Series 408 Modifications to Approved Protocols

I. Types of Modifications

After a protocol has been approved, researchers may need to make modifications. For guidance on modifications to Exempt projects, please see SOP 404 Section III. This SOP describes modifications for protocols that have been reviewed via the Expedited or Convened IRB Review processes.

Modifications may be minor, or they may be major. Minor modifications are those which, in the judgment of the IRB, makes no substantial alteration in the level of risks to participants, the research design or methodology, the participant population, the qualifications of the research team, the facilities available to support safe conduct of the research, or any other factor that does not impact the assessment of the Criteria for Approval in SOPs 405 and 406.

Major modifications are those which, in the judgment of the IRB, changes the risk level to participants, substantially changes the research design or methodology, involves a new type of participant population, impacts the qualifications of the research team, impacts the facilities or resources available to support safe conduct of the research, or any other factor that impacts the assessment of the Criteria for Approval in SOPs 405 and 406.

Certain minor modifications might be eligible for Administrative Review, which is described in Section VI, below.

II. Process for Proposing Minor Modifications

Minor modifications must be submitted as an Amendment to an Approved protocol. Amendments must be filed in advance of the change the research team wishes to make, and must be approved by the IRB before the change can be implemented (except where the change is necessary to eliminate an immediate hazard to participants). Changes implemented to eliminate an immediate hazard to participants should be reported to the IRB as a Reportable Event within five business days of implementing the change; if the need for this change will persist, an Amendment should be filed following the filing of a Reportable Event. Please see SOP 601 for details about the Reportable Events.

Amendments must contain all of the information necessary for the IRB to clearly determine whether the modification is minor and whether it is approvable via the Expedited Review process. This includes:

1. A clear and thorough description of the changes
2. Modified or new documents supporting those changes, including Informed Consent documents, which must use the most recent approved version and must display the tracked changes if applicable
3. Consistent protocol materials (e.g. a change that proposes to modify compensation should make sure that the information regarding compensation is consistent throughout the protocol – on recruitment materials, in the consent documentation, and in the fields of the protocol template that mention compensation)

Incomplete Amendments will be disapproved, retaining the Approval that existed before the Amendment was filed. Investigators will be informed, in writing, how to remedy a disapproval on the basis of insufficient materials.

III. Process for Reviewing Minor Modifications

Minor modifications are reviewed using the Expedited Review process for Amendments. The Expedited Review process for Amendments permits one or more qualified members of the IRB to review the Amendment submission, alongside the Reviewer’s Checklist documenting the criteria for approval and the completed, updated protocol materials. If the assigned reviewer(s) find that the Amendment represents a minor modification, they may approve the Amendment. If the assigned reviewer(s) find that the Amendment represents a major modification, they may elect to disapprove the amendment and retain the existing approval of the protocol.

Changes that are more than minor modifications cannot be approved using the Amendment process. The Amendment process is only appropriate where determinations made on the Reviewer’s Checklist can remain unchanged. Amendments that are not approved will be disapproved, which retains the existing, underlying approval that existed before the Amendment was filed. Researchers will receive a written justification for Amendment disapproval. If an investigator disagrees with the determination, they may appeal that determination using the procedures outlined in SOP 411.

Changes that are minor modifications will be approved, and the research team will be notified, in writing, of the approval. If the changes proposed modifications to the informed consent documentation, the research team must go into their protocol to obtain the updated informed consent documentation before implementing the changes with participants.

IV. Process for Proposing & Reviewing Major Modifications

Major modifications cannot be processed using the Expedited Review process for Amendments. Major modifications require a reviewer to document new findings that impact the Criteria for Approval, and requires a review under SOPs 405 or 406. Two processes are available for seeking major modifications:

1. New Protocol Submission
   
   • The research team may submit a new protocol, proposing the major modifications. During the review of this new protocol, the underlying protocol approval remains in force. The new protocol will be reviewed in line with SOPs 404-406.
2. Adjust Review of Existing Approval
   
   • The research team may file an amendment that poses a major modification to the protocol that has already received approval. If the research team elects to do that, the underlying protocol approval must be suspended while that review process takes place using the procedures outlined in SOPs 404-406.

In both situations, a new Reviewer’s Checklist must be completed by the qualified IRB member reviewer(s), and new approvals issued. Where the proposed change impacts determinations regarding informed consent or regulatory compliance issues, the new reviewer may rely on the determinations regarding risks, benefits, scientific validity, alternative procedures, equitable selection of subjects, qualifications of the research team, privacy, and confidentiality made previously, and document only the new findings related to informed consent or regulatory compliance issues before a new Expedited approval is granted.

V. Examples

The table below gives some common examples of minor and major modifications.

Minor Modification	Major Modification
Removal and addition of CITI-Trained Investigators with similar qualifications	Shift in PI to someone outside of USU
A change in targeted accrual of + 15% in participant population that does not impact the scientific integrity of the research	Participant populations that are more than a + 15% change from what was previously approved and which impact the research team’s ability to address the research questions or conduct the analyses represented in the protocol
Reduction in time for a certain procedure, once piloted	Addition of an entirely new procedure
Removal of a vulnerable population from a study that had several non-vulnerable populations included	The addition of a new type or materially different vulnerable population
Switching data storage methods to a more secure platform	A reduction in privacy or confidentiality protections
The addition of a new research site involving similarly qualified personnel	The addition of a new research site that intends to recruit different types of participants
Adding a recruitment follow-up that does not result in coercion, undue influence, or inappropriate pressure	Any increase in risk to any population

Administrative Review

Certain changes to a protocol are eligible for Administrative Review, which allows for increased efficiency in the disposition of amendments. Administrative Review permits any member of the HRP Office (i.e. not restricted to HRP staff who also serve on the IRB) to grant approval to that change, due to the change being negligible in nature. Minor modifications eligible for Administrative Review are those which are mere updates that do not impact the substantive approval or review determinations, such as replacing a graduated student researcher with a current student researcher, adjusting the formatting or spelling in recruitment material or an informed consent document, or updating a field in a protocol to be consistent with previously-approved changes. These administrative review items should still be filed as Amendments, in order to ensure that the research team is keeping their protocol up-to-date as required in SOP 301.