protection of research participants: the irb process—current overview and future directions ethics...
TRANSCRIPT
Protection of Research Participants: The IRB Process—Current Overview
and Future Directions
Ethics in Patient-Oriented Research October 17, 2012
Sharon FriendDirector, OHRPP
IRB Charge and Function
3
Human Research Is…
any research or clinical investigation that involves people or identifiable data from people.
4
UCLA’s Institutional Review Board (IRB)
An independent internal review committee that reviews and approves human research
Composed of UCLA faculty with relevant expertise, at least one nonscientific member, and at least one nonaffiliated member
Reviews proposed research involving human subjects conducted by UCLA faculty and students regardless of funding source and usually regardless of site
Based on federal criteria, IRB has the authority to approve, require changes or disapprove human research.
5
What is the mission and charge of UCLA IRBs?
Support and facilitate the conduct of human research at UCLA by
Ensuring ethical principles are applied to the conduct of human research;
Assuring federal criteria for approval of human subjects research and institutional policies are met; and
Promoting and facilitating the protection of the rights and welfare of human subjects in research.
6
What do both IRB and PI need to consider in applying the
ethical principles? Beneficence (Be nice!) – Design studies to
Minimize risk to the extent possible Maximize benefit (both individual and societal)
Respect for Persons (Be respectful!) Obtain informed consent before involving participants
(or using private identifiable information) in research Assure confidentiality provisions are in place.
Justice (Be fair!) Select participants who are likely to benefit from
research participation Do not systematically include or exclude participants
for convenience.
7
What Are the Primary Federal Criteria for IRB
Approval?
Risks to participants are minimized by using procedures consistent with sound research design and which do not unnecessarily expose participants to risk.
Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result.
What Training Does IRB Require?
At UCLA, and most academic sites throughout USA: on-line CITI training Collaborative Institutional Training Initiative.
Required every three years at UCLA for IRB approval.
Plenty of additional training available (in addition to, not instead of CITI) and may be required by departments and programs
8
Tips for Preparing an Excellent IRB Submission
10
Tip #1: Determine if Science is Sound
Sound Scientific Basis and Rationale:
Is the protocol scientifically sound and based on well-established scientific principles?
Is there convincing clinical and/or preclinical evidence that the trial will have valuable results?
Do preclinical studies demonstrate promising results regarding safety and potential efficacy?
11
Science continued…
Is proposed study design appropriate? Are the primary and secondary objectives sound? Is the study designed to meet objectives? Does the protocol distinguish between standard and/or routine care
and research? Are patient populations and associated criteria for
inclusion/exclusion well defined? Is the statistical design appropriate? Are the endpoints clearly defined?
Are study personnel qualified?Are there sufficient resources to conduct the study?
Science continued…
Preferably, scientific review, by a group of peers, occurs before submitting a full committee application to the IRB. If it does not occur beforehand,
the UCLA IRB will conduct the scientific review.
Cancer Center ISPRC provides scientific review.
12
13
Tip #2: Determine if IRB Review is
RequiredIs the project research? DHHS regulations define human research as a
systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
FDA regulations define a clinical investigation as any experiment that involves a test article and one or more human subjects…the results of which are intended to be…submitted to…the FDA.
14
Does the research involve human subjects?
DHHS: a living individual about whom an investigator (faculty or student) conducting research obtains data Through an intervention or interaction with the
individual, or
Access to identifiable, private information.
FDA: an individual who becomes a participant in research, either as a recipient of the test article or as a control
15
What is not Human Research?
The following are types of studies that may not be considered human research at UCLA:
Analysis of data or specimens that do not include private health or personally identifying information (PHI or PII)
Studies using public data sets 3 or fewer individual case studies Quality improvement/assurance activities
How Do You Confirm?
Use short questionnaire in webIRB Check UCLA OHRPP Guidance and decision
trees: (http://ohrpp.research.ucla.edu/pages/policies-guidance#4):
Determining Which Activities Require UCLA OHRPP/IRB Review
Determining When Collection or Use of Data and Specimens for Research Requires IRB Review
Call the OHRPP.
16
17
When Is IRB Review Required?
All human subjects research requires prior IRB review and approval before initiation (New Studies)
All modifications or changes made to an IRB-approved study require IRB approval prior to initiation (Amendments)
All continuation of an IRB-approved study beyond its approval period (usually one year) requires IRB approval (Continuing Review)
18
Tip #3: Assess Risk and Determine Level of Review
Identify risks associated with the research: How are risks different than those risks the subject
would encounter if not participating in the research?
Consider the subject population: Are the research participants particularly sensitive or
vulnerable to the risks posed by the research?
Do the risk(s) meet the federal definition of minimal risk?
Does research fit into an expedited category of review or does it require full committee review?
19
Regulatory Definition of Minimal Risk
“Minimal risk” means that 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
of the general population or during the performance of routine physical or
psychological examinations or tests.
20
Which potential risks need to be considered for all levels of
IRB review? Loss of Confidentiality
Has to do with issues surrounding data Data security needs to established and described—
seek IT help if needed Primary source of complaints to IRBs (beyond “Why
didn’t I get paid on time?”)
Loss of Privacy Has to do with personal privacy Important in recruitment and screening as well as
clinical practice
21
What are the levels of IRB Review?
Three levels of IRB Review, depending on level of risk:
Full Committee for more than minimal risk
Expedited review for minimal risk studies
Exempt certification for studies that fall into one of six federal categories
22
Expedited Research
No more than minimal risk to subjects
“Expedited” protocols are reviewed by an IRB subcommittee
Seven federally-defined categories
Informed consent or waiver of consent or waiver of signed consent with appropriate justification required
23
Full Committee Research
Greater than minimal risk to subjects
Full committee protocols are reviewed at a convened IRB meeting
Informed consent required in almost all cases
Includes most clinical trials: studies involving non FDA-approved drugs and devices or medical interventions
24
Examples of Expedited or Full Committee Research or Research
Not Requiring IRB Review
Randomized double-blind study for the safety and efficacy of investigational drug XYZ
Review of medical records of patients in hospital from 1990 to present to study correlation of Alzheimer’s and heart disease
Randomized study to compare two approved treatment regimens for cervical cancer
Comparison of psychotherapy vs medication for the treatment of depression
25
Examples continued
Study of elder abuse among caregivers
Skin samples collected via punch biopsy for SCNT (somatic cell nuclear transfer) study
Skin samples sent from UCSF with or without PHI (private health information)
Collection of saliva samples from people who developed a cold and cough within the last 48 hours to study the genes related to asthma
26
Tip #4: Allow Sufficient Time for IRB Process
From time of complete submission to time of full IRB approval:
Full Committee: ~ 4 to 8 weeksExpedited:
No Subject Contact ~ 2 weeks Subject Contact ~ 4 weeks
Continuations: Expedited < two weeks Full Committee ~4 weeks
27
What are the Special Issues for Industry-Sponsored Clinical
Trials?
Need to coordinate IRB approval and contract Sponsor pays IRB Review Fees Consent form needs to be revised to
Use UCLA standard requirements for indemnification and ownership of tissue
Be in lay language and not overly legal
Data Safety Monitoring Boards usually required IRB does not typically require a major change in
the science and expect the company to revise the protocol—review is either thumbs up or thumbs down
Tip #5: Apply for via webIRB On-Line Application
Web-based system for IRB submission, review and trackingAll levels of review use the same webIRB application with branching based on responses to questionsHelp text and links within applicationUploads of supporting materials requiredTraining available
28
#6: Understand the IRB Review Process
Administrative pre-review by staff to check for completeness
IRB review (UCLA does not ask researchers to be present unless study may be disapproved)
Post Review communication of IRB actions via webIRB, including Approval Accepted pending modification Deferral Disapproval
29
30
UCLA IRB Review Process
Triage byReview LevelReview Type
Full Committee Pre-Review
Expedited Pre-Review
Back to the PI for
Changes
To the Committee for Review
Back to the PI for
Changes
Correspondence Approval!
To the Chair or Delegate for Review
Correspondence Approval!
31
#7: Use UCLA Consent Templates and Refer to
Standards
Minimal Risk Consent Templates More than Minimal Risks Consent
Templates Child and Adolescent Assent Templates Addendum Consent Templates Screening Templates Consent Standards and Sample Language
32
#8: Ask for Help; Use On-OHRPP References
Ask for help within department Check with OHRPP--Medical IRBs
Telephone: (310) 825-5344E-mail: [email protected]
Contact webIRB Help Desk310-267-1887 [email protected]
Refer to OHRPP Website: www.research.ucla.edu/ohrpp
Sign up for Human Research News
33
Bonus Tips!
Grouping Studies Do not group related full committee studies
into a complicated application. Submit a separate application for each study or phase of study.
Do group data analysis or retrospective chart reviews into one study when useful for your purposes.
34
Writing Musts
Consider the audience! Avoid acronyms and jargon in protocol and consent
documents Use lay language for recruitment and consent
documentsBe consistent! Within the application Make sure that study aims, methods, risks, benefits
and alternatives are consistent Between application and consent documents Between application and funding documents Use the same name for the study drugs throughout
the submission
35
Winds of Change
Use of IRB Agreements to Rely on Other IRBs
Increased Interest in Developing Informed Consent for• Use of Residual Tissue and• Use of Health Care Information
for Future Unspecified Research
"The Winds of Change are Coming....
What Is an IRB Reliance Agreement?
By mutual or collective written agreement, one or several IRBs agree to rely on the IRB review of one or several other IRBs.
The agreement is typically called an “MOU” (Memorandum of Understanding).
36Particle Accelerator in Switzerland
37
IRB MOUs
Outline responsibilities of PIs (Both Lead and Relying) Reviewing IRBs and Relying IRBs
Describe need for Registration for PI from relying institution
Do not provide implementation guidelines or procedures for each campus or institution
38
How a Reliance Agreement Works*
Reviewing IRB assumes full
responsibility as IRB of record
reviews entire study assures local issues are
identified and addressed coordinates
communication with all PIs
Relying IRB accepts determinations
made by Reviewing IRB in their entirety
has responsibility for ensuring that ancillary approvals (MRSC, COI, IBC) are in place
*NOTE: This is model commonly used by commercial IRBs
39
>Two CTSI’s Involved in IRB Reliance Agreements for UCLA Investigators
UCLA Cedars-Sinai Medical Center Charles Drew University of Medicine and Science LA Biomedical Institute at Harbor UCLA Medical Center UCLA
UC Medical Centers UC Davis UC Irvine UCLA UC San Diego UC San Francisco
How to Use the UC MOUs
General process is the same for both UC MOU and UCLA CTSI MOU but because UC process is web-based procedures are slightly different.
Review information on UCLA CTSI site for “CTSI IRB Reliance Review Process” at http://ctsi-vhome.ctrl.ucla.edu/research/pages/irb
Review information on “UC IRB Reliance Registry for Studies under the UC MOU” on UC Berkeley site at http://cphs.berkeley.edu/irbreliance.html
40
Other External IRBs Available to UCLA Researchers
See OHRPP website for details: The National Cancer Institute Central
IRB (NCI CIRB) for some oncology groups studies (submit through webIRB)
Western IRB Rand Rarely, others may approved on a case-
by-case basis
41
“Global Informed Consent”
Being developed at UCLA for UC medical centers for• Unspecified use of residual biological samples
and associated health care data• To be incorporated into a UCLA BioBank and• To be able to be transferred to other approved
scientific databases, i.e., NIH dGAP.
• Will include study of DNA, cell lines, and stem cells
42