Transcript Document
Integrating genomics in health care
Service development in oncology and cardiology
Martina Cornel, Professor of community genetics & public health genomics Quality of Care Community Genetics, Dept Clinical Genetics EMGO Institute for Health and Care Research
Public Health Genomics: definition
• The responsible and effective translation of genome-based knowledge and technologies into public policy and health services for the benefit of population health • genome-based knowledge and technologies=GBIT • PACITA report p. 88 (and elsewhere)
Learning goals
• The student can describe the fast scientific developments in genome-based knowledge and technologies • The student can discuss what is needed for translation of genomics knowledge into health
care
2000: genome sequence published
• Bill Clinton: We are here to celebrate the
completion of the first survey of the entire human genome …
• With this profound new knowledge, humankind is
on the verge of gaining immense, new power to heal. Genome science will have a real impact on all our lives -- and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.
Collins FS (Right at photo). Nature 2010 & © AP PHOTO/RON EDMONDS
http://www.genome.gov/images/content/cost_per_megabase2.jpg
Result of large scale genomic research
Shifting focus: • From single gene
(Mendelian)
conditions – cystic fibrosis, Duchenne muscular dystrophy,
Huntington’s disease
• To common, complex conditions – diabetes, cardiovascular disease, schizophrenia
Gene or environment?
Cystic fibrosis Duchenne muscular dystrophy Heart disease PKU Fragile X Cancer Diabetes Rheumatoid arthritis Multiple sclerosis Asthma Schizophrenia Alzheimers Motor vehicle accident TB Obesity Meningococcus Autism Struck by lightning Totally Genetic Totally Environmental
Understanding the cause of disease
• Genome wide association studies (GWAS) – Common disorders – SNPs that contribute little to the risk • Array and sequencing techniques – Rare disorders (rare variants of common disorders) – Panels to analyse several genes at once • Information technologies (high throughput) – Faster and cheaper analysis
Extending scope of testing?
Will shifting research lead to shifting health care?
– From reproductive tests to predictive testing • Clinical genetics for infants with MR/MCA, but increasingly
oncogenetics & cardiogenetics?
– From reproductive decision making to personal risk
reduction
– From rare monogenic to common complex diseases • Monogenic subtypes – From families to large (sections of) healthy populations • Screening
Learning goals
• The student can describe the fast scientific developments in genome-based knowledge and technologies • The student can discuss what is needed for
translation of genomics knowledge into
health care
– From bench to bedside – Phases of translation (Khoury) – Stakeholders (Rigter) – Guidelines (PPPC)
Genetics: “bench” or “bedside”?
Science and/or health care?
http://education-portal.com/academy/lesson/james-watson contributions-double-helix-quiz.html#lesson http://www.umcutrecht.nl/subsite/erfelijkheid/erfelijkheidsv oorlichting/Wanneer_erfelijkheidsonderzoek.htm
On the left: Watson and Crick describe the structure of DNA Above: clinical geneticist explains the consequences to patients
Translation needed
www.st-hughs.ox.ac.uk/library Libraries cannot be built fast enough to keep up with modern scientific output. But moving this knowledge off the shelves and into practice.. requires translation.
Lenfant NEJM 2005;349:868
“Lost in translation” in Lenfant 2005
… the last and perhaps most important segment, … taking the findings of clinical investigations and translating them into the practice of medicine at the community level. 1981 benefits of beta-blockers for patients who were recovering from myocardial infarction 1996 beta-blockers were being prescribed for only 62.5 percent of patients who had had a myocardial infarction
“Lost in translation” in Lenfant 2005
Late 1980s … benefits of cholesterol lowering in patients with coronary heart disease 1999: only half to three quarters of patients who have had a myocardial infarction are even being screened for elevated serum cholesterol levels, much less being prescribed cholesterol-lowering regimens
Phases in translational research
• The continuum of translation research in human genetics: types of research
Khoury M et al. Genet Med. 2007;9:665-74.
Framework for translational research
• T1 : BRCA mutation is associated with breast cancer • T2 Determine the positive predictive value of BRCA mutations, develop guidelines for testing • T3 What proportion of women from BRCA families are tested?
• T4 Does BRCA testing contribute to living longer and healthier?
– These steps need to be planned, they do not come automatically
How translational is human genomics research?
Premature translation??
Translation
• Doesn’t happen automatically – Only small percentage of research budget devoted to translation • May come premature – Valorisation=making money/value after investment • If you feel a change is needed: look for opportunities and other stakeholders involved
People don’t like change
• We work in a certain structure, culture & practice • Dynamics within or outside this constellation may cause instability • Opportunity for change!
– 2005: cardiac arrest young footballplayer in Sweden • Sense of urgence, not only for clinical geneticists but also for cardiologists etc.
Rigter, J Community Genet (2014) 5:337–347
Learning goals
• The student can describe the fast scientific developments in genome-based knowledge and technologies • The student can discuss what is needed for translation of genomics knowledge into health
care
– From bench to bedside – Phases of translation (Khoury) – Stakeholders (Rigter) – Guidelines (PPPC)
What is needed for responsible translation?
Source: PhD thesis Tessel Rigter Ch 8 http://dare.ubvu.vu.nl/handle/1871/51733
We need other stakeholders!
• A new technique in the laboratory • A clinical geneticist can explain the test results • Who will inform the patient that the test is available?
• Who will refer?
• For many fields (cancer, cardiovascular disease, diabetes) too many patients to counsel in genetic centres • Collaboration needed, new division of tasks
What is needed for responsible translation?
Sources: PhD thesis Tessel Rigter Ch 1 http://dare.ubvu.vu.nl/handle/1871/51733 And Achterbergh et al. Health Policy 2007;83:277-286.
Scaling up
• Changes start at a small scale and need deepening, broadening, and scaling up before a full transition is accomplished and a new constellation (with adapted culture, structure, and/or practice) – Maturity Onset Diabetes of the Young (MODY) testing UK – initiative of a consultant diabetologist, a molecular geneticist, and a diabetes specialist nurse – Network of diabetic nurses
Rogers technology adoption life cycle
Source: wikipedia
Hereditary cancer program in Catalonia, Spain • Initiated within the Catalan Institute of Oncology by a group of clinicians and geneticists at the Department of Prevention and Cancer Control in 1998 • Most referrals come from medical specialists • More than 1,000 carriers of highly penetrant cancer predisposing genes have been identified and are under surveillance • More than 900 healthy relatives have been withdrawn from intensive surveillance because they had not inherited the pathogenic mutation
What determines success?
• Clinical need • Evidence for clinical validity, clinical utility • Perceived need – Stakeholder’s priority and awareness (patients, payers, doctors, etc.) – Public priority and awareness • Health economic evaluation – Are the benefits outweighing the costs?
New constellation?
• The service is paid for by the Catalan health system • Nowadays, similar services are available in other regions in Spain (scaling up) without clear national guidance.
• Little comparable services are offered for other conditions than cancer because it seems hard to convince other disciplines of the importance of cascade screening.
• In addition, private companies are increasingly offering testing, which could keep patients and/or family members from utilizing the services offered in regular health care.
Learning goals
• The student can describe the fast scientific developments in genome-based knowledge and technologies • The student can discuss what is needed for translation of genomics knowledge into health
care
– From bench to bedside – Phases of translation (Khoury) – Stakeholders (Rigter) – Guidelines (PPPC)
Developing guidelines: example
• Stakeholder meeting • Circulate draft consensus statement to participants • Invite comments from other experts / www • Finalize • Evaluate results • Plan, do, check, act in due time.
PPPC guidelines
• Genetic testing in common disorders • Direct-to-consumer genetic testing • Genetic testing in minors • Whole genome sequencing in health care • Whole genome sequencing for newborn screening
PPPC guidelines
• Not a ‘law’ • But influential (Council of Europe, IVD regulation) • Pinpoint relevant issues for policy making in country • Provide & clarify argumentation why something is important • May help you to contribute to translation!
Conclusion
• Integrating genomics techniques in health care needs you!
• Phases in translation – Protocol, training, evaluation • Other stakeholders involved • Scaling up from small initiatives • Use a structured approach