Genomic Malpractice:
Drivers and Evidence
Gary Marchant, Ph.D., J.D .
Regents’ Professor of Law
Workshop on Genetics and Liability
November 2, 2015
The Genetic Era is Here
Part I: Potential Liability Drivers for
Personalized Medicine
1.
Rapidly Changing Technology/
Standards
2.
Physician Unfamiliarity/Education
3.
Expert Disagreement/Uncertainty
4.
Established Plaintiffs Bar
5.
Novel Legal Claims
6.
Supply of Adverse Outcomes
Liability Driver 1:
Rapidly Changing Technology/
Standards
New Medical Technology &
Liability
“Although technology is generally
seen as a boon to safety, no other
factor historically has surpassed it
as a stimulus for litigation. Gains
in clinical competence redefine
success upward and make delay
actionable.”
New Medical Technologies
Increase Liability Risks
“Dramatic and genuine medical
advances are invariably followed by
heightened, and frequently excessive
professional and lay expectations….
[I]mproved procedures more often than
not require greater learning, skill, and
care…. Consequently, technological
advancement carries with it greater
opportunity for error or accident.”
DeVille, Historical Origins of Medical Malpractice Litigation
As You Can Do More, The More
Can Go Wrong
As there are more that physicians
can do with genomics, there is more
opportunity for mistakes or errors
e.g., kidney dialysis and medical
negligence
Marc Grady, N.W.L. Rev (1987)
Liability Driver 2:
Clinical Pharmacology & Therapeutics 91(3): 450-458 (March 2012)
AMA/Medco Survey of 10,303 Doctors
97.6% agreed that geneticvariations may influence drug response
10.3% felt adequately informed about pharmacogenomic testing
12.9% of physicians had
ordered a test in the previous 6 months, and 26.4% anticipated ordering a test in the next 6 months
29.0% of physicians
overall had received any education in the field
Liability Driver 3:
Expert Disagreement/Uncertainty
Expert Disagreement/ Uncertainty
Significant disagreement/
uncertainty about which genetic
tests are clinically appropriate:
Warfarin
Plavix
CYP2A9/tamoxifen
Breast cancer recurrence/gene
expression assays
Liability Driver 4:
Liability Driver 5:
Novel Legal Claims
Potential Novel Claims Raised by
Genetics
Wrongful birth/ wrongful life?
Duty to warn family members?
Loss of chance?
Duty to follow-up and update
results?
Liability Driver 6:
Supply of Adverse Outcomes
ADRs are the fifth
leading cause of
death in the US.
Lazarou, et al, JAMA, 1998
“Poisons and
medicines are often
the same substance
given with different
intents.”
Peter LathamPart I: Drivers - Conclusion
“Bummer of a birthmark, Hal”
Adapted from Robert Milligan Today’s Physician
Part II: Evidence
Overall Statistics
Types of Cases:
Prenatal testing
Genetic Susceptibility
Pharmacogenetics
Novel Claims
0 2 4 6 8 10 12 14 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 # of cases reported per year
Value of Case ($mil)
Mean total
$4.46
Median total
$1.70
Mean verdict
$7.22
Median verdict
$2.45
Mean settlement
$2.38
Median settlement $1.29
Failure Mode: Diagnosis
Failure to diagnose genetic disorder in time
to prevent adverse outcome.
Examples include
failure to diagnose PKU in an infant before brain damage occurred due to build-up of toxic metabolites
failure to diagnose Marfan’s syndrome in somebody who was dying from an aortic dissection which is a common cause of death in Marfan’s patients
failure to diagnose hemochromatosis in time to offer treatments that can prevent eventual organ
Failure Mode: Interpretation
Failure to appropriately interpret the
results of genetic tests and explain
the results fully to patients/families.
Examples include
failure to interpret a genetic test result
showing a “truncating mutation” as the
presence of a heritable disorder
(Angelman syndrome, in that case)
failure to interpret the results of a quad
screen in pregnancy appropriately to
recognize that it reflected a higher risk of
Down syndrome in the fetus
Failure Mode: Offer Testing
Failure to offer genetic screening despite
indications that it was warranted
Examples include
failure to recognize high risk of genetic disorder related to maternal age (e.g. Down syndrome) strong family history of disease (e.g breast and
ovarian cancer, famililal mental retardation syndromes)
high risk ethnicities (e.g. Asian couple not offered testing for blood dyscrasias, Ashkenazi Jewish couple not offered testing for CF)
Failure Mode: Return of Results
Failure to return test results to
patients
Examples include:
tests were run but results never
communicated to the patients, either
because the lab didn’t return them, the
doctors didn’t follow-up, etc.
Type of Negligence
Failure to Diagnose
23
Failure to Interpret
52
Failure to Offer
90
Failure to Return
30
Genetic Testing/Medical
Malpractice: Causes of Action
Design defect Failure to warn Wrongful conception Wrongful birth Wrongful life Informed consent Lost chance Delayed diagnosis Negligence
Negligent infliction of emotional distress Negligent preconception counseling Negligent misrepresentation Duty to third parties Breach of confidentiality
3 Main Categories of Physician
Cases
1.
Prenatal testing
Wrongful Life
Wrongful Birth
2.
Disease predisposition testing
e.g., BRCA testing
3.
Pharmacogenomic testing (drug
susceptibility)
1. Prenatal Testing
Prenatal Testing:
Wrongful Life/Wrongful Birth:
3 states permit both types of
lawsuits(California, New Jersey,
Washington)
26 states recognize only wrongful
birth lawsuits
10 states (including Arizona, Georgia,
Idaho, Kentucky, Michigan,
Minnesota, Utah, N. Carolina,
Missouri, S. Dakota) prohibit both
types of lawsuits
Law in remaining States undecided
Wrongful Birth: Example
July 2007 – Florida jury awards $21
million to parents of 2 year–old child
with rare genetic disorder involving
cholesterol synthesis
child unable to communicate and needed
constant care
Non-Invasive Prenatal Testing
NIPD – Rapid Uptake
Only 2% of pregnant women currently undergo
amniocentesis or CVS (100,00 per year)
NIPD has potential to greatly increase prenatal
genetic testing (to >3 million per year in U.S.)
Sequenom and Ariosa already each reporting annual test run rates of over 150,000
Already >$1 billion industry within first year
“the pace at which this technology has been integrated into clinical care is
unprecedented.” Nature Biotech (July 2013)
Genetic Predispositions:
“We Are All Mutants”
Every individual
carries many different
genetic predisposition
variants
Each of us estimated to
have ~300 disease
predisposition genes
(Nature Rev. Genetic.
1:40 (2000))
These genes increase
risk of disease, but
are neither sufficient
nor necessary for
disease
“The Angelina Effect”
Example:
Roe v. ABC Corp. and
XYZ Hospital
48 year old Ashkenazi Jewish woman with history of
breast cancer underwent BRCA testing at recommendation of her oncologist at XYZ hospital
Genetic test erroneously interpreted as positive by
employees at ABC testing laboratory
Woman had her remaining breast, uterus and
ovaries removed based on report she had BRCA1 mutation
Additional testing revealed original genetic tests was erroneously interpreted,, woman did not have BRCA1 mutation
3. Pharmacogenetic Testing
Source: Felix Frueh, FDA
PGx Labeling by Year
Scholz v. Kaiser Found. Hospital,
Cal.
Sup. Ct. (Almeda County, filed Jan. 30, 2012)
Irma Scholz, an American of Asian
descent, was prescribed
carbamazepine to treat myelitis
She developed Stevens-Johnson
Syndrome, a life threatening, painful
and disfiguring skin condition
Scholz has sued her doctor and the
hospital for not recommending a
genetic test before prescribing
Carbamazepine Label:
FDA Black Box Warning
Novel Claims
Duty to 3rd party:
Polaski v. Whitson, Ct. of Common
Pleas (PA, 2015):
Plaintiff died of hypertrophic cardiomyopathy
2 yrs earlier physician had treated plaintiff’s father and had uncovered facts that should have led him to genetically test father for risk factor that would have warned son
Court: doctor has duty to advise his patient for benefit of a non-patient third person
Future Accelerators
More validated genetic tests
e.g., randomized control trials
More FDA-approved PGx labels
Growing disparities in medical
practice
Increasing familiarity/precedents by
Future Impediments/Protections
Against Liability
Local custom standard of care
Difficulty in finding testifying
experts
Ignorance/risk adversity of
plaintiffs’ bar
Medical malpractice protections in
state laws
Lack of evidence of clinical utility
The Future of Genetic Testing?
Acknowledgment
Collaborator: Rachel Lindor, Mayo
Clinic
Funding for this work was provided
by NHGRI ELSI Grant
#R01HG006145-01A1
