Ethics, Privacy, and Owership in Medical Research

Lecture 6 Ethics, Privacy, and Owership in Medical Research: Institutional Review Boards (IRBs): must approve all research involving human subjects, standards influence our expectations outside of the research realm ● Nuremberg Code "the voluntary ● consent of the human subject is absolutely essential.” ● capacity to consent ● freedom from coercion ● minimization of risk and harm ● a favorable risk/benefit ratio ● qualified investigators using appropriate research designs ● freedom for the subject to withdraw at any time Thalidomide 1950s: ● Prescribed for nausea during pregnancy ● Caused significant birth defects ● Incomplete drug safety review Declaration of Helsinki – 1964: ● Established ethical principles r.e. human experimentation ● Not binding itself, but has driven legislation worldwide ● Right to self-determination, informed decisions ● Individual welfare over benefits to society ● Ethical considerations more important than law ● Constantly revised (latest, 2013) Henry Beecher – New England Journal of Medicine (1966) ● Highlighted widespread studies where therapies had no ● therapeutic effects and were done without patient consent. ● Led to legislation in US Ethical problems motivated Legislative advances, albeit slowly Tuskegee Syphilis Study (1932-1972) ● (1932) 600 African American rural sharecropper men had syphilis for a short-term experiment. Offered free medical care, food, burial (treatments not effective -> funds lost so became a long-term observational trial ● (1947) penicillin was an effective treatment for syphilis, but the participants didn't know they had syphili or were treated ● (1964): Study not revisited after Declaration of Helsinki ● (1965 & 1966): Irwin Schatz & Peter Buxtun physician concerns about the ethics. CDC supported continuation ● (1972) Buxtun went to press for congressionnal hearings -> study termination and National Research Act of 1974. 28 dead from syphilis, 100 dead from related complications ● (1979) Belmont Report led to Federal Policy for the Protection of Human Subjects (and what we now call the 'Common Rule’, which is the basis for IRBs) ● Institutional review boards (IRBs), including laypeople, were established in scientific research groups and hospitals to review study protocols and protect patient interests, to ensure that participants are fully informed. ● (1994) Conference at UVA led to a committee recommending a formal apology Modern Institutional Review Boards (IRBs): ● Emphasis on Confidentiality/Privacy/Anonymity in genome use ● Research should not collect unnecessary information ● Identifiers should be removed, and designed to preserve anonymity. ● Only the investigators and research team can identify the responses of individual subjects. ● Anonymity of information collected: either the project does not collect identifying information of individual subjects (name, address, etc.), or can't link individual responses with participants Issues with IRBs and the Common Rule: ● Ownership: Tissues from millions of Americans are used in research without their knowledge ○ “Clinical biospecimens” are leftovers from blood tests, biopsies and surgeries. The Common Rule doesn’t require consent for “non-identifiable” samples. ○ Herietta Lacks 1920: 1951 John Hopkins reported a "knot" in her womb from malignant adenocarcioma of the cervix and died. Uconsented samples were cultured to HeLa Cell Line which were commercialized and used in biomedical research. 1980s: Unconsented release of family medical records. 2013: unconsented genome published. Now involved in NIH for use of her genome. HHMI accept donations for the family ■ Even if she gave consent, could she have seen what she was giving consent to? ○ Moore v. Regents of the University of California 1990: Leukemia patient, John Moore, at UCLA in 1976 consented to surgery and dispose of severed tissue by cremation. 1983 granted all rights to all cell line and product obtained" Discovered a patent on his cell line "Mo" and stock shares for it. Sued and lost 2x ● ● ● ● ■ Moore signed a contract, but did he really provide a full understanding of consent? Incidentalomas: Patients can't be informed of conditions discovered that fall outside the research ○ Ambiguity with info but if there are incidental findings that were not in present condition, Who determines what you deem important to my medical care or my son’s medical care ○ Should we be asking beforehand if patients would like to be informed when unexpected results arise? [that would violate current IRBs] ○ What happens when new there are new research findings? ○ How do patients grant informed consent when even the researchers don't know what will be found and what the implications of genetic data are for future health outcomes? ○ The same issues arise in all forms of personalized genomics - would you talk to your family before signing up for 23andMe? Afterward? NIH All of Us Research returns first genetic results to participants ○ Core value of committing to ensuring that participants have access and choice to their own info and has genetic counselors to answer any questions Controversy: should genomic studies tell about unrelated disease mutations ○ Researchers, physicisans -> opportunity to boost health of millions ○ Bioethicists: hesitation to receieve info that might cause genetic discrimination ○ NIH Study: 2% opt-out by choice but then changed their mind. Black were more likely opt-out and not change their minds. ○ ACMG: actionable genes that should be reported to all (BRCA1, BRCA2, APOE4) Anonymity: Anonymity of genomic data is a myth ○ Anonymity is difficult to guarantee and there are de-anonymization algorithms that could thwart privacy protections in medical research Take Home Messages (Privacy and Medical Research) ● The Ethics of medical research practices have evolved, from the Nuremberg code, to the Declaration of Helsinki. ● Lessons learned from unethical conduct over the years, most egregiously the Tuskegee Syphilis experiment, prompted legislation and ethical/privacy protections in medical research. ● Modern IRBs (also know as the common rule), strive to protect confidentiality and privacy, but problems arise, especially with genomic data that is ● ● ● ● inherently personal, is stored indefinitely, and we do not know how important this information is or will be. Anonymity in medical research can mean that individuals may be denied ownership of their own information. Anonymity can mean that researchers cannot report ‘incidentalomas’ to patients. Anonymity of genomic data is very likely a myth. Some seek IRB revisions such as more openness between researchers and subjects, sharing of research agendas and outcomes. If privacy is lost, build trust that the information is properly used