Modifications (Amendments/Revisions) to Currently Approved Research
The terminology used to describe a change to a protocol may vary, including terms such as modification, amendment or revision. Typically outside sponsors may call any change to the protocol an amendment. For purposes of this document the term modification will be used to designate a change.
All modifications to currently approved research are required to have IRB review and approval prior to implementation except when necessary to eliminate apparent immediate hazards to the subject.
The modification application should include any required changes to the protocol, IRB protocol or application (regardless of study study status) and consent(s)/assent(s) (if open to enrollment) and/or other study documentation. The modification reviewer has access to the same documentation as the initial or continuing reviewer and is expected to conduct the review with the same diligence as an original or continuing review regardless of whether or not the review is expedited or full board review.
Regulations permit the use of expedited procedures for review of minor changes to previously approved research during the period for which the approval is authorized. Modifications that alter the risk/benefit ratio are assigned to a primary reviewer and presented to the full board at a convened meeting.
The essence of the study should be summarized by the reviewer for IRB members and the reviewer should state what the proposed modification is and how it will affect the conduct of the study, the risk/benefit ratio, and whether or not the modification should be approved as written. If the modification requires a change in the informed consent document, then the reviewer must review that change and recommend appropriate board action. Modifications submitted to the IRB, along with supporting correspondence, are entered into the IRB database, and placed in the study file.
Investigators are notified in writing of the decision of the IRB and of any changes required. Modification approval is not granted until all required changes have been made and submitted for review and approval. Once approved, the investigator is sent a modification approval form. The IRB may only approve modifications through the current approval expiration period, unless considered at the time of continuation review. Upon receipt of the approval for the modification, the investigator may initiate the modification.
If approved research is changed to eliminate an apparent immediate hazard(s) to the subject, the investigator is required to notify the IRB of the change(s) promptly (within five (5) business days). The IRB will review at the next convened meeting to determine if the change(s) instituted were consistent with the subject's continued welfare.
DEFINITIONS AND EXAMPLES: MINOR VS MAJOR MODIFICATIONS
The following definitions may be helpful to determine the level of approval to pursue; investigators are encouraged to contact the IRB-HSR office with any questions prior to submitting the request if uncertain about the review type required.
Level of Approval: Expedited
Definition: Minor changes have no substantive effect upon an approved protocol or reduce the risk to the subject
Examples of minor changes are:
- Changes in research personnel that do not alter the competence of the research team to conduct the research
- Scientific and/or therapeutic changes that leave the research population at the same or lower risk than risk(s) already approved
- A minor increase or decrease in the number of participants (<25% change) or a >25% increase in the # of participants to be enrolled, but the # of participants to be "treated" remains the same. (e.g. - increase in # consented due to a higher than expected rate of screen failures) or a larger % increase in # of subjects which does not affect the statistical plan.
- Changes in research procedures that have a minor impact on risks of harm, such as changes in the amount and frequency of blood draws ( which remain within the expedited criteria), addition of a clinic visit that involves no new procedures, or addition of a questionnaire that does not introduce new subject matter.
- An increase in the number of study visits for the purpose of increased safety monitoring
- Minimal changes in remuneration
- Changes to improve the clarity of statements, enhance comprehension or to correct typographical errors, updating to current template, without altering the content or intent of the statement
- Clarification of discrepancies within the IRB review materials (protocol cover sheet, protocol, consent) such as numbers of subjects, number and identity of research sites, timing, nature, and duration of research procedures.
Level of Approval: Full Board
Definition: Major changes are changes that may increase the research population's risk or are of questionable risk.
Examples of major changes that are considered to increase the risk to the subject
- Knowledge of a new risk which might affect the risk/ benefit ratio (For example, if a risk that is serious, life-threatening, or could potentially result in permanent disability). The addition of these sorts of risk might affect the IRB's view of the risk/benefit ratio and should therefore be reviewed by the full board.
- Increasing the length of time a subject is exposed to experimental aspects of the study.
- Increasing the dose/strength of an investigational drug.
- Changing the originally targeted population to include a more at-risk population (example: previous exclusion for those with renal failure are now allowed to enroll, or adding children or pregnant women to the study.)
- Adding additional procedures where the risk of the additional procedure is greater than minimal risk.
- Adding a blood draw such that the total amount of blood drawn or frequency of blood draws exceeds what is considered expeditable. Expedited criteria for blood draws can be found in AG 3-2.
- Adding an element that may breech the confidentiality of the subject such as specimen banking or genetic testing.
- An increase >25% in the # of participants to be "treated” which affects the statistical plan for the study.
- Requesting surrogate assent for a full board study.
- Additional exposure to radiation as part of the study (i.e. additional x-rays, DEXA scans).
Submission of Materials and Feedback Time Frame
Approval of a modification does not extend or otherwise change the project's expiration date.
Deadlines for submissions only apply to full board reviews. Refer to the Meeting Dates schedule on the IRB website. Full board reviews must be submitted by a deadline that is usually 7 days prior to the convened meeting.
Expedited modifications can be reviewed at anytime and will be, typically, reviewed within 3-5 business days after which the researcher will receive feedback from the review.
Protocol Modifications for IRB-HSR
For additional information see: Modifications Process
For Submission Deadlines see: Calendars & Deadlines