Ethics’in’the’Genomic’Age’ - Cornell · PDF...

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  • Ethics in the Genomic Age

    Luce Skrabanek ICB, WMC

    May 30, 2013

  • History and EvoluEon of Research Ethics

  • Timeline 1906 Pure Food and Drug Act 1948 Nuremberg Code (from the 1946 Nuremberg Trials)

    1962 Kefauver Harris Amendment to the Food, Drug and CosmeEc Act (in response to the Thalidomide scandal)

    1964 DeclaraEon of Helsinki (updated 1975, 1983, 1989, 1996, 2000, 2008)

    1974 NaEonal Research Act (in reacEon to the 1932-1973 Tuskegee Syphilis Study)

    1979 Belmont Report

  • 1906 Pure Food and Drug Act Generally considered to be the birth of the FDA, although

    not named as such unEl 1930 Up unEl then, many patent medicines had high alcohol

    contents, infant syrups contained opiates Another contribuEng factor was the study of common food

    preservaEves such as borax, benzoate, formaldehyde, sulfites, and salicylates Young men recruited to eat meals with increasing doses of these

    common preservaEves were called The Poison Squad Truth in adverEsing

    Required that certain special drugs, including alcohol, opium, cocaine, heroin, morphine, and cannabis, be accurately labeled with contents and dosage

    1938 Replaced by the Food, Drug and CosmeEc Act

  • 1948 Nuremberg Code 1946 Nuremberg Trials Medical experiments conducted on thousands of concentraEon camp prisoners without their consent, resulEng in the death or permanent crippling of many of them

    Includes 10 points: Voluntary consent of parEcipants is essenEal Benefits of research must outweigh the risks Avoid all unnecessary harm and suffering

    First advocacy of voluntary parEcipaEon and informed consent

  • Nuremberg Code 1 The voluntary consent of the human subject is absolutely essenEal. 2 The experiment should be such as to yield fruiful results for the good of society, unprocurable

    by other methods or means of study, and not random and unnecessary in nature. 3 The experiment should be so designed and based on the results of animal experimentaEon and

    a knowledge of the natural history of the disease or other problem under study that the anEcipated results will jusEfy the performance of the experiment.

    4 The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

    5 No experiment should be conducted where there is a prior reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

    6 The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

    7 Proper preparaEons should be made and adequate faciliEes provided to protect the experimental subject against even remote possibiliEes of injury, disability, or death.

    8 The experiment should be conducted only by scienEfically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

    9 During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where conEnuaEon of the experiment seems to him to be impossible.

    10 During the course of the experiment the scienEst in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a conEnuaEon of the experiment is likely to result in injury, disability, or death to the experimental subject.

  • 1962 Kefauver Harris Amendment Drug Efficacy Amendment In response to the Thalidomide scandal Used as a sedaEve and an anE-emeEc for morning sickness

    Approved for used in Europe; no FDA approval in the US, although many US women took it anyway

    Caused severe deformiEes in fetuses Drug manufacturers required to prove to the FDA that their products were effecEve and safe, and to disclose accurate informaEon about side effects Requires clinical trials with informed consent

  • 1964 DeclaraEon of Helsinki Set of ethical principles regarding medical research developed by the World Medical AssociaEon

    First significant effort of the medical community to regulate research itself

    Incorporated Nuremberg Code with DeclaraEon of Geneva (updated HippocraEc Oath)

    Not a legally binding instrument in internaEonal law

    Updated 1975, 1983, 1989, 1996, 2000, 2008

  • DeclaraEon of Helsinki Basic principles Research with humans should be based on the results from lab and animal experimentaEon

    Research protocols should be appropriately examined

    Informed consent Research should be undertaken by scienEfically/medically qualified people

    Benefits must outweigh risks

  • DeclaraEon of Helsinki The US FDA rejected the 2000 and subsequent revisions, only recognizing the third (1989) revision, and in 2006 announced it would eliminate all reference to the DeclaraEon Disagreement over whether placebos were an acceptable control, even when proven treatments were known

    As of October 2008, the DeclaraEon of Helsinki is replaced by Good Clinical PracEce in the US

  • 1974 NaEonal Research Act In reacEon to the Tuskegee Syphilis Study (1932-1973) ProspecEve longitudinal study on the natural progression of untreated syphilis, even aker penicillin shown to be effecEve

    CreaEon of the NaEonal Commission for the ProtecEon of Human Subjects of Biomedical and Behavioral Research Tasked with idenEfying basic ethical principles that should underlie biomedical research, and to develop guidelines on their incorporaEon

    Belmont Report

  • 1979 Belmont Report 1. Respect for persons Individuals should be treated as autonomous agents People with diminished autonomy should be protected

    Informed consent ParEcipants must be given the opportunity to choose what shall and shall not happen to them

    Consent process includes InformaEon Comprehension Voluntary parEcipaEon (no coercion)


  • Belmont Report: principle 2 2. Beneficence and non-maleficence Human parEcipants shall not be harmed unnecessarily

    Research should maximize possible benefit and minimize possible risk

    Assess risks and benefits in a systemaEc manner ProtecEon of confidenEality

  • Belmont Report: principle 3 3. JusEce Benefits and risks must be distributed fairly Research parEcipants must be selected using fair procedures

    PaEents have a right to access and receive care that is non-discriminatory, suitable and fair

    Healthcare resources should be allocated in a fair and equitable manner

  • Other principles Many other factors also in play here When we talk about ethics, we also implicitly include ELSI: ethics, legal and social implicaEons Introduced by the Human Genome Project

    This implies that we not only take into consideraEon the medical ethics from the Helsinki DeclaraEon, and the research ethics put forward in the Belmont Report, but also various legal rights (e.g., privacy), as well as implicaEons of informaEon for the individual, the individuals family, and society in general.

  • Right to privacy First implicit declaraEon of a U.S. right to privacy

    1890, Warren and Brandeis, Harvard Law Review Many people argue that no such right exists or that the right to

    privacy should not be defined as a separate legal right Universal DeclaraEon of Human Rights, ArEcle 12:

    No one shall be subjected to arbitrary interference with his privacy, family, home or correspondence, nor to alacks upon his honor and reputaEon. Everyone has the right to the protecEon of the law against such interference or alacks

    The U.S. Supreme Court finds: The ConsEtuEon implicitly grants a right to privacy against

    governmental intrusion Also, many states grant the right to privacy and recognize the

    following torts: Intrusion upon seclusion or solitude, or into private affairs Public disclosure of embarrassing private facts Publicity which places a person in a false light in the public eye AppropriaEon of name or likeness

  • Privacy How does health data fit into privacy concerns? It can be harmful to the subject for certain health informaEon to be made public Imagine that a poliEcian has been diagnosed with a predisposiEon to Alzheimers. Public knowledge of this informaEon may result in his not geqng re-elected.

    But privacy is not absolute Imagine you have been diagnosed with SARS. Do you have a right to keep that private?

    HIPAA ensures some protecEon of healthcare informaEon

  • HIPAA 1996 Health InformaEon Portability and Accountability Act Requires that health care providers and others protect the privacy of health informaEon

    Sets boundaries on the use and release of health records

    Empowers individuals to control certain uses and disclosures of their health-related informaEon

    GeneEc informaEon is considered health informaEon, and is covered by HIPAA

  • Genomic data

  • Genomics data SNPs, CNVs, genotype data, complete sequences

    Trying to decipher the geneEc basis for diseases Many of the single-gene Mendelian diseases already known (OMIM)

    Complex diseases will be affected by many genes, some of which will have very small effects

    Need large amounts of data to get enough staEsEcal power to be able to alribute causaEon to variants

  • Benefit