Most studies require modifications to keep the investigative team current, to incorporate changes to the protocol, study instruments or consent form(s). Amendments to approved studies represent the single largest volume of IRB submissions. No changes may be made to the approved research plan without first submitting a request to the IRB and obtaining the IRB's approval, unless there is need to eliminate an immediate hazard facing the subject as outlined in 45 CFR 46.103(b)(4).
Amendments that are minor may be reviewed and approved by the IRB using Expedited Review procedures. IRB SOP 403: Amendments & Reports of New Findings to Approved Research defines Minor Amendment to mean A proposed change in the research related activities that does not materially affect assessment of the risks and benefits of the study and does not substantially change the specific aims, objectives or design of the study. A modification may not be considered “minor” if the changes involve the addition of a procedure that is more than minimal risk or a procedure that cannot be reviewed under Expedited Categories.... The Appendix 2 of IRB SOP 401: Expedited Review Procedures includes a list of examples of minor modifications to approved research.
Common Issues with Study Amendments
Creating a Cover Letter
The cover should include the following:
- an overview of the global changes included in the amendment with the rationale (scientific or other justification) for the changes;
- an assessment of the impact of the change to current and future subjects (changes in the risk or benefits to subjects);
- a list of each change made to the protocol, consent form and other study documents.
- type of change (protocol, consent form, study instruments, investigator's brochure, eIRB application);
- justification for the change;
- old text
- new text
The updated documents should be attached to the eIRB application. Each updated document should include a tracked version and a clean version (all changes accepted) with updated version and version date.
Amendments can be more complicated and harder for the IRB to review than initial submissions. It takes attention to detail, on the investigator's part, to fully explain the changes that are proposed, the reasons for those changes and to ensure that all of the applicable study documents consistently incorporate the proposed changes throughout.
Frequent Reasons for Amendments to Fail to Obtain Approval During Initial Review
Amendment fail to obtain IRB approval during their initial review due to the following:
- failure to explain the rationale for the proposed change;
- failure to consistently implement the proposed change throughout the protocol, eIRB application, consent form, etc.;
- failure to update the analysis plan and sample size to account for the changes in objectives, endpoints, measurements or sample size;
- submitting the wrong documents or incorrect versions of documents to the IRB; and
- inclusion of changes in study documents that are not discussed or listed in the cover letter or list of changes document.
Careful review of each revised document prior to submission can prevent unnecessary delays.
Unless the change is very minor, each Amendment should be accompanies by a Cover Letter that explains what is being changed and why it is being changed. The IRB provides an Amendment Cover Letter template that investigators can use to explain the changes they are proposing. The box one the right outlines the typical content for a cover letter.
Not infrequently an amendment involves a new request for a waiver of consent, assent, HIPAA or documentation of consent. When a new waiver is requested, the IRB needs to have a complete discussion of the justification for the new waiver.
Amending the Protocol vs Creating a New Study
When the amendment involves a new study population, new inclusion/exclusion criteria, and new analysis plans, an amendment is no longer appropriate. The investigator should develop a new protocol rather than try to amend an existing one. The IRB strongly prefers that investigators complete their approved study and open a new one rather than trying to amend a previously approved study. If uncertain, consult one of the IRB chairs and discuss the proposed changes.