AZ, 21 March 2013.
  3. American College of Medical Genetics and Genomics (ACMG). Points to consider in the clinical application of genomic sequencing. Genet Med 2012;14:759761.
  4. Evans JP, Berg JS, Olshan AF, Magnuson T, Rimer BK. We screen newborns, don’t we?: realizing the promise of public health genomics. Genet Med 2013;15:332334.
  5. Ajioka RS, Kushner JP. Hereditary hemochromatosis. Semin Hematol 2002;39:235241.
  6. Begg CB. On the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 2002;94:12211226.
  7. Wilson JMG, Jungner F. Principles and Practice of Screening for Disease. Public Health Papers No. 34, World Health Organization, Geneva, 1968.
  8. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990;335:827838.
  9. Daskalopoulou SS, Khan NA, Quinn RR, et al.; Canadian Hypertension Education Program. The 2012 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy. Can J Cardiol 2012;28:270287.
  10. Deyo RA. Cascade effects of medical technology. Annu Rev Public Health 2002;23:2344.
  11. US Preventive Services Task Force Draft Recommendation Statement. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. http://www.uspreventiveservicestaskforce.org/draftrec.htm. Accessed 10 May 2013.
  12. Zimmern RL. Issues concerning the evaluation and regulation of predictive genetic testing. J Community Genet 2012; e-pub ahead of print 8 July 2012.
  13. Burke W, Coughlin SS, Lee NC, Weed DL, Khoury MJ. Application of population screening principles to genetic screening for adult-onset conditions. Genet Test 2001;5:201211.
  14. Grosse SD, Rogowski WH, Ross LF, Cornel MC, Dondorp WJ, Khoury MJ. Population screening for genetic disorders in the 21st century: evidence, economics, and ethics. Public Health Genomics 2010;13:106115.
  15. Harris R. Overview of screening: where we are and where we may be headed. Epidemiol Rev 2011;33:16.
  16. Rothstein MA. The case against precipitous, population-wide, whole genome sequencing. J Law Med Ethics 2012;40:682689.
  17. Viera AJ. Predisease: when does it make sense? Epidemiol Rev 2011;33:122134.
  18. Welch G, Allen NA, Zagarins SE, Stamp KD, Bursell SE, Kedziora RJ. Comprehensive diabetes management program for poorly controlled Hispanic type 2 patients at a community health center. Diabetes Educ 2011;37:680688.
  19. Getz L, Sigurdsson JA, Hetlevik I. Is opportunistic disease prevention in the consultation ethically justifiable? BMJ 2003;327:498500.
  20. Meisel A, Cerminara KL. The Right to Die: The Law on End-of-Life Decision Making, 3rd edn. Aspen: New York, 2004.
  21. Spatz ES, Spertus JA. Shared decision making: a path toward improved patient-centered outcomes. Circ Cardiovasc Qual Outcomes. 2012;5(6):e75e77.
  22. American College of Medical Genetics and Genomics. Incidental findings in clinical genomics: a clarification. Genet Med 2013; 15:664666.
  23. American Academy of Pediatrics Committee on Bioethics, Committee on Genetics and the American College of Medical Genetics and Genomics Social, Ethical and Legal Issues Committee. Policy statement: ethical and policy issues in genetic testing and screening of children. Pediatrics 2013;131:620622.
  24. Ross LF, Saal HM, David KL, Anderson RR; American Academy of Pediatrics; American College of Medical Genetics and Genomics. Technical report: ethical and policy issues in genetic testing and screening of children. Genet Med 2013;15:234245.
  25. National Human Genome Research Institute. Clinical sequencing exploratory research. http://www.genome.gov/27546194. Accessed 10 May 2013.
  26. University of North Carolina Center for Genomics and Society http://genomics.unc.edu/genomicsandsociety. Accessed 10 May 2013.
  27. Goddard KA, Whitlock EP, Berg JS, et al. Description and pilot results from a novel method for evaluating return of incidental findings from next-generation sequencing technologies. Genet Med 2013; e-pub ahead of print 4 April 2013.

Author information

Affiliations

  1. Department of Bioethics and Humanities, University of Washington, Seattle, Washington, USA

    • Wylie Burke
  2. Ethics Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    • Armand H. Matheny Antommaria
  3. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA

    • Robin Bennett &
    • Gail P. Jarvik
  4. Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA

    • Jeffrey Botkin
  5. Center for Biomedical Ethics and Society and School of Law, Vanderbilt University, Nashville, Tennessee, USA

    • Ellen Wright Clayton
  6. Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    • Gail E. Henderson
  7. Division of Genetics, Boston Children’s Hospital, Boston, Massachusetts, USA

    • Ingrid A. Holm
  8. The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, Massachusetts, USA

    • Ingrid A. Holm
  9. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

    • Ingrid A. Holm
  10. Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    • Muin J. Khoury
  11. Centre of Genomics and Policy, McGill University, Montreal, Quebec, Canada

    • Bartha Maria Knoppers
  12. Schools of Nursing and Medicine, Oregon Health and Science University, Portland, Oregon, USA

    • Nancy A. Press
  13. Department of Pediatrics and the MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, Illinois, USA

    • Lainie Friedman Ross
  14. Institute for Bioethics, Health Policy and Law, University of Louisville School of Medicine, Louisville, Kentucky, USA

    • Mark A. Rothstein
  15. Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    • Howard Saal
  16. Division of Molecular Medicine and Genetics, Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA

    • Wendy R. Uhlmann
  17. Treuman Katz Center for Pediatric Bioethics, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, Washington, USA

    • Benjamin Wilfond
  18. Law School, Medical School, and Center for Bioethics, University of Minnesota, Minneapolis, Minnesota, USA

    • Susan M. Wolf
  19. Foundation for Genomics and Population Health, Cambridge, UK

    • Ron Zimmern

Corresponding author

Correspondence to:

No hay comentarios:

Publicar un comentario