Protection of Research Participants The IRB ProcessCurrent Overview

Protection of Research Participants: The IRB Process—Current Overview and Future Directions Ethics in Patient-Oriented Research October 17, 2012 Sharon Friend Director, OHRPP

IRB Charge and Function

Human Research Is… any research or clinical investigation that involves people or identifiable data from people. 3

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. 4

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. 5

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. 6

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. 7

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

Tip #1: Determine if Science is 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? 10

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? 11

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

Tip #2: Determine if IRB Review is Required Is 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. 13

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 14

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 15

How Do You Confirm? § Use short questionnaire in web. IRB § 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

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 IRBapproved 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) 17

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? 18

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. 19

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 20

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 21

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 signed consent with appropriate justification required 22

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 23

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 24

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 25

Tip #4: Allow Sufficient Time for IRB Process From time of complete submission to time of full IRB approval: Ø Full Committee: ~ 4 to 8 weeks Ø Expedited: § No Subject Contact ~ 2 weeks § Subject Contact ~ 4 weeks Ø Continuations: § Expedited < two weeks § Full Committee ~4 weeks 26

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 27

Tip #5: Apply for via web. IRB On-Line Application § Web-based system for IRB submission, review and tracking § All levels of review use the same web. IRB application with branching based on responses to questions § Help text and links within application § Uploads of supporting materials required § Training 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 web. IRB, including § § Approval Accepted pending modification Deferral Disapproval 29

UCLA IRB Review Process 30

#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 31

#8: Ask for Help; Use On-OHRPP References § Ask for help within department § Check with OHRPP--Medical IRBs Ø Telephone: (310) 825 -5344 Ø E-mail: MIRB@RESEARCH. UCLA. EDU § Contact web. IRB Help Desk Ø 310 -267 -1887 Ø web. IRBhelp@research. ucla. edu § Refer to OHRPP Website: www. research. ucla. edu/ohrpp § Sign up for Human Research News 32

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. 33

Writing Musts Consider the audience! § § Avoid acronyms and jargon in protocol and consent documents Use lay language for recruitment and consent documents Be 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 34

"The Winds of Change are Coming. . 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 35

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). Particle Accelerator in Switzerland 36

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 37

How a Reliance Agreement Works* Reviewing IRB Relying IRB § accepts determinations § assumes full responsibility as IRB of made by Reviewing IRB record in their entirety § reviews entire study § assures local issues are identified and § has responsibility for addressed ensuring that ancillary § coordinates approvals (MRSC, COI, communication with all IBC) are in place PIs *NOTE: This is model commonly used by commercial IRBs 38

>Two CTSI’s Involved in IRB Reliance Agreements for UCLA Investigators Ø UCLA § § Cedars-Sinai Medical Center Charles Drew University of Medicine and Science LA Biomedical Institute at Harbor UCLA Medical Center UCLA Ø UC Medical Centers § § § UC Davis UC Irvine UCLA UC San Diego UC San Francisco 39

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 web. IRB) § Western IRB § Rand § Rarely, others may approved on a caseby-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 Bio. Bank and • To be able to be transferred to other approved scientific databases, i. e. , NIH d. GAP. • Will include study of DNA, cell lines, and stem cells 42