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1. Navigating the IRB
2. IRB: An Alternate Reality?
3. Research Wheel of Fortune
4. Learning Objectives Describe the role of the IRB in clinical research
Describe some principles of ethical human search
Discuss how to work with your IRB
Discuss the differences between clinical research and clinical care
5. Take Home Points Research with human subjects is not easy; it is complicated
IRB is PRO-research�intended to help, not hinder
IRB staff are highly skilled and knowledgeable and service oriented
6. Start at the beginning�training CITI Training
CITI = Collaborative Instructional Training Initiative
Web-based training for investigators
Subject protection
Link at IRB website
Registration is trickiest part
7. Role of the IRB is to:
Protect research participants by reviewing human subject research from the standpoint of its ethical conduct
8. Why do IRBs exist? Public (dis)trust�is the bottom line
9. Why wouldn�t the public trust clinical researchers?
10. M.H. Pappworth �No physician is justified in placing science or the public welfare first and his obligation to the individual, who is his patient or subject, second. No doctor, however great his capacity or original his ideas, has the right to choose martyrs for science or for the general good.�
Pappworth M.H. Human Guinea Pigs: Experimentation on Man; Boston: Beacon Press, 1967; pg. 27
11. Resources for Protecting Human Subjects Ethical Codes
Nuremberg Code
Declaration of Helsinki
Belmont Report
Federal Regulations
Regarding Informed Consent
Regarding IRB�s
IRB Standard Operating Procedures
Internal policies governing how your IRB does business
12. Ethical Principles in Belmont Report Respect for Persons
Informed consent, privacy and confidentiality, special protections for vulnerable populations
Beneficence
Do good; do no harm
Minimize risks, balance risks and benefits
Justice
Select research participants equitably
Share the risk; share the benefit
13. Where do the regulations come from?The Government of the United States I am a visual learner- so it is very helpful for me, and I hope for you, to see how these agencies fit together by looking a couple org charts.
Here we have DHHS listed under the Executive Branch of our federal government I am a visual learner- so it is very helpful for me, and I hope for you, to see how these agencies fit together by looking a couple org charts.
Here we have DHHS listed under the Executive Branch of our federal government
14. Department of Health & Human Services Under DHHS you will find the Inspector General, the NIH and the FDA. The FDA regulations include 21CFR50 and 56. You will also find OCR- which has the HIPAA regulations- 21CFR 160 and 164. Under the Assistant Secretary for Health you will find the Office of Public Health Sciences and under them you will find OHRP . The OHRP regulation we deal with most is 45CFR46 which is also known as the common rule. Believe me, it took us HOURS and HOURS of internet searching trying to figure all this out. You would think the fed gov website would have this org chart, but it does not exist. . I finally called someone I knew at OHRP and waived the white flag-Under DHHS you will find the Inspector General, the NIH and the FDA. The FDA regulations include 21CFR50 and 56. You will also find OCR- which has the HIPAA regulations- 21CFR 160 and 164. Under the Assistant Secretary for Health you will find the Office of Public Health Sciences and under them you will find OHRP . The OHRP regulation we deal with most is 45CFR46 which is also known as the common rule. Believe me, it took us HOURS and HOURS of internet searching trying to figure all this out. You would think the fed gov website would have this org chart, but it does not exist. . I finally called someone I knew at OHRP and waived the white flag-
15. DHHS Regulations: OHRP
45 CFR 46, Subpart A: Adopted in 1981
Became known as Common Rule in 1991
Subpart B- Protections pertaining to research, development, and related activities involving fetuses, pregnant women and human in vitro fertilization
Subpart C- Protections pertaining to biomedical and behavioral research involving prisoners as subjects
Subpart D- Protections for children involved as subjects in research
16. Food & Drug Administration Separate regulations
21 CFR 56 � IRBs
21 CFR 50 � Informed consent
Based primarily on use of FDA regulated products: drugs, devices, or biologics
17. FDA & DHHS Regulations Basic requirements for IRBs and for Informed Consent are similar
Differences in applicability
DHHS based on federal funding
FDA regulations based on FDA-regulated products ( study involves a drug, device or biologic)
18. Ethics versus Regulations Both intend to protect human subjects
Belmont report does not mention how human subjects are to be protected
Federal regulations scarcely mention ethics nor the function of ethics in protecting human subjects
IRBs must �put a hand in each glove�
19. Distinction between clinical practice & clinical research Clinical practice, defined:
interventions that are designed solely to enhance the well-being of an individual patient and that have a reasonable expectation of success
Clinical research, defined:
activity designed to test a hypothesis, permit conclusions to be drawn, and thereby develop or contribute to generalizable knowledge; usually described in a formal protocol that sets forth an objective and a set of procedures
20. The blurred line� Confusion between research and care
Distribution of possible risks & benefits is different in research versus therapy
Therapeutic misconception
Misunderstanding by patients that they will benefit, even after informed consent
Blurred roles of physician and researcher
Potentially conflicting role is difficult for patients to understand
21. Basic Protections for Subjects in Human Research Institutional Assurances
IRB Review
Informed Consent
22. What is an institutional assurance?
Called an FWA ( Federal Wide Assurance)
The documentation of an institutional commitment to comply with Federal regulations and maintain adequate programs and procedures for the protection of human subjects
The principle mechanism for compliance oversight by OHRP
23. What is an institutional review board? Committee established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated
24. IRB Review The IRB reviews and has authority to approve, require modification in, or disapprove all research activities, including proposed changes in previously approved human research
25. IRB Continuing Review Conducts continuing review of approved research at intervals appropriate to the degree of risk, but not less than once per year
Has authority to suspend or terminate previously approved research that is not being conducted in accordance with IRB requirements, or that has been associated with unexpected serious harm to subjects.
26. Requirements for approving human subjects research Risks to subjects are minimized
Risks to subjects balanced by anticipated benefits to subjects and/or society
Equitable selection of subjects
Informed consent appropriately obtained
Informed consent appropriately documented
Adequate procedures in place to monitor subject safety
Adequate procedures in place to protect privacy and confidentiality
Per federal regulations 45 CFR Part 46.111 (DHHS) and 21 CFR Part 56.111 (FDA)
27. Informed Consent Unless authorized by IRB, no investigator may involve a human being as a subject in research unless the investigator has obtained the legally effective informed consent of the subject or the subject�s legally authorized representative
28. It�s NOT just the IRB!!! Human subject protections must span beyond the work of the IRB:
The the approved protocol provides the �skeleton�
Ethical decision making process
Consent forms vs informed consent
Conflicts of Interest
Financial interests and arrangements
Professional (publications; promotion; stature)
Vulnerable Populations
29. IRB protocol review categories Exempt review: for clinical research, mostly involves no-risk research
Expedited review: minimal risk research
Waiver of consent: usually associated with expedited review
Full committee review: reserved for research that poses more than minimal risk to subjects
30. Required protocol pre-review REQUIRED for protocols, both full board and expedited
Email an electronic copy (no signatures) of protocol/consent
Email full board forms to Eileen Sembrowich (ecs3b@virginia.edu, 3-6542)
Email expedited protocols to Blaise Spinelli (rjs4c@virginia.edu, 4-2546)
Five-day turn around, forms emailed back with comments tracked
You can then accept changes, get signatures, etc
Time management is the key to this!
Full board protocols: keep in mind any sponsor requirements/deadlines, full board deadline days
31. In addition to IRB full board review� If applicable to your research, you might need approvals from other committees
Protocol Review Committee (PRC)
General Clinical Research Center (GCRC)
Radiation Safety Committee (RSC)
Institutional Biosafety Committee (IBC)
Materials Support Services (Device Studies)
SOM Clinical Trials Office (Physician sponsored IND or IDE or physician-sponsored multi-site trials)
Contact information found in Protocol Builder
32. Review by IRB-HSR Full Board
33. What do IRB-HSR full board members do? Review purpose of study
Methods involved
Therapeutic or not
Recruitment strategies
Requests for waiver of consent
Data safety and monitoring plans/boards
Involvement of minors and other vulnerable populations
Use of investigational drugs or devices
Discussion of PI�s protocol and consent form content
Methods of data analysis
Risk benefit analysis
HIPAA Privacy board
34. Process
Five possible review outcomes:
Approved
Approved Pending Minor Modifications
Withheld Approval Pending Major Modifications
Tabled
Rejected
Timeframe from submission to comments back takes about two weeks Full board review
35. Advertisements
Modifications
Continuing review
Adverse event reporting
Protocol/grant closure
Life after IRB approval�
36. IRB-HSR Submission Process IRB-HSR website
http://www.virginia.edu/vpr/irb
IRB Online and Protocol Builder
First time using Protocol Builder or just need help?
Please contact Karen Mimms, IRB Associate Director, kcm6t@virginia.edu (3-9847) or Margaret Ball, IRB Coordinator, at mnw2h@virginia.edu (3-0639)
37. Take Home Points Research with human subjects is not easy; it is complicated
IRB is PRO-research�intended to help, not hinder
IRB staff are highly skilled and knowledgeable and service oriented
38. IRB versus the Institution? ��the IRB is an agent of its own institution; its purpose is to uphold the value system of the institution. Respect for persons, beneficence, and justice are (or should be) principles that your institution values greatly and not just because they were once published in the The Federal Register.�
39. Time for discussion �Everything should be made as simple as possible, but not one bit simpler.�
-Albert Einstein
�USA Today has come out with a new survey � apparently, three out of every four people make up 75% of the population.�
-David Letterman
40. Let�s go to the website(s)�time allowing UVA Office of the Vice President for Research, Institutional Review Boards
http://www.virginia.edu/vpr/irb
UVA IRB-HSR
http://www.virginia.edu/vpr/irb/hsr/index.html
IRB Online
http://www.irb.virginia.edu/