Transcript Personalized Medicine in the Era of Genomics Burke

Personalized Medicine
in the Era of Genomics
Wylie Burke MD PhD
Department of Medical
History and Ethics
Center for Genomics and
Healthcare Equality
University of Washington
Personalized medicine
One view
The right treatment, for the
right patient, at the right time
Personalized medicine
Another view
– Attending to the whole person, in context
of personal & medical history and life
circumstances
Safran 2003 Ann Intern Med 138:248
– “Working alliance” of doctor & patient
– Agreement on goals of treatment
– Collaboration
– Liking and trust
Fuertes et al 2006 Pat Ed Counsel 66:29
Newborn screening for PKU
Screen for newborn for elevated
phenylanaine

Identify affected newborns

Diet to prevent mental retardation
Personalized care for
children with PKU
– Cost of diet
– Social barriers to maintaining diet
– Child’s commitment to lifetime diet
Pathways from genetic research
to clinical benefit
Testing to diagnose
or identify risk
Research
on genetics
& disease
Improved disease
classification
Innovative therapy
Medullary thyroid cancer
& RET mutation testing:
Multiple Endocrine Neoplasia 2 (MEN2)
Medullary thyroid
cancer
Medullary thyroid cancer,
RET mutation +
If RET +, offer prophylactic thyroidectomy
Predicting toxicity
from chemotherapy
Retrospective analysis of clinical trial data
% with toxicity in children with leukemia
100
80
60
40
20
0
JNCI 1999;
91: 2001
Low
High
Thiopurine methyltransferase (TPMT) activity
Pathway from test to benefit
ACTION
Test
+ Result
Health
benefit
Spectrum of genetic
contribution to disease
Mostly
Genetic
Cystic
fibrosis
Genes and
Environment
Mostly
Environment
Diabetes
Asthma
Chicken pox
Gene variants associated with
common complex diseases
– Low relative risk (most <2.0)
– Polygenic
– Often account for only a small
percentage of disease cases
Multiple contributors to asthma
Genetics
-beta-adrenergic
receptor
-GSTM1, GSTT1
-IL-4, IL-4RA, IL-13
-TNF-alpha
-30-50 others
Asthma
Environment
-mites
-cockroaches,
-pollens
-animal danders,
-cigarette smoke,
-diesel fuel
Can genetic test results provide a
threshold for clinical intervention?
+
Genetic
test
ACTION
Improved
outcome
USUAL CARE
or
NO ACTION
No reduction in
outcome
Estimate of lifetime diabetes risk
Based on presence/absence
of disease-associated mutation
100
80
60
40
20
0
%
No copy
1 copy
2 copies
PPARG CAPN10 TCF7L2
Janssens & Khoury, It J Pub Health 2005; 3:35-41
Risk of age-related macular degeneration
Effect of population variation in 3 genes
1% have > 50% risk of AMD
MOST have risk close to average
Nat Genet 2006;
38:1055-9
Data gaps
Often not known:
–Whether testing leads to improved health
outcome
–Whether testing influences management
decisions
–Whether testing is associated with direct or
indirect harms
Policy questions if benefit
is present
– Does the benefit outweigh potential
harms?
– Who participates in decisions about
appropriate use?
– How is equitable access assured?
Guiding principle
(After Osler)
“More important to know the patient
who has the genotype than the
genotype that has the patient”