Lecture 22-23 Research Integrity Ethics IRB (1) PDF

The VCOM Institutional Review Board The role of the VCOM IRB is to oversee and foster the ethical treatment of human research participants in VCOM research studies. • Governed by the Department of Health and Human Services: OHRP – 45.CFR.46 – the “Common Rule” • • Specific guidance given for edu...

The VCOM Institutional Review Board The role of the VCOM IRB is to oversee and foster the ethical treatment of human research participants in VCOM research studies. • Governed by the Department of Health and Human Services: OHRP – 45.CFR.46 – the “Common Rule” • • Specific guidance given for education applications Also governed by the Food and Drug Administration – 21.CFR.50 and 21.CFR.56 – FDA Regulations The VCOM IRB is also service oriented, seeking to help new and experienced investigators develop human subjects research projects and navigate the application process. At all times, the IRB’s goal is to foster research. Why are Protections Needed? • Nuremburg trials: The Nuremburg Code 1947 As part of the verdict, the court enumerated rules for "Permissible Medical Experiments," now known as the "Nuremberg Code." These rules include, among other ethical principles: • • • • A requirement for voluntary consent That the research have scientific merit That the benefits of the research outweigh risks That the subjects have the ability to terminate participation in the research at anytime The Beecher Article • 1966 Henry Beecher article “Ethics and Clinical Research,” detailed 22 published medical studies presenting risk to subjects without their knowledge or approval. • Huge revelations – huge controversy – huge trouble ensued in the medical research field. • Beecher continued his work for years and was accepted by some but ostracized by many. Tuskegee Syphilis Study • “Tuskegee Study of Untreated Syphilis in the Negro Male” – Public Health Service study 1932-1972 • Sought to learn the natural course of untreated syphilis in “black American men”. – All subjects impoverished sharecroppers from Macon County, Alabama – subjects were not aware or informed they were part of a study. – Patients were not told they had syphilis – Not offered effective treatment when it came available in late 1940s • Study shut down in 1972 when public became aware of this. Other Studies • Willowbrook studies 1956-1970 – Series of studies: best known is children with intellectual disabilities deliberately infected with the hepatitis virus • Jewish Chronic Disease Hospital study 1963 – Live cancer cells injected into 22 cognitively impaired patients • Many studies involving prisoners in correction facilities National Research Act 1974 1973 Senate Committee Hearings on Medical Research led to the National Research Act of 1974 • Established the "National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research" (The National Commission) to identify the basic ethical principles underlying human subjects research and develop guidelines for ensuring that human subjects research is conducted according to those guidelines. • It required the establishment of Institutional Review Boards (IRBs) at organizations receiving PHS support for human subjects research. The Belmont Report National Commission – 1975 to 1978 • Considered human subjects and vulnerable populations • Created guidelines for ethical treatment of human subjects and recommendations for laws governing human subject research. Culminated in final 1979 report "Ethical Principles and Guidelines for the Protection of Human Subjects of Research" (The Belmont Report). Forms the foundation of the current regulations for human subjects research. The Belmont Report • The Belmont Report identified three basic principles relevant to the ethical conduct of research involving human subjects: – Respect for Persons – Beneficence – Justice • These three principles are designed to "provide an analytical framework that will guide the resolution of ethical problems arising from research involving human subjects" (The National Commission 1979). Respect for Persons • Ethical Concept: Persons should be treated as autonomous agents. – Subjects decide what will or will not happen to them. – Based on the fundamental right to “Informed Consent,” and “Privacy.” – Information, comprehension, willing to volunteer freely – Privacy not part of Belmont Report, but has arisen as a key component of human subjects research Beneficence • Ethical Concept: Researchers have the obligation to strive to do no harm, maximize benefits and minimize harms. • Risks to subjects must be very carefully considered and identified. – All research carries risk. The requirement is that they be known and communicated truthfully to subjects. • Researchers must make every effort to minimize risks. – Not all risk can be removed – and it doesn’t have to be. But often steps can be taken to decrease these risks without compromising the study. Justice • Ethical concept: Selection of subjects must be equitable. – Previously, much research done with vulnerable populations, while benefits went to general population. • Equitable selection requires subjects to be as close as possible to the group the research is meant to benefit. Federal Regulations • 1974 National Research Act à PHS guidelines à Federal Regulations • 45 CFR 46 "Regulations for the Protection of Human Subjects of Biomedical and Behavioral Research.” • Called the “Common Rule” • Amended in response to the Belmont Report – and updated several times since then – – – Subpart B: Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research Subpart C: Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects Additional Protections for Children Involved as Subjects in Research • This doesn’t mean studies can’t be done with these subjects…just that they have special protections. • In fact, the NIH says to include children whenever possible in relevant studies, for example. Similar Regulations • 45 CFR 46 was revised in 1981. • Changes to the Common Rule went into effect January 21, 2019. • Food and Drug Administration – adopted 21 CFR 50 on informed consent in 1980 and 21 CFR 56 on IRBs in 1981. – adopted regulations on investigational medical devices (21 CFR 812) in 1980 and investigational drugs and biologics (21 CFR 312) in 1981. Everything Fixed? • Despite Common Rule and guidelines, problems still persisted in human subject research. – Grey areas in rules – Well meaning studies that went poorly. Human Research Protections Policy • A comprehensive and organized system of shared responsibility at an organization to ensure the protection of human subjects participating in research. • Objective: to assist organizations in meeting ethical principles and regulatory requirements for the protection of human subjects in research. • Results – – – – Higher standards for IRB review Increased responsibility for researchers Increased requirements regarding conflict of interest The accreditation of Human Research Protection Policies Institution HRPP • Academic and research institutions are required to have their own policies governing research and human subject research. • The baseline (minimum) regulations are 45 CFR 46 and 21 CFR 50 • Institutions may have more regulations or guidelines, and often times are more strict than the Federal guidelines. – E.g., 45 CFR 46 pertains primarily to any study that is Federally funded. However, VCOM policy states at all human subject research will be governed under the same rules, regardless of funding status. The VCOM IRB Website http://www.vcom.edu/institutional-review-board • Information about the Application Submission Process and IRBnet. • Specific instructions • Required training (human subjects research) • Policies and Procedures • Contact information for help and guidance – Ms. Eryn Perry: project design, application guidance and help – Ms. Debbie Geiger: application submission and compliance with requirements Research at VCOM and VCOM-Affiliated Sites • Oversight of human subjects research is dependent on several factors: – Research onsite at VCOM by Faculty / Students • Direct oversight by the VCOM IRB – Research at a VCOM Clinical Partner Training Site • Depends on agreement and whether site has its own IRB • Usually written into agreement or a relationship exists between IRBs – Research by VCOM Faculty / Students at other sites • Requires interaction with other site IRB, or creation of IRB relationship Important Rule! Absolutely NO HUMAN SUBJECT RESEARCH may be done at VCOM or by VCOM personnel at other sites prior to approval by the VCOM IRB. Any human subject data/samples collected prior to approval…or during a “lapsed” protocol…is void and cannot be used or published in any way. It is recommended that the data/samples be destroyed. NO RETROACTIVE APPROVAL OF RESEARCH PROTOCOLS Principal Investigators VCOM Students may not serve as the PI on an IRB study. § Students must have a faculty mentor on the project that serves as the PI. § Students are still encouraged to be heavily involved with application development § Faculty or clinician PIs are expected to mentor students as their projects are developed and processed by the IRB § For help with project development, status determination, or documentation questions, the PI (not the students) may contact the VCOM IRB Coordinator, Ms. Debbie Geiger Getting Started with Human Subject Research • First, a researcher develops his/her idea for a study – Develop a research proposal first! • • • • Work out your ideas Plan your study Enlist your co-investigators and students. Next, one must determine if this is human subject research…and what level of review is needed for this project – Not research or no human subjects? IRB waiver – Exempt: lowest risk studies, public data, survey data, normal clinical or educational activities – Expedited: only minimal risk, but significant interaction with subjects / sample collection. – Full Board: more than minimal risk, special populations Decision Charts http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html The Office for Human Research Protections (OHRP) under the Department of Health & Human Services (HHS) provides decision charts as a guide for institutional review boards (IRBs), investigators, and others who need to decide if an activity is research involving human subjects that must be reviewed by an IRB under at 45 Code of Federal Regulations part 46. The decision charts address decisions on the following: § whether an activity is research that must be reviewed by an IRB § whether the review may be performed by expedited procedures, and § whether informed consent or its documentation may be altered or waived. § Specific help with these decisions can be obtained from Eryn Perry: § Ask for help and guidance early in the process for maximum benefit and time savings. Is it Human Subjects Research? Is the study Exempt? Expedited Review Who Decides? The IRB (usually the IRB Chair) is the decision maker as to whether any proposed study is human subject research and what level of IRB review is needed. Many institutions require even exempt human subject research to be reviewed on an annual basis as it is easy for a study to morph into one that needs IRB review without a research team realizing it. General Rule: it is far better to seek IRB approval…even for an exemption…than risk being wrong. Next: Get the Required Training http://www.vcom.edu/required-education • IRBs, institutions, and sponsors generally require key research personnel to complete formal training in the protection of human research subjects. – – VCOM uses the CITI Training System https://www.citiprogram.org/ – Other equivalent training will be accepted • https://phrp.nihtraining.com/users/login.php • This training must be completed prior to submission of a protocol to an IRB. Proof of certification required! It is the investigator’s responsibility to complete his / her training and receive proof of certification, and to keep a record of this certification for use with IRB applications. • Absolutely NO human subjects research may be conducted without certification of IRB training. Investigators, students, primary project persons. Forms, forms and more forms! (All within IRBnet site) • IRB Application Form (required) – This is a SUMMARY of the overall research proposal. It is NOT the proposal. – Also has a section that requests the level of IRB Review (Exempt, Expedited, Full Board) • Consideration of Consent or waiver of Consent – Optional based on design of study – Waiver of Informed Consent or Documentation of Informed Consent • Informed Consent Documents (Required unless waived) Informed Consent • Most adult subjects: Consent Document – • • They can agree (assent) to be part of study Parents CANNOT consent for the child Parents CANNOT force child to participate Parent(s) / Guardian(s) Permission Form: – – – The informed consent document may be modified depending on the type of study and risk involved with the study • Documenting informed consent can be waived by the IRB under special circumstances 18 years old and up Minors: Assent Document – – – • Provide permission for their child to participate Is not the same thing as consent or assent Child may refuse even if parent says yes – Most commonly for anonymous surveys where the informed consent would be the only link between the participant and the survey. HIPAA and Research https://www.hhs.gov/hipaa/for-professionals/specialtopics/research/index.html • The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule is the comprehensive Federal protection for the privacy of protected health information (PHI). • PHI relates to any data or information about a patient or subject that is personally identifiable and/or link the information directly and uniquely to the patient/subject. • HIPAA focuses mostly on health care delivery rather than research, but if research activities access PHI or generate new PHI, HIPAA is a consideration for that research. – – Example of HIPAA requirement: direct examination of patient medical records without the consent of the patient. Contrast: Physician with regular access to medical records may provide de-identified data from records • Note: even in this case, many hospitals / clinics still require HIPAA waiver or consent from patient. • So human subjects research may or may not be subject to the HIPAA Privacy Rule. • The IRB will help make this determination and to facilitate getting the proper permissions / waiver as needed.