SLIDE 1 Finding a Better Way:
Genomic Distinctiveness
Kyle B. Brothers
Genomics and Ethics in Research and Medical Decision-Making Cincinnati, OH March 13, 2015
SLIDE 2 Overview
exceptionalism
- Clinical analogies
- Genomic Distinctiveness
SLIDE 3
Genomic Exceptionalism
SLIDE 4 Definitions
- -ome = noun suffix indicating “all of the specified
constituents of a cell, considered collectively or in total”
- -omic = adjective suffix with same meaning
SLIDE 5 Genomic Exceptionalism
- Large number of findings generated
simultaneously
- High likelihood of secondary finding
SLIDE 6 Genomic Exceptionalism
Results may need filtering due to:
- Genomics
- Overwhelming number of secondary findings
- Genetics
- “Right not to know”
- “Right to an open future”
SLIDE 7
Debate Over ACMG Recommendations
SLIDE 8
ACMG Recommendations
“[W]e felt that clinicians and laboratory personnel have a fiduciary duty to prevent harm by warning patients and their families about certain incidental findings and that this principle supersedes concerns about autonomy, just as it does in the reporting of incidental findings elsewhere in medical practice.”
SLIDE 9
Critique of Recommendations
“Rejecting the need for the patient’s informed consent to look for mutations in a predetermined list of 57 genes is a profound departure from prevailing law and norms.”
SLIDE 10
Response to Critique
“To date, the traditions of genetic testing and reporting have exceptionalized all genetic risk information as potentially dangerous to the well- being of patients. This tradition, in the era of genome sequencing, must be reconsidered.”
SLIDE 11
Clinical Analogies
SLIDE 12
Imaging
SLIDE 13 Imaging
“whole” part of the body
- High likelihood of incidental
findings
risky Genomics
genome
- High likelihood of secondary
findings
risky
SLIDE 14 Imaging
- Images display incidental
findings by default
sophisticated image processing
Genomics
hidden by default
- Filtering can be achieved by
narrowing analysis
SLIDE 15 Imaging
infrequent
findings Genomics
secondary findings
findings related to every
SLIDE 16 Imaging vs. Genomics
- Similar in some ways, different in others
- These differences could justify differences in
practice
SLIDE 17
Newborn Screening
SLIDE 18 NBS
mass spec) provides cheap, easy alternative to multiple existing technologies
number of results that were not previously obtained Genomics
provides cheap, easy alternative to multiple existing technologies
number of results that were not previously obtained
SLIDE 19 NBS
reflect circumstances that are ambiguous – not clear- cut pathology
take time, cause stress Genomics
reflect circumstances that are ambiguous – not clear- cut pathology
take time, cause stress
SLIDE 20 NBS
- Results:
- Reflect current metabolic
state
signs and symptoms
- Reflect potential current
disease state Genomics
composition
signs and symptoms
- Typically reflect disease
risk
SLIDE 21 NBS
- Typically performed:
- In public health setting
- On healthy patients
- In infants
Genomics
- Typically performed:
- In research or clinical
setting
- On patients with clinical
indication
SLIDE 22 NBS vs. Genomics
- Similar in some ways, different in others
- These differences could justify differences in
practice
SLIDE 23
Routine Laboratory Panels
SLIDE 24 Typical Laboratory Panels
- Complete Blood Count:
- Parameters for variety of cells in the blood
- Basic Metabolic Panel:
- 7-8 parameters reflecting fluid and electrolyte status
- Complete Metabolic Panel:
- BMP + liver and nutritional parameters
SLIDE 25 Routine Lab Panels
- Laboratory devices generate
“package” of findings
- Not practical to account for
individual preferences in components of package
- Generates unexpected findings
that may need to be addressed
Genomics
- Secondary findings could be
considered “part of the package”
- Concerns about practicality of
accounting for preferences
findings that may need to be addressed
SLIDE 26 Routine Lab Panels
- Limitations and implications
well understood
- “Package” is routinely filtered,
since laboratory devices can generate more parameters than requested
Genomics
- Limitations and implications still
poorly understood
- Concern that failure to analyze
for important incidental findings would be unethical
SLIDE 27 Imaging vs. Genomics
- Similar in some ways, different in others
- These differences could justify differences in
practice
SLIDE 28
Antibiotic Sensitivities
SLIDE 29
SLIDE 30 Antibiotic Sensitivity Reports
- Potential to generate large
number of findings
- Total number determined by
analytical decisions
Genomics
- Potential to generate large
number of findings
- Total number determined by
analytical decisions
SLIDE 31 Antibiotic Sensitivity Reports
- Filtering is common practice;
sensitivities to expensive or restricted antibiotics are suppressed to influence provider practice
Genomics
include:
- Liability for not reporting
potentially useful information
practices
SLIDE 32 Antibiotic Sensitivities vs. Genomics
- Similar in some ways, different in others
- These differences could justify differences in
practice
SLIDE 33
Genomic Distinctiveness
SLIDE 34
Genomics is different, should be treated differently. Genomics is the same, should be treated the same.
Dualist Perspectives
SLIDE 35 Exceptionalism in Practice
- In many debates, both sides accuse the other of
exceptionalism
- Most deny accusations of exceptionalism
- Not useful for clarifying the issues
SLIDE 36 Distinctiveness
- Every domains of medicine reflects distinctive
traits
- Each trait is shared with other domains
- Unique combination of traits defines each domain
SLIDE 37
Genomic Distinctiveness
Identify Partial Analogy Claim Practice Should Be The Same
SLIDE 38 Genomic Distinctiveness
Identify Relevant Traits Determine Implications
Decide on Practices
SLIDE 39 Thanks!
- Aaron Goldenberg
- Nanibaa’ Garrison
- Rich Sharp
- Jen McCormick
