The Office of Graduate Studies Office and the Office of Academic Research present The IRB Fundamentals: Everything You Need to Know by Michael L. Gillespie, M.P.A., M.A., CRA, CIP Research Compliance Officer Office of Academic Research mgillesp@csusb.edu 909-537-7588 Goals and Objectives • Workshop Topics – Why we have the IRB? – What is human subjects (participants) research? – The Belmont Report – The IRB Application Process – Ethical Considerations – Research Misconduct – It’s Your Time for Questions and Answers! Why we have the IRB? • IRB derives from Medical Research without informed consent – Nuremburg Code – Nazi experimentation on humans – cruel, inhumane treatment, harm – Tuskegee syphilis experiment 1932 – 1972 • No Informed Consent • “The study initially involved 600 black men – 399 with syphilis, 201 who did not have the disease.” • “Researchers told the men they were being treated for "bad blood," a local term used to describe several ailments, including syphilis, anemia, and fatigue. In truth, they did not receive the proper treatment needed to cure their illness. In exchange for taking part in the study, the men received free medical exams, free meals, and burial insurance. Although originally projected to last 6 months, the study actually went on for 40 years.” Why we have the IRB? • IRB protections moved from medical research to include social behavioral research due to: – Milgram experiment in 1961 conducted by Stanley Milgram of Yale University – focusing on the conflict between obedience to authority and personal conscience. Related to Nuremburg trials and German soldiers and doctors justifying their action as “just following orders.” – http://www.youtube.com/watch?v=xOYLCy5PVgM Why we have the IRB? • Another famous/infamous social experiment – Stanford Prison Experiment – 1971 study that asked, “What happens when you put good people in an evil place? Does humanity win over evil, or does evil triumph? – Another obedience to authority study • You can view various documentaries on Youtube. https://www.youtube.com/results?search_query=stanfor d+prison+experiment+documentary Why we have the IRB? • Federal regulation establishes the requirements for Institutional Review Boards, informed consent, benefitrisk assessment, and subject selection • Common Rule (45 CFR 46) • FDA (Title 21) • Individual Professional Codes of Ethics and Conduct • CSUSB Faculty Senate Policy (FAM 845.72) defines authorities, roles, and responsibilities of the CSUSB faculty and the Institutional Review Board • CSUSB Federalwide Assurance filing (2003) FWA 000004865 for the Protection of Human Subjects in Research describes the measures CSUSB will take • CSU Chancellor Executive Letter 890 • CSUSB Policy – Faculty and Student Misconduct Policy Federal definition of human subjects • Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities. • Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains – – (1) Data through intervention or interaction with the individual, or (2) Identifiable private information. What is human subjects research? Federal definition of an intervention with a human subject is: • Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. Why we have the IRB? • CSUSB’s Federalwide Assurance – We will apply the Belmont Report principles to all human subjects research regardless of funding. – Federal rules will apply whenever CSUSB becomes engaged in human subjects research or the IRB provides review and oversight of federally funded research. – We will comply with Title 45 Code of Federal Regulations Part 46 (45 CFR 46) and Subparts B, C, and D (children, prisoners, pregnant women, fetuses, and embryos). – Unless exempted all research requires written informed consent. – We will train and certify all university officials and researchers – CITI Human Subjects Training – The university will provide adequate resources to IRB. Human Subjects Include • Persons – First person and third person reporting • Data about persons, including secondary data. – Non-electronic – Electronic – Images – Recordings • Biological samples drawn from persons – Fluids, tissues, scrapings – Genetic encoding Title 45 Code of Federal Regulations Part 46 (45 CFR 46) • Defines “research.” • Defines “human subject.” • Provides regulatory requirements for institutional review boards’ (IRB) structure and processes. • Defines elements of informed consent. • Establishes categories of IRB review. • Defines exempt and nonexempt research. The Belmont Report • “In July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law, there-by creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles. In carrying out the above, the Commission was directed to consider: (i) the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine, (ii) the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects, (iii) appropriate guidelines for the selection of human subjects for participation in such research and (iv) the nature and definition of informed consent in various research settings. The Belmont Report attempts to summarize the basic ethical principles discussed by the commission.” The Belmont Report Basic Ethical Principles • Respect for Persons: – “Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy.” The Belmont Report Basic Ethical Principles • Beneficence: – Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their wellbeing. Such treatment falls under the principle of beneficence. The term "beneficence" is often understood to cover acts of kindness or charity that go beyond strict obligation. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms. • The Hippocratic maxim (Oath) "do no harm" has long been a fundamental principle of medical ethics. The Belmont Report Basic Ethical Principles • Justice: – “Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense of "fairness in distribution" or "what is deserved. There are several widely accepted formulations of just ways to distribute burdens and benefits. Each formulation mentions some relevant property on the basis of which burdens and benefits should be distributed. These formulations are (1) to each person an equal share, (2) to each person according to individual need, (3) to each person according to individual effort, (4) to each person according to societal contribution, and (5) to each person according to merit.” The Belmont Report Basic Ethical Principles • Justice (continued): – For example, during the 19th and early 20th centuries the burdens of serving as research subjects fell largely upon poor ward patients, while the benefits of improved medical care flowed primarily to private patients. Subsequently, the exploitation of unwilling prisoners as research subjects in Nazi concentration camps was condemned as a particularly flagrant injustice. In this country, in the 1940's, the Tuskegee syphilis study used disadvantaged, rural black men to study the untreated course of a disease that is by no means confined to that population. These subjects were deprived of demonstrably effective treatment in order not to interrupt the project, long after such treatment became generally available. 45 CFR 46 PARTS B, C, D Vulnerable Populations • Know your study population and especially if they are vulnerable populations afforded additional federal protections. – Subpart B. Pregnant Women, Fetuses and Embryos – Subpart C. Prisoners – Subpart D. Children – Those with impaired decision and mental capabilities, groups that are stigmatized and marginalized, and the economically and socially disadvantaged may also qualify as vulnerable. The IRB Application Process The IRB Review Process • The IRB weighs the risks and benefits of the research study. Do the risks outweigh the benefits? If so, the IRB attempts to help the researcher(s) minimize those risks and asks for revisions. Those revisions are provided to you through email correspondence. • Make yourself familiar with the IRB website. Training, Submission Dates, Application, & Resources that are available. – http://irb.csusb.edu The IRB Application Process The IRB Review Process • Application: – The 3 C’s: Is it clear, concise, and coherent. – Use language the IRB can understand. – If your using specific words, acronyms, abbreviations, related to your college/department/program discipline make sure to define and spell those out for the IRB. – Explain your research methods clearly and how you will apply them (procedures you will follow). – The reviewers like step-by-step processes and procedures. Again, make sure they are 3 C’s. Recruitment of Participants • Describe sources of potential participants, how they will be selected and recruited, and how and where you will contact them. Include all relevant characteristics with regard to age, ethnicity, sex, institutional status (i.e., patients or prisoners), and general state of physical and mental health (i.e., know the demographics of your population). – Pay close attention to those that are described as a protected population (subpart B, C, and D). Description of the Project • Briefly describe the objectives and methodology of your research (including hypothesis and/or research questions), data collection procedures, and features of the research design that involve specific procedures or special conditions for participants (including frequency, duration, and location of participation. It is helpful to the IRB to divide up the project description into the categories below. a. b. c. d. e. f. Objectives of the Study Hypothesis Methodology Data Collection Data Analysis Dissemination Confidentiality of Data • Clearly indicate specific procedures (e.g., coding of responses, aggregate reporting, etc.) to protect the confidentiality of participants and safeguard identifiable records and data. This includes safe and secure storage of the collected information and when the data will be destroyed after the data collection process has been completed. If not possible, state why. Confidentiality of Data • Safeguarding the data from unauthorized access can be accomplished in various ways: – Collect data without identifiers – Remove all direct identifiers as soon as possible – Substitute codes or pseudonyms for identifiers – Maintain code lists ("keys") and data files in separate secure locations – Use accepted methods to protect against indirect identification, such as aggregate reporting or misleading identifiers – Use and protect computer passwords – Access and store data on computers without Internet connections – Encrypt data Privacy Rights and Research • Private information – includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record or student record). – Anonymous, confidential, private, and personally identifiable may have different operational meanings in different research protocols, data formats, and under federal and state laws. Risks in Research IRB Review and Risks and Benefits – Assessment of Risks and Benefits • Little to no risk, minimal risk, more than minimal risk – Informed Consent Process – Selection of Subjects and Protection of Vulnerable Populations • Nature of Risk – Concept of Minimal Risk – Nature of Harm • Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Risks in Research • IRB weighs the risks related to: – Harms commensurate with daily life, requiring no special protection: – Inconvenience – Harms that have the potential for serious effects – Emotional or psychological harm – Social harm – Physical harm – Financial harm – Legal harm – Moral harm Benefit in Research • Research participation founded on concept of volunteerism, where no personal benefit, only societal, is realized. • Examples of things that are not benefits but incentives. – Payments, – extra credit, – opportunities for drawings or lotteries, – health improvement, – and insights in own self. Risks and Benefits • Describe in detail any immediate, short-term, or long-range risks that may arise for participants as a result of procedures associated with your study. Risks may be physical, psychological, social, legal, or economic; they would include side effects, risks of placebo, delay in customary treatment, etc. Indicate any precautions that will be taken to minimize risks. Also indicate any anticipated benefits to participants and/or society from the knowledge that may reasonably be expected to result from the study. Levels of IRB Review Informed Consent • Required Elements of Informed Consent: – – – – – – – – Purpose and Procedures Risks Benefits Alternatives Confidentiality When There is Greater than Minimal Risk Persons to Contact You must tell prospective participants whom to contact if they have questions about the research and their rights as a study participant, and whom to contact if they have an injury that may be related to the research. Informed Consent • Voluntary Participation, Refusal, and Withdrawal. – You must state that participation is voluntary, that the participant may decline to participate at anytime with no questions asked, and that there are no loss of benefits to which the person is otherwise entitled (if research conducted in a classroom setting that deciding not to participate will not affect their grade in any way). • If classroom assignment remember you must separate the two (i.e., what is research versus what is required classroom participation). If the student decides not to participate then another non research related assignment must be assigned and their decision honored. The alternate assignment may be another normal non-research related classroom activity. Ethical Considerations Issues of Volunteerism • Fundamental Ethical Principle • Use of students as subjects problematic – review your discipline’s ethical statements. • Be sensitive to subtle coercion. • Provide alternative activities and rewards for students. • Build into protocol regular checks on subject’s willingness to continue. Ethical Considerations • Remember that consent is an ongoing process. If the protocol last longer than 6 months it is always a good idea to go over the consent again and ask if they have any questions. If participant asks then your ethically obligated to go over consent again. • Consent required 3 critical items. – Information: Elements of informed Consent – Comprehension: Understandable language at the participants reading and comprehension level. Also includes language translations – Voluntariness: Right to agree or not to agree to participate Research Misconduct • Remember that there is a Faculty and Student research misconduct policy. – Research Misconduct includes: • Fabrication, • Falsification, • And Plagiarism. • CSU/CSUSB polices and regulations along with federal regulations located at: • http://irb.csusb.edu/policiesRegulations.html Researcher Responsibilities • Plan ahead! • Provide evidence of certification in human resources protection from CSUSB – CITI Human Subjects Training. • You must not deviate from protocol once approved. Deviations from the protocol require IRB approval before they can be implemented in your study (protocol change form required). • Only stamped informed consent document may be used. • Changes in investigators or funding requires notification to IRB. • Must notify IRB of project ending or of need for continuation. • Annual continuing review and approval must be obtained. • Must notify Research Compliance Officer and IRB Chair of any unanticipated adverse events. Student Research Supervisors • You are responsible party, not the student. • Plan ahead! • Incorporate ethical discussion into research planning. • Be knowledgeable of all relevant policies, laws, and regulations applicable to student’s methodology. • Review IRB application with student before signing. Editing and Proofreading • Remember to edit and proofread the application before submitting. Ensure that your advisor reads and reviews the entire application. This is critical to the review of your application. – The IRB’s mission is to review the risks and benefits of your protocol not edit it. Editing distracts from the review of your protocol. – It is highly recommended to have another person besides your advisor review your protocol. This could be a cohort colleague, another faculty member, or a fellow student. It’s Your Time for Questions and Answers! References YouTube Milgram (October 27, 2014). Milgram Experiment: Experiment - Big History NL, threshold 6. Retrieved from http://www.youtube.com/watch?v=xOYLCy5PVgM. Zambardo, P., (October 27, 2014). Stanford Prison Experiment. Retrieved from http://www.prisonexp.org/. Centers for Disease Control and Prevention (October 27, 2014). Tuskegee Syphilis Experiment. Retrieved from http://www.cdc.gov/tuskegee/timeline.htm. Office of Human Research Protections (October 27, 2014). Code of Federal Regulations. Retrieved from http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.102 U.S. Department of Health and Human Services (October 27, 2014). The Belmont Report. Retrieved from http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. University of Southern California (October 28, 2014). ORPS Office Types of IRB Review. Retrieved from http://oprs.usc.edu/review/typesofirb/ . San Francisco State University (October 28, 2014). The IRB Review Process at a Glance. Retrieved from http://research.sfsu.edu/protocol/review_process/review_process. Joseph. L., (October 27, 2014). Protection of Human Research in Research Workshop 2005. Portions of Powerpoint derived from former CSUSB IRB Chair, Dr. Joseph Lovett, Ph.D.