ETHICAL ISSUES IN PHARMACOGENOMICS Mark A Rothstein, J.D Herbert F Boehl Chair of Law and Medicine Director, Institute for Bioethics, Health Policy and Law University of Louisville School of Medicine © April 2009 WHY PHARMACOGENOMICS? SAFETY EFFICACY ADVERSE EVENTS FROM MEDICATIONS • Annual deaths due to medical errors, 40-100K mostly adverse drug reactions (4th-6th leading cause of death) • Annual cost of drug-related problems in ambulatory care $200B • Percentage of in-patients with serious adverse drug reactions 6.7% • Percentage of in-patients with fatal drug reactions 0.3% SELECTED MEDICATION EFFICACY RATES FOR COMMON CONDITIONS Condition Efficacy Rate (%) Analgesics (Cox2) 80 Depression (SSRI) 62 Asthma 60 Cardiac arrythmias 60 Diabetes 57 SELECTED MEDICATION EFFICACY RATES FOR COMMON CONDITIONS Condition Efficacy Rate (%) Migraine (acute) 52 Migraine (prophylaxis) 50 HCV 47 Incontinence 40 Alzheimer's 30 Oncology 25 Source: Manasco & Arledge (2003) The Promises of Pharmacogenomics More effective medications Fewer side effects Faster and cheaper clinical trials “Rescue” drugs DRUG DEVELOPMENT 10-15 years Up to $800,000,000 each PROFESSIONAL RESPONSIBILITIES Physicians, Nurses, and Pharmacists • Order genetic testing • Interpret tests • Provide counseling MANUFACTURER RESPONSIBILITIES  Research and development  Clinical trials  Warnings  Marketing WARNINGS Cassidy v SmithKline Beecham (C.P Chester County, Pa., filed December 1999) Class action lawsuit alleging that manufacturer of vaccine for Lyme disease (Lymerix) failed to warn that some individuals, based on their genotype (HLA-DR4+), would be susceptible to “treatment-resistant Lyme arthritis.” On December 23, 2004, a new drug application was submitted to the FDA in which approval was sought only for African American patients Approval was granted, June 23, 2005 Stock Price of Nitromed, Inc On February 2, 2009, Deerfield Capital (a private equity firm) agreed to buy Nitromed, Inc for $0.80 per share Why has BiDil been a commercial failure? • Substitution by physicians? • Rejection by patients? Research on Vulnerable Populations Individual genetic variations are not distributed equally throughout the population because of endogamy, migration, geographic isolation, founder effect, genetic drift, and other principles of population genetics Some genetic traits have a higher frequency among subpopulations socially defined by race or ethnicity There is a great potential for discrimination and stigma when an increased risk of an undesirable health condition is associated with a particular population group, especially when the group is a racial or ethnic minority in a society These groups are said to be “vulnerable.” Because of the social risks of genetic research, special efforts are needed to: Consult with leaders and members of affected subpopulations at all stages of the research Be careful about inclusion and exclusion criteria for studies as well as the use of convenience sampling Make special efforts to ensure that informed consent documents and other aspects of the study (e.g., recruitment, medical exams, return of biological specimens) are developed with due regard for social sensitivities In publications and public pronouncements, be careful not to overgeneralize about the findings or place undue emphasis on the study group Provide for health screening or interventions, where appropriate, for vulnerable individuals identified in the study Consider benefit-sharing or similar measures for commercially valuable research findings FINAL THOUGHT SOCIAL JUSTICE Is it ethical for society (public and private sectors) to spend substantial resources on developing expensive new therapies that may be only slightly safer or slightly more effective than existing medications –  when tens of millions of people even in some developed countries (e.g., USA) lack access to health care?  when hundreds of millions of people in developing countries lack basic sanitation, clean drinking water, immunization, and preventive health services? ... to invest in developing a targeted therapeutic The Orphan Drug Act of 1983 defines an "orphan drug" as one affecting fewer than 200,000 persons in the U.S., and it gives incentives (e.g tax incentives)... supposed to provide warnings to the consumer? Are product labels, package inserts, or other types of warnings sufficient? Is there a danger in having too many warnings? LEARNED INTERMEDIARY Can a... to pay in cash? Privacy Pharmacogenomics will result in an increase in genetic information at a time when electronic data exchange increases the possible scope of disclosures Will the information