What is an IRB and Why Should I Care?

1. What is an IRB and Why Should I Care? Beth Taraban Research Integrity Office

2. IRB--Definition • An Institutional Review Board is a committee whose primary responsibility is to protect rights and welfare of human research participants. • IRB review is required for all federally-funded research involving human participants. The procedures for research review are set out in the Code of Federal Regulations (CFR).

3. IRB Definition--Continued • Most institutions (including TTUHSC) have elected to abide by the CFR regulations for human research review even for research that is not federally funded. • The FDA also requires IRB review and approval of research for any research involving a drug, a biologic or a medical device.

4. Federal Regulations--General • Biomedical IRBs are regulated by two groups: Department of Health & Human Services (DHHS)—Office of Human Research Protection (OHRP) DHHS rules for IRBs can be found in 45 CFR 46 and subparts B,C, and D which offer special protections for pregnant women, fetuses/neonates, prisoners and children And by the Food and Drug Administration (FDA) FDA rules can be found in 21 CFR 50 and 21 CFR 56

5. The “Common Rule” (45 CFR 46) • The Common Rule is a federal policy regarding Human subjects Protection that applies to 17 Federal agencies and offices that have signed the agreement and is enforced by OHRP • The main elements of the Common rule include requirements for: • Assuring compliance by research institutions • Researchers’ obtaining and documenting informed consent • Institutional Review Board (IRB) membership, function, operations, review of research, and record keeping • The Common Rule includes additional protections for certain vulnerable research subjects • Subpart B-Pregnant women and fetuses • Subpart C- Prisoners • Subpart D- children

6. Federal Regulations--continued • Failure to follow either the DHHS regulations or the FDA regulations can result in penalties for individual researchers and for the institutions themselves—a single rogue researcher can halt ALL HUMAN RESEARCH at an institution!

8. What is research? Research is defined as any systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Source: 45 CFR 46.102(2)

9. What is human research Human subjects are defined as living individuals about whom an investigator conducting research obtains • Data through intervention or interaction with the individual or • Identifiable private information Source: 45 CFR 46.102(f)

10. So, is this research or not?? When in doubt, Contact your local IRB Administrator Lubbock—Karen Douglas—806-743-4753 Amarillo—Kathy Thomas—806-354-5419 OR Check the very cool decision trees at the OHRP website: http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html

13. OK, it’s human research, I need IRB approval. Now what? Training requirements for ALL study personnel involved in human research at TTUHSC : CITI Biomedical Investigator Course (13 modules) Retraining required every 3 years CITI Financial Conflicts of Interest Course (2 modules) Retraining required every 4 years www.citiprogram.org

14. I finished CITI. Now CAN I SUBMIT MY PROJECT? • Not yet. First, you need to get access to the iRIS program—this is an internet based program through which all communication TO and FROM the IRB takes place. • Obtain iRIS access by clicking the “Request a New Account” button at the iRIS website: www.sobmrimedris.ttuhsc.edu Training specific to using iRIS can be arranged through the IRB office.

15. A Little More on CITI • Registering at www.citiprogram.org is pretty simple. • However, if you would like step-by-step instructions, with pictures, you can find answers at the CITI Support Center. • Here is the link to the “How do I enroll in a CITI course for the first time?” instructions (updated 1/24/14) • http://citiprogram.desk.com/customer/portal/articles/163300-how-do-i-enroll-in-a-citi-course-for-the-first-time-

16. I have CITI and iRIS. Can I send my study for IRB review NOW? Almost! You are SO CLOSE! Do you have an up-to-date financial disclosure form on file? YES, goshdarnit—and believe me, that’s not the word I was really thinking!! OK. You can submit your research project for IRB review now.

17. IRB Composition • Federal regulations govern IRB composition: • At least 5 members • At least one “scientist” member • At least one “non-scientist” member • At least one member who is otherwise unaffiliated with the institution • At least one member who is considered a “participant advocate.” • Diversity regarding gender, background, etc. to represent the types of research reviewed

18. TTUHSC IRB Composition • TTUHSC has 2 IRBs (Lubbock/Odessa/Midland and Amarillo/Dallas/Abilene) • Most IRB members are TTUHSC faculty • The members spend, on average 4-6 hours per month preparing for and attending the IRB meeting • Current list of members available on IRB website: www.ttuhsc.edu/research/hrpo/IRB

19. IRB regulations—Research approval • Risks to subjects are minimized • Risks are reasonable in relation to potential benefits • Selection of subjects is equitable • Informed consent will be sought and documented for each subject • Ongoing monitoring will occur to ensure subject safety • Adequate provisions exist to protect privacy • Special safeguards are in place for vulnerable subjects

20. What is the IRB looking for? TTUHSC IRB reviewers are looking for: • Protection of subject safety and well- being) 1a) Scientific validity of the research project 1b) Qualification of investigators to conduct research 1c) Adherence with federal regulations and TTUHSC policies.

21. Types of IRB review • Exempt projects • Expedited • Full Board review

22. IRB Review--Exempt Projects Exempt studies are “exempt” from the federal regulations Generally, these are: • studies that are done as part of normal classroom procedures for which you don’t collect any identifying information • surveys or questionnaires of adults in which you don’t get any identifying information and don’t ask any sensitive questions or • retrospective research in which all of the data are already in existence and you won’t be recording any identifying information.

23. A-ha! My study is EXEMPT from IRB review, so I don’t have to submit anything to you, right? ~~WRONG~~ The federal regulations say that the investigator can not be the one to decide if a project is exempt. TTUHSC has decided that the IRBs will make that decision.

24. Submitting an exempt study If it’s a retrospective chart review, you need to submit: • Your IRB application • Your protocol • Be sure in your protocol to clearly state the following two things: 1) The data are all in existence AS OF THE DATE of the IRB application. Often people will say something like, “Medical records dated 1/1/2003 through 12/31/2013 will be examined” The important part is that the end date is from a time BEFORE your submit your IRB application 2) You will not be recording any identifiable information—this includes DATES associated with the patient • Your data collection sheet • A HIPAA Waiver of Authorization form (allows you access to medical records for research purposes)

25. Submitting an exempt study--continued If it’s an anonymous survey, you need to submit: • Your IRB application • Your protocol • Your survey (or a link to the survey if it’s web-based) • Any flyers or letters that you’ll be using to recruit respondents

26. My study isn’t exempt—what else could it be? • Your study might meet criteria to be expedited. This means that the study can be reviewed by one or two experienced IRB reviewers and you don’t have to worry about deadlines or meeting dates. • Expedited studies are always minimal risk studies--no investigational drugs, no protected populations, no very sick people and no highly sensitive procedures.

27. Expedited reviews • Note that an “expedited” review doesn’t necessarily mean a “quick” review. Regulations require that an expedited review be given the same scrutiny that a submission to the full board would receive. • An expedited reviewer can APPROVE or REQUIRE MODIFICATIONS to a study but can not disapprove a study.

28. My study is neither exempt or expedited • In this case, your study will require Full Board review. You will need to submit all required materials by the deadline date. You can find all IRB deadline dates and IRB meeting dates on the TTUHSC IRB website: www.ttuhsc.edu/research/hrpo/irb. • The Full Board reviews proposed research that is greater than minimal risk, uses vulnerable populations, has any unapproved drugs or devices, deception of subjects, surveys with sensitive questions or any other project that doesn’t quite meet the definition for expedited review.

29. Submission requirements for a full board review: • Complete IRB application form • Protocol • Informed consent and HIPAA Authorization form • Recruiting materials • Letters of support from collaborating sites • Data collection forms • Grant applications • All surveys, questionnaires, videotapes, etc. For investigational drug or device studies, we also need • IND or IDE number from the FDA • Investigator’s brochure • Documentation of approval by other committees (Radiation Safety; Institutional Biohazard Committee; Conflict of Interest Committee)

30. IRB Review—Full Board • Two (or more) reviewers will be assigned to read and review all of the materials you’ve submitted. Prior to the meeting, the PRIMARY reviewer will write an objective summary of your project and both reviewers will add a subjective review of the project • All of the other IRB members will have access to the materials in iRIS and they, too, can add information (subjective or objective) to the review. • At the IRB meeting, the primary and secondary reviewers will present the study along with their recommendations about what should happen to the study. • Principal investigators may ask or be asked to attend the IRB meeting at which their study is presented.

31. Full Board review--continued • The members will discuss the study and then vote on it. The Board can vote to: • APPROVE the study as it is • REQUEST ADDITIONAL INFORMATION prior to approval or • DISAPPROVE the study. • You will receive an e-mail through iRIS, usually within 24 hours of the IRB meeting, telling you the outcome of the review. • If the Board requests additional information, the email will provide detailed STIPULATIONS—things that need to be addressed prior to approval. You have 30 days to respond to the stipulations.

32. Full Board review--continued • If the Board disapproves the study, you will be provided written notification of the reason for the disapproval. You can request reconsideration within 10 days of receiving the notice. If, after reconsideration, the Board still disapproves the project there will be no further activity—TTUHSC officials can not approve research that has been disapproved by the IRB (45 CFR 46.112)

33. They asked for additional information and I answered them—Now what? • Depending on how many stipulations you had and the nature of the stipulations, either one IRB member or the Full Board will review your responses. If everything has been adequately addressed, your informed consent and HIPAA documents will be stamped and you will get an official Approval Letter from the IRB. • Once you have that approval letter in your hand (AND NOT BEFORE!!) you are ready to start your study.

34. Using PHI in Research Protected health information (PHI) is any information, including demographic information, that is transmitted or maintainedin any medium (electronically, on paper, or via the spoken word) that is created or received by a health care provider…that relates to or describes the past, present, or future physical or mental health or condition of an individual… and that can be used to identify the individual.

35. IDENTIFIABLE PHI Names Medical Record Numbers Geographic subdivisions smaller than a State Dates (except year) directly related to an individual including Date of birth Admission date, discharge date, date of death All ages over 89, including dates and year Telephone numbers, fax numbers, E-mail addresses, internet URLs, IP addresses Social security numbers Account numbers, Certificate/license numbers License plate numbers/VIN numbers Device identifiers and serial numbers, Finger and voice prints, Full face photographic images and any comparable images Any other unique identifying number, characteristic, or code

36. So, What Do I have to do? • If you need PHI to do your research (and most biomedical research does), you MUST do one of two things: • 1 Obtain written authorization from your potential participants allowing you to access their medical record for research purposes. Can generally be done as part of the informed consent process • Or • 2) Ask for (and be approved for) a WAIVER OF AUTHORIZATION. • You must attest that: • there is minimal risk to the privacy of the research participants (generally because you will not be recording any personally identifiable information); • you will not reuse or disclose any of the PHI that you access; • the research could not practicably be conducted without access to PHI; and • the research could not practicably be conducted without the waiver of authorization.

37. Anything else? • If you want to make ANY CHANGES* to your study from what the IRB originally approved, you must submit a Change/Request Amendment to the IRB (through iRIS). You can’t actually make the change until you get the amendment approved. * Yes, we do mean ANY changes—changes in study personnel, changes in methodology, changes in where data are stored, ANYTHING that is different from what you originally said in the protocol.

38. Anything else—part 2 • The IRB also wants to know about any* unexpected events—anything that didn’t go according to plan • The IRB requires ongoing progress reports. The IRB will determine the frequency, but regulations require continuing review at least once every 365 days. * Yes, ANY…no unexpected event is too minor…

39. Anything else—part 3 Clinical Trial Registration: • If you are conducting a clinical trial, the project MUST be registered at ClinicalTrials.gov prior to enrolling your first subject.   • Also, the FDA mandates specific language in the consent document regarding ClinicalTrials.gov registration. • For more information, see http://prsinfo.clinicaltrials.gov; or www.icmje.org/clintrialup.htm or www.fda.gov/cder/guidance/4856fnl.htm 

40. Anything Else—Part 4 Unanticipated events that occur during the study need to be reported to the IRB—PROMPTLY. Unanticipated event types: • Protocol deviations (affect one participant—don’t increase risk of study) 2) Unanticipated Problems Involving Risks to Subjects or Others (Affect the conduct of the study more generally—bigger deal) 3) Serious Adverse Events (defined elsewhere) 4) Unanticipated Adverse Device Effects

41. Is this all really as complicated as it sounds? • Nah, not at all. The Office of Research and IRB really DO want to help you get your research done. Come and talk to us. OR • Check the IRB website: www.ttuhsc.edu/research/hrpo/irb OR • Check the OHRP website: http://www.hhs.gov/ohrp

42. To Summarize: • If you are going to do research with people, an IRB will be involved. • You will ALWAYS be better off asking questions first. • The primary goal is always protection of participants, but institutional, state and federal policies and regulations also have to be followed.