Exempt and Expedited Reviews What Requires IRB and R&D Approvals

1. Exempt and Expedited Reviews What Requires IRB and R&D Approvals Kimberly Summers, PharmD Deputy ACOS for Research and Development South Texas Veterans Health Care System Research & Development Service

2. Overview • Determining if a Protocol is Human Subjects Research • Types of Human Subjects Research Reviews • Exempt • Expedited • Convened Board • What needs IRB Approval? • What needs R&D Approval? • Summary

3. What is Human Subjects Research? • There are two definitions of Human Research that must be considered. • An activity may meet either definition • Definition from Department of Health and Human Services (DHHS), or • Definition from the Food and Drug Administration (FDA)

4. DHHS Definition of Research • Is the activity research? • The distinction between practice and research is blurred, partly because they often occur together, partly because departures from standard practice are called experimental (not carefully defined). • For the most part, the term "practice" refers to interventions that are designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success. • Research designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships). • Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.

5. DHHS Definition of Human Subjects • Does the research involve human subjects? • A human subject is: • A living individual about whom an investigator (whether professional or student) conducting research obtains • Data through intervention or interaction with the individual, or • Identifiable private information

6. FDA Definition of Research • Is the activity a clinical investigation (research)? • If the activity involves an FDA regulated test article • Use of a drug, other than the use of a marketed drug in the course of medical practice; or • Use of a device to evaluate safety or effectiveness of that device; or • Data from the activity will be submitted to, or held for inspection by, the FDA in support of a marketing or research application for an FDA-regulated product

7. FDA Definition of Human Research • Does the research involve human subjects? • The test article will be used on one or more humans; or • The data obtained from controls will be submitted to, or held for inspection by the FDA in support of a marketing or research application for an FDA-regulated product; or • The data obtained from use of a device on tissue specimens will be submitted to, or held for inspection by, the FDA in support of a marketing application or research application for an FDA regulated product.

8. Definition of VA Research • Research sponsored by the VA • Research conducted using any property or facility of STVHCS • Research conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHCS during and in connection with her/his STVHCS responsibilities • Funds for the research activities are managed by the STVHCS or Biomedical Research Foundation of South Texas • Research which recruits subjects at the STVHCS or uses the STVHCS's nonpublic information to identify or contact human research subjects for research purposes

9. Is the activity research? • Does the activity involve human subjects? • Is the activity VA research? • Where does Quality Improvement (QI) fit?

10. HHS/OHRP Definition of QI • Activities whose purposes are limited to: • (a) implementing a practice to improve the quality of patient care, or • (b) collecting patient or provider data regarding the implementation of the practice for clinical, practical, or administrative purposes

11. IRB Definition of QI • Systematic, data-guided activities designed to bring about immediate, positive changes in the delivery of health care in particular settings • QI involves deliberate actions to improve care, guided by data reflecting the effects (e.g., types of practical problem solving; an evidence-based management style; the application of science of how to bring about system change; review of aggregate data at the patient/provider/unit/ organizational level to identify a clinical or management change that can be expected to improve care). • Not designed to contribute to generalizable knowledge.

12. QI or Research? • A group of affiliated hospitals implements a procedure known to reduce pharmacy prescription error rates, and collects prescription information from medical charts to assess adherence to the procedure and determine whether medication error rates have decreased as expected.

13. Designed to test an hypothesis? • Designed to permit conclusions to be drawn? • Designed to develop or contribute to generalizable knowledge? • Implementing a practice to improve the quality of patient care? • Collecting patient or provider data regarding the implementation of the practice for clinical, practical, or administrative purposes

14. QI or Research? • A clinic increasingly utilized by geriatric patients implements a widely accepted capacity assessment as part of routine standard of care in order to identify patients requiring special services and staff expertise. The clinic expects to audit patient charts in order to see if the assessments are performed with appropriate patients, and will implement additional in-service training of clinic staff regarding the use of the capacity assessment in geriatric patients if it finds that the assessments are not being administered routinely. • An abstract of the data will be presented at a VA National Conference

15. Does the activity represent a systematic investigation in which the person engaged in such activities intended to develop or contribute to generalizable knowledge?

16. QI and Publishing the Results • The intent to publish is an insufficient criterion only for determining whether a quality improvement activity involves research • Was the original intent to contribute to “generalizable knowledge” • If the purpose of the activity changes as preliminary results are analyzed and the intent becomes to produce information that could be generalized it may be research • Conversely, a quality improvement project may involve research even if there is no intent to publish the results

17. QI or Research? • A provider wants to review the records of transplant patients that were using medication X in order to determine if the medication has had an effect on the stem cell collection. • Patients will be identified by computer mediated search of medical records (CPRS) of transplant patients that were using medication X during the transplant procedure. • All collected data will be de-identified after extraction from CPRS • If an effect of recent medication use on stem cell collection efficacy is identified, then a clinical protocol will be developed for IRB submission to have a more complete look at the records of these patients to include all other aspects of their diagnosis, care, other medications etc.

18. Designed to test an hypothesis? • Designed to permit conclusions to be drawn? • Designed to develop or contribute to generalizable knowledge? • Implementing a practice to improve the quality of patient care? • Collecting patient or provider data regarding the implementation of the practice for clinical, practical, or administrative purposes

19. Preparatory to Research? • Pilot Project?

20. “Preparatory to Research” • Obtaining aggregate data or reviewing individually-identifiable information by a VA investigator to prepare a research protocol does not require IRB or R&D approval • Examples: to generate a hypothesis, determine feasibility to conduct a study, determine the number of eligible patients • In the VA, using individually-identifiable information to contact potential research subjects as part of recruitment into a research protocol is NOT considered “preparatory to research” • VA regulations differ from those described in the HIPAA Privacy Rule • IRB and R&D Committee review and approval required • IRB approved waiver of authorization and waiver of informed consent required

21. “Pilot Studies” • An initial or preliminary investigation designed to test research hypotheses, gather data, and validate the scientific approach and methodology for a particular area of research interest • Pilot studies are NOT considered part of the activities “preparatory to research” • IRB and R&D Committee review and approval required • Small exploratory study vs pilot study

22. Types of Review • Not research or research not involving “human subjects” • Human research eligible for exemption • Human research (non-exempt) eligible for expedited IRB review • Human research (non-exempt) that is not eligible for expedited review and must be reviewed by a convened meeting of the IRB

23. Exempt Review • Study does not extend beyond minimal risk, as defined by federal regulations • “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.”(45 CFR 46.102(i))

24. Exempt Review • Activities meet a category for exempt research in DHHS regulations for human subjects protections • Educational Research • Research using surveys, interviews, educational testing • Research using surveys, interviews, educational testing involving elected/appointed public officials or where confidentiality of data is protected by federal statue • Research using existing specimens/data • Research or demonstration projects approved by Federal Department /Agency Head • Taste and food quality evaluation or consumer acceptance

25. Exempt Research May NOT Involve… • Prisoners as participants • Test articles subject to FDA regulations except in accordance with 45 CFR 101(b)(6) Taste and food quality evaluation and consumer acceptance studies • Involve children under category 2(b) UNLESS research involves observations of public behavior AND the investigators do not participate in the activities being observed

26. Research Using Existing Specimens / Data • An investigator will review CPRS records for all subjects who have received a heart catherization • The following elements will be extracted from the medical record: risk factors, co-morbidities, demographic information, additional cardiac procedures, number of hospitalizations, concomitant medications, dates of hospitalizations, dates of death • All extracted data elements will be de-identified

27. Exempt Research Involving Existing Data • Does the research qualify for exempt status? • Is a HIPAA Waiver of Authorization required? • If the information collected is de-indentified can a code be maintained separate from the research data? • Are amendments required for exempt research?

28. Individually-identifiable - Data HIPAA Identifiers 1. Names 2. ALL geographic subdivisions smaller than the state 3. All elements of dates smaller than a year and all ages over 89 4. Phone numbers 5. Fax numbers 6. E-mail addresses 7. Social Security numbers (SSN) 8. Medical record number 9. Health plan beneficiary numbers 10. Any other account numbers 11. Certificate/license numbers 12. Vehicle identifiers and license plate numbers 13. Device identifiers and serial numbers 14. WEB URL's 15. Internet IP address numbers 16. Biometric identifiers (fingerprint, voice prints, retina scan, etc) 17. Full face photographs or comparable images 18. Any other unique number, characteristic or code

29. Common Rule • Identity of the subject can not be readily ascertained by information remaining after removal of all 18 HIPAA identifiers • VA regulations require de-identification by both HIPAA regulations and the Common Rule

30. Expedited Review • Study does not extend beyond minimal risk, as defined by federal regulations • Activities meet a category in DHHS guidance for expedited review • May not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, insurability, reputation, or stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal

31. Categories for Expedited Review • FDA regulated • Approved drugs • In-vitro diagnostic testing • FDA approved devices being used in an approved manner • FDA approved device being used in an unapproved manner • Collecting blood samples • In healthy, non-pregnant adults • From unhealthy adults, pregnant adults, or children • Collecting biological specimens (non-invasive) • Non-invasive data collection • Clinical (non-research) materials • Recordings • Survey / Interview, program evaluation

32. Medical Record/Chart Review/Clinical Database Research Studies • May qualify for either Exempt or Expedited review • Will you be maintaining identifying information? • If retaining identifying information (name, medical record number, etc.) for any amount of time, provisions must be in place to maintain confidentiality of subject information • The IRB reviewer of the research makes the final determination as to whether research is exempt or expedited

33. What Needs IRB Approval? • Answer: All Human Research must be reviewed and approved by the IRB before research is started • What is Human Research? • Answer: There are two definitions of Human Research that must be considered. If the activity meet either definition, it must be approved by the IRB • Definition from Department of Health and Human Services (DHHS), or • Definition from the Food and Drug Administration (FDA)

34. IRB Guidance

35. What Needs R&D Approval? • Answer: All exempt, expedited, or convened IRB reviewed research protocols that meet the definition of “VA Research” • R&D submission process and forms are the same for all types of research

36. VA R&D Approval • Must have R&D approval letter prior to any of the following being conducted at the VA • Recruitment • Obtaining informed consent • Having an IRB approved VA consent form does NOT constitute R&D approval • Enrollment • Providing patient follow up • An IRB approval letter does NOT constitute R&D approval

37. Conclusion • Human research and quality improvement are similar but different activities • Distinction between practice and research is often times blurred • Questions about Quality Improvement activities should be directed to the IRB and the VA R&D office • IRB approval is required for all human subjects research • VA R&D approval is required for any research meeting the definition of VA research

38. Questions? Kimberly Summers, PharmD Office: (210) 617-5300 ext 15969 Email: kimberlyk.Summers@va.gov