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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Hrsg. v. Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Band 54, Heft 3

Hefte

The side effects of translational omics: overtesting, overdiagnosis, overtreatment

Eleftherios P. Diamandis
  • Korrespondenzautor
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
  • Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • E-Mail
  • Weitere Artikel des Autors:
  • De Gruyter OnlineGoogle Scholar
/ Michelle Li
Online erschienen: 07.10.2015 | DOI: https://doi.org/10.1515/cclm-2015-0762

Abstract

High-throughput technologies such as next-generation genomics, transcriptomics and proteomics are capable of generating massive amounts of data quickly, and at relatively low costs. It is tempting to use this data for various medical applications including preclinical disease detection and for prediction of disease predisposition. Pilot projects, initiated by various research groups and Google, are currently underway, but results with not be available for a few years. We here summarize some possible difficulties with these approaches, by using examples from already tried cancer and other screening programs. Population screening, especially with multiparametric algorithms, will identify at least some false positive parameters and screening programs will identify abnormal results in otherwise healthy individuals. Whole genome sequencing will identify genetic changes of unknown significance and may not predict accurately future disease predisposition if the disease is also influenced by environmental factors. In screening programs, if the disease is rare, the positive predictive value of the test will be low, even if the test has excellent sensitivity and specificity. False positive results may require invasive procedures to delineate. Furthermore, screening programs are not effective if the cancer grows quickly, and will identify indolent forms of the disease with slow-growing tumors. It has also been recently shown that for some cancers, more intensive and radical treatments do not usually lead to better clinical outcomes. We conclude that new omics testing technologies should avoid overdiagnosis and overtreatment and need to be evaluated for overall clinical benefit before introduction to the clinic.

Keywords: escape from cure; high-throughput omics; incidental findings; indolent disease; overdiagnosis; overtesting; overtreatment; side effects

References

  • 1.

    Hood L, Balling R, Auffray C. Revolutionizing medicine in the 21st century through systems approaches. Biotechnol J 2012;7:992–1001.Web of ScienceGoogle Scholar

  • 2.

    Flores M, Glusman G, Brogaard K, Price ND, Hood L. P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med 2013;10:565–76.Google Scholar

  • 3.

    Xu S, Zhang Y, Jia L, Mathewson KE, Jang K-I, Kim J, et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 2014;344:70–4.Web of ScienceGoogle Scholar

  • 4.

    Gibbs WW. Medicine gets up close and personal. Nature 2014;506:144–5.Web of ScienceGoogle Scholar

  • 5.

    Hood L, Lovejoy JC, Price ND. Integrating big data and actionable health coaching to optimize wellness. BMC Med 2015;13:4.CrossrefWeb of ScienceGoogle Scholar

  • 6.

    Kaiser J. Google X sets out to define healthy human. Science insider 2014. Available from: http://scim.ag/googlehuman.

  • 7.

    Diamandis EP. The hundred person wellness project and Google’s baseline study: medical revolution or unnecessary and potentially harmful over-testing? BMC Med 2015;13:5.CrossrefWeb of ScienceGoogle Scholar

  • 8.

    Wilcken B. Newborn screening: gaps in the evidence. Science 2013;342:197–8.Web of ScienceGoogle Scholar

  • 9.

    Wilson MG, Jungner G. Principles and practice for screening for disease. Public Health Papers 34; Geneva: World Health Organization, 1968.Google Scholar

  • 10.

    Welch HG. Overdiagnosis and mammography screening. Br Med J 2009;339:182–3.Web of ScienceGoogle Scholar

  • 11.

    Skeggs LT Jr. Persistence…and prayer. From the artificial kidney to the autoanalyzer. Clin Chem 2000;46:1425–36.Google Scholar

  • 12.

    Anonymous. Bargain genome. Nature 2014;505:458–9.Google Scholar

  • 13.

    Chrystoja CC, Diamandis EP. Whole genome sequencing as a diagnostic test: challenges and opportunities. Clin Chem 2014;60:1–10.Web of ScienceGoogle Scholar

  • 14.

    Yang Y, Muzay DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502–11.Web of ScienceGoogle Scholar

  • 15.

    Esplin ED, Oei L, Snyder MP. Personalized sequencing and the future of medicine: discovery, diagnosis and defeat of disease. Pharmacogenomics 2014;15:1771–90.CrossrefWeb of ScienceGoogle Scholar

  • 16.

    Van Allen EM, Wagle N, Stojanov P, Perrin DL, Cibulskis K, Marlow S, et al. Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat Med 2014;20:682–8.Web of ScienceCrossrefGoogle Scholar

  • 17.

    Garralda E, Paz K, López-Casas PP, Jones S, Katz A, Kann LM, et al. Integrated next-generation sequencing and avatar mouse models for personalized cancer treatment. Clin Cancer Res 2014;20:2476–84.Web of ScienceGoogle Scholar

  • 18.

    Ellis MJ. Mutational analysis of breast cancer: guiding personalized treatments. Breast 2013;22:S19–21.CrossrefGoogle Scholar

  • 19.

    Anonymous. The FDA and me. Nature 2013;504:7–8.Google Scholar

  • 20.

    Annas GD, Sherman E. 23andMe and the FDA. N Engl J Med 2014;370:985–8.Google Scholar

  • 21.

    Church G. Genomics is mired in misunderstanding. Nature 2013;502:143.Google Scholar

  • 22.

    Roberts NJ, Vogelstein JT, Parmigiani G, Kinzler KW, Vogelstein B, Valculescu VE. The predictive capacity of personal genome sequencing. Sci Transl Med 2012;4:133ra58.CrossrefWeb of ScienceGoogle Scholar

  • 23.

    Castle PE. Teaching moment: why promising biomarkers do not always translate into clinically useful tests. J Clin Oncol 2014;32:359–61.Web of ScienceGoogle Scholar

  • 24.

    Esserman LJ, Thompson IM Jr, Reid B. Overdiagnosis and overtreatment of cancer. An opportunity for improvement. J Am Med Assoc 2013;310:397–8.Google Scholar

  • 25.

    Schiffman M, Solomon D. Cervical – cancer screening with human papillomavirus and cytologic cotesting. N Engl J Med 2013;369:2324–31.Web of ScienceGoogle Scholar

  • 26.

    Levin TR, Corley DA. Colorectal – cancer screening – coming of age. N Engl J Med 2013;396:1164–6.Google Scholar

  • 27.

    Kistler CE. Colorectal – cancer incidence and mortality after screening. N Engl J Med 2013;396:2354–5.Google Scholar

  • 28.

    Bleyer A, Welch HG. Effect of three decades of screening mammography on breast – cancer incidence. N Engl J Med 2012;367:1998–2005.Web of ScienceGoogle Scholar

  • 29.

    Biller-Andorno N, Juni P. Abolishing mammography screening programs. A view from the Swiss Medical Board. N Eng J Med 2014;370:1965–7.Google Scholar

  • 30.

    Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, et al. Results of the two incidence screenings in the national lunch screening trial. N Engl J Med 2013;369:920–31.Google Scholar

  • 31.

    Maldonado F, Peikert T, Midthun D. Cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013;396:2060–1.Web of ScienceGoogle Scholar

  • 32.

    McWilliams A, Tammemagi MC, Mayo JR, Roberts H, Liu G, Soghrati K, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013:369:910–9.Web of ScienceGoogle Scholar

  • 33.

    Moyer VA. Screening for lung cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 2014;160:330–8.Web of ScienceGoogle Scholar

  • 34.

    Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK collaborative trial of ovarian cancer screening (UKCTOCS). Lancet Oncol 2009;10:327–40.CrossrefWeb of ScienceGoogle Scholar

  • 35.

    Andriole GL, Crawford ED, Grubb RL III, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009:360:1310–9. Erratum in: N Engl J Med 2009;360:1797.Google Scholar

  • 36.

    Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8.Web of ScienceGoogle Scholar

  • 37.

    Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012;366:981–90. Erratum in: N Engl J Med 2012;366:2137.Google Scholar

  • 38.

    Wade J, Rosario DJ, Macefield RC, Avery KN, Salter CE, Goodwin ML, et al. Physchological impact of prostate biopsy: physical symptoms, anxiety, and depression. J Clin Oncol 2013;31:4235–41.Google Scholar

  • 39.

    Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H, et al. Screening for prostate cancer with prostate-specific antigen testing: American society of clinical oncology provisional clinical opinion. J Clin Oncol 2012;30:3020–5.Web of ScienceGoogle Scholar

  • 40.

    Thompson IM, Tangen CM. Prostate cancer – uncertainty and a way forward. N Engl J Med 2012;376:270–1.Web of ScienceGoogle Scholar

  • 41.

    Hayes JH, Barry MJ. Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence. J Am Med Assoc 2014;311:1143–9.Web of ScienceGoogle Scholar

  • 42.

    Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367:203–13.Web of ScienceGoogle Scholar

  • 43.

    Froehner M, Writh MP. Early prostate cancer – treat or watch? N Engl J Med 2011;365:568–9.Google Scholar

  • 44.

    Solomon BD. Incidentalomas in genomics and radiology. N Engl J Med 2014;370:988–90.Google Scholar

  • 45.

    MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J, Abecasis GR, et al. Guidelines for investigating causality of sequence variants in human disease. Nature 2014;508:469–76.Web of ScienceGoogle Scholar

  • 46.

    Fisher B, Redmond C, Poisson R, Margolese R, Wolmark N, Wickerham L, et al. Eight-year results of randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822–8.Google Scholar

  • 47.

    Anonymous. Prostate cancer: send away the PSA? Lancet 2012;380:307.Google Scholar

Artikelinformationen

Corresponding author: Eleftherios P. Diamandis, MD, PhD, FRCP(C), FRSC, Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, 60 Murray St. Box 32, Floor 6, Rm L6-201, Toronto, M5T 3L9 ON, Canada, Phone: +(416) 586-8443, E-mail: ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada


Erhalten: 06.08.2015

Angenommen: 28.08.2015

Online erschienen: 07.10.2015

Erschienen im Druck: 01.03.2016


Quellenangabe: Clinical Chemistry and Laboratory Medicine (CCLM), Band 54, Heft 3, Seiten 389–396, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-0762.

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