1 / 21

Genetic Screening: Criteria in the Age of Genomics

This presentation discusses genetic screening criteria, different phases in life for screening, the goal of neonatal screening, and various diseases tackled through screening programs. It also covers sources of information and the importance of balancing benefits and disadvantages in screening programs.

mrosado
Download Presentation

Genetic Screening: Criteria in the Age of Genomics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Genetic screening criteria in the age of genomics Rome 15.03.2010 Martina Cornel, MD, PhD Professor of community genetics & public health genomics Community Genetics, Dept Clinical Genetics

  2. Screening: Definition US Commission on Chronic Illness 1951: The presumptive identification of unrecognized disease or defect by the application of tests, examinations or other procedures which can be applied rapidly. Screening tests sort out apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment.

  3. National screening program NL • Breast cancer • Cervical cancer • Prenatal screening (infections, Rh) • Neonatal screening (heelprick & hearing loss) • Familial Hypercholesterolaemia cascade screening Not in National Program: prenatal screening Down syndrome (information only)

  4. Phases of life & genetic screening • Preconceptional • Antenatal • Neonatal • Later in life

  5. Neonatal screening (heelprick)

  6. Goal: avoid irreparable damage • Heelprick; standard in all (99,75%) newborns • Blood sampling during first week of life • Combined with screening for hearing loss

  7. Neonatal screening NL 2006-2007 • 2006 • PKU (from 1974) • Congenital hypothyroidism • Congenital Adrenal Hyperplasia • Medication or • diet to avoid • mental retardation or • sudden death • Biotinidase deficiency • Cystische fibrosis (conditional; pilot 2008) • Galactosemia • Glutaric aciduria type I • HMG-CoA-lyase deficiency • Holocarboxylase synthase deficiency • Homocystinuria • Isovaleric acidemia • Long-chain hydroxyacyl CoA dehydrogenase deficiency • Maple syrup urine disease • MCAD deficiency • 3-methylcrotonyl-CoA carboxylase deficiency • Sickle cell disease • Tyrosinemia type I • Very-long-chain acylCoA dehydrogenase deficiency

  8. Why more diseases? • More treatment available • Early detection: less health damage • More tests available (high throughput) • MS/MS • Many more promises in the age of genomics: how to proceed?

  9. Sources of presentation: • Health Council of the Netherlands. Screening: between hope and hype. The Hague: Health Council of the Netherlands, 2008; publication no. 2008/05E. Available from www.gr.nl. • 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;13:106–115.

  10. Screening: between hope and hype • the rate at which useful new screening opportunities become available is not as rapid as reports in the media might sometimes indicate. • cultural, social and economic factors contribute to a situation in which various types of screening (including self-testing kits) are placed on the market without any proper investigation having been conducted to ascertain whether the benefits for those affected outweigh the disadvantages that always also exist. www.gr.nl Screening between hope and hype. Presentation of report.

  11. New technological possibilities • Attunement between parties Achterbergh et al. Health Policy 2007; 83: 277-286.

  12. Neonatal screening NL: disease categories • Considerable, irreparable damage can be prevented (category 1) • Add 14 diseases (biotinidase deficiency, galactosemia, glutaric aciduria type I, HMG-CoA lyase deficiency, holocarboxylase synthase deficiency, homocystinuria, isovaleric acidemia, longchain hydroxyacyl-CoA dehydrogenase deficiency, maple syrup urine disease, MCAD deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, sickle cell disease, tyrosinemia type I and very-long-chain acyl-CoA dehydrogenase deficiency). • Less substantial or insufficient evidence of prevention of damage to health (category 2) • Consider adding cystic fibrosis if better test becomes available (improve specificity) • No prevention of damage to health (category 3)

  13. Screening criteria: W&J still apply! • When to screen? • Wilson en Jungner WHO 1968. • A variety of sets of criteria derived from W&J • Important public health problem (prevalence & severity) • Is treatment available? Does early treatment help? • Course of disease known; frequency known • Good test (high sensitivitity; high specificity; high positive predictive value) • Uniform treatment protocol; knowing whom to treat • Etc

  14. Balancing pros and cons Good test available? • False positives • Specificity (1-FP) • False negatives • Sensitivity (1-FN) • Positive predictive value

  15. Screening criteria(Grosse et al, Public Health Genomics 2010) • Evidence • Early treatment leads to less mortality, morbidity, loss of weight, days in hospital, pain, suffering, better QoL • Economics • Limited health care resources; cost per QALY under limit • Ethics • More pros (longer and healthier life) than cons (false positives; mild cases; incidental findings)

  16. What’s new? (Grosse; Tab 1) • Quality of the overall screening program • monitored & assured • Informed choice • Equity in access • Acceptability

  17. Economic criteria • Cost saving? Averted cost>> intervention cost? • If not, good value for money? • NICE-UK:GBP 30.000 per QALY Nat Health Service • €80.000 per QALY NL • USA: wide range of cost per QALY

  18. Ethics • Informed consent; mandatory neonatal screening; parental consent or awareness required; opt out; • Promotion of informed participation • USA: Voluntary screening for disorders for which the evidence of benefit to the child is less compelling? • NL: always voluntary, but parents not informed of the option to decline screening • France: written consent for DNA (99,8%)

  19. Ethics: goal is identification of serious disease • Mild forms (cystic fibrosis) • Unintended findings • Carrier status • Relevant information -> inform parents? • Not relevant for infant… right not-to-know • Even more unintended findings in whole genome diagnostics (BRCA carrier as result of mental retardation diagnostics)

  20. An active approach is needed (Health Council 2008) • Responsible screening should be available and accessible • Strong proactive engagement government • Protect citizens against risk of unsound screening • Quality mark: information, education, exposure, trust

More Related