Protection of Research Participants: The IRB Process

Ethics in Patient-Oriented Research October 16, 2013

Marcia Malmet, RN Manager, Quality Improvement

OHRPP

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Overview

Charge and Function of the IRB Quick Guide to IRB Process

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What is an Institutional Review Board (IRB)?

An independent internal review committee:

Composed of: institutional members (UCLA faculty) with relevant expertise and at least one nonaffiliated member and at least one nonscientific 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

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Mission and Charge of UCLA IRBs

IRBS: Ensure ethical principles are applied to the

conduct of research.

Assure federal criteria for approval of human subjects research and institutional policies are met.

Promote and facilitate the protection of the rights and welfare of human subjects in research.

Support and facilitate the conduct of human research.

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IRB and PI Considerations in Applying Ethical

Principles Beneficence (Be nice!) – Design studies to: Minimize risk to the extent possible and 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.

Quick Guide to IRB Process

For the Researcher

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Human Research Is…

any research or

clinical investigation that involves people or identifiable data from people.

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#1: 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.

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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

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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 or personally identifying information Studies using public data sets 3 or fewer individual case studies Quality improvement/assurance activities

Short questionnaire in webIRB 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

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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).

#2: Complete Training Required Courses

At UCLA, and most academic sites throughout USA: on-line CITI training (Collaborative Institutional Training Initiative)

Required every three years at UCLA

Additional optional training available

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Risk/Benefit Ratio

Risk: probability of physical, social, psychological, or economic harm as a result of participation in a research study.

Benefit: applies to the potential of the research treatment to improve a condition or treat a disease, but results cannot be guaranteed.

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Role of IRBS

Determine the risk versus benefit for clinical studies: Physical risk is not disproportionate to the benefits Physical risk is minimal they must determine that

psychological and social risks such as stigma are not important.

Not ethical to conduct a study in which and individual or a group is labeled so as to be stigmatized to be made less employable or insurable.

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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.

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#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 definition of minimal risk?

Does research fit into an exempt or expedited category of review or does it require full committee review?

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Potential Risks 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

practice

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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.

Exempt Categories Federally Exempt Categories: 1. Research conducted in established or commonly accepted educational settings involving normal educational practices 2. Research involving the use of educational tests: cognitive, diagnostic 3. Research involving the collection of study of existing data, documents 4. Research and demonstration projects which are conducted by or subject to the approval of federal government: examine public benefit or service programs. 5. Taste and food quality evaluation without additives.

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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.

Expedited Categories

Seven Federally Defined Categories: 1. Research on drugs for which an IND isn’t required

and/or research on medical devices for which an IDE isn’t required.

2. Collection of blood samples by finger stick, heal stick, ear stick or venipuncture from healthy, non-pregnant adults weighing at least 110 lbs.

3. Prospective collection of biological specimens for research purposes by non-invasive means: hair and nail clippings, external secretions.

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Expedited Categories

4. Collection of data through non-invasive procedures: EKG. 5. Research involving materials that have been collected, or will be collected solely for non research purposes: data, records, or specimens 6. Collection of data from voice, video, digital, or image recordings made for research purposes. 7. Research on individual or group characteristics or behavior: motivation.

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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.

Informed Consent Process

IRB reviews content of consents: assure investigators are obtaining legally

effective informed consent of each subject or their legally–authorized representative assure meets federal requirements for

human subjects research protection assure subjects are fully informed of research

procedures according to IRB approved protocol

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Effective Informed Consent Process

Conducting the process in a manner and location that ensures participant privacy

Giving adequate information about the study in language understandable to the participant

Providing adequate opportunity for the participant to consider all options

Responding to the participant’s questions Ensuring that the participant has comprehended the

information provided Obtaining the participant’s voluntary agreement to

participant and Continuing to provide information as the participant or

research requires.

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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.

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#4 Allow Sufficient Time for IRB Process

From time of complete submission to time of full IRB approval: Full Committee: ~ 4 to 8 weeks Expedited: No Subject Contact ~ 2 weeks Subject Contact ~ 4 weeks

Continuations: Expedited < two weeks Full Committee ~4 weeks

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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 cannot require a major change in the science and expect the company to revise the protocol

#5: Apply via webIRB On-Line Application

Web-based system for IRB submission, review and tracking.

All levels of review use the same webIRB application with branching based on responses to questions.

Help text and links within application. Uploads of supporting materials required.

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How does it support PIs and Research Staff?

Homepage with access to information on all studies

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How does it support PIs and Research Staff?

Track status of submissions

Receive feedback and approvals online

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Writing Musts

Consider the audience Not all IRB members are scientists Avoid acronyms 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 sponsor protocols or grants Use the same name for the study drugs throughout

the submission

#6: Understand the IRB Review Process

Administrative pre-review by staff to check for completeness IRB review (UCLA does not include

researchers present) Post Review communication of IRB

actions via webIRB, including Approval Accepted pending modification Deferral Disapproval

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#7: Understand Your Responsibilities

Obtain prospective IRB approval for

modifications.

Obtain IRB continuing review approval at least annually.

Submit post-approval reports of events that are unanticipated problems that may adversely affect the safety of participants.

Submit closure report.

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#8: Ask Questions; Refer to OHRPP Website

Medical IRBs Telephone: (310) 825-5344 E-mail: MIRB@RESEARCH.UCLA.EDU

webIRB Help Desk 310-267-1887 webIRBhelp@research.ucla.edu

OHRPP Website:

www.research.ucla.edu/ohrpp

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Tips!

Useful Tips: 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.