Researcher Responsibilities after IRB Review

Approval of a research project by the IRB is not the end of the process.  There are a number of post-review requirements that researchers should be mindful of. Among these are reporting of problems or significant changes to the research, maintaining records for both UC/sponsor requirements and for potential audit, and protocol renewals or closure.  Please review the materials below for more information.

Protocol Amendments

When and How to Amend an IRB Approved Human Research Study

Amendments to IRB approved protocols are submitted via Kuali Research Protocols (KRP).

Per federal regulations, once a human research study has received IRB approval, any subsequent changes to the study must be reviewed and approved by the IRB prior to implementation except when necessary to avoid an immediate, apparent hazard to a subject.

Per UCI Human Research Protections (HRP) policy, amendments are NOT required for the following administrative determinations:

  • Non-Human Subjects Research (NHSR)
  • Exempt Self-Determination

Amendments for these determinations are to be tracked by the Lead Researcher independently outside of KRP. If the amendment changes the level of review to where IRB review is required, a new protocol must be submitted.

Alignment with the 2018 Common Rule

For research that was initially approved before January 19, 2019, the IRB may request additional changes to the protocol to align with the 2018 Common Rule.  Changes may include, but are not limited to:

  • addressing new questions in the KRP form
  • updating the consent form to the current UCI template
  • revising the level of review

For more information, see: Checklist - Transition 2018 Common Rule.

Amendment to Exempt Research that requires IRB Approval

Research activities in which the only involvement of human subjects will be in one or more of the categories specified under 45 CFR 46.104 (d) are exempt from the requirements of the basic Health and Human Services Policy for the Protection of Human Research Subjects (Subpart A). Because of this, and in an effort to streamline, the UCI HRP has implemented several efficiencies related to exempt research. Examples:

Significant Changes to Exempt research - DO submit an amendment to the UCI IRB when:

  1. When adding a new population as follows:
    1. A targeted recruitment of children
    2. A targeted recruitment of adults (age 18 or older) who may not be legally/mentally/cognitively competent to consent
    3. A targeted recruitment of prisoners
    4. A targeted recruitment of American Indian/Alaska Native tribes
    5. A targeted recruitment of undocumented people
  2. Adding non-UCI personnel engaged in research: a) intervening or interacting with the participants and/or b) having access to participant identifiable private information for research purposes.
  3. Adding the use of the UCI Social Science Human Subject Lab (SONA).
  4. Adding an international research site
  5. Adding questions about sensitive aspects of the participants’ behavior such as illegal conduct, drug use, sexual behavior or use of alcohol – to a survey or interview
  6. For a change in study LR
  7. To disclosure a new financial interest
  8. When adding Department of Justice (DOJ) funding
  9. For any change that makes the study no longer eligible for Certification of Exemption (study will require expedited or full committee review)

Minor Changes to Exempt Research - DO NOT submit an amendment to the UCI IRB when:

  1. Making editorial or administrative revisions to consent documents or other study documents
  2. Adding non-sensitive questions to a survey or interview or revising current questions
  3. Adding a new recruitment material that follows IRB guidelines
  4. Increasing or decreasing the number of participants - unless adding a new population as noted below**
  5. Making study team/personnel changes - except a change in Lead Researcher (LR)

Non-Exempt Research Amendment

Types of Amendments

Amendments are categorized into minor and significant changes.

Minor change - A proposed change in research related activities that does not significantly affect an assessment of the risks and benefits of the study and does not substantially change the specific aims or design of the study.

Significant change - A proposed change in research related activities that significantly affects an assessment of the risks and benefits of the study or substantially changes the specific aims or design of the study.

Level of Review for Amendment

An amendment to an approved human research study will generally be reviewed at the same level of review in which the study was first reviewed, however, it is the level of risk posed to the subject that helps determine the review process (via subcommittee or full committee).

  • Minor changes may undergo subcommittee review
  • Significant changes require review by the full committee (Please be aware of the submission deadlines for full committee review of amendment requests).

Examples of Minor and Signification Non-Exempt Research Amendments:

IRB Submission Deadlines & Meeting Dates

2022 IRB Full Committee Calendar

Significant changes to a study may include, but are not limited to, the following:

  • Broadening the range of inclusion criteria;
  • Narrowing the range of exclusion criteria;
  • Alterations in the dosage or route of administration of an administered drug;
  • Extending substantially the duration of exposure to the test material or invention;
  • The deletion of laboratory tests, monitoring procedures, or study visits directed at the collection of information for safety evaluations;
  • The addition of serious unexpected adverse events or other significant risks to the Informed Consent Disclosure; or
  • Changes, which, in the opinion of the IRB chairperson or his/her designee, do not meet the criteria or intent of a minor modification;
  • The addition of a qualified investigator with a disclosable conflict of interest.

Minor changes to a research study include but are not limited to, the following:

  • The addition of research activities that would be considered independent of the main research protocol;
  • An increase or decrease in proposed human research subjects' enrollment;
  • Narrowing the range of the inclusion criteria;
  • Broadening the range of the exclusion criteria;
  • Alterations in the dosage form (e.g., tablet to capsule or oral liquid) of an administered drug, provided the dose and route of administration remains constant;
  • Decreasing the number or volume of biological samples collections, provided that such a change does not affect the collection of information related to safety evaluations;
  • A decrease in the length of hospitalization or number of study visits, provided that such a decrease does not affect the collection of information related to safety evaluations;
  • Alternations in human research participant payment or alteration of the payment schedule with proper justification;
  • Changes to improve the clarity of statements or to correct typographical errors, provided that such a change does not alter the content or intent of the statement;
  • The addition or deletion of qualified investigators;
  • The addition of study sites (which may require a Federal Wide Assurance (FWA) and appropriate IRB approval) or the deletion of study sites; or
  • Minor changes specifically requested by the Conflict of Interest Oversight Committee (COIOC); the Institutional Biosafety Committee (IBC); the Scientific Review Committee (SRC); or other University Committees with jurisdiction over the research.

Notification of IRB Approval

Approval of amendment requests are documented in an approval letter to the Lead Researcher, and copied to the Faculty Sponsor (if applicable).

Amendment approvals will be uploaded in KRP.

Reminder: Approved amendments do not extend the approval period of the protocol.

Protocol Renewal

When and How to Renew an IRB Approved Human Research Study

All renewals must be submitted to the IRB via a Renew&Amend transaction in Kuali Research Protocols (KRP).

A Renew&Amend transaction is required even if there are no changes to the protocol. This is required to facilitate the approval process in KRP.

Be sure to upload all relevant documentation for the continuing review; additional documentation includes, but is not limited to, offsite IRB approval letters, updated letters of permission, multi-site progress report, data safety monitoring report, deviation tracking log, etc.

Alignment with the 2018 Common Rule

For research that was initially approved before January 19, 2019, the IRB may request additional changes to the protocol to align with the 2018 Common Rule.  Changes may include, but are not limited to:

  • addressing new questions in the KRP form
  • updating the consent form to the current UCI template
  • revising the level of review

For more information, see: Checklist - Transition 2018 Common Rule.

Renewal of Minimal Risk (Exempt/Expedited) Research

An abbreviated continuing renewal must be submitted prior to the end of the IRB approval period. Completion of this application should take no more than 15 minutes. The information provided will help verify what research projects remain active at UCI.

Exceptions: Expedited IRB protocols that meet the following criteria must submit a full continuing renewal annually (not more than 365 days):

  • research is subject to Food and Drug Administration (FDA) regulations
    • Involves a drug
    • A clinical investigation of a medical device
  • research is funded/supported by the Department of Justice (DOJ)
  • current approval period is 1 year or less

Per OHRP Continuing Review Guidance, and FDA IRB Continuing Review after Clinical Investigation Approval Guidance:

Expedited Category 8 - Under OHRP category 45 CFR 46.110(F)(8), and for FDA regulated research 21 CFR 56.110(b), an expedited review procedure may be used for the continuing review of research previously approved by the convened IRB as follows:

 

Expedited Category 8(a)* where all of the following are true:

    • the research is permanently closed to the enrollment of new subjects; and
    • all subjects have completed all research-related interventions; and
    • the research remains active only for long-term follow-up of subjects;

*NOTE: Under expedited review category (8)(a), OHRP and FDA interpret “long-term follow-up” to include:

      • Research interactions that involve no more than minimal risk to subjects (e.g., quality of life surveys); and
      • Collection of follow-up data from procedures or interventions that would have been done as part of routine clinical practice to monitor a subject for disease progression or recurrence, regardless of whether the procedures or interventions are described in the research protocol.

In contrast, OHRP and FDA interpret “long-term follow-up” to exclude:

      • Research interventions that would not have been performed for clinical purposes, even if the research interventions involve no more than minimal risk.

OR

Expedited Category 8(b)** where both of the following are true:

    • no subjects have been enrolled; and
    • no additional risks have been identified;

**NOTE: while the criterion that “no subjects have been enrolled” is interpreted by OHRP and FDA to mean that no subjects have ever been enrolled at a particular institution, the criterion that “no additional risks have been identified” is interpreted to mean that neither the investigator nor the IRB at a particular institution has identified any additional risks from any institution engaged in the research project or from any other relevant source since the IRB’s most recent prior review.

OR

Expedited Category 8(c) *** where the remaining research activities are limited to data analysis.

***NOTE: Under expedited review category 8(c), an IRB may use an expedited review procedure to conduct continuing review when the only remaining human subjects research activity is the analysis of data that includes identifiable private information and the IRB chairperson (or another experienced IRB member designated by the chairperson) determines that this activity involves no more than minimal risk.

 

Expedited Category 9 - Under category 45 CFR 46.110(F)(9), an expedited review procedure may also be used for the continuing review of research previously approved by the full Committee when the research is not conducted under an investigational new drug application (IND) or investigational device exemption (IDE) where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

Federal Requirements for Protocol Renewal

For research meeting the following criteria, DHHS and FDA regulations require the IRB to continually review ongoing research at intervals appropriate to the potential risk to participants, but at least annually.

  • Research that involves greater than minimal risk to subjects
  • Research that is FDA regulated:
    • Involves a drug
    • Clinical investigation of a medical device
  • Research that involves no greater than minimal risk to subjects, funded/supported by federal entities, and initially approved by the IRB prior to January 21, 2019.

While initial IRB review is based on the researcher's best assessment of the anticipated benefits, risk, and procedures, the continuing review process is important because it is based on the conduct of the study; actual risk can be evaluated and preliminary results used to assess the risk/benefit ratio. In addition, the risk/benefit ratio may change not only because of unexpected results and effects of the research intervention itself, but because new knowledge resulting from related research may affect the balance.

Per OHRP, continuing review must be substantive and meaningful. The criteria to grant continuing IRB approval are the same criteria required for initial IRB approval of the research (45 CFR 46.111 and 21 CFR 56.111)

  • Risks to subjects are minimized.
  • Risks to subjects are reasonable in relation to anticipated benefits.
  • Selection of subjects is equitable.
  • Selection of subjects is equitable.
  • Informed consent will be sought.
  • Informed consent will be appropriately documented.
  • When appropriate... adequate provision for monitoring the data.
  • When appropriate... adequate provisions to protect the privacy and confidentiality.
  • Appropriate safeguards have been included to protect vulnerable subjects.

Per OHRP and FDA, when conducting continuing review of the research the IRB must be provided with the following information:

  • The number of participants enrolled;
  • A summary of adverse events and any unanticipated problems involving risks to participants
  • The number of participants that have withdrawn including the reasons;
  • A summary of any complaints about the research;
  • A summary of any relevant recent literature, interim findings, and modifications to the research since the last review;
  • A current risk/benefit assessment based on the existing study results;
  • Any other relevant information, especially information about risks associated with the research; and
  • A copy of the current informed consent document.

If approval of the research is suspended or terminated, the IRB is required to report its decision promptly to the researcher, the Department Chair, the institutional official, and the appropriate federal department or agency head (or designated office, such as FDA and OHRP).

Alternatively, the IRB may impose additional precautions or reassess special requirements it had previously imposed on the research. For example, the IRB has authority to observe, or have a third party observe, the consent process as well as the research itself. The IRB determines the frequency of continuing review (at least annually) for each study based on the complexity and risk involves in the study adequate to assure the continued protection of the rights and welfare of research participants.

IRB Submission Deadlines & Meeting Dates

2022 IRB Full Committee Calendar

Expiration and Lapses in IRB Approval

Investigators must plan ahead to meet required continuing review dates. If an investigator fails to submit a renewal to the IRB or the IRB does not approve continuation of the research before the date of expiration, the research must stop. All of the following research procedures must stop:

  • Subject recruitment or enrollment
  • Collection of data/information from or about living individuals
  • All research-related interventions or interactions with currently enrolled subjects*
  • Data analyses involving subject identifiable data

*Exception: Research-related interventions or interactions with currently enrolled subjects can continue only if stopping the research would jeopardize the rights or welfare of current subjects. The IRB must make this determination and decide which subjects should continue with the intervention during the lapse. A request for such an exception must be made in the writing to the IRB by the Lead Researcher.

Failure to maintain current approval may disqualify data intended for submission to the FDA (e.g., studies of investigational drugs and devices), other federal agencies, and sponsors. It may also result in embargo of data collected during a lapse of approval. Performance of study procedures during lapses in approval also may result in regulatory committee (IRB) sanctions.

Timing to Avoid Expiration of Approval

As a courtesy, the Human Research Protection Program sends the Lead Researcher and Administrative Contact an email reminder to submit for continuing approval. The email reminder is sent 90, 60, and 30 days prior to the expiration date of the IRB approval. Investigators should plan their submissions accordingly to avoid expiration of IRB approval.

  • There are no formal submission deadlines for Expedited or Exempt research. Renewals are reviewed on a rolling basis; usually within 3-4 weeks.
  • There are submission deadlines for Full Committee research. Renewals must be received by 5 pm on the deadline day to be considered for the IRB meeting agenda.
  • Other prerequisite UCI Reviews may impact the timing of the continuing review.

 

IRB Approval Period

Federal regulations make no provision for any grace period extending the conduct of research beyond the expiration of IRB approval. Therefore, continuing review and re-approval of research must occur on or before the date when IRB approval expires. Investigators are responsible for submitting a renewal and maintaining current IRB approval (or exempt registration) until all the following occur:

  • Subject recruitment has concluded (i.e., no subject recruitment is in progress or anticipated)
  • All subject specimens, records, data have been collected (i.e., no further collection of data/information from or about living individuals is needed)
  • All interactions or interventions with subjects are completed (i.e., no further contact with subjects is necessary or anticipated)
  • Analyses of subject identifiable data, records, specimens are finished (i.e., use or access to subject identifiable data is no longer necessary.

Note: Investigators performing industry-sponsored research should discuss study closure with the study sponsor or Clinical Research Organization before formally closing human research studies with the IRB. Once a study is closed, all data collection and analysis of subject identifiable data and review of source documentation must stop.

Reporting a Problem

The most common reporting issues are listed below, followed by an explanation of what steps the IRB may take in instances where repeated problems arise, along with some additional resources.

Reporting a Protocol Deviation

Minor Deviation

A minor deviation is an unintentional change to or noncompliance with the research protocol that does not have a significant effect on the subject's rights, safety or welfare, and/or on the integrity of the data. Deviations may result from the action of the participant, researcher, or research staff. Examples of deviations include:

  • Follow up visits occurring outside the protocol required time frame because of the participant’s schedule
  • Blood samples being obtained at times close to but not precisely at the time points specified in the protocol
  • Failure to collect an ancillary self-report questionnaire
  • Failure to use the IRB stamped Consent Form when consenting a subject
  • Over-enrollment of subjects on minimal risk studies
  • Use of translated consent documents without first submitting to the HRP for review and approval

The UCI IRB does not require a report of minor deviations. However, if the Sponsor requires the submission of a report to the IRB, a Deviation Tracking Log may be submitted at the time of renewal.

Major Deviation

There are two types of major deviations that can occur: 1) emergency deviations and 2) non-emergency deviations.

All major deviations must be promptly reported to the UCI IRB as follows:

Emergency deviations involve a departure from the approved protocol to avoid an immediate hazard to the participant. Emergency deviations may occur without time for prospective IRB review and approval. However, a report of the event must be submitted within 5 business days of the Lead Researcher (LR) learning of the event. If the emergency deviation meets the definition of an Unanticipated Problem, log into Kuali Research Protocols (KRP) and submit a Reportable Event-Unanticipated Problem (UP); otherwise, submit an Amendment.

Non-emergency deviations are planned (non-emergent) and represent a major change in the approved protocol. Major, non-emergency deviations should be submitted to the UCI IRB for prospective review (in advance of the event). Log into KRP and submit an Amendment or a Prospective Deviation (see below).

Prospective Deviation Request

A prospective deviation is an anticipated and/or intentional and known deviation to the protocol for no more than 3 subjects before they occur.  Examples of prospective deviations to a research study include but are not limited to, the following:

  • Inclusion/exclusion criteria deviation
  • Allowing subject to remain in study despite reaching an endpoint or progression of disease
  • Dosing variance

If the deviation will occur within 96 hours, log into KRP and submit a Reportable Event-Prospective Deviation; otherwise, submit an Amendment.

Reporting Noncompliance

Noncompliance (Not reportable to the IRB)

Noncompliance is when a research team fails to comply with the requirements of an applicable law, regulation, or institutional policy pertaining to the protection of human subjects, and/or with the requirements or determinations of an IRB. Often noncompliance that is not serious or continuing is considered a minor deviation.

The UCI IRB does not require a report of noncompliance; unless it constitutes an unanticipated problem and/or serious and/or continuing noncompliance. However, if the Sponsor requires the submission of a noncompliance report to the IRB, a Deviation Tracking Log may be submitted in Kuali Research Protocols (KRP) at the time of renewal.

Serious and/or Continuing Noncompliance (Reportable to the IRB)

Serious noncompliance is noncompliance that has a significant adverse impact on the rights or welfare of participants or on the integrity of the data.

Continuing noncompliance is a pattern of noncompliance that indicates an inability or unwillingness to comply with applicable laws, regulations, or institutional policies pertaining to the protection of human subjects and/or with the requirements or determinations of an IRB.

Possible examples of serious and/or noncompliance may include:

  • Failure to obtain prospective IRB approval for an additional research related activity not currently listed on the IRB approved protocol
  • Failure to obtain signed informed consent or HIPAA from subjects as required from the IRB
  • Failure to collect screening labs before initiation of study procedures.
  • Enrolling a participant who does not meet the inclusion criteria

All incidents of serious and/or continuing noncompliance that occurs either at a UCI site (UCI Main Campus, UCIMC, including UCIMC satellite clinics), or occurs at a non-UCI site where the UCI IRB is the IRB of record, must be reported to the IRB within 5 business days of the occurrence or within 5 business days from the date in which the LR learned of the occurrence. If the serious and/or continuing noncompliance meets the definition of an unanticipated problem, log into KRP and submit a Reportable Event.

Reporting Unanticipated Problems

Definition of an Unanticipated Problem

UCI considers both OHRP and FDA guidance when assessing whether an event constitutes an unanticipated problem. In accordance with Federal regulations and HRP policies, an Unanticipated Problem (UP) is defined as:

  1. Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; and
  2. Related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Reasonable judgment must be used when determining what constitutes an Unanticipated Problem. Researchers must consider the psychological, emotional, economic and social harms, not merely physical harms. When in doubt, it is best to err on the side of reporting the event or contact the Human Research Protections (HRP) staff for guidance.

External Unanticipated Problems

FDA guidance on Adverse Event Reporting to IRBs — Improving Human Subject Protection states that it is neither useful nor necessary for reports of individual adverse events occurring at other multi-center sites to be distributed routinely to investigators or IRBs at all institutions conducting the research.

The LR is expected to review any external unanticipated problem reports and determine whether the report indicates a change in the risk/benefit profile. If the report indicates a change in the risk/benefit profile, log into Kuali Research Protocols (KRP) and submit an Amendment with the appropriately revised IRB-approved documentation.

If UCI is the coordinating site and IRB of record, the LR will need to assess if the change to the risk/benefit profile necessitates the submission of a Reportable Event-Unanticipated Problem (UP).

Responsibility to Report Unanticipated Problems

Unanticipated problems must be reported when:

  • The event occurred at a UCI site (UCI Main Campus, UCIMC, including UCIMC satellite clinics) where UCI is the IRB of record (the reviewing IRB) OR
  • The event occurred at a non UCI site, with a non-UCI researcher, where the UCI IRB is the IRB of record (the reviewing IRB)

Reporting Timeframe and Method

Log into KRP and submit a Reportable Event-Unanticipated Problem (UP) within 5 business days of the occurrence or within 5 business days from the date in which the LR learned of the occurrence.

A timely submission of follow-up UP is required if the unanticipated problem is unresolved at the time of the initial report or if the unanticipated problem results in a chronic condition or death.

Unanticipated Adverse Device Effect (UADE)

Devices may have an UADE to participants or others.  The investigational device exemption (IDE) regulations define an UADE as “any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects”.

UADEs must be reported by the clinical investigator to the sponsor and the IRB (via an UP), as described below:

  • For device studies, investigators are required to submit a report of a UADE to the sponsor and a UP to the UCI IRB as soon as possible, but in no event later than 5 business days after the investigator first learns of the event (§ 812.150(a)(1)).
  • Sponsors must immediately conduct an evaluation of a UADE and must report the results of the evaluation to FDA, all reviewing IRBs, and participating investigators within 10 working days after the sponsor first receives notice of the effect (§§ 812.46(b), 812.150(b)(1)).

Unanticipated Problems Related to a Humanitarian Use Device (HUD)

Whenever the physician or health care provider receives or otherwise becomes aware of information, from any source, that reasonably suggests that a HUD has or may have caused or contributed to the death or serious injury of a patient, the physician or health care provider must report such findings to the FDA and submit a UP to the UCI IRB as soon as possible, but no later than 5 business days after the physician first learns of the event/problem. This reporting is in addition to, not a substitute for, FDA and/or manufacturer reporting requirements in accordance with 21 CFR 803.30.

The physician or health care provider must promptly report any FDA action regarding the death or serious injury to the patient to the IRB.

Significant Findings Discovered from Unanticipated Problems

Federal regulations require that research participants be informed of all significant new findings identified during the course of the research.  A significant new finding may affect the willingness of subjects to continue to participate in the research.  

Significant findings almost always involve necessary changes to the Protocol and Consent Form (e.g., the addition of new risks posed to participants).  If the Unanticipated Problem involves significant findings, in addition to submitting a UP, submit an Amendment with the appropriately revised IRB-approved documentation. It is helpful to reference the UP when submitting the Amendment.

Reporting Protocol Violations

A protocol violation is an accidental or unintentional change to or noncompliance with the IRB-approved protocol that increases risk or decreases benefit and/or affects the subject's rights, safety, welfare, and/or the integrity of the data. A protocol violation is generally either an unanticipated problem and/or serious noncompliance and must be reported within 5 business days of the occurrence or within 5 business days from the date in which the LR learned of the occurrence. If the protocol violation constitutes an unanticipated problem, log into Kuali Research Protocols (KRP) and submit a Reportable Event.

Reporting Data Breaches and Data Safety Monitoring

Data Breaches

A data security breach (e.g., a stolen laptop or misplaced thumb drive) involving identifiable data almost always constitutes an unanticipated problem. If this occurs, log into Kuali Research Protocols (KRP) and submit a Reportable Event-Unanticipated Problem (UP) within 5 business days of the occurrence or within 5 business days from the date in which the LR learned of the occurrence.

For a data security breach that involves protected health information (PHI) under HIPAA, the LR must contact the UCI Health Privacy Compliance Officer at 714-456-3672 or hacompliance@uci.edu.

In addition, it is strongly advised that the LR contact the OIT Response Center at (949) 824-2222 to report that a potential security breach has occurred and request immediate notification of the OIT security staff and the Security Breach Lead Campus Authorities. Information may be sent via email to security@uci.edu with a copy to security-lca@uci.edu.

Data Safety Monitoring Board Reports

The LR is expected to review any Data and Safety Monitoring Board (DSMB) reports and determine whether the report indicates a change in the risk/benefit profile. If the report indicates a change in the risk/benefit profile, log into KRP and submit an Amendment with the appropriately revised IRB-approved documentation.

If UCI is the coordinating site and IRB of record, the LR will need to also assess if the change to the risk/benefit profile necessitates the submission of a UP. If the LR determines that an UP report is not necessary, the DSMB report should be submitted at the time of renewal.

Reporting Serious Adverse Events

Adverse Events and Safety Reports

Adverse events are untoward or unfavorable occurrences in a human subject, including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research. Safety Reports are external adverse events.

Adverse events should only be reported to the IRB when the event changes the risk/benefit profile of the study and/or when the IRB-approved documents (e.g., protocol and consent form) must be revised. Log into Kuali Research Protocols (KRP) and submit an Amendment with the appropriately revised IRB-approved documentation.

Serious Adverse Event Reporting Requirements for Human Gene Transfer Research

Human gene transfer (a.k.a. "gene therapy") protocols have additional adverse event reporting responsibilities. The NIH Guidelines require that any significant problems, violations, or any significant research-related accidents and illnesses” be reported to the NIH Office of Science Policy (OSP) within 30 days.  If the gene transfer study is supported by an external sponsor, this reporting should be coordinated with the sponsor. In addition to submitting a serious adverse event (SAE) to the OBA, the LR must submit SAEs to the UCI Institutional Biosafety Committee (IBC), and any unanticipated problems to the UCI IRB via a Reportable Event-Unanticipated Problem (UP).

Failure to report gene transfer SAEs to the federal oversight bodies (FDA, NIH-OSP) may result in sanctions for the LR and for the institution. For more information regarding the additional reporting responsibilities for human gene transfer research, please refer to the OSP main webpage, the OSP FAQ page on incident reporting, or contact the UCI IBC.

IRB Review of Unanticipated Problems and Serious and/or Continuing Noncompliance

The UCI IRB will review the Reportable Event in a timely manner and confirm whether the submission constitutes an unanticipated problem involving risk to participants or others. The IRB will consider a range of possible corrective actions such as:

  • Suspend or terminate the research
  • Notify current participants when such information might be related to their willingness to continue to take part in the research (e.g., reconsenting participants)
  • Require modifications to the protocol and/or consent documents
  • Provide additional information to past participants (e.g., long-term risks have been identified that could affect them)
  • Increase the frequency of continuing review
  • Impose additional monitoring requirements
  • Require additional training of the researcher and research team
  • Notify other UCI committees or departments

The UCI IRB will report any unanticipated problems to the LR, appropriate UCI officials, the funding agency or study sponsor, if applicable, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA) and other applicable regulatory authorities.

The UCI IRB has the authority to suspend or terminate approval of research that has been associated with unexpected serious harm to participants. When an IRB Committee takes such action, it is required to provide a statement of reason for the action and to promptly report this action to the LR, appropriate UCI officials, the funding agency or study sponsor, if applicable, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA) and other applicable regulatory authorities.

Resources

Lead Researcher Recordkeeping Responsibilities

Overview

The Office of Research (OR) maintains an official protocol file for each study to meet the University's regulatory obligations for record keeping. The IRB staff is not responsible for maintaining study documents for the researchers, or for providing copies of official documents to research staff. Keeping accurate and complete protocol records is the responsibility of the Lead Researcher.

General IRB Records Retention Requirements

Effective April 1, 2020:

In accordance with UC Office of the President policy, research records must be retained for 10 years after the end of the calendar year in which the research is completed unless otherwise specified in the award agreement.

If research involves the investigation of FDA regulated products: Information/biospecimens must be retained for two years after an approved marketing application. If approval is not received, the information/biospecimens will be kept for 2 years after the investigation is discontinued and the FDA is notified per FDA sponsor requirements.

For more information on UCOP Retention and Disposition Requirements as of October 2018, visit their web page to view the matrix.*

*While signed consent forms are not considered an IRB administrative record for the purposes of this matrix, OHRP and FDA regulations require that signed consent form documents must be retained for a minimum of three years past the completion of a study. If a research study accesses protected health information (PHI) and is covered under the Health Insurance Portability Accountability Act (HIPAA) policy, consent forms are to be retained for a minimum of six years after the completion of a study.

Preparation and Maintenance of a Research Audit File

Purpose of a Research Audit

To preserve subject welfare and integrity of research data, various internal and external entities may request access to a Lead Researcher's study records for purposes of conducting an audit. Audits may be conducted for cause (i.e., to investigate an allegation) or for quality control purposes.

Examples of internal entities that may audit research records are the:

  • UCI IRB and Office of Research Administration staff,
  • UCIMC Office of Clinical Research Oversight and other authorized UCIMC personnel;
  • UCI Office of Internal Audit
Calculator Pen And Journal

Examples of external entities that may audit research records are:

  • U.S. Food and Drug Administration,
  • Office for Human Research Protections (OHRP), and
  • For-profit sponsors of research (such as pharmaceutical companies)

External Audits

Any time an audit of study records is conducted by an external entity other than the UCI IRB, it is the responsibility of the Lead Researcher to inform the IRB promptly. If the Lead Researcher is given notice of an audit by an external entity, the IRB may send a representative to observe proceedings of any "exit interview" which may occur. Finally, the written report of any audit findings for a UCI study must be forwarded to the IRB for their records.

When UCI personnel receive notices about external audits (on-site and remote), they should immediately contact Internal Audit Services (IAS) at 949-824-7459 or 949-824-6757.  A copy of the Sponsor's audit notification letter should be sent to Loran Lerma (LLerma@uci.edu).

Documentation

Documentation is an integral and important component of conducting research with human subjects. From the first draft of a protocol application to the completion of a study, much that occurs in between is dependent on the consistency, accuracy and accountability of the study's accumulated documentation (e.g., correspondence between the investigator and the Institutional Review Board, a study sponsor, a funding agency, regulatory agencies; various reports including case report forms, personal and/or medical information on subjects, etc.).

Suggested Ways to Organize Documents

The following is provided to assist investigators and their staff to organize the numerous documents, making them easily retrievable when needed. (In funded studies, sponsors may require such files, maintained in a specific fashion.) Although the information provided below is weighted toward clinical studies, variations of it can be employed in almost any research study with human subjects.

  • All files should be kept in one designated area (e.g., the Lead Researcher's office, lab, etc.)
  • All documents should be maintained in chronological order. A sturdy three ring binder, containing dividers with some or all of the following headings (depending on the study), is recommended; however, researchers may also consider maintaining their records electronically:
    • Sponsor Correspondence if the study is formally funded or sponsored (e.g., NIH, NSF; drug/device company).
    • Investigator's Assurance and other forms, such as the HHS form 596 and/or FDA 1572, 1573, 1574 forms.
    • IRB Approvals...

IRB Approvals can be subdivided, as follows:

  • Initial Approval
    • Retain and insert a copy of the original IRB application form, signed by the Lead Researcher, faculty sponsor (if necessary) and Department Chair.
    • The original IRB approval letter.
    • A copy of the final, IRB approved, dated protocol along with any amendments. ** (If there is a "master" protocol, it, along with revised sections, might also be filed separately under the heading "Master Protocol" toward the back of the file, or in a separate binder.)
  • Modification Forms - Requests/Approvals
    • Include a copy of the e-IRB modification form submitted electronically by the Lead Researcher.
  • Continuing Review - Applications/Approvals
    • Include a copy of the continuing review application signed by the Lead Researcher. Add (clip or staple) the new, original IRB approval letter covering the next approval period as well as the original, stamped consent form.
  • Adverse Event Reports - "AEs"
    • Include a copy of each, noting the dates that each report was sent to the IRB, sponsor, FDA, etc. If any change to the protocol or consent form is made as a result of adverse experiences, maintain a copy of the changes with the pertinent AE reports.
  • Approved Consent form(s)
    • Include a copy of each (if there are more than one) approved consent form (with the IRB's stamp affixed thereon). **The most currently approved consent form is the one from which copies are to be made when enrolling new subjects.
    • If the consent form requires revision during the course of the study, retain the original in the file and send a copy of it with a revised original for IRB review and approval.
    • To avoid the possibility of using an obsolete version, retain the most currently approved version on top, and draw a diagonal line through each page of the obsolete version when the newly approved one is received.
    • Subdividers can be used to separate years (e.g. 2001 approval, 2002 approval, 2003 approval, etc.) for studies which will continue over several years.
  • Approved Advertising (when applicable)
    • Maintain a copy of each advertisement (including flyers, posters, "scripts," etc.) approved for use by the IRB (and containing the IRB stamp).
    • Notes can be made on each advertisement showing when it was placed and where. Any correspondence relating to advertising can be maintained in this section as well.
  • Study Closure/Completion
    • Complete the "IRB Closing Report" and submit it to the IRB to close a study. The report must be submitted by the Lead Researcher electronically.

** For documents approved prior to June 2008, the Lead Researcher should keep the original purple stamped copy for the research record.

In studies sponsored by a drug or device company, the following, additional sections will likely be required:

  • Subject Enrollment/Assignment Log
  • Drug Dispense/Return Log and Drug Receipt/Ship Log
    • These will be the originals received from the sponsor for drug receipt, dispensing date, drug count, and final return.
  • Shipment Receipts/Lab Supplies
    • If the study requires that samples be sent to a central lab, or if the sponsor provides lab supplies (special catheters, test kits, etc.) the accompanying invoices, shipment logs, or UPS/Fed Ex receipts will need to be retained.
  • Monitor Visit Log (as applicable)
  • Master Protocol
    • As mentioned previously, a large, bulky master protocol may be maintained in a separate section.
    • When revisions/amendments to protocols are made by a sponsor, most sponsors will provide investigators dated replacement pages. Unless the sponsor specifically requires the old pages be discarded, it is suggested that a horizontal line be drawn through the page(s) or section(s) being revised and the new information inserted.
  • Sponsor Agreement(s)/Contract(s)
    • This material should include the UCI Sponsored Projects (SP) Administration Clinical Study Agreement, signed by SP officer and the sponsor, and any other documents pertaining to agreements between the institution and the sponsor relative to performance of the study.

Closing a Protocol

A study may be closed when all the following apply:

  • All subject recruitment and enrollment is complete (i.e., no new subject recruitment or enrollment are ongoing)
  • All subject specimens, records, data have been obtained (i.e., no further collection of data/information from or about living individuals will be obtained)
  • No further contact with subjects is necessary (i.e., all interactions or interventions are complete and no further contact with enrolled subjects is necessary)
  • Analysis of subject identifiable data, records, specimens are complete (i.e., use or access to subject identifiable data is no longer necessary. Note: this includes review of source documents by study sponsors.

In order to close an IRB protocol officially, submission of a closing report in KRP is required.

Once the closure has been received and accepted by the IRB, a confirmation email will be sent to the Lead Researcher (LR) and Administrative Contact.

Note: The official retention period for UCI's IRB records begins on the date a closing report is submitted to the IRB by the LR. For more information about the LR's IRB record retention responsibilities, please see Lead Researcher Recordkeeping Responsibilities (hyperlink) and Preparation and Maintenance of a Research Audit File. (hyperlink)