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Modifications to Approved Research

When and How to Modify an Approved Human Research Study

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. See Reporting of Unanticipated Problems.

To request approval of a proposed modification, complete and submit a Modification (MOD) Request.

Note: If the proposed modification changes any IRB approved documents (e.g., the protocol narrative, the informed consent form, study information sheet etc.), the investigator must submit an updated version of each document for IRB review. Upload two (2) versions of the revised documents with the MOD request:

  • a clean copy of each revised document (changes not highlighted), and
  • a highlighted copy of each revised document (all changes highlighted).

NEW UPDATE FOR EXEMPT RESEARCH ONLY: 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. Reseaerchers can read more about this, including information on the recently expanded exempt self-determination process on the Office of Research HRP Listserv here: https://news.research.uci.edu/?s=exempt 

Examples of minor changes to exempt research: Do NOT submit a modification 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)

There are exceptions when a modification application must be prospectively submitted to the UCI IRB for review and approval.  These align with the exceptions in the Exempt Self-Determination Tool.  Please note the following significant changes that would require UCI IRB review:

Examples of significant changes to exempt research: DO submit a modification to the UCI IRB when:

1.    **When adding a new population as follows:
       a.    A targeted recruitment of children
       b.    A targeted recruitment of adults (age 18 or older) who may not be legally/mentally/cognitively competent to consent
       c.    A targeted recruitment of prisoners
       d.    A targeted recruitment of American Indian/Alaska Native tribes
       e.    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)

Types of Modifications - Non Exempt Research

Modifications are categorized into minor changes and significant changes.

Minor modification/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 modification/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.

Examples:

Examples of minor changes to a research study include but are not limited to, the following:

  • The addition of research activities that would be considered independent from 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); Institutional Biosafety Committee (IBC); the Scientific Review Committee (SRC); or other University Committees with jurisdiction over the research.

Examples of 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.

Modifications can also occur as prospective deviations to the protocol.

Prospective Deviations – 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:

  • Continuation of research activities during lapse in IRB approval
  • Inclusion/exclusion criteria deviation
  • Allowing subject to remain in study despite reaching an endpoint or progression of disease
  • Dosing variance

To request approval of a proposed prospective deviation, complete and submit a Prospective Deviation Request.  Do not use this form for routine, non-significant reporting of issues such as out-of-window or rescheduled visits. 

Level of Review for Modifications - Non Exempt Research

A modification/change to an approved human research study will generally be reviewed at the same level of review in which the study was first reviewed, either by the Expedited review process or by the full Committee.

  • Minor changes may undergo Expedited (subcommittee) review
  • Significant modifications/changes require review by the full Committee.

Sponsor Modifications

Modifications can be made only to IRB approved studies. A sponsor may modify the research protocol before the study has received final approval from the IRB. If this occurs, it is recommended that investigators await receipt of the IRB approval letter before making changes to the research protocol.

Sponsor generated modifications (or addenda) require review and approval by the UCI IRB. The UCI investigator should provide the IRB with all sponsor documentation and summarize in the e-mod request how the changes affect the UCI approved protocol, recruitment, enrollment, treatment and follow-up of UCI participants. The sponsor documentation can be uploaded via the MOD request process.

Notification

Approval of electronically submitted modification requests are documented in an approval letter to the Lead Researcher, and copied to the Faculty Sponsor (if applicable). Approved modifications are appended to the protocol in the official IRB file.

Note: Approved modifications do not extend the approval period of the protocol.

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