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Genomische Medizin und Assekuranz
Thomas D. Szucs
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Disclaimer
Die vorgetragenen (vorliegenden) Ausführungen, Meinungen und
Fakten entsprechen der persönlichen Betrachtungsweise des/der
Vortragenden (Verfassers/Verfasserin). Die hier vertretenen
Ansichten stellen insbesondere nicht den offiziellen Standpunkt der
Helsana dar und sind dementsprechend für Helsana in keiner Weise
bindend.
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Herausforderungen aus Sicht Krankenversicherer - Prozesse
Genomische Medizin bedingt Prozessinnovation
Zwei gegenläufige Trends?
Automatisierung
Personalisierung
Anzahl Positionen, Personen und Leistungen total pro Kapitel und
pro Jahr
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Assekurranz und genomische Medizin - Chancen
The „new normal“
WZW
Weniger Giesskanne Rx
AMTS
Kosten ê Qualität é
Geschwindigkeit é
Effizientere klinische Forschung
Bessere Kalkulation der Prämien
(VVG > KVG)
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Sind Gentests allgemein wirtschaftlich?
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Sind Gentests allgemein wirtschaftlich?
Es kommt drauf an
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1996
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Liga Tabelle Pharmakogenetisches Screening Gen Medikament
Eregbnis (outcome) Inkrementale Kosten-Effektivität
CYP2C9 Coumarin Vermiedene Blutungen EUR 7326 pro vermiedene
Blutung
CYP2C9 Coumarin Vermiedene Blutungen EUR 4233 pro vermiedene
Blutung
CYP2C19 Protonen-pumpenhemmer
Wirtschaftlich
CYP2C19 Protonen-pumpenhemmer
Vermiedene Ulkusblutung
Dominant
CYP2C19
Protonen-pumpenhemmer
Erfolgreiche Eradikation Dominant
TPMT Azathioprim Vermiedene Nebenwirkungen Dominant
TPMT Azathioprim Gewonnene Lebensjahre EUR 1348/gewonnenes
Lebensjahr
TPMT 6-Mercaptopurin Gewonnene Lebensjahre EUR 4800/gewonnenes
Lebensjahr
Mehrere Clozapin QALY EUR 36‘186/QALY
MTHFR Methotrexate Medikamentenabbruch Dominant
HLA Abacavir Vermiedene Hypersensitivitätsreaktion
Dominant bis EUR22811/vermiedene Reaktion
A1555G Aminoglykoside QALY EUR 59‘759/QALY
Vegter S et al. Pharmacoeconomics 2008; 26: 569
Wirtschaftlich
Adaptation durch Versicherer
§ Stärke der Evidenz = wichtigster Faktor für die
Erstattungsentschediung
§ Stärke der Evidenz variiert in Abhängigkeit der
Technologie
§ Leitlinien der Fachgesellschaften beeinflussen die
Erstattung sehr stark § Zur Zeit scheinen regulatorische
Aspekte und Daten
zur Wirtschaftlichkeit die Erstattung nicht massgeblich zu
beeinflussen
Modified from Meckley & Neumann; Health Policy 2010
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Wirtschaftlichkeit ist abhängig von
Stärke der Intervention
Ausgangs-risiko
... und den Folgekosten !!
Warum wurde vieles nicht schon früher klinisch umgesetzt?
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• Kosten
• Qualität
• Geschwindigkeit
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Fragen zur Wirtschaftlichkeit von genomischen Untersuchungen §
Wie häufig ist die genetische Variante? § Wie stark ist die
Assoziation zwischen Genotyp und
Phänotyp (Penetranz)? § Wird der Phänotyp durch metabolische,
Umwelt- oder andere
signifikante Faktoren beeinflusst? § Wie hoch ist die
Sensitivität und Spezifität des
genomischen Tests? § Gibt es alternative Methoden? § Wie
prävalent ist die Krankheit? § Welches sind die charakteristischen
Ergebnisse der
Erkrankung mit und ohne Therapie? § Wie beeinflusst die Genomik
diese Ergebnisse?
Herausforderungen der Genomik - Herausforderungen
Somatisch versus
Keimbahn
Incidentalome
Novitaet für LERBs
Novitaet für KV’er
ELSI
Underwriting
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§ Obwohl im Bereich der meisten Privatversicherungen eine
Offenlegung von Ergebnissen früherer präsymptomatischer
Untersuchungen im Rahmen der Gesundheitsprüfung statthaft wäre,
wird auf eine entsprechende Frage verzichtet.
§ Es werden auch keine vom Antragsteller freiwillig vorgelegten
Ergebnisse berücksichtigt.
Praxis Helsana
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Aktuelle Praxis wird beibehalten !
KEINE LIFESTYLE TESTS IM KVG
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Ancestry analysis
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LIFESTYLE
Neanderthal ancestry
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LIFESTYLE
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Global similarity map
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LIFESTYLE
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rs53576(G;G)
• ... optimistic and empathetic • ... better at accurately
reading the emotions
of others by observing their faces • ... less likely to startle
when blasted by
a loud noise ... 23
LIFESTYLE
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Keimbahn Somatische
Mutationen
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Umgang mit dem Inzidentalom
565
© American College of Medical Genetics and Genomics ACMG POLICY
STATEMENT
Exome and genome sequencing (collectively referred to in this
report as clinical sequencing) are rapidly being integrated into
the practice of medicine.1,2 The falling price of sequencing,
coupled with advanced bioinformatics capabilities, is creating
opportunities to use sequencing in multiple medical situa-tions,
including the molecular characterization of rare diseases, the
individualization of treatment (particularly in cancer),
pharmacogenomics, preconception/prenatal screening, and
population screening for disease risk.3,4 In all of these
applica-tions, there is a potential for the recognition and
reporting of incidental (or secondary) findings, which are results
that are not related to the indication for ordering the sequencing
but that may nonetheless be of medical value or utility to the
order-ing physician and the patient. Considerable literature
discusses
In clinical exome and genome sequencing, there is a potential
for the recognition and reporting of incidental or secondary
findings unre-lated to the indication for ordering the sequencing
but of medical value for patient care. The American College of
Medical Genetics and Genomics (ACMG) recently published a policy
statement on clinical sequencing that emphasized the importance of
alerting the patient to the possibility of such results in pretest
patient discussions, clini-cal testing, and reporting of results.
The ACMG appointed a Work-ing Group on Incidental Findings in
Clinical Exome and Genome Sequencing to make recommendations about
responsible manage-ment of incidental findings when patients
undergo exome or genome sequencing. This Working Group conducted a
year-long consensus process, including an open forum at the 2012
Annual Meeting and review by outside experts, and produced
recommendations that have been approved by the ACMG Board. Specific
and detailed recom-mendations, and the background and rationale for
these recommen-
dations, are described herein. The ACMG recommends that
labora-tories performing clinical sequencing seek and report
mutations of the specified classes or types in the genes listed
here. This evaluation and reporting should be performed for all
clinical germline (consti-tutional) exome and genome sequencing,
including the “normal” of tumor-normal subtractive analyses in all
subjects, irrespective of age but excluding fetal samples. We
recognize that there are insufficient data on penetrance and
clinical utility to fully support these recom-mendations, and we
encourage the creation of an ongoing process for updating these
recommendations at least annually as further data are
collected.Genet Med 2013:15(7):565–574Key Words: genome; genomic
medicine; incidental findings; per-sonalized medicine; secondary
findings; sequencing; whole exome; whole genome
ACMG recommendations for reporting of incidental findings in
clinical exome and genome sequencing
Robert C. Green, MD, MPH1,2, Jonathan S. Berg, MD, PhD3, Wayne
W. Grody, MD, PhD4–6, Sarah S. Kalia, ScM, CGC1, Bruce R. Korf, MD,
PhD7, Christa L. Martin, PhD, FACMG8,
Amy L. McGuire, JD, PhD9, Robert L. Nussbaum, MD10, Julianne M.
O’Daniel, MS, CGC3, Kelly E. Ormond, MS, CGC11, Heidi L. Rehm, PhD,
FACMG2,12, Michael S. Watson, PhD, FACMG13,
Marc S. Williams, MD, FACMG14 and Leslie G. Biesecker, MD15
Disclaimer: These recommendations are designed primarily as an
educational resource for medical geneticists and other health-care
providers to help them provide quality medical genetic services.
Adherence to these recommendations does not necessarily ensure a
successful medical outcome. These
recommendations should not be considered inclusive of all
proper procedures and tests or exclusive of other procedures and
tests that are reasonably directed to obtaining the same results.
In determining the propriety of any specific procedure or test,
geneticists and other clinicians should apply their own
professional judgment to the specific clinical circumstances
presented by the individual patient or specimen. It may be prudent,
however, to document in the patient’s record the rationale for any
significant deviation from these recommendations.
Submitted 11 April 2013; accepted 11 April 2013; advance online
publication 20 June 2013. doi:10.1038/gim.2013.73
1Division of Genetics, Department of Medicine, Brigham and
Women’s Hospital and Harvard Medical School, Boston, Massachusetts,
USA; 2Partners Healthcare Center for Personalized Genetic Medicine,
Boston, Massachusetts, USA; 3Department of Genetics, University of
North Carolina at Chapel Hill School of Medicine, Chapel Hill,
North Carolina, USA; 4Division of Medical Genetics, Department of
Human Genetics, UCLA School of Medicine, Los Angeles, California,
USA; 5Division of Molecular Pathology, Department of Pathology
& Laboratory Medicine, UCLA School of Medicine, Los Angeles,
California, USA; 6Division of Pediatric Genetics, Department of
Pediatrics, UCLA School of Medicine, Los Angeles, California, USA;
7Department of Genetics, University of Alabama, Birmingham,
Alabama, USA; 8Autism and Developmental Medicine Institute,
Geisinger Health System, Danville, Pennsylvania, USA; 9Center for
Medical Ethics and Health Policy, Baylor College of Medicine,
Houston, Texas, USA; 10Division of Genomic Medicine, Department of
Medicine, and Institute for Human Genetics, University of
California, San Francisco, San Francisco, California, USA;
11Department of Genetics, Stanford University, Stanford,
California, USA; 12Department of Pathology, Brigham and Women’s
Hospital and Harvard Medical School, Boston, Massachusetts, USA;
13American College of Medical Genetics and Genomics, Bethesda,
Maryland, USA; 14Genomic Medicine Institute, Geisinger Health
System, Danville, Pennsylvania, USA; 15National Human Genome
Research Institute, National Institutes of Health, Bethesda,
Maryland, USA. Correspondence: Robert C. Green
([email protected]) or Leslie G. Biesecker
([email protected])
Genet Med
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Genetics in Medicine
10.1038/gim.2013.73
ACMG Policy Statement
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11April2013
© American College of Medical Genetics and Genomics
20June2013 GENETICS in MEDICINE | Volume 15 | Number 7 | July
2013
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Conditions recommended for return of incidental findings in
clinical sequencing
• Hereditary breast and ovarian cancer • Li–Fraumeni syndrome
• Peutz-Jeghers Syndrome • Lynch syndrome • Familial adenomatous
polyposis • MYH-associated polyposis;
adenomas, multiple colorectal, FAP type 2; colorectal
adenomatous polyposis, autosomal recessive, with pilomatricomas
• Von Hippel–Lindau syndrome • Multiple endocrine neoplasia
type 1 • Multiple endocrine neoplasia type 2 • Familial medullary
thyroid cancer • PTEN hamartoma tumor syndrome • Retinoblastoma
• Hereditary paraganglioma–
pheochromocytoma syndrome
• Tuberous sclerosis complex • WT1-related Wilms tumor •
Neurofibromatosis type 2 • Ehlers–Danlos syndrome, vascular
type • Marfan syndrome, Loeys–Dietz
syndromes, and familial thoracic aortic aneurysms and
dissections
• Hypertrophic cardiomyopathy, dilated cardiomyopathy
• Catecholaminergic polymorphic ventricular tachycardia
• Arrhythmogenic right-ventricular cardiomyopathy
• Romano–Ward long QT syndrome 192500 types 1, 2, and 3,
Brugada 613688 syndrome
• Familial hypercholesterolemia • Malignant hyperthermia
145600
susceptibility
Green RC, Genet Med 2013
Beispiele
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Ausbildung ist zentral
192 VOLUME 94 NUMBER 2 | AUGUST 2013 | www.nature.com/cpt
PERSPECTIVES
is not yet clear how multigene panels and more comprehensive
sequencing applica-tions will be addressed in the new coding
system. Using the old system, exces-sively high reimbursement could
result for multi-gene panels coded with stacks of codes. The new
system will undoubt-edly require adjustments as diagnostics make
the transition from single-gene, single-variant analyses to genomic
mul-tigene analyses.
Finally, intellectual-property limitations associated with human
gene sequences may pose an additional barrier to genomic testing in
the clinical laboratory. Human gene sequences have historically
been patentable, and providers of testing ser-vices are required to
secure a license and pay royalties for testing and interpreta-tion
of human genetic sequences covered by patents, e.g., ASPA in
Canavan disease, BRCA1/2 in breast cancer, and APOE*E4 in
Alzheimer’s. As testing makes the tran-sition from single-gene
analysis to more comprehensive genomic analysis, clinical
laboratories introducing genomic assays could face an enormous
burden of licens-ing obligations and stacked royalties. It is
noteworthy that the patentability of human genes was reviewed by
the US Supreme Court in the case Association of Molecular Pathology
vs. Myriad Genet-ics, Inc.; the outcome will have significant
implications for access to genomic test-ing, the cost of testing,
and its utilization in health-care delivery.9
Clinical laboratory directors are enthu-siastic about the
application of human genomic testing and its impact on patient
care. It is likely that early applications will focus on multigene
panels designed to address specific medical situations where
clinical utility has been more adequately substantiated. Examples
of such emerg-ing clinical utility can be seen in prena-tal
screening, inherited-disorder carrier screening, identification of
rare genetic conditions involving defined genes, tumor
characterization to guide targeted thera-peutic choices, and panels
for identify-ing drug metabolism status. Multigene panels will
create a foundation for more comprehensive whole-genome testing,
and expansion of available phenotype–genotype correlative data will
accelerate the application of genomic testing. Con-
currently, sequencing-platform manufac-turers and associated
software developers are designing applications to meet the rigor
and standards of clinical diagnos-tics. Despite the many hurdles
yet to be overcome, genomic diagnostics are mov-ing into the
clinical laboratory and will ultimately guide better therapeutic
choices and improved patient management.
CONFLICT OF INTERESTThe author was a full-time employee of
Laboratory Corporation of America, a provider of clinical
diagnostic services, when the manuscript was submitted.
© 2013 ASCPT
1. Manolio, T.A. et al. Implementing genomic medicine in the
clinic: the future is here. Genet. Med. 15, 258–267 (2013).
2. Cressman, A.M. & Piquette-Miller, M. Epigenetics: a new
link toward understanding human disease and drug response. Clin.
Pharmacol. Ther. 92, 669–673 (2012).
3. Lai-Goldman, M. & Faruki, H. Abacavir hypersensitivity—a
model system for pharmacogenetic test adoption. Genet. Med. 10,
874–878 (2008).
4. Faruki, H. & Lai-Goldman, M. Application of a
pharmacogenetic test adoption model to six oncology biomarkers.
Personalized Med. 7, 441–450 (2010).
5. Cordero, P. & Ashley, E.A. Whole-genome sequencing in
personalized therapeutics. Clin. Pharmacol. Ther. 91, 1001–1009
(2012).
6. Skirton, H., Goldsmith, L., Jackson, L. & O’Conner, A.
Direct to consumer genetic testing: a systematic review of position
statements, policies and recommendations. Clin. Genet. 82, 210–218
(2012).
7. Bellcross, C.A., Page, P.Z. & Meaney-Delman, D.
Direct-to-consumer personal genome testing and cancer risk
prediction. Cancer J. 18, 293–302 (2012).
8. American Medical Association. Press release. AMA announces
CPT code changes for 2013 that address constantly evolving
healthcare advancements (17 September 2012).
9. Cook-Degan, R. Law and science collide over human gene
patents. Science 338, 745–747 (2012).
Educational Challenges in Implementing Genomic MedicineE
Passamani1
Clinical medicine is about to embark on an exciting, although
harrowing, period of innovation, the result of astonishing advances
in genomic science. The current workforce—physicians, nurses,
pharmacists, and others—will soon need to adapt to substantial
change, driven by genomics, in diagnostic and therapeutic
strategies. If errors of omission and commission are to be
prevented, sustained efforts in workforce education will be needed
on the part of medical schools, training programs, and professional
societies.
1Division of Policy, Communications, and Education, National
Human Genome Research Institute, Bethesda, Maryland, USA.
Correspondence: E Passamani ([email protected])
doi:10.1038/clpt.2013.38
The scientific revolution in genomics has entered its third
decade.1 Advances in understanding the clinical consequences of
genomic variants are now beginning to drive diagnostic and
therapeutic strategies in some cancer patients and are facilitating
diagnoses in rare, often devastating mono-genic disorders. More
broadly, genom-
ics has the potential to help physicians improve efficacy and
avoid toxicity when choosing medications for the individual
patient.
As the science of genomics becomes more clinically relevant, all
health-care providers, especially physicians, will need to become
more knowledgeable
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Versicherer müssen
§ … sich in dieses neue Thema einbringen § … klare
Erstattungsrichtlinien entwerfen und
verabschieden
§ … neue Erstattungsmodelle entwerfen, ggf mit Fokus auf “pay
for performance”
§ … mit Herstellern im Dialog bleiben, um neue Entwicklungen
frühzeitig zu erkennen
§ … bestehende Leistungsdaten analysieren, um das nicht
ausgeschöpfte Potential der personalisierten Medizin zu
erkennen
§ …Mut haben
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Sonntagsblick 30. Juni 2013
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Vielen Dank für Ihre Aufmerksamkeit
