The Genetic Era is Here

Transcription

1 Genomic Malpractice: Drivers and Evidence Workshop on Genetics and Liability November 2, 2015 Gary Marchant, Ph.D., J.D. Regents Professor of Law The Genetic Era is Here In More Ways Than One 1

2 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. Sage, Medical Liability and Patient Safety 2

3 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: Physician Knowledge/Education 3

4 AMA/Medco Survey of 10,303 Doctors 97.6% agreed that genetic variations 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 Clinical Pharmacology & Therapeutics 91(3): (March 2012) 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 4

5 Liability Driver 4: Established Plaintiffs Bar 5

6 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 6

7 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 Latham Part I: Drivers - Conclusion Today s Physician Bummer of a birthmark, Hal Adapted from Robert Milligan Part II: Evidence Overall Statistics Types of Cases: Prenatal testing Genetic Susceptibility Pharmacogenetics Novel Claims 7

8 # 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 8

9 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. 9

10 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) e.g., warfarin 10

11 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 Parents older child had same condition; physician failed to identify genetic disorder (Smith-Lemli-Opitz syndrome) and warn that subsequent children might be at risk 11

12 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) 2. Predisposition Testing 12

13 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 She sued hospital and laboratory case settled for $2 million (lab paid $1.9 million, hospital $0.1 million) - 22 No. 4 Verdicts, Settlements, and Tactics 155 (2002) 13

14 3. Pharmacogenetic Testing PGx Labeling by Year Source: Felix Frueh, FDA 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 14

15 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 plaintiff s bar Direct to consumer genetic testing NIPD/Whole genome sequencing 15

16 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 #R01HG A1 16