IRB Frequently Asked Questions (FAQs) and Submission Guidance

All submissions should be routed using the University-wide IRB system, AURA. Please log in to the IRB module in AURA through the AURA website: http://aura.uchicago.edu

Many new protocols require a full review, but if you believe your new research project qualifies for expedited review, please complete the Expedited Review section on the electronic submission form.

Alternatively, if you believe your study can be exempted from review, request "Exempt" review and fill out only those sections of the electronic submission form that appear in AURA. Please also upload any necessary documentation (e.g. a copy of the survey). The IRB office will then notify you if indeed your study qualifies as exempt or if you will need to complete the entire protocol submission form.

The IRB will make the final decision regarding level of review.

Incomplete submissions will not be reviewed until all necessary materials have been received regardless of the date the initial submission was received.

The BSD/UCMC IRBs require a protocol document to be submitted with all non-exempt new submissions. A sponsor protocol document used by multiple sites can be submitted, or, for a single-site study, the investigator should prepare a local protocol document. The protocol document, "protocol narrative," or "protocol" is submitted with the original submission of the protocol and revised versions, as necessary, with amendments. There is no required format, but the document must be sufficiently detailed to permit the IRB to evaluate the soundness of the procedures proposed and the potential risks and benefits to research subjects. The sample protocol narrative outline prepared by the IRB office demonstrates content that is generally requested by the IRB:

Protocol narrative outline

For non-interventional studies, such as chart reviews and specimen repositories, a sample template is also provided below:

Non Interventional Protocol Document

The OCR has templates for other protocol-related documents posted on the "Tools and Templates" page. 
 

The Biostatistics Clinic, part of the Biostatistics Laboratory in the Department of Public Health Sciences, offers free, short term statistical consultation. This might include discussion on protocol design, sample size calculations, or other assistance. For further information, please visit: https://health.uchicago.edu/research/biostatistics-laboratory .

Protected health information (“PHI”) is any information that might directly or indirectly identify an individual, including

• Physical or mental health information
• Past, present, or future information
• Information collected, created or received
• Information in any medium: electronic, paper, oral 

Inclusion of any of the below listed items, alone or in combination, is considered use of protected health information.

• Name – including the use of initials
• Address – All geographical identifiers smaller than a state, except for the initial three digits of a zip code
• Names of relative(s)
• Names of employer(s)
• Dates – any specific date, including date of discharge and date of birth, and including year‐month combinations (year of event alone, without month or day, is not PHI)
• Telephone number
• Fax number
• E-mail address
• Social Security number
• Medical record number
• Health Plan or Account number
• Certificate or license number
• Vehicle or device serial number
• Web URL
• IP Address
• Voiceprints
• Fingerprints
• Photographs ‐ full face
• Code
• Any other unique identifying number, characteristic, or code

Per local policy, the IRB reviewer must make the final determination regarding exemption status. Never commence any study procedures until receiving notification of exemption or approval from the IRB. Investigators should submit an exemption request through AURA with enough detail to determine whether the protocol meets exemption requirements. You should be notified within a week of the status of your exemption request.

If you make changes to an existing study that has previously been determined to be exempt, a new request for exemption should be submitted, as research activities may have changed such that the exempt requirements are no longer met.

Please contact the IRB staff for further information regarding specific studies that may be exempt from IRB review.

In addition, if you have received approval or exemption from a non-University of Chicago IRB, please contact the U of C IRB office to determine approval or exemption procedures at our site.

Federal regulations require an Institutional Review Board (IRB) to review research on human subjects if the research involves federal funding. The University of Chicago has determined that all research undertaken at this institution, or by those persons affiliated with this institution, must undergo a similar level of review as research that falls under federal regulations. The University has obtained a Federalwide Assurance (FWA), which signifies that the University and the University of Chicago Medical Center are in compliance with the Federal requirements for the protection of human subjects. For details on the University's FWA, please visit the IRB home page or the University Research Administration's website.

The University of Chicago currently has five IRBs: the Social and Behavioral Sciences Division IRB, the Crown Family School of Social Work, Policy, and Practice and Chapin Hall Institutional Review Board (Crown-CH IRB) Institutional Review Board, and 3 Biological Sciences Division IRBs (known as Committees A, B, and C). Each IRB is fully constituted with the appropriate number of scientific and non-scientific, affiliated and non-University-affiliated members, as well as members from different genders and ethnic backgrounds, as required by federal regulations. For current BSD IRB rosters, please see the OCR intranet site.

The Biological Sciences Division (BSD) Institutional Review Boards are administered by the Office of Clinical Research. The BSD IRBs are responsible for all biological or medical research conducted at the University of Chicago and/or the University of Chicago Medical Center and all human subjects research conducted by UCMC faculty, unless review has been ceded to an external IRB. If you are a BSD faculty member, the IRB submission system, AURA, will automatically route your submission to the BSD IRBs for review, regardless of the nature of the research and/or subject population. For more information on the Crown-CH IRB or Social and Behavioral Sciences IRB, please follow the links above.

“Research” is defined by the Department of Health and Human Services as “a systematic investigation, including research, development, testing, and evaluation, designed to develop or contribute to generalizable knowledge” (45CFR46.102(l)). 

Research studies may involve a variety of invasive or non-invasive procedures, including removal of body tissues or fluids, administration of drugs, exposure to various forms of radiation, alteration of diet or environment, interviews, surveys, simple observation, administration of questionnaires, or review of records.

Note that research is systematic, and thus the writing up of a single case report would typically not be considered "research." On the other hand, some quality improvement and quality assurance activities are systematic, but are not designed to contribute to generalizable knowledge (that is, those overseeing the project are not planning to share results outside this institution or results are not generalizable to a larger group). These quality assurance activities would therefore not be research and would not require review by the IRB.

Please see the following topics in this section for further information.

“Human Subject” is defined as of January 21, 2019 as “a living individual about whom an investigator (whether professional or student) conducting research (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens, or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens” (45CFR46.102(e)(1)).

Interventions may be physical procedures by which data are gathered or manipulations of the subject or the subject's environment that are performed for research purposes.  “Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.” (45CFR46.102(e)(2)) “Interaction includes communication or interpersonal contact between investigator and subject.” (45CFR46.102(e)(3))

Obtaining identifiable private information may include a review of medical records or collection of data from surveys or from existing databases. 45CFR46 clarifies that “private information” includes “information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place” and information “that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g. a medical record).” (45CFR46.102(e)(4))

If an investigator obtains data about a living individual in such a way that she or he has no identifiable private information about the subject, then the project is not considered to involve human subjects. In this case, the data must be coded or anonymous, and the investigator conducting the research, as well as the entire research team, must have no access to any code which links the information or material used in the research back to specific individuals.

If investigators have created the code between identifiable information and study data or will have access to the code, the project may qualify for an exemption from IRB review. However, it is still considered human subjects research and some type of submission to the IRB is necessary in this case.

Please see further guidance below for definitions of “coded” versus “de-identified” data.

The regulations for the protection of human subjects in research at 45CFR46 do not apply to research on deceased individuals. Similarly, BSD/UCMC policies typically do not apply to research on deceased individuals. However, while most regulations concerning humans in research refer to “living” individuals, the HIPAA regulations at 45CFR164 apply to all persons, whether living or no longer living. As a result, activities that may not be subject to IRB review because all subjects are deceased may still require a minimal submission process to the IRB office because HIPAA regulations still apply. The IRB at the University of Chicago is designated to perform this HIPAA-related function.

Investigators pursuing a research project involving solely deceased individuals should fill out the form for a “Request for Research on Decedents.”

Per OHRP guidance, "OHRP recognizes that many institutions and individuals (e.g., the principal investigator, statistical centers, community physicians, educators, data repositories) may work together on various aspects of a human subjects research project. However, not all participating institutions and individuals need to be covered by an FWA or certify IRB review and approval of the research to the HHS agency conducting or supporting the research. This guidance aims to assist institutions in determining whether they must meet those requirements, that is, whether they are engaged in activities covered by the regulations." 

Please see the 2008 OHRP guidance "Engagement of Institutions in Human Subjects Research" for help in determining whether an individual or institution is engaged in research:

https://www.hhs.gov/ohrp/regulations-and-policy/guidance/guidance-on-engagement-of-institutions/index.html

Institutions not “engaged” in research would not be required to submit for IRB review. For questions about whether external sites or individuals are considered “engaged” in research, please contact the IRB Reliance team at IRBReliance@bsd.uchicago.edu

The Office of Clinical Research maintains an email mailing list for IRB contacts through University IT Services. This mailing list will allow researchers and support staff to receive information on upcoming IRB training and meeting dates. Researchers and support staff will also be updated on new or revised policies, forms, or procedures for submitting to the IRB through this mailing list. 

As you sign up for the list yourself, you have the freedom to remove yourself from this list at any time.

To sign up for the list, please go to this website:
https://lists.uchicago.edu/web/info/irbcontacts

Once you sign up at this website, you will receive an email to confirm your subscription.

If you have a specific question about a submission in process, please contact the person listed as the "IRB Administrator" on the workspace for that submission in AURA. Contact information for IRB administrators can be found here on the IRB Contacts page. 

If you have a general question or are unsure whom to contact, you can contact the IRB administrator on call for the day according to the monthly schedule posted at the above address. (Click on the link to "On Call Schedule" for that month)

The BSD/UCMC IRB office has also established a general email address to which questions or comments may be sent by the research community. The email address is: bsdirb@bsd.uchicago.edu

Emails sent to this address will be answered within 1-3 business days. If you have a general question about IRB policies, questions about a planned IRB submission, or a question about other IRB-related issues, please consider contacting this email address. If you do not know the specific IRB administrator to contact about a particular submission, you can also use this address and your email will be directed to the appropriate person to respond.

If you have a question about IRB Reliance Agreements and/or single IRB of record, please email IRBReliance@bsd.uchicago.edu

IRBs review research that involves human subjects. The types of research that are covered include clinical trials, behavioral research, epidemiological and survey research, outcomes research, anthropological research, educational research, field and international research, oral histories, and psychological research. Research can range from a clinical trial to the use of human cell lines. In addition, quality assurance activities may or may not also be considered to be research activities. 

How the results will be used affects whether or not a project is research. If there is any intent to publish or otherwise make known the results in a research journal, and the project involves human subjects, the project likely should be submitted to the IRB. For example, if the project is being undertaken with the notion that a paper or journal article may be published, or that a poster or paper may be presented at a conference or community gathering that is not specifically designated as quality improvement, the project may qualify as research and thus would be subject to review by the Institutional Review Board.

If you are unsure about your project, please check with the IRB staff to help you determine if it is “research” involving “human subjects” as defined by the institution and federal regulations.

Certain types of human subjects research may qualify as exempt from IRB review. In order to be exempt, research must meet specific, federally-designed criteria, including that the research involve only minimal risk to human subjects. Exempt research under the purview of the BSD IRB cannot involve either sensitive data (data linked to specific individuals that may be painful or embarrassing to reveal) or certain special populations (such as prisoners). Research involving children may be exempted under certain circumstances.

Per University policy, the IRB must make the final determination regarding exemption. Investigators should not begin any human subjects research until the IRB has determined that it is (1) approved or (2) exempt from IRB review.

In addition, if you have received approval or exempt determination from a non-University of Chicago IRB, please contact the U of C IRB office to determine submission requirements at our site.

The 6 exempt categories allowed by local policy are described at45CFR46.104(d)(1-6).

Minimal risk is defined in the federal regulations as situations wherein “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 or during the performance of routine physical or psychological examinations or tests” (45CFR46.102(j)).

Federal regulations define research as “a systematic investigation … designed to develop or contribute to generalizable knowledge.” Research is usually designed with the intent to publish the results of a research hypothesis being tested.

However, physicians at the University of Chicago Medical Center occasionally come across a patient who presents with a unique condition or whose stay at the hospital presents an interesting discrepancy from the normal course of treatment or reaction to treatment. In these instances, a physician may wish to publish a case report on this one patient in order to contribute to medical knowledge. 

Although this case reporting does involve the intent to publish results, it does not involve the intent to ask or answer a specific research question. Consequently, the wish to publish a single case report is not considered to be research and the IRB does not require the submission of a protocol in order to publish the case report.

If more than one case occurs of the specific condition or medical anomaly, or the investigators begin to formulate a hypothesis or attempt to gather further information on cases of this type with the intent to publish, activities cross into what could be considered “research” and it becomes necessary to submit a research proposal to the IRB.

Although publishing a case report may not require submission to the IRB, investigators should be aware of the use of individually identifiable health information in their publications. Under HIPAA, the disclosure of an individual’s protected health information must be authorized by that individual. In other words, if a case report contains any identifiers as defined by the HIPAA regulations, authorization to disclose this information in a publication should be sought from the individual whose information is being disclosed. The subject or a designated representative should sign a consent form (HIPAA authorization) to disclose this information.

It should be noted that case reports often involve reporting on a rare disorder, condition, or course of treatment. In such cases, individuals may be more easily identified as being the subject of a publication than individuals with a more common disease or condition. Consequently, this rare disorder may fall under the category of “any other unique identifying characteristic” under the HIPAA regulations, and thus be considered Protected Health Information. Physicians and other researchers should then obtain a subject’s authorization before publishing a report, even when no other identifiers are being disclosed, because the subject may be able to be identified by their disorder. 

When deciding whether or not to submit a proposal to the IRB, it is important to consider the intent of the potential publication. Medical or educational activities are not considered to be research. However, once medical activities become methodical evaluation, “designed to develop or contribute to generalizable knowledge,” this is research as defined by the federal regulations.

Identifiable data can fall under two categories: PHI and PII.

PHI stands for “Protected Health Information” and under the HIPAA Privacy Rule, includes elements such as:

PII stands for “Personally Identifiable Information,” which refers to information that can be used to distinguish or trace an individual’s identity, either alone or when combined with other personal or identifying information that is linked or linkable to a specific individual. PII is a term that applies to data that are or are not regulated by the HIPAA Privacy Rule, while PHI is a term used for HIPAA-regulated data.

Identifiable data are study data that contain PHI or PII.

Coded data are study data that are separated from identifiers but CAN be linked back using a code (words, letters, figures, symbols, or a combination that is NOT derived from or related to the personal information). With these data, a spreadsheet or similar is created that links the code to identifiers (i.e. a “key”). This is the most typical method of collecting data/samples.

De-identified data are study data that do not contain PHI or PII and can never be linked back to a subject.

Questions to consider:

• What identifiers do I need to use in order to conduct my research? Keep in mind, this includes using identifiers to access medical records. 
• Are these identifiers needed throughout my entire study? Can they be deleted at a certain point (i.e. can data be removed or “stripped” of identifiers at the end of the study)?
• Is there a way for me to keep these identifiers separate from the data/samples that I want to collect?
• What is the source of the data? Am I directly collecting data from the medical record, or am I obtaining data from another source, such as the Clinical Research Data Warehouse (CRDW) through the CRI?
• If I am sharing data with others who are not a part of my institution, how will the data be transferred? Will I send identifiers to the collaborating institution?
• Sometimes, you can have more than one type of data to be used for your study. This is typically in the event that data and/or specimens are shared with collaborators. When this is the case, it is helpful to make the distinction for how the data and specimens will be shared. For example, the data that you collect may be identifiable or coded, but how will the researchers at the collaborating institution receive these data? Will the researchers at the collaborating institution receive coded data as well? De-identified? Depending on how these data and specimens are shared and if there is a contract, it is possible that a Data Use Agreement (DUA) or Materials Transfer Agreement (MTA) may need to be executed through URA.

For more information or any questions about your study, please feel free to contact a BSD IRB administrator.

For more information:

1. https://hhs.gov/answers/hipaa/what-is-phi/index.html
2. https://www.gsa.gov/reference/gsa-privacy-program/rules-and-policies-protecting-pii-privacy-act
3. https://ura.uchicago.edu/page/data-sharing-agreements
4. https://ura.uchicago.edu/page/material-transfer-agreement

Please access the following resources for guidance on use and storage of research data.

OCR Guidance (UChicago intranet) -- includes guidance on involvement of Center for Research Informatics (CRI)

UChicago Sensitive Data Usage Guide

University of Chicago Research Data Protection Policy

UChicago Secure Research Data Usage Guide

Data Classification Policy and Handling Procedures (UCMC intranet link)

Minimum Security Standards - IT Responsibilities and Standards (UCMC intranet link)

The BSD Information Security Office has a process in place to assist Information System Owners with conforming to security best practices and ensuring systems align with organizational cyber security policies.

Any planned, new or existing information systems that support BSD  research activities are expected to complete the Security Assessment and Authorization process.

Please see the BSD ISO website for information on the SAA process: https://security.bsd.uchicago.edu/bsdsaa/

Please also see BSD Guidelines for Use of Software with Research Health Information:

https://bsdis.uchicago.edu/sites/bsdis/files/2024-03/Guidelines-for-Use-of-Software-with-RHI.pdf

The University has recently updated its policy on payments to research subjects. This includes clarification on when gift cards rather than checks may be used as payment.

See University policy at
http://finserv.uchicago.edu/payroll/independent/subjects.shtml

Highlights:

• Payments to subjects over $100 per occurrence must be paid directly to the individual via University check. Gift cards, gift certificates or in-kind payments over $100 per occurrence are not permitted as remuneration for participation in a research study.
• Payments $100 and under per occurrence can be processed via University check or other methods including petty cash, gift cards or in-kind payments.
• Reimbursement for parking, meals, and/or transportation to and from study visits are not taxable. Reimbursement may be made only if a receipt for the expense is provided by the subject. Reimbursements for subjects’ time are taxable. 

Note, if subjects will be entered in a raffle/drawing to win a gift with value of at least $100, the researchers need to record the name of the individual receiving the gift.

If total amount of payment may exceed $600, the University will need to issue a W9, and therefore name and social security number will need to be collected. If total amount is expected to be less than $600, researchers should maintain a log of payments, including name of payee.

Questions? Contact University of Chicago Financial Services Office.
Questions about petty cash? Contact cash-management@uchicago.edu.

Please describe any planned payment/compensation for research subjects in the AURA IRB submission form.

The IRB is charged with the protection of human subjects in research. In order to fulfill that responsibility, the IRB must ensure that research studies comply with applicable federal, state, local, and institutional regulations and policies, as well as with the IRB Committee’s own ethical guidelines. At the federal level, the regulations the IRB must follow are mainly codified at 45CFR46 (DHHS), 21CFR11, 50 and 56 (FDA), and 45CFR164 (HIPAA).

The University of Chicago IRBs must abide by Illinois state laws applicable to research as well as by any city or local rules. Examples of applicable state law include the IL Health Care Surrogate Act and Medical Patient Rights Act (concerning those who cannot consent for themselves), IL Genetic Information Privacy Act, and IL AIDS Confidentiality Act. Examples of city or other local regulations include the requirements for approval or acknowledgement of research when conducting research at specific sites, such as the Chicago Public Schools.

These federal, state, and other requirements are addressed by the IRB mainly through the protocol submission form. Many of the submission form questions employ language taken directly from the federal regulations. Other questions address University of Chicago/Biological Sciences Division/UCMC requirements.  One example of an institutional requirement is the need for CTRC review of any study involving cancer patients. Review by the PBUC, IBC, or other institutional committees may also be needed.  

Thus it is to your advantage to fill out these forms as completely as possible when submitting to the IRB, as additional information may be requested if there is insufficient justification or description provided for the IRB to make a required finding.

Chart reviews are a common method of gathering information on a specific medical condition or set of patient characteristics. Although chart reviews do not involve direct interaction with subjects, chart reviews fall under IRB review because they involve obtaining private information about human subjects. Federal regulations define a human subject as “a living individual about whom an investigator … conducting research (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens, or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.” [45 CFR 46.102(e)(1)]

When submitting a chart review proposal to the IRB, a protocol narrative is needed. This narrative may be brief, but should include a defined purpose for the data collection. The narrative must also include the beginning and end dates of collection. For example, if you plan to review the medical record of every asthma patient seen in clinic in 2023, you should state exactly what information you are obtaining about the patients, explain the data you hope to find, and specify the beginning and end dates of data collection. These dates are the dates during which the data were originally recorded, such as “January 1, 2023 through December 31, 2023.”

Chart reviews may be prospective or retrospective, or a combination of the two. To qualify as retrospective, all information must be collected from a time period prior to the date the study is reviewed. Thus, if you expect IRB review on March 17, 2024, the endpoint of data collection must be on or before March 16, 2024 in order to be considered "retrospective." Investigators are advised to provide justification for a waiver of consent for the retrospective review of medical records. Note that the decision to grant a waiver of consent is the IRB Committee’s; in certain cases, the Committee may require that an attempt be made to obtain written consent from potential subjects, even if the information was previously collected in the chart and no prospective collection is anticipated.

In general, prospective collection of information from medical records will require written consent/authorization. Ethical guidelines indicate that if it is possible to obtain consent from potential subjects, the attempt should be made to do so. The IRB Committee will usually require that a written consent/authorization form be prepared to prospectively collect data from medical records. This includes outcomes data that has not yet occurred (e.g. you want to record 1 year follow up data on a surgery that occurred yesterday).

The Committee is also mindful of “protocol creep.” In other words, amending the protocol in the future to include information that would be retrospective then but is prospective now is not generally allowed. For example, your original protocol is approved in March 2022 to examine information from March 2018 to February 2022. Eventually, you will also want to examine the charts from March 2022 to February 2025. Rather than submit an amendment in a year, if you know now that you will want the 2022-2025 data, this request should be included in your current proposal. 

CRDW: Use of data from the CRDW may or may not require IRB review. If data are provided in a de-identified format, and the research team will not be accessing medical records for additional information, the research may not require IRB review. However, if the research team will receive ANY identifying information from the CRDW and/or will access medical records directly to supplement CRDW data, then IRB review will likely be needed.

Devices can include traditional devices (syringes, shunts, pacemakers, etc.) as well as assays, software and mobile applications. If the product in question is not a drug, and it is intended for use in diagnosis or treatment, mitigation, or prevention of disease in humans, it could be a medical device under the FDA regulations. If you are submitting a new study and are uncertain whether to list a product to be used on study as a device in the device section in AURA-IRB, please consider the attached flowchart. 

Device decision tree

Most studies involving cancer patients or their data must be reviewed by the Clinical Trials Review Committee (CTRC). Please note that with rare exceptions, protocols must be reviewed by the CTRC before they are reviewed by the IRB. For more information on the CTRC submission process or to find out if your protocol requires CTRC review, please contact Amber Burnett in the Cancer Research Center at 4-0357 or aburnett@medicine.bsd.uchicago.edu.

If the study uses existing materials (“on the shelf”), review by the Pathology Biospecimen Utilization Committee (PBUC) review is sufficient and additional review by the CTRC is not required.  On the other hand, for any study with cancer related objectives proposing to obtain prospective tissue samples, the study would require CTRC review in addition to PBUC review. 

Nurse investigators wishing to implement clinical research involving nursing staff and/or nursing care are required to obtain approval from the Nursing Research Committee (NRC) as well as from the IRB before proceeding with their study. Nurses who are hired to do research and collect data for physicians' research or those hired as Clinical Research Associates are not required to submit proposals to the NRC. Nurses who are doing research independent of this are required to submit their proposal to the NRC. NRC approval must be obtained prior to submitting a proposal to the IRB, and a copy of the NRC approval should accompany the IRB submission.

For more information on the NRC submission process or to find out if your protocol requires NRC review, please contact Dr. Nicole (Pierce) Bohr, Manager of Nursing Research, in the University of Chicago Medical Center or email nursingresearch@uchicagomedicine.org .

The NERC submission form is available here: https://redcap.link/8yjz6qwb

In order for a new submission to be accepted for IRB processing, certain elements must be included as noted in the Accepted for IRB Processing Checklist.

Within a week after a study is accepted for IRB processing, the IRB administrators conduct a pre-review. Often, this pre-review will result in a request for additional information or documentation. Certain documents are required before the Committee can review a protocol and the IRB administrators will inform you as soon as possible if your submission is missing any such required elements. The submission will not be reviewed by the Committee until all required elements are received, regardless of the date of the original submission.  Please see the Ready for Review Checklist. If you do not wish to respond to certain comments, or if you would like to provide an alternative response, please document this when submitting back to the IRB so that the IRB is aware of any issues that should be considered during its review.

Administrators will also make other suggestions for revisions. While you are not required to submit these other revisions prior to the Committee meeting, it has been the IRB’s experience that Committee members generally incorporate administrator suggestions into their own review by including these suggestions in the pending conditions for study approval. For this reason, we recommend responding to all pre-review comments prior to the IRB meeting in order to reduce the time necessary for review and approval of your study.

If, at the meeting, the Committee feels that further information or documentation is needed before approval can be granted, the protocol will be given “deferred” or “pending-conditional” status.  The Principal Investigator will receive a letter detailing the outstanding issues after the meeting, usually within the following one to two weeks. If a protocol is deferred, it must be reviewed again at a scheduled meeting. Additional information may still be required after the second meeting, and a second deferral or a pending-conditional letter may be sent. Pending-conditional studies can be approved without returning to a meeting once all pending issues have been appropriately addressed, although the Committee may review a pending-conditional response at another meeting at its discretion. 

Generally, non-expeditable studies require at least one month from day of submission to approval. Two months is an expected timespan from submission to approval. If a study is deferred, or pending comments are not adequately addressed, approval can take several months or more. Studies that can be expedited generally require about 2-3 weeks.

During a pre-review, the IRB administrators and IRB reviewer will determine if they believe your study can be expedited. Many studies are not granted expedited review even when it is requested. The IRB, not the investigator, has the final decision on whether a study can be expedited.

In addition, expedited review is determined not by a need for quick approval but rather by the minimal level of risk and specific nature of the research. Only studies of minimal risk falling into one of the federally-defined, IRB-approved categories are eligible to be expedited. 

The following may be a reason why you have not received approval:

• the study has not been accepted for IRB processing. Your submission may be missing a required documentation element.
• your study is not eligible for expedited review. The IRB staff will notify you at the time of pre-review if this is the case.
• the IRB staff or chair has requested further information, which has not yet been received. Check with other members of the study team to see if they are working on a response.

The IRB staff makes every effort to expedite qualifying protocols as quickly as possible. However, due to the large volume of protocols, we are not always able to immediately process expedites. If you submit a study you believe qualifies for expedited review, and you do not hear anything after two weeks, please contact one of the IRB administrators to check on the status of your protocol.

If any study procedures are ongoing, the study should be renewed if the study is FDA regulated. This includes studies with subjects still on study drug(s), undergoing study procedures, or being followed, or studies for which data is still being collected or analyzed. Even if the subject’s own involvement in the study is finished, if you are still working with identifiable subject data IRB approval is needed. You should submit continuing review documents at the appropriate time.

If all study-related procedures are complete, and you are not planning to do any further data analysis, then the study can be terminated. If data analysis will be done at another site, and this site has completed all study procedures, the study can be terminated at this site, unless you feel that the sponsor may request additional data from your site. If you still need to look at subjects’ medical records for information to report to the sponsor, you will need to keep the study active. 

If your study is not FDA-regulated, and the IRB has determined that continuing review is not required, you will be formally notified by the IRB during the approval process that continuing review is not required. If you are not certain whether your approval letter indicates that continuing review is required, please contact the IRB office. 

If your study is not FDA-regulated, but subjects remain on study, continuing review may or may not still be required. Please check your approval letter or contact the IRB office.  

Federal regulations require that studies be reviewed by the IRB at least once every year. This means that the IRB has one year from the date a protocol is reviewed at a convened meeting, or in the case of expedited reviews, the day the expedited approval is reviewed and approved, to review the study again, either at a convened meeting or through expedited review procedures.

If your protocol was last reviewed at a meeting in March, but did not get final approval until September, it must still be reviewed prior to one year from the day in March it was reviewed at a meeting.

Researchers should check the IRB website for renewal deadlines posted on the Meeting Dates page. Typically continuing reviews should be submitted 90-120 days prior to their expiration date.

Note that for studies that cannot be expedited, it is imperative to meet renewal deadlines, as renewal forms must be reviewed at a convened meeting. If there is no meeting scheduled before your study’s expiration date, it will expire. 

The AURA-IRB system sends out renewal reminders approximately 4 months before studies expire. These are automatically sent to the email address on the "Profile" page for the PI and primary contact from the email address _aura-irb@uchicago.edu. This is not a monitored email address; please do NOT use this email to communicate with the IRB office.

The goal is to review the studies at the meeting 1-2 months before the expiration. If any problems arise during the review or revised documents are requested, the PI thus has time to respond before the protocol’s expiration date. Note that the IRB makes every effort to notify investigators prior to study expiration regarding the need for renewal; however, the principal investigator is ultimately responsible for ensuring a protocol's continued approval.

To be accepted for processing, all questions on the continuing review (CR) form should be completed and any applicable documentation uploaded, including any relevant data monitoring committee reports. Please see the Checklist below for the necessary materials to be accepted for processing:

CRs: Accepted for Processing Checklist

After a CR has been submitted, the IRB administrative team will review the submission and determine if any information is missing or if more information or documentation is needed. The IRB administrative team uses a "pre-review checklist" to document the administrative review. Any outstanding items or issues noted in this pre-review will be communicated to the study team via email. The administrative pre-review checklist is provided below for your reference:

CR Pre-review Administrative Checklist

Ideally, a PI should always be well informed of the literature relating to the particular field of study and should be conducting reviews of the available literature on a regular basis. The need for a literature search to assess the risk level and alternatives to participation of each study was given additional emphasis following the federally-imposed halt on research at Johns Hopkins University in 2001. A volunteer on a Hopkins research study died after being exposed to a drug for which the government determined that risk information had not been adequately researched. 

Consequently, the federal agencies governing research have heightened their emphasis on the need for a thorough review of available applicable literature both before research is started and as an ongoing process throughout the research. The University of Chicago BSD/UCMC IRB therefore requires that a literature search be conducted and the results presented to the IRB at the time of original submission as well as at each continuing review (renewal).  During the original submission, references in a written protocol may suffice in lieu of a literature search.

PIs should search on one or more web-based search engines for articles relating to 1) the condition being studied and 2) the specific drug/device/process/intervention being studied. For example, for studies of a new drug for IBD, researchers should not only search for articles on the risk of that drug, but should also search for articles on new treatments for IBD that would present available alternatives to study procedures. The Committee is also concerned with the applicability of the proposed research; that is, if a literature search reveals that the study being proposed replicates studies that have already been completed with definite results, the PI should consider whether the study is likely to yield new information and if not, if the study should be performed. 

While the IRB has faith that investigators are responsibly conducting research, the IRB does not accept merely a statement that a literature search has been performed. The Committee requests that PIs provide the IRB with the name of the search engine that is used, the search strategy (keywords), and the results of the search, along with a description of the results’ impact on the risk level and/or alternatives to participation of the research.

Example of an acceptable literature search for a renewal: 

SEARCH ENGINE: PubMed 
SEARCH TERMS: Drug Name (generic), Drug Name (brand), Disorder Name 
RESULTS: 1200 articles. 
SUMMARY: Most of the articles were not applicable to the study at hand as they dealt with the risks of or descriptions of standard of care drugs for this disorder. Searching on the drug itself yielded only a few results having to do with animal studies; these are already covered in the investigator’s brochure. One article, “DRUG XYZ in Disease Y” by A. Jones, indicated a possible new alternative therapy, but this is still in Phase I development. Overall, there is nothing in the literature to indicate any new information on the risks or benefits of this study. Risks found in the literature are already covered in the protocol and consent form for this project.

If your study is still enrolling subjects OR if enrollment is closed, but subjects are still actively participating in study procedures or receiving study drug, then a literature review should be submitted. 

If your study is permanently closed to enrollment and all subjects have completed all research-related interventions, then a literature review may not be required. However, the IRB does require that you provide a justification for not providing a literature search. (“Not applicable” is not considered a sufficient justification. Please explain why a search is not applicable.) Also, the IRB may determine that a literature search is needed to ensure that there is no new information that should be provided to subjects in follow up, e.g. new safety information about the drug tested in the study. Please contact the IRB staff for more guidance on your specific protocol, if needed.

If continuing review is required, continuing review (CR) must take place at a convened meeting at which a majority of the IRB members are present unless the research qualifies for review under an expedited review procedure (45 CFR 46.108(b)).

IRBs may use an expedited review procedure to conduct continuing review of research that:

• Involves only procedures described in one or more of the nine categories of expeditable research activities (see OHRP Expedited Review Categories); and
• Currently involves no more than minimal risk to the subjects (45 CFR 46.110(b))

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 or during the performance of routine physical or psychological examinations or tests. (45 CFR 46.102(j))

See attached decision tree for more information. 

Any change to an approved study, including changes to the consent form, advertisement, recruitment procedures, study personnel, or protocol design, should be submitted as an amendment to the protocol. Minor changes can be approved through expedited procedures, but still must be submitted for approval. All requested changes should be described in detail on the amendment submission form, which must be electronically signed by the PI and submitted along with any documents that are being changed.

No change should be implemented until it is approved by the IRB.

Amendments cannot be processed on protocols that have not yet been approved. Changes to protocols that have not yet been approved should be addressed through memos or responses to the IRB Committee.

Study activities should NOT deviate in any way from the protocol that is approved by the IRB unless a change is necessary to eliminate immediate hazard to an individual. The investigator should notify the IRB as soon as possible after a change is made to eliminate hazard(s) to subjects or others, and a formal amendment should follow within 5 working days of implementation of the change.

Studies for which continuing review is not required are still required to submit amendments prior to initiating changes to approved study procedures. 

The BSD/UCMC IRB does not have a protocol “exception” policy. Accordingly, when any revision to an approved research protocol is desired, including a change in research design or eligibility criteria, for one subject or multiple subjects, the investigator must submit an amendment. The amendment form should explain what changes are desired and provide a rationale for those changes. A revised copy of the pertinent original documents (e.g. protocol, consent form, etc.) should also be submitted with the changes identified.

Amendments to approved protocols may not be initiated until IRB approval has been obtained, except where necessary to eliminate apparent immediate hazards to the subject, in which case the IRB should be notified as soon as possible. Eliminating immediate hazards to a subject should be considered in the light of treatment rather than research. If it is in the best interests of the patient/subject to be given or removed from study drug/procedures, then this should be done regardless of the approved protocol or the need for an amendment. The appropriate paperwork may be completed later.

In other words, treatment decisions should be made separately from research decisions. An investigator/ physician may believe that the best treatment for a patient is an experimental drug. However, as an investigator, that same physician should note that if a treatment decision for a particular patient does not fit within or differs from approved research procedures, the patient may not be able to remain on or be enrolled in the research.

The IRB is often informed that “treatment” may be delayed if an amendment is not approved immediately. In practice, treatment decisions must be made by the treating physician regardless of a research opportunity. Participation on a research study is often not a patient’s only treatment option. Alternative approved drugs/procedures or other drugs given off label may represent other treatment options for a potential patient for a study or a subject already enrolled on a study.

When a PI makes a decision as to whether to treat a person and/or to keep that person on a research study, there may be other entities involved in the decision regarding this person, including the study sponsor and IRB. A sponsor may or may not allow the person to remain on study if procedures for that individual will differ from study procedures. In addition, this event would require reporting to the IRB as an unanticipated problem if the PI has not requested prior approval for the change to approved study procedures. The IRB may then determine that using data from that individual is not appropriate on the study. Again, this does not affect the treatment decision; it only affects the research.

An IRB is required by federal regulations to ensure prompt reporting of serious or continuing noncompliance with regulations or noncompliance with the IRB’s own requirements/ determinations. Deviations from the approved protocol, i.e., changes made without prior IRB approval, fall under the category of noncompliance. Deviations must be reported to the IRB. Once reported, the IRB can make a decision regarding appropriate response or remedial action, or determine that no remedial action is necessary. Remedial actions may include asking an investigator to exclude data that was obtained inappropriately or outside approved study parameters.

A protocol deviation occurs when the study departs from the IRB-approved protocol in any way, including use of a non-approved or outdated document (consent, advertisement, etc.), change in procedures (drug dosing, scheduling of study visits, re-ordering of study activities), change in personnel conducting study procedures, and inclusion of a subject not meeting eligibility criteria.

It is the expectation of the IRB that all approved protocol procedures are being followed without alteration unless the IRB has been informed of a protocol change (through an amendment) or deviation (through an Unanticipated Problem report or continuing review update).

Example #1:
Patient A was screened for a research study. All the necessary screening labs were done as well as a medical history review. Inclusion/exclusion criteria were verified by the PI and the patient was found to be eligible and started on study. Later, it was discovered that Patient A had a condition diagnosed at an outside facility that was not recorded in the medical history. This condition is among the protocol exclusion criteria. The study physician would like to keep Patient A on study.

Potential issues arising from this example:
1) If this is a sponsored study, the sponsor should be informed that a subject was enrolled who was ineligible. The sponsor must decide whether this person may continue on study.
2) If there are immediate health or safety issues that would require that this person remain on study (e.g drug is only available as part of the research and there may be consequences to abrupt withdrawal of drug, etc.), and the PI believes that remaining on study is in the best interest of the person, then to protect the safety of the subject that person should remain on study drug, if possible. This should be documented in the research file, the medical chart, and in an unanticipated problem report.
3) An unanticipated problem should be reported in any case as soon as possible. The IRB will consider whether to protect human subject(s), its recommendation would be that this subject should continue to be on study or that the subject should be taken off study, if the subject has not already been removed from the study.

Example #2:
Patient A is an otherwise-eligible 70 year old. The protocol inclusion criteria for this drug trial states that persons ages 18-69 may be enrolled. The study physician feels that Patient A may benefit from the drug and would like to enroll the patient on the study. Patient A is coming to the hospital for a clinical care visit tomorrow. The PI wants to approach Patient A to participate in the study at that visit.

Potential issues arising from this example:
1)If this is a sponsored study, the sponsor should be queried as to whether an exception to eligibility criteria would be allowed. The sponsor must decide whether this person may be enrolled on study and if allowed, should provide documentation to the PI to that effect.
2) As this is a change to the approved research design, IRB approval should be requested prior to enrollment of this individual. As noted above, approval is needed whether this change applies only to this one individual or whether eligibility criteria are expanded for all future potential subjects.
3) It is unlikely that the IRB will be able to approve an amendment prior to the scheduled clinical care visit. The PI may wish to reschedule or explore other appointment options or opportunities with this patient.

The IRB receives multiple requests for amendments to be processed more quickly due to patients waiting. Note that due to the volume of amendments requiring processing and the limited availability of IRB reviewers, the IRB cannot accommodate all requests for quicker processing. Note, too, that if an amendment qualifies for expedited review the IRB will likely expedite it regardless of whether or not expedited review was requested. If it does not qualify for expedited review, it will require review at the nearest convened meeting for which a reviewer is able to review it. If possible and upon request, the IRB may be able to review the amendment at an earlier meeting than the one for which deadline it was submitted. Please contact the IRB office for such a request. Please copy the PI on all such requests.

If a proposed change involves re-consenting of all subjects, it is unlikely that the amendment will receive expedited review.

If you have an IRB-approved consent form and enrollment has not been halted for safety or other concerns, you are free to enroll subjects using that approved consent form. If, however, in the PI’s opinion a change described in an upcoming amendment is a change that potential subjects should be aware of due to safety or other concerns that might affect a subject’s willingness to participate, the subject should not be enrolled until that person can be informed appropriately and with an approved consent form that adequately reflects approved study procedures.

Yes, if the study requires continuing review. Amendments deal with changes to the approved study. Approval of an amendment indicates specific approval of that change. Once approved, an amendment becomes a part of the approved study. On the other hand, a continuing review is a review of the entire study, including all amendments up to that date, to evaluate whether the study continues to meet all requirements for approval. If a continuing review is not approved prior to the study’s expiration date, the study will expire.

You can, although the submission of overlapping documents for both can be tricky. Remember that the continuing review is a review of the approved study and your submitted amendment has not yet been approved or may never be approved. If an amendment is approved after you have submitted your continuing review documents but before renewal approval, you may need to update your continuing review submission to reflect any changes made with the amendment. Conversely, if your consent form is revised during the time of continuing review, you may need to submit a revised consent form for any pending amendment to incorporate renewal changes with amendment changes to the consent form. 

Especially with consent forms, be aware of whichever version is approved last. It becomes the approved version. Amendment changes are nullified if the renewal consent form, approved after the amendment, does not reflect the amendment changes. Another amendment must then be submitted to approve the revised consent form before it can be used.

Yes, the compensation amount can be stated. However, it should not be put in large type or emphasized in any way.

Advertisements submitted to the University of Chicago BSD/UCMC Institutional Review Board should include:

• The purpose of the research
• Summary of eligibility criteria
• Estimated time commitment
• Name of the PI
• Location of the research
• Contact information
• Identification as advertisement for "research"

but 

• NOT Promise free medical care or free medications
• NOT Emphasize payment or amount to be paid by such means as larger or bold type
• NOT Name unapproved study drugs by name
• NOT Contain therapeutic claims

Please also see the FDA Information Sheet on “Recruiting Study Subjects” at http://www.fda.gov

Several IRBs have been asked to review protocols that propose to recruit subjects though temporary employment agencies. Per University Research Administration, this method of recruitment is inherently problematic. Temporary employment agencies are intended for employment opportunities, while participation as a human volunteer in a research project is NOT considered an employment opportunity. Employment agencies have access to disadvantaged populations, who may feel compelled to accept assignments to research projects either for the financial incentive alone or in order to maintain their relationship with a temporary employment agency to secure future placements. Thus, temporary employment agencies should not be used as a recruitment resource for research projects.

Research-related injury language is generally negotiated with the sponsor during the contract negotiations. The University of Chicago provides consent form language concerning research-related injury that is expected to be used unless the IRB is notified otherwise by the U of C contract team.

For more information, please see the above FAQ, "Does our site have a policy on research-related injury."

Over the course of conducting a research study, investigators may find that changes to the protocol are indicated, whether due to newly discovered risks, a change in protocol design, or some other factor. Whatever the change, it may require re-obtaining consent from previously consented subjects in order to continue their participation in the study.

The need to re-consent derives from the federal regulations governing research, which require that subjects be informed of significant new information that may affect their continued willingness to participate. This new information may include the following:

• increase in study length
• increased number of study visits
• a change in study venue(s)
• increased risks to subjects
• decreased benefit to subjects revealed than previously believed to be present

Therefore, investigators should evaluate the need for re-consenting previously enrolled subjects when such types of changes occur, or other changes that may affect willingness to participate.

In addition, if a study is terminated or expires while subjects are still on study, subjects will need to be informed of the study termination or expiration and study procedures must be halted. Study procedures may only continue on a terminated study if immediate withholding of study drug or procedures from subjects would affect their health or welfare. In that case, the IRB must be kept informed of subjects’ welfare and a new protocol submitted as soon as possible in order to keep subjects on study. In any case of study termination or expiration, if investigators wish to continue study procedures a new protocol and consent form will be required by the IRB. This new protocol and consent must be approved by the IRB and subjects should be re-consented using the new consent form version before they continue their participation. 

The decision to re-consent subjects on an active protocol should be made by the principal investigator during the time of amendment submission. When amending the protocol to include the new information, the investigator will be asked to provide an assessment of whether re-consenting is required, and to submit a revised consent form as applicable. However, even if an investigator feels that re-consenting is not required, the IRB retains the final decision concerning re-consenting and may request that it be done if the IRB feels that subjects’ decisions regarding participation may be affected by this new information. 

In a related situation, investigators with protocols involving the use of proxy consent may also need to obtain the consent of previously-consented subjects. In this case, if and when subjects for whom someone else has given proxy consent regain the ability to consent for themselves, the investigator must obtain the consent of that subject directly in order for the subject to continue on the study. While not technically “re-consenting,” as the subject did not originally participate in a consent process, this circumstance does require that a subject who had previously been enrolled may only continue participation after another consent process has taken place. 

Optional consent forms should contain all required elements of informed consent. Since the decision to participate is optional and is made outside the decision to participate in the “main” study, it is an independent consent form and process and thus all required elements should be included.

Addendum consent forms that are used to provide new information about an existing agreement to consent could contain sections with text to “refer to main consent” or similar. For example, a consent form for dosing beyond disease progression is an agreement to continue participation in the main study despite new information (i.e. progression of disease). Therefore, it could refer a subject back to the main consent form for information such as the dosing schedule or confidentiality protections, as long as those were not altered by the disease progression. Any new information regarding risks or procedures should be clearly described in the addendum.

For any type of consent, the AURA submission form should be clear about when each consent process will occur. For example, consent to dosing beyond disease progression would not be expected to occur until a subject had actually progressed, and therefore it would be expected that the consent discussion would occur at a later time point than the main consent discussion. It would also be expected that there would be some kind of “refresher” discussion and/or reference to the main consent form contents when discussing the agreement to continue on study beyond disease progression. In other words, the addendum consent form would be used in conjunction with the main consent form that had already been signed.  

For research in which investigators expect to enroll non-English speaking subjects, a consent form translated into the native language of the subjects to be enrolled must be provided to the IRB with the original submission or, if this study population is being added, with the amendment. A certified translator should perform the translation and proof of certification should be provided to the IRB along with the translated consent form. 

Any recruitment materials (flyers, radio advertisements, etc.) that have been translated should also be provided to the IRB. In addition, investigators should translate all study materials that will be distributed to non-English-speaking subjects, such as surveys or questionnaires, and submit these to the IRB when the translated consent is submitted. 

The translated documents must be approved by the IRB before non-English speaking subjects can be enrolled into the study. 

Note that the exclusion criteria in certain protocols may specifically exclude non-English-speaking subjects from participating. Check your full written protocol for inclusion/ exclusion criteria before enrolling non-English speaking subjects.  

Please ensure that a person who speaks the language of the subject to be enrolled conducts the consent discussion and is available throughout the study, as applicable. 

In some cases, a non-English speaker may be eligible for a study for which there is no translated consent document, and for which the study investigators could not have foreseen enrollment of a potential subject who speaks that language. In this case, investigators may choose to enroll the potential subject using a "short form" consent that has been translated into the subject's native language. 

The consent process must involve a translator who can verbally translate the information in the full written informed consent into the subject's native language. A witness to the translation must also sign the consent form; the translator may function as the witness. 

If PHI will be used and/or disclosed as part of the research, the subject should also sign a HIPAA authorization for this use/disclosure written in a language understandable to the subject. Please contact the HIPAA Program Office for more information on translated HIPAA authorization forms.
A general authorization in Spanish for use/disclosure of PHI is available on that website.

Like the translated full written consent document, the IRB must approve the translated short form consent prior to its use. However, expedited review of an amendment to approve a translated short form consent is possible if the IRB has previously approved both the protocol in question and the protocol's full English-language informed consent document. 

The IRB has approved a short form consent document and has had this consent translated into several languages. Several translations have also been provided by the Cancer Clinical Trials Office (CCTO) (thanks to the CCTO for allowing the IRB office to share these). For the languages listed below, please contact the IRB for a copy of the translated document when submitting an amendment to use the short form consent.

For any language not listed below, the investigator is responsible for obtaining a certified translation.  The English language short form is available below for download:

Short form consent (English) - study was approved under 1991 Common Rule requirements

Short form consent (English) - study was approved under 2018 Common Rule requirements
 

1991 Common Rule versions available from the IRB office include Spanish, Arabic, Bosnian-Serbian, Bulgarian, Cantonese, Greek, Hebrew, Hindi, Korean, Macedonian, Mandarin, Polish, Portuguese, Romanian, Russian

A person who speaks and understands English, but does not read and write, can be enrolled in a study by “making their mark” on the consent document.

If you wish to enroll a person who can understand and comprehend spoken English, but is physically unable to talk or write, or a person who cannot read the consent form (e.g. illiterate persons), you may do so as long as the person is competent and able to indicate approval or disapproval by other means. The person must:

1. retain the ability to understand the concepts of the study and evaluate the risk and benefit of being in the study when it is explained verbally (still competent) and
2. be able to indicate approval or disapproval to study entry.

The consent form should document the method used for communication with the prospective subject and the specific means by which the prospective subject communicated agreement to participate in the study. An impartial third party should witness the entire consent process and sign the consent document. A video tape recording of the consent interview is recommended.

Note that for any study for which enrollment of illiterate persons is expected, this should be clearly indicated during the time of original protocol submission. If an approved study now wishes to enroll an illiterate person or persons, an amendment will need to be submitted to request approval for a change in eligibility criteria, describe the consent process for this individual or individuals, and describe how it will differ from the approved consent process.