IRB Fundamentals

1. The Office of Academic Research and Office of Graduate Studies presents IRB Fundamentals by Michael L. Gillespie, M.P.A., M.A., CRA Research Compliance Officer Office of Academic Research mgillesp@csusb.edu 909-537-7588

2. Goals and Objectives • Workshop Topics • Why is there an IRB? • What is human subjects (participants) research? • The Belmont Report • The IRB Application Process • Ethical Considerations • Research Misconduct • What is Research Integrity? • What is Research Misconduct? • Ethical Issues in Research – Retraction Watch • It’s Your Time for Questions and Answers!

3. Why is there an IRB? • IRB derives from Medical Research without informed consent • Nuremburg Code – Nazi experimentation on humans – cruel, inhumane treatment, and harm inflicted on humans • 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. These men did not receive the cure to their illness. They were compensated with medical exams, meals, and burial insurance. Although originally projected to last 6 months, the study actually went on for 40 years.

4. Why is there an IRB? • The IRB is a ethical research review committee mandated by the federal government to review research that involves human subjects • Federal regulation establishes the requirements for Institutional Review Boards, informed consent, benefit-risk assessment, and subject selection • HHS - Federal Policy for the Protection of Human Subjects commonly referred to as the Common Rule (45 CFR 46, Subpart A) • FDA (Title 21 Part 50 and Title 21 Part 56) • CSUSB Faculty Senate Policy (FAM 845.72) defines authorities, roles, and responsibilities of the CSUSB faculty and the Institutional Review Board • Federalwide Assurance (#FWA000004865) was filed by CSUSB with the Office of Human Subjects Research (OHRP). The assurance outlines the university’s responsibilities for protecting the rights and welfare of human subjects of research conducted at or sponsored by CSUSB. • CSU Chancellor Executive Order 890and Executive Order 991 • CSUSB Policy – University Policy on Misconduct in Research and Authorship

5. Why is there an IRB? • Requirements of 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 (B = pregnant women/human fetuses/neonates, C = prisoners, D = children) • 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

6. Federal definition of a human subject Human subject is defined as: a living individual about whom an investigator (whether professional or student) conducting research obtains • Data through intervention or interaction with the individualor • Identifiable private information

7. Federal definition of an intervention with human subjects • Intervention-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- Information about behavior that occurs: • In a context in which an individual can reasonably expect that no observation or recording is taking place • Information which has been provided for specific purposes by an individual • 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.

8. The IRB Application ProcessThe IRB Review Process • The IRB weighs the risks and benefits of the research study. • Do the risks outweigh the benefits? • IRB helps minimize risks • Changes to IRB are made through the Cayuse System • Make yourself familiar with the IRB website. Training, Submission Dates, Application, & Additional Resources that are available. • https://www.csusb.edu/institutional-review-board

9. Why is there an IRB? • IRB protections moved from medical research to include social behavioral research due to: • Milgram experiment of 1961 conducted by Stanley Milgram of Yale University – focused 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.” • https://www.youtube.com/watch?v=xOYLCy5PVgM

10. Why is there an IRB? • Another 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 • “What happens to really good people when you put them in a bad place?” (Philip Zimbardo) • https://www.youtube.com/watch?v=oAX9b7agT9o

11. Human Subjects Include • Persons • Data collected from people (individuals and/or groups) • Data about persons, including secondary data. • Non-electronic • Electronic • Images • Recordings • Biological samples drawn from persons • Fluids, tissues, scrapings • Genetic encoding

12. 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.

13. The Belmont Report • National Research Act (Pub. L. 93-348)- created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission identifies the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and develops guidelines which assures that such research is conducted in accordance with those principles. The Commission considers: • (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.

14. 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.”

15. 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 well-being. Such treatment falls under the principle of beneficence. In this document, beneficence is understood 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.

16. 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.”

17. 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. • The exploitation of unwilling prisoners as research subjects in Nazi concentration camps was condemned as a particularly flagrant injustice. • The Tuskegee syphilis study used disadvantaged, rural black men to study the untreated course of a disease that was by no means confined to that population. These subjects were deprived of effective treatment in order not to interrupt the project and long after such treatment became generally available (e.g., discovery of penicillin in 1928)

18. 45 CFR 46 PARTS B, C, DVulnerable 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 disadvantagedmay also qualify as vulnerable.

19. IRB Review Process & Levels of IRB Review

20. The IRB Application ProcessThe IRB Review Process • Application: • The 3 C’s: 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.

21. 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(e.g., know the demographics of your population). • Pay close attention to those that are described as a protected population (subpart B, C, and D).

22. 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. Objectives of the Study b. Hypothesis and/or Research Questions (though it is rare - in some cases there may be no hypothesis or research questions. This occurs when the study is exploratory in nature and/or a pilot study designed to develop an hypothesis and/or research questions c. Methodology d. Data Collection e. Data Analysis f. Dissemination

23. 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.

24. 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

25. 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.

26. 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.

27. 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

28. 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.

29. 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.

30. Informed Consent • Required Elements of Informed Consent – the consent document is the contract between you and the participant and built on information and trust) • Purpose – describe the purpose of the study • Procedures – describe the procedures the participant must follow to be part of the study • Risks of participating in the study • Note there may be no risks to the participants in the study (no foreseeable risks) • Risks may include feeling uncomfortable being video or audio recorded and/or psychological risks if the questions being asked are of a sensitive nature • Benefits of participating in study • Note there may be no direct benefits to participating in the study. There may be benefits to the field/discipline and/or to the literature in the area • Alternatives – alternative activities for non-participants to complete if they choose not to participate in the study. This is especially important if the researcher is the instructor/teacher of the students • Confidentiality – Must ensure the confidentiality measures are included to protect the participants information. This is your duty as a researcher to protect the confidentiality of the participants data when the data is collected and after the study has been completed. • When there is greater than minimal risk additional protections may be needed to protect the participants • Researcher/Investigator contact information • 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. You can include the researcher compliance officer as the contact, Mr. Michael Gillespie, Research Compliance Officer, Office of Research, California State University, San Bernardino, Email: mgillesp@csusb.edu and Phone: 909-537-7588.

31. 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.

32. Ethical ConsiderationsIssues 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 (i.e., review the informed consent with them periodically or ask them if they have any questions about the study so far)

33. 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 requires 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

34. 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). • 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 and/or adverse events (OHRP website).

35. Faculty Advisors & Supervisors • Faculty is the 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.

36. Advisor and PI Responsibilities Source Hyperlink

37. 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.

38. What is Research Integrity? The National Institutes of Health (2017) states research integrity includes: • the use of honest and verifiable methods in proposing, performing, and evaluating research • reporting research results with particular attention to adherence to rules, regulations, guidelines, and • following commonly accepted professional codes or norms. National Institutes of Health. (2017). Research integrity: What is research integrity? Retrieved from: https://grants.nih.gov/grants/research_integrity/whatis.htm

39. What is Research Integrity? • Shared values in scientific research that includes: • HONESTYconvey information truthfully and honoring commitments • ACCURACYreport findings precisely and take care to avoid errors • EFFICIENCYuse resources wisely and avoid waste • OBJECTIVITYlet the facts speak for themselves and avoid improper bias • Steneck, N. H. (2007). ORI - Introduction to the responsible conduct of research link to external site, Washington D.C. , U.S. Government Printing Office, p.3.

40. Research Integrity According to ORI • These practices include: • Honesty and fairness in proposing, performing, and reporting research; • Accuracy and fairness in representing contributions to research proposals and reports; • Proficiency and fairness in peer review; • Collegiality in scientific interactions, communications and sharing of resources; • Disclosure of conflicts of interest; • Protection of human subjects in the conduct of research; • Humane care of animals in the conduct of research; • Adherence to the mutual responsibilities of mentors and trainees. • While science requires vigorous defense of one's ideas and work, ultimately research integrity means examining the data with objectivity and being guided by the results rather than by preconceived notions.

41. Research Misconduct (RM) • RM can occur in publications, presentations, posters, grant applications whether they are funded or unfunded. • RM affects everyone – tainted research can have negative implications on individuals in the lab, the larger research community, and in the public’s trust in science. • The Office of Research Integrity reported that within there misconduct cases from 2011 to 2015. • 12% were reported by research trainees. • 40% were committed by research trainees. • The DHHS makes about 13 findings of research misconduct each year. • In 45 cases of research misconduct committed by trainees, 72% of supervisors had not reviewed the source data.

42. NIH Definition of Research Misconduct • According to NIH (2017) research misconduct (FFP) is: • (F) Fabrication: Making up data or results and recording or reporting them • An example of fabrication: In order to meet recruitment pressure and expectations, a study coordinator completed trial enrollment forms using faked names and participants' information. • (F) Falsification: Manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record. • Investigators might falsify results by 'splicing and pasting' together different segments of western blot images so that the final image presented appeared to have come from a single western blot procedure. • (P) Plagiarism: The appropriation of another person's ideas, processes, results, or words without giving appropriate credit. • Note that Research misconduct does NOT include honest error or differences of opinion Source: https://grants.nih.gov/grants/research_integrity/research_misconduct.htm

43. What drives people to behave unethically (e.g., engage in research misconduct)? • Poor supervision – not checking the raw data • Inadequate training – lab training, using scientific equipment, and research ethics training, assistance in reporting result • Competitive pressures- can include pressures in grant funding which included applying for, maintaining, and renewing the funding • Publish or Perish - this is reinforced by a research community that is highly competitive • Personal Circumstances – feeling pressured for results • Individual Psychology – fear of failing

44. Ethical Issues – Retraction Watch • Retraction Watch - List of Retractions by Year • Retraction Watch - Leader Board • Office of Research Integrity Case Summaries

45. It’s Your Time for Questions and Answers!

46. 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.