Understanding Research: Getting Your Project Ready for the IRB

1. Understanding Research: Getting Your Project Ready for the IRB Jill Stoltzfus, Ph.D. Director, Research Institute stoltzj@slhn.org

2. Today’s Objectives • Present the general purpose and (very brief) historical background of the Institutional Review Board (IRB). • Determine which types of research require IRB approval at St. Luke’s. • Explore the IRB’s roles and responsibilities. • Your turn: Preparing your research for the IRB review process. • Q & A • Wrap up

3. What is the IRB, and Where Did it Come From? • The IRB’s sole purpose is to protect people who are enrolled in clinical research. • The concept of the IRB came from the “Declaration of Helsinki” document in 1964, which set up an international standard for biomedical research with human subjects. • Prior to this, federal guidelines for conducting medical research in the United States only applied to research at the National Institute of Health (NIH).

4. The Uglier Side of Research Over the Years • Thalidomide Experience (1950s): Women were routinely given thalidomide as an investigational drug to help them cope with pregnancy symptoms, but severe growth deformities started occurring in infants as a result. Unfortunately, these women were never fully informed about the “experimental” nature of thalidomide and the fact that it was still in the testing phase. • Willowbrook Hepatitis Studies (1950s): In order to see which factors might lead to hepatitis transmission, mentally retarded children living in a long-term care facility in New York were fed a concoction containing feces from children with active hepatitis.

5. The Uglier Side of Research Over the Years • Jewish Chronic Disease Hospital Studies (1960s): In order to see how a compromised immune system might influence the spread of cancer, researchers injected live cancer cells into demented patients at a chronic disease hospital in New York City. • San Antonio Contraception Study (early 1970s): Poor, indigent patients from a contraception clinic in Texas were given either contraception or a placebo without being told they were in a research study or that they might be getting inactive birth control. • Tearoom Trade Study (early 1970s): A social scientist named Laud Humphries wanted to study homosexual behavior in public settings, so he spent time at public restrooms watching people engage in anonymous sex. Then he recorded their license numbers and used this information to track them down and interview them about their background and family life. He eventually published his findings.

6. The Uglier Side of Research Over the Years • Miligram Studies of Obedience to Authority (1960s): In order to determine why people obey authority figures even when asked to perform cruel acts, psychologist Stanley Miligram recruited people to read word pairs to people sitting out of sight behind a wall, then to deliver increasing “shocks” each time a wrong answer was given, from 45 to 450 volts. A hired actor screamed and complained about his heart condition as the “shocks” increased in intensity. • Despite the discomfort expressed by several participants at delivering these “shocks”, 65% of them delivered what they thought was the maximum of 450 volts. • When this study was repeated in other settings and other countries, between 61-66% of people responded in the same way!

7. The Uglier Side of Research Over the Years • Tuskegee Syphillis Study (1932 - 1972): In order to determine the effects of untreated syphillis on the human body, the U.S. Public Health Service observed poor, uneducated black sharecroppers in the rural South over a four-decade period. Participants were never told about the nature of this research, nor did they fully understand their disease state. Additionally, they thought they were getting good medical care due to the many tests and procedures to which they were subjected. One negative long-term effect of this study has been the reluctance of many black people to participate in research given their suspicions about whether they are being “experimented” upon in similar fashion to the men in the Tuskegee study.

8. Who Sets the Rules and Regulations for IRBs? • Two organizations within the Department of Health and Human Services (HHS) are most influential in deciding what IRBs must do: • Food and Drug Administration (FDA):Applies to research involving all products regulated by the FDA. • Office for Protection from Research Risks OPRR):Applies to research involving human subjects that is conducted or funded in any way by HHS. • In addition, individual institutions may (and often do) have their own rules and regulations.

9. Which Types of Research Require IRB Approval at St. Luke’s? • Some institutions have different types of IRB review procedures depending on the nature of the research study (e.g., full review for more intrusive or potentially harmful studies; expedited review for minimal risk studies.) • However, at St. Luke’s,all research proposals must first go through the IRB to determine whether they require full review or can be exempted--even the projects that seem relatively harmless (e.g., a retrospective chart review). • Once this happens, the IRB committee sends you either a letter indicating the need for full review or a letter of exemption from full review.

10. Who Serves on the IRB? • The Department of Health and Human Services (HHS) requires IRBs to have at least 5 members to ensure adequate review of all research projects and proposals: • There must be at least one non-scientist (e.g., attorney, clergy member) • There must be at least one person who isn’t affiliated with the institution or isn’t an immediate family member of someone affiliated with the institution. • Ideally, there should be a diverse mixture of members from different racial/ethnic, gender, cultural and community backgrounds. • Any IRB member with a conflict of interest (meaning a financial or other stake in the research) is excluded from reviewing that particular research proposal.

11. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Risk/benefit analysis • Informed consent • Selection of subjects • Privacy and confidentiality • Monitoring and observation • Safeguards • Incentives for participation • Continuing review • Record keeping

12. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Risk/benefit analysis • Is there a high likelihood of physical, psychological, social or economic harm/injury that might result from participating in a research study? • Physical harm: Pain, discomfort or injury due to medical procedures or possible side effects of medication. • Psychological harm: Depression, confusion, hallucinations or other negative changes in emotions and thought processes. • Social and economic harm: Criminal prosecution, being humiliated, loss of employment or other negative outcomes due to being labeled as “sick”.

13. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Risk/benefit analysis • Are the risks no greater than what you might experience in daily life or during a routine checkup? • Example of acceptable risk: Drawing blood from healthy study participants (since this could happen during a regular medical appointment.) • Example of a risk with possible problems: Denying potentially effective treatment to participants in the placebo group of a randomized control trial. • Example of a situation where greater risk might be allowed: Testing a new drug for a life-threatening condition (such as metastatic cancer).

14. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Risk/benefit analysis • Is the desired outcome in balance with the potential risks? • Will the study investigator be able to carry out the research with a high level of competence? • Are there adequate safeguards in place to protect participants (with special protection for more vulnerable populations such as fetuses, pregnant women, children and prisoners)? • Will study procedures and practices be monitored on a frequent basis? • The perception of some risks might be subjective, depending on the participant (e.g., hair loss as a side effect might be viewed differently by a teenager than by a 75-year-old man.)

15. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Risk/benefit analysis • Are the benefits likely to improve participants’ quality of life and increase the medical field’s knowledge in concrete ways? • In other words,is this study worth the time, energy and effort to even bother conducting in the first place????

16. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Informed consent • The big question:Have participants been adequately informed about what they’re getting themselves into BEFORE the study begins? • Interesting historical tidbit: Informed consent has its roots in the Nuremburg Code of post-WWII, when Nazi physicians were tried for the experiments they performed on concentration camp inmates (who obviously did NOT give their informed consent beforehand!)

17. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Informed consent: Required components • Statement saying that the study is indeed “research”. • Detailed explanation about the research and participants’ roles and responsibilities. • Expected length of the study. • Projected benefits and possible risks. • Presentation of any alternative treatments or approaches (even those that might be better than what’s in the current study). • Any limitations to privacy and confidentiality (e.g., who has access to research records.) • Provisions in case of injury during the study • Statement that participation is voluntary and can be ended at any time.

18. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Informed consent: Additional (but not required) components • Statement about unforeseeable risks that might occur along the way. • Situations in which participants’ involvement might be ended without the participant’s consent (e.g., unethical or dangerous participant behaviors). • Extra costs that might arise as the study progresses. • The number of participants in the study.

19. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Informed consent: How does it work? • Once participants sign the form (or their legal representative does so), they must receive a copy. • Any oral presentations about the informed consent process must be witnessed by a third person who then signs both the consent form and a copy of the written summary of the presentation. • When can informed consent be waived? • Research involving minimal risk (e.g., the only real risk to participants is a possible breach of confidentiality.) • Emergency situations. • If participants’ rights won’t be adversely impacted.

20. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Selection of subjects • The big question: Is the chance to participate both fair and equitable? Not always the case in past years: • In the 19th and early 20th centuries, poor patients in hospital wards were usually chosen for research studies, with little to no protection or recourse if something went wrong. • During the Tuskegee trials (1932 - 1972), low-income black sharecroppers were enrolled to track the effects of untreated syphilis on the human body, but these participants weren’t even told they had the disease, and they weren’t given the option of being treated once penicillin was discovered. • As a result of these historical blunders, IRBs are now supposed to determine whether certain groups (e.g., racial/ethnic minorities, low-income people) are being selected for the wrong reasons.

21. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Selection of subjects • Other situations IRBs need to consider regarding whether subjects are being selected fairly and equitably: • If students (e.g., the ubiquitous Psych 101 college class) or military personnel are available for studies, will they be led to believe that their grades or performance reviews depend on their participation? • If employees are available for studies, might they feel undue pressure to participate, lest they be passed over for raises? • Are institutionalized persons or prisoners told that their participation will make things better for them or possibly reduce their length of stay?

22. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Selection of subjects • At the same time, researchers shouldn’t go out of their way to exclude people from participating. • IRBs must not overprotect vulnerable populations from participating if they really want to (although they should carefully consider things like discomfort, inconvenience and potential embarrassment for these populations.) • IRBs need to consider how subjects are being recruited to make sure people from diverse backgrounds have an equal chance of getting selected for a study. • In fact, if women and racial/ethnic minority populations aren’t being represented proportionately in a study, the researcher should give a very good reason why this is so.

23. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Privacy and confidentiality • The big question: Does the research adequately protect participants’ personal information? • For research on preexisting data (like chart reviews): Contact people to ask their permission to review records for a new study; let people know ahead of time that their records may be used for future research; substitute codes for names; and store research documents in locked cabinets. • For observational research: In general, IRB review is only needed if a) minors are involved; b) the study’s observations can be directly linked to participants (e.g., through social security numbers); c) the observations may harm participants’ reputation or financial standing; and d) the observations put participants at risk of civil or criminal liability.

24. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Monitoring and observation • The big question: Does the research plan include a specific description of how data will be collected, monitored and analyzed? • This is critical to ensure that the overall risk to participants doesn’t increase as time passes, and that the research is therefore worth continuing.

25. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Safeguards • The big question: If the research involves certain populations (e.g., children, pregnant women, prisoners) that may be vulnerable to coercion or undue influence, have special efforts been made to protect these participants’ rights and overall well being? • This could include getting the co-consent of parents, relatives or neutral third parties.

26. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Incentives for participation • The big question: If any rewards are offered for study participation, are they given in good faith? • Currently, there are no federal guidelines for evaluating incentives within the context of a research study. • Rewards should not be used to pressure participants to remain in the study if they don’t wish to do so. • Rewards can also become a problem if they prompt participants to lie, conceal information or engage in other unethical behaviors simply to get the reward. • Some rewards (e.g., access to free medical care) may introduce selection bias if only certain people (e.g., those with low incomes) choose to participate in the study.

27. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Continuing review • The big question: Once a research study gets the initial IRB stamp of approval, it must continue to be followed up through a structured review process. • At the initial review, the IRB committee decides how often to conduct the follow-up reviews (usually dependent on the level of risk involved in the study.) • Regardless of how many follow-up intervals are established, all research must be reviewed at least once annually. • The initial IRB approval is only temporary and may be revoked at any time if problems arise over time. In fact, the IRB committee can require the study to be stopped completely if things get really bad.

28. What are the Specific Roles and Responsibilities of the IRB at St. Luke’s? • Record keeping • Federal guidelines require all IRBs to keep the following records for at least three years after the research study is completed: • Progress reports of approved informed consent documents; reviewed research proposals; and reports of participant injuries • Meeting minutes showing attendance and the number voting for, against and abstaining from research proposal decisions • Records of all continuing review activities • A comprehensive list of IRB committee members, including their names, earned degrees, licenses, role on the IRB committee, and any relationship with St. Luke’s

29. Your Turn: How Do You Prepare for the IRB Review? • Step 1: Make sure your research proposal is complete and well-organized before submitting it to the IRB. • What is your research hypothesis--what are you trying to discover/prove/learn? • How were participants selected, and how many are included? (Should have an accompanying power analysis to ensure a proper sample size--see me for this!) • How do you propose to collect data? Are your data easily quantifiable/measurable? • Are the potential risks and benefits to participants clearly given? • What are your qualifications for conducting this research? • If applicable, is your informed consent document written in easy-to-understand language? Is it thorough?

30. Your Turn: How Do You Prepare for the IRB Review? • Step 2: Go to the IRB website (http://slhechowebsvr/manny/irb/irbframe.htm), where you’ll find everything you need to complete the application process, including: • A general description of the IRB, including when it meets (first Tuesday of each month) and the deadline for submission of research proposals (usually the 15th day of the preceding month). • An overview of the research process at St. Luke’s. • A flowchart revealing how research is approved through the IRB. • Links to frequently used policies and procedures (including the “Initial IRB Application” form, which is required for all St. Luke’s research.)

31. Your Turn: How Do You Prepare for the IRB Review? • NOTE: If the previous link doesn’t work, go to: • St. Luke’s Intranet site (http://slhnweb/) • “Departments and Services” link • “Bethlehem” link • “Institutional Review Board” link

32. Your Turn: How Do You Prepare for the IRB Review? • If you really believe your research study poses little to no risk to participants, you could first try getting an exemption from IRB review. • Go to the“Exemption of Research from IRB Review” linkin the St. Luke’s Intranet site and follow the instructions (keeping in mind that your research must meet one of the following criteria): • Is conducted in established educational settings. • Focuses on the use of educational tests, surveys or observation of public behavior (with some exceptions). • Involves the collection or study of existing data that is publicly available or recorded in a way that protects privacy. • Examines public benefit or service programs. • Addresses taste or food quality evaluation (with some exceptions).

33. Your Turn: How Do You Prepare for the IRB Review? • Step 3: Wait to hear back (in writing) from the IRB committee about the status of your research proposal (meaning whether it requires full or expedited review).

34. Summary of Steps to Prepare for IRB Review • Step 1:Make sure your research proposal is complete, accurate and well-organized before submitting it to the IRB. If you need help with this, come see me. • Step 2:Go to the IRB website(http://slhechowebsvr/manny/irb/irbframe.htm) to find all of the necessary forms, policies and procedures depending on the type of research you plan to conduct. • Step 3:Wait to hear back (in writing) from the IRB committee about the status of your research proposal.

35. Q & A • Clarification of today’s lecture points? • Something more you’d like to know?

36. Summary of Today’s Objectives • Presented the general purpose and (very brief) historical background of the Institutional Review Board (IRB) • Determined which types of research require IRB approval • Explored the IRB’s roles and responsibilities • Discussed how to adequately prepare for the IRB review process

37. Understanding Research: Getting Your Project Ready for the IRB Jill Stoltzfus, Ph.D. Director, Research Institute stoltzj@slhn.org