STVHCS Human Research Protection Program

1. STVHCS Human Research Protection Program Kimberly Summers, PharmD Assistant Chief for Clinical Research South Texas Veterans Health Care System Research & Development Service

2. Human Research Protection Program (HRPP) • The systematic and comprehensive approach by an organization to ensure human subject protection in all research • STVHCS HRPP is a focus on responsibility and compassion, not only compliance

3. What are the ethical principles that govern the HRPP? • Beneficence • Benefits outweigh risks • Autonomy • Informed consent must be obtained • Justice • Recruitment is fair and equitable • Study population represents the group that will benefit from the research

4. Who is the Institutional Official for the STVHCS Research Program?

5. STVHCS Research Program Institutional Official • RICHARD J. BALTZCenter DirectorSTVHCS • Responsible for oversight of all VA investigators and IRB activities as they related to VA research • Must ensure VA IRB members and PIs are knowledgeable to conduct research in accordance with ethical standards and all applicable regulations

6. When is research human subject research? • Is the project designed to produce generalizable knowledge? • Is the research systematic? • Is the information about a living individual? • Is the information about the participants gathered through any direct or indirect interaction with those participants? • Is there any intervention via physical procedures or manipulation of a subjects environment? • Is any private information obtained or used in the research individually identifiable?

7. Which of the following are defined by the VA as human subjects research? • A systematic investigation designed to develop or contribute to generalizable knowledge • DHHS definition • Experiment that involves a test article and one or more human subjects • FDA definition • Research involving human biological specimens • Considered research by VA

8. Which of the following are considered VA research? • Research sponsored by the VA • Research conducted by or under the direction of a VA employee • Salaried or WOC • During official tour of duty or in connection with STVHCS responsibilities • Research conducted using any property or facility of VA • Includes use of CPRS for recruitment or obtaining PHI

9. Which of the following is an FDA regulated activity? • Involves the use of an approved or unapproved drug • Testing the efficacy or safety of a medical device • Use of an approved drug in the practice of medicine • Generating data to be presented to the FDA

10. What distinguishes QI activities from research? • Designed solely for internal program evaluation purposes • No external application or generalization • NOTE: • If the intent of the activity changes after it is initiated and a desire to generalize and disseminate the results develops • IRB approval is required

11. UPIRSO Unanticipated Problem Involving Risk to Subjects or Others

12. What are the three elements which define an UPIRSO? • Unanticipated • Not consistent with either the described risks in the research documents or not expected as part of natural progression of subjects underlying condition • Increases in frequency or severity are considered to be unanticipated • At Least Possibly Related • More likely than not that the event is at least partially related to the study intervention or interaction • Greater Risk of Harm • Places subjects or others at greater risk of harm than was previously known or recognized • Includes physical, psychological, economic, or social harm

13. What are the reporting requirements for study-related, non-serious adverse events (AEs)? • No reporting requirements • Wrong answer • Summary is provided to IRB as part of the progress report • OK answer • As part of the DSMP adverse events are monitored regularly for trends and changes, when incidence or severity changes as a result of the cumulative events the IRB is notified (UPIRSO) and the protocol and or informed consent is modified as needed. A summary of cumulative events is also provided to the IRB as part of the progress report. • More complete answer

14. What are the reporting requirements if an non-serious adverse event occurs that is not related to the study? • No reporting requirements • Must be at least possibly related to study participation • Wrong answer • No reporting requirements • Must be serious • Wrong answer • Summary is provided to IRB as part of the progress report • Correct answer

15. Report to IRB as an UPIRSO Must be reported by investigator within 48 hours (consider all UPIRSO criteria in order) IRB reports UPIRSO to Office of Human Research Protection (OHRP) IRB reports UPIRSO to VA R&D office VA R&D office reports UPIRSO to Office of Research Oversight (ORO) What are the reporting requirements for deaths that may be related to study participation?

16. What are the reporting requirements for deaths that are not related to study participation? • No reporting requirements • Must be at least possibly related to study participation • Wrong answer • All deaths are summarized and provided to IRB as part of the progress report • Correct answer

17. Who makes the determination whether research is exempt from federal regulations? • Any member of the study team • Principal Investigator • Sponsor • IRB • Any of the above

18. Who must approve human subject research before it can be conducted at the VA? • IRB • ACOS for R&D • Chief of Staff • Director • R&D Committee • Subcommittee for Research Safety

19. The STVHCS R&D Committee cannot approve a human subject research protocol that has not been approved by the UTHSCSA IRB The STVHCS R&D Committee can disapproval a human subject research protocol that has been approved by the UTHSCSA IRB

20. What types of research have special restrictions for conduct at the VA? • Research involving children • Waiver from the Chief Research and Development Officer • Must present no greater than minimal risk • Meets all requirements of the DHHS and FDA regulations • VA Medical Center Director must certify that the facility is able to respond to pediatric emergencies • Pregnant women • Adequate provisions to monitor the risks to the participant and the fetus • Adequate consideration is given to the manner in which prospective participants are going to be selected • Adequate provision is made to monitor the actual consent process • Prisoners • Waiver from the Chief Research Development Officer

21. What research populations and situations are NOT conducted at the STVHCS? • Research in which the subject is a fetus, in-utero or ex-utero (including human fetal tissue) • Research related to in vitro fertilization • Planned emergency research

22. When can non-veterans be enrolled in a VA study? • Non-veterans may be entered into VA approved research studies only when there are insufficient veterans available to complete the study and accordance with all federal regulations • All regulations pertaining to veterans as research subjects pertain to non-veteran subjects enrolled in VA approved research

23. Who can serve as the legally authorized representative if a potential subject is decisionally-impaired? • Health care agent appointed by the person in a durable power of attorney for health care • Court appointed guardian of the person • Next of kin in the following order of priority • Patient’s spouse • An adult child of the patient who has the waiver and consent of all other qualified adult children of the patient to act as the sole decision-maker or a majority of the patient’s responsibly available adult children • Patient’s parents • Patient’s adult sibling • Patient's grandparent • Patient’s adult grandchild • Since VA and Texas state law differ, follow the more restrictive regulation • Consult with legal counsel in cases of uncertainty

24. Who can dispense an investigational drug to a research subject? • Research Pharmacy • All investigational medications must be dispensed through the VA research pharmacy • Principal Investigator • Only under exceptional situations when a contractual agreement is in place with the VA research pharmacy may the PI dispense medication directly to a research subject • Research Coordinator • Under no circumstances • Study coordinator may receive the dispensed medication from the research pharmacists (or PI if agreement is in place) and then provide the medication to the research subject

25. Study problem Relevance of the project Literature review Specific study objectives Research methods Selection of subjects and recruitment Data collection Intervention Statistical considerations What are the elements of sound study design?

26. Who is ultimately responsible for ensuring a research protocol has sound design and minimizes risks to subjects? • IRB • R&D Committee • Principal Investigator • Research Coordinator • Hospital Director

27. Which of these educational programs and activities are required to conduct research at the VA? What educational programs and activities are available to investigators and their study staff? • On line CITI course in the Protection of Human Research Subjects • Monthly research Training Seminars • IRB Forums • UTHSCSA Course in “Conducting Clinical Research” • STVHCS Investigator Handbook • Individualized Training

28. Monitoring of compliance with human subjects research regulations is conducted by who at the STVHCS? • STVHCS Compliance Office • UTHSCSA Compliance Office • At the request of the IRB • R&D Committee • Through the QI/QA subcommittee • Sponsor of the study • STVHCS Compliance Executive Board • STVHCS Compliance Office reports to this committee

29. UTHSCSA IRB STVHCS R&D Office Research non-compliance or alleged improprieties may be identified through self-reporting by the PI or by other members of the study team. To whom should research non-compliance be reported?

30. How should subject complaints be handled and reported? • Gather information related to the complaint • Evaluate the complaint on a case-by-case basis • Make an effort to correct at the administrative level • Forward complaint to R&D office when • Corrective action can not be implemented at the study staff / PI level • If an ethical conflict exists with review by study staff/ PI • If complaint is an alleged impropriety which involves potential harm to subjects or others • R&D Chairman and IRB Director must be notified • Notification may be through the R&D office

31. What happens when you fail to submit the continuing review paperwork for an approved protocol by the deadline? • Research protocol expires • All research activity must cease • Except for those activities required for patient safety reasons • Exception to continue for safety reasons must be approved by the IRB Director and the VA Chief of Staff • Research activities may resume when all paperwork for continuing review is received, reviewed, and approved

32. Who has the authority to suspend or terminate a research protocol? • STVHCS Director • R&D Committee • IRB • ACOS for Research

33. What are the requirements for financial disclosure before or during the conduct of human research proposals? • COI form must be completed for each study personnel • COI form must be updated at the time of any change • As part of the continuing review process, each PI must verify for ALL collaborators (all study personnel approved for a protocol) • Either no COI changes have occurred • All changes have been provided to the R&D office

34. Preserves the public trust in the integrity and quality of research carried out by the investigators at the STVHCS What is the importance of disclosing financial conflicts of interest in the conduct of human research?

35. What is the difference between privacy and confidentiality? • Privacy • Control over the extent, timing and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others • Confidentiality • Pertains to the treatment of information that an individual has disclosed in a relationship of trust and with the exception that it will not be divulged to others in ways that are inconsistent with the understanding of the original disclosure without permission

36. To eliminate an immediate hazard for enrolled subjects This includes calling subjects to let them know about a new risk to determine if they want to continue, halt or not start enrollment until new consent form is approved When can you implement a change in your study without having IRB approval?

37. How are other providers within the STVHCS notified regarding study related enrollment and events for a veteran subject ? • Informed consent and enrollment are documented in CPRS through a “Research Consent/Enrollment Note” • Informed consent updates and addendums are documented in CPRS through a “Research Consent/Update Note” • Research procedures, treatments, or interventions that may impact a patient’s clinical care are documented in CPRS through a “Research Progress Note” • All informed consents and drug information records are scanned into CPRS • Disenrollment or termination is documented in CPRS through a “Research Disenrollment/ Termination Note” • Use of the note templates ensures CPRS is flagged to indicate when the participant is either enrolled or disenrolled in a research study

38. What approaches for subject recruitment may be utilized at the VA? • IRB-approved mechanisms • Physician referral • Posting of IRB-approved advertisements • “Preparatory to Research” by HIPAA Privacy Rule • VA guidelines are more restrictive • 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” and requires IRB and R&D approval

39. Advertisements should include: The name and address of investigator and/or research facility The condition under study and/or purpose of the study A summary of the criteria used to determine eligibility A brief list of participation benefits, if any The amount of time or other commitment required of subjects The location of the research A person or office to contact for further information Advertisements should not include: Claims that the test article is safe or effective for the purpose of the investigation Claims that the test article is known to be equivalent or superior to any other drug Terms which imply the receipt of newly improved products of proven worth such as “new treatment”, “new medication”, or “new drug”. The advertisement must explain that the drug or device is investigational. Promises of free medical treatment when intent is only to state that subjects will not be charged for taking part in the investigation Emphasis of payment for participation What are the requirements for recruitment ads for research protocols?

40. Sponsor provided bonuses for subject recruitment Prohibited by UTHSCSA and STVHCS Finder’s fees Prohibited UTHSCSA and STVHCS What incentives are allowed that assist in recruiting patients into studies?

41. What is the difference between a data safety and monitoring plan and a data safety monitoring board? Local PI Responsibilities

42. Local PI Responsibility • DSMB • Limited to collecting information and forwarding to DSMB for analysis • Implementing local actions based on DSMB analysis if needed • Studies which include an established DSMB by an external entity still require a local DSMP • DSMP • Capturing and collecting data • Monitoring collected data • Interpretation and analysis of collected data • Reporting results of analysis • Implementing actions based on analysis if needed

43. Studies Which Require a DSMP • All studies considered to be more than minimal risk • Involve high risk populations and/or high risk therapies • Multi-site research where UTHSCSA is the coordinating site • Studies where there is an NIH or FDA requirement for a plan • Studies when requested by the IRB

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