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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 Adverse Events, Unanticipated Problems and Violations.

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).

Types of Modifications

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.

Level of Review for Modifications

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.
    • Investigators submitting minor modifications are required to submit the following hard copies:
      • 1 copy of the updated Sponsor/Master protocol and/or Investigator Brochure (if applicable)
      • 1 copy of any required documentation not previously uploaded via the MOD process (e.g., no electronic version of permission letter)
  • Significant modifications/changes require review by the full Committee.
    • Changes to the informed consent document for full Committee studies usually require full Committee review.
      • There are submission deadlines for Full Committee review of modification requests. Full Committee modifications and all required hard copies must be received in ORA no later then 5 pm of the meeting deadline to be considered for the IRB meeting agenda.
    • Investigators submitting full Committee modifications are required to submit the following hard copies:
      • 2 copies of the updated Sponsor/Master protocol and/or Investigator Brochure (if applicable)
      • 2 copies of required documentation not previously uploaded via the MOD process (e.g., no electronic version of permission letter)

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; however hard copy documentation (see above) must also be received by the Office of Research. Please reference the HS# and MOD number when submitting hard copy documentation.

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.