the institutional review board · – “an experiment is ethical or not at its inception. it...

The Institutional Review Board

Clifford J. Gunthel, MD, Emory IRBCo-Chair

Spring 2020

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1. IRB: structure, function, and history2. Nuts and bolts3. Submitting an application4. Pitfalls and solutions5. Reportable events6. Online resources

Outline

Modern Landmarks in Ethical Research

• Nuremburg Code 1947 – required informed consent• Henry Beecher 1966 NEJM article:

– The physicians thought they were right – but weren’t in hindsight. “Science is not the highest value to which all other orders of values… should be subordinated” (Pope Pius IV, cited in Beecher)

– “Consent in any fully informed sense may not be obtainable. Nevertheless… it remains a goal toward which one must strive… There is no choice in the matter.”

– “An experiment is ethical or not at its inception. It cannot become ethical post-hoc – ends do not justify means.”

• 1971-1991: Tuskegee surfaces, Belmont Report’s Three Principles, national atonement for studies gone wrong. Led to IRB model for one-site studies, federal regulations

• 1990s – 2000s: Rise of multi-site studies, transnational research, shut-downs; more studies gone wrong

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Belmont Report Principles

Respect for personsInformed, comprehending consent assuming rational

autonomy; safeguards for those with limited autonomy

BeneficenceMinimize risk, maximize benefit

JusticeEnsure fairness of subject selection, balancing of burdens

and benefits

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• US DHHS Title 45 CFR 46 Subparts A-D• Subpart A, Common rule• Rule of ethics all government-funded human

subjects research must abide by• Main elements:

– Informed consent– IRB review

Common Rule, 1981 and 2019!

• US DHHS Title 21 CFR 50 (consent) and 56 (IRBs)

• Rules required for FDA-regulated clinical investigations

• Definitions and applicability differ from Common Rule (e.g. even deidentified specimens are “human subjects”; fewer waivers of consent, no exemption categories, no Subparts for vulnerable populations)

• Also Parts 312-14 (drugs) and 812-14 (devices)

FDA, 1978-81

• Institutional Review Board• Facilitates ethical human subjects research• Biomedical: 5 panels, meets monthly• Sociobehavioral: 1 panel, meets PRN• Adverse event/noncompliance panel: meets

monthly• ~110 members• ~20 full-time staff

Emory IRB structure and function

Co-Chairs

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Cliff is Associate Professor of Infectious Disease at SoM and chairs Committee B1.

Aryeh is Professor of Global Health at RSPH and chairs Committee Q (compliance).

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Jill Perry-Smith, VC of Socio-behavioral Cmte

Larry Tune, MDComedian, Psychiatrist,

Biomed VC

Carlton Dampier, MDHem/Onc, Biomed VC

Amy Langston, MDHem/Onc, Biomed VC

Ann Haight, MDHem/Onc Peds, Biomed VC

Where the IRB fits intoResearch Administration…

What is the Emory IRB?

New SVP of Research

“As senior vice president for research Bruner will partner with other research leaders across Emory to identify and facilitate interdisciplinary research, including breaking down institutional and cultural barriers to encourage opportunities for collaboration through academic activities that reach across schools, colleges, centers and institutes.”

Tools for Navigating…

Nuts and bolts of IRB review

• Levels of IRB review• What is “research”?• What is a “human subject”?

Not everything needs IRB review!

Use automated tool at http://irb.emory.edu/forms/review/request.html

• DHHS: Systematic investigation designed to develop or contribute to generalizable knowledgeRevised Common Rule contains examples of what is not

research, e.g. journalism, public health surveillance

• FDA: any experiment in which a drug, biologic, or significant risk device is administered or dispensed for use involving human subject(s)

• Non-research: describes a local phenomenon, or benefits a local sample alone

• Publication is not part of defining research

What is “research”?

Research or Not?Generalizable knowledge: is information gathered to

draw general conclusions beyond the study population. Intention of extrapolating from the chosen sample to generate knowledge about a larger reference group.

Non-Research projects: gather information about a chosen sample to describe a local phenomenon, or draw conclusions that are intended to be used for the benefit of that local sample alone.

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“Research” or Not?

Not “Research” might be…

• Trying a new way to improve Emory medical education• Implementing a new best practice to see if it improves

quality of care, or evaluating an existing clinical program at Emory

• <6 case reports• Study of nurse and doctor behavior to formulate new

communication tools• State-wide surveillance of infectious disease and

outcomes• But… it always depends.

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Research (45 CFR Section 46.102(d)): a systematic investigation designed to develop or contribute to generalizable knowledge.

PublishingI want to publish, so it’s research, right?

• Common misconception

• One can publish works that meet - or do not meet - the IRB definition of “research.”

• Publishing is simply sharing information with an external audience.

• The Emory IRB can give you email or letter with determination, for publishers.

• If not research, publication should not attempt to generalize conclusions. Should report on what you did and how well it worked –“you’re mileage may vary.”

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Quality Improvement/Assurance and Program Evaluation

If the goal/intent is:• to assess the success of a program, • to improve the performance of an institutional practice in

relation to an established standard, or • to improve the health outcomes of patients; Or if the primary intent is:

• to improve a local system of care or • To promote “betterment” of a process of care, clinical

outcome, etc.

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Then

• it is not “Research” for IRB purposes.

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• DHHS:– Living Homo sapien– Investigator obtains data through

intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens OR

– Investigator obtains identifiable private information or biospecimens

• FDA: an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient (or a sample with no identifiers…).

What is a “human subject”?

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“Human Subjects” or Not?

• Analysis of previously collected, de-identified (per HIPAA definition) specimens(Note: at present, Emory IRB considers genetic samples to be capable of de-identification.)

• Would this be “human subjects”?

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“Human Subjects” or Not?

• No. Not identifiable.

• What if you were testing a new in-vitro diagnostic device on the samples?

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“Human Subjects” or Not?

• YES. FDA treats the deidentified samples as “human subjects” in a “clinical investigation” (though consent may be waived in certain circumstances)

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Levels of IRB reviewType of Review When? How? Examples # active

protocols

Full More than minimal risk Full board Clinical Trial;biopsies; radiation

~1700

Expedited Minimal risk, falls into “expedited categories”

Single Reviewer Chart review, noninvasive tests, blood draw

~2100

Exempt (fromfull review)

Very low risk, falls into “exempt categories” -confidentiality protections in place or anonymous/not sensitive data

IRB analyst review/Limited IRB Review Surveys, medical education (no peds)

--

Not human subjects research

Not human subjects,Not research

IRB web toolhttp://irb.emory.edu/forms/review/request.html

QI projects,Previouslyanonymized

--

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Review Outcomes

• Approved • Approved pending minor modifications• Deferred to another meeting (full board only)

– Major issues, or missing information Disapproved (very rare) – must be done by full board Tabled (lack of quorum, immature application)

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The Carrot

• Compliant research• Assurance that all applicable

regulations are followed• Avoid research participant

misunderstanding

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The Stick

• The IRB may:– Suspend enrollment– Suspend approval of a study– Terminate a study– Bar an investigator from conducting HSR or certain

kinds of HSR (e.g., more than minimal risk)

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Meeting schedulesAnalyst phone #s

New submission guidance and

templates

Enter eIRB

• Protocol guidelines – new versions must be used with upgrade– Biomedical – Sociobehavioral– Retrospective chart review– Secondary data analysis– Registries/Repositories

• Advertising and recruiting• Genetics research guidance• Identifiers examples• Online survey providers• Questionnaires, rating scales, interviews• DSMP / DSMB guidance• Modular consent language• Combined clinical consent / HIPAA templates

Resources www.irb.emory.eduForms & Guidance, New submissions

1. Research protocols and Lay Summary– Follow IRB templates http://irb.emory.edu/forms/new.html– DO NOT submit grant applications as protocol

2. Consent form language– Follow IRB templates– Plain language – 8th grade level, short sentences

3. Ancillary reviews– OSP/OTT (grants/contracts) and OCR (office of clinical

research) – IRB may need consent info from them4. Release of grant funds

– Office of Sponsored Programs (OSP; grants office) must have IRB approval of the actual grant in order to release funds

• Genomic Data Sharing Plans– Need prospective IRB approval for NIH

Pitfalls and Solutions

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Hot Topics At Emory• Site monitoring – for investigator-initiated studies

• Amendments to add new funding/projects

• Data and Safety Monitoring Plans – cannot pass “Go” without one, for more-than-minimal risk studies

• PI responsibilities – assessing safety events, ensuring adequate training and qualifications of staff, not being over-extended

• Don’t underestimate the amount of record-keeping needed

• Use of internet for research

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• Reporting guidelines• http://irb.emory.edu/forms/reportable.html

Reportable eventsInternal deaths considered unrelated At Continuing Review

Internal related events (not UP) At Continuing Review

External SAEs that are not UPs Never

External deaths not related or UPs Never

Internal deaths considered unrelated At Continuing Review

Internal related events (not UP) At Continuing Review

External SAEs that are not UPs Never

Internal deaths considered related Promptly

Internal deaths considered unrelated At Continuing Review

Internal related events (not UP) At Continuing Review

External deaths not related or UPs Never

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• Get to know your IRB staff. They are here to help you.

• Start early. Avg 1-2mo to get IRB approved

• Use Emory IRB templates and guidelines

Happy researching!

Take home points

Why we all do this…

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Community trust in research

Willing subjects

Continued funding

• IRB@emory.edu for general inquiries• www.irb.emory.edu for info and eIRB entry• 404-712-0720• 1599 Clifton Road, 5th floor• IRB Director: Rebecca Rousselle, CIP

rrouss2@emory.edu• Hitchhiker’s guide to navigating mandatory

research compliances and approvals at Emory http://medicine.emory.edu/research/internal-research-resources/hitchhikers-guide/index.html

Key information

Questions

Menu of Other Topics

• More Consent Form Tips• Chart Review Do’s and Don’t’s• Registries and repositories• Using the Short Form to consent non-English

speakers• Required Trainings, Office of Quality Checklist• Research on Dietary Supplements• What to do when a subject wants to withdraw*• Research using the internet*

* No slides, just discussion

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Chart Review Do’s

• Be clear as to the date range– Retrospective = all data exist as of IRB initial

submission. Otherwise, it’s prospective.

• If prospective, or very small number of subjects, justify clearly why consent would be impracticable.

• Include maximum number of charts –exceeding that is technically a HIPAA violation

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Registries and repositories• Registries, databases set up for research purposes do, by

default, require prospective informed consent and IRB approval

• When the primary use is clinical practice, data could all be found in clinic/medical record, and no additional data is gathered with a research question in mind, may not need IRB approval or consent. Retrospective research on these data may be possible, similar to a chart review, with waiver of consent and HIPAA authorization.

• Best to consult the IRB early on… • If for research, need to set out policies and scope for future

research use and sharing

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Training and Checklist Requirements

• CITI biomed or behavioral (sole IRB requirement)

• Clinical trials investigators and their residents/fellows acting as coordinators:

“Key Concepts” course through ELMS/OCRhttp://www.ocr.emory.edu/training/courses/index.html

• Clinical research at Emory Healthcare sites:Office of Quality Checklist

http://www.irb.emory.edu/forms/clinical.html

Neither would apply to chart reviews or non-clinical studies

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SHORT FORM FOR ENROLLING NON-ENGLISH SPEAKERS

Do’s and Don’t’s

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Do Use Short Form When…• The participant* does not speak/understand English;

and• You weren’t anticipating people of this language

group to be common in the study population; and• A full translated consent form in that language has

not been approved by the IRB; and• There is not enough time for to get a full translated

consent written and IRB-approved

* or LAR

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The short form IS NOT intended for studies in which it is expected that study recruitment will include a

large number of persons who do not speak English.

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How to Enroll via Short Form

• Get IRB approval of translated short form*• Have English full consent form orally translated• Get attestation of translator’s qualifications• Have a witness to the oral presentation (can be the

translator), and have that witness sign short form and English consent

• Have subject sign the short form only• Make sure to note the participant’s choices if there

are optional aspects to the study* may be changing soon

STUDIES OF VITAMINS AND SUPPLEMENTS

Do’s and Don’t’s

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When are Dietary Supplements Treated as Drugs?

• If the dietary supplement is claimed to be for use in the diagnosis, cure, mitigation, treatment or prevention of a disease and its’ associated symptoms, then the dietary supplement is considered to be a drug.

• Dietary supplements that claim only to affect the structure or function of the body of humans or animals are NOT considered drugs.

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Do Clinical Investigations of Dietary Supplement Require an IND?

• NO IND REQUIRED IF lawfully marketed dietary supplement is studied for how it affects the structure or function of the body.

• AN IND IS REQUIRED IF the dietary supplement is being studied for whether it cures, treats, mitigates, prevents or diagnoses a disease or associated symptoms.

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MORE CONSENT GUIDANCEDo’s and Don’t’s

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Keep Your Sentences Short and Simple.

• Say one thing per sentence and say it plainly.

• Your participation in the main study will not be affected in any way if you chose to not allow your left-over samples to be used for research not specified in this protocol. – 14.8 grade level, unclear language, excessive use of the word “not.

• You may continue to be in the main study even if you do not agree to future use of your samples. – 8.3 grade level, one clear point.

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Keep Your Words Small

• Use words and phrases found in common conversations, not legal documents.

• About vs. Approximately• Take part/Be in vs. Participate• End vs. Terminate• Do vs. Perform• Get or Have vs. Receive (a treatment)

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Other Tips

• Bulleted Lists are your friends, particularly in Risks/Side Effects sections.

• Use initials instead of check-marks, especially for opt-in sections for future use of tissue for research.

• Older patients (and IRB members) appreciate larger fonts.

• Use the current templates. We’re always updating and improving them!

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Paragraphs

• Keep paragraphs short• One idea per paragraph• Keep section headings simple

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