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Utilization and Impact of a New
Diagnostic Genetic Test for Hereditary
Hemorrhagic Telangiectasia (HHT)
SUMR Scholar: Brittany Milliner
Mentor: Shimrit Keddem
Principal Investigator: Barbara Bernhardt
Center for the Integration of Genetic Healthcare Technologies
(Penn CIGHT)
Genetics 101
Nucleotides
DNA
Genes
Chromosomes
• The study of inherited traits
and variation in living
organisms.
• DNA is composed of a chain
of four different types of
nucleotides—the sequence
of these nucleotides is the
genetic information
organisms inherit.
• Genes correspond to
regions within DNA that
code for certain traits
• Genes are arranged linearly
along long chains of DNA
sequence, called
chromosomes.
Genetics 102
• Children receive one copy of
their chromosome from their
mother and one from their father
• Humans have 46 chromosomes
(23 copies)
• Alleles are variations of a gene
• Some of the traits that we have
are based on simple inheritance
where one version of a gene
(dominant allele) masks the
expression of the other version
of that gene (recessive allele)
• Mutations are any change in an
organisms’ DNA
Hereditary Hemorrhagic
Telangiectasia (HHT)
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Autosomal dominant disorder
Mutation in one of at least 5 genes
Affects approx. one in 5000 individuals
Diagnosed by (Curacao Criteria):
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Epistaxis (nosebleeds),
Telangiectases,
Brain and visceral arteriovenous malformations (AVMs).
Family history
• Nearly all people with HHT have a positive family
diagnosis
• A definitive diagnosis of HHT requires positive findings
in 3 of 4 of the criteria; “suspect” if two
• Signs and symptoms are age-dependent and there is
great variability in severity, even in one family
Images of HHT
Genetic Testing
• Testing became available in November
2003
• Shows vulnerabilities to inherit diseases
• If a mutation can be identified in a
person with definite HHT, relatives can
be screened for that particular diseasecausing mutation to determine
definitively whether or not they are
affected
• Genetic testing was unusually marketed
to patients (consumers) rather than
providers
• Costly imaging studies and surveillance
would then be recommended only for
those family members who carry
mutations
What is the problem that needs to be
addressed?
• Many individuals with HHT remain undiagnosed
or even if diagnosed, may not be managed
appropriately
• Left untreated, AVMs can lead to stroke, brain
abscess, transfusion dependency and death
Goals of the Study
1.
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To describe the development and
pattern of early utilization of a new
genetic test
To compare the economic impact of
two methods for diagnosing HHT in
families
To collect further data on reasons for
testing, understanding of test results,
reactions to testing, and barriers to
testing
To use online deliberation to explore
stakeholders’ views about screening
and to develop policy
recommendations
Online Deliberations
• Individuals with HHT or an affected
first degree relative, health care
providers and genetic testing lab
personnel were recruited
• Reminder phone calls
• 75 minutes of pre-arranged “chat
information” designed to assess
views of testing, who should get it,
barriers, who should order it, and
implications of results
• 12 discussions included people with
HHT or their first degree relatives
– Approx. 10 individuals per patient
group
• There were also 2 groups of mixed
providers (physicians, genetic
counselors, lab personnel), with
approx. 8-10 participants per group
• Pre- and post-surveys were
completed
Patient Demographics
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92.4% have been diagnosed with HHT
41.2% have had genetic testing
73.1% of participants were female
92.4% were Caucasian
92.4% had at least some college
Average age: 52.3 years
The Good, The Bad, & The Ugly
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Wide range of patient group dynamics
“I bleed mostly inside my nose and sinuses and mouth, and I
have a lung AVM”
“We are such a ‘bloody’ funny group”
“Trashcans full of our own blood”
“Last transfusion I had, I walked in dressed as Dracula, the
nurses loved it…”
“Do your dogs like your used tissues, or is it just mine?”
“I believe it is also our responsibility as patients to educate
our doctors. We have a rare disease and what's wrong with
taking the bull by the horns, so to speak?”
“A stigma you can live with. A fatality from HHT you can't.”
“The first step to treating HHT is diagnosis”
More Quotes
• “An important issue is to try to calculate the numbers and cost
to public health so that HHT becomes an important disease to
cure. In the future, genetic testing will be done in the
womb with transplants of the chromosomes that were
missing.”
• “If your children are negative, there is no need for your to
get genetic testing.”
• “If no other family history before Colleen, good chance she is
not yet diagnosed. If no family memories of past generations
having had symptoms, she might still consider genetic testing.
This thing can skip lots of folks in the family.”
Analyzing Data
• Transcripts were formatted and uploaded to NVivo
• Data was coded twice: for general and specific
categories
• Summaries were written for selected nodes
NVivo
Preliminary Data
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119 Participants
Summaries for:
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Barriers to Genetic Testing
Importance of Genetic Testing
Implications of Test Results for Child and Proband
PCP Ordering Test
Other Physicians Ordering Test
Family Response to Being Approached
More Data
• Barriers:
– Denial
– Cost
– Lack of Knowledge/Misinformation
• Ordering testing:
– PCP’s responsibility to order testing; part of care
– Specialists and HHT Centers are also capable
• Family response:
– Some get tested, others don’t
– “That darn denial again”
Next steps
• Continue data analysis
• Develop recommendations to improve diagnosis
and screening
• Disseminate recommendations
Project #2: Chart Abstraction
•Scanned paper medical records for the following information:
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Genetic Mutation
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Ethnicity
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Procedures done
Marital Status
Curacao Criteria Met –
Complaint of Headaches
or Migraines
– Pulse ox
Height and Weight
Signs of Generalized
Connective Tissue
Disorder
Aortic root diameter
Acknowledgements …