NCCIH Policy: Protocol Amendments
Guidance on Changes to Clinical Studies in Active Awards—When Is Prior NCCIH Approval Required? (Updated November 8, 2023)
National Institutes of Health (NIH) policy requires prior approval from the NIH awarding Institute/Center for a change in scope (NIH Grants Policy Statement (GPS) 22.214.171.124). A change in scope is a change in the direction, aims, objectives, purposes, or type of research training identified in the approved project. A change in scope includes significant changes to the clinical study approved by NCCIH at the time of award, including a change to the approved involvement of human subjects, scientific intent, or study design (grants.nih.gov/grants/guide/notice-files/NOT-OD-12-129).
What is a significant change to an NCCIH-funded clinical study?
- Change that affects patient safety (change in eligibility criteria; inclusion/exclusion criteria; study intervention; data collection procedures; recruitment and retention plans)
- Change in risk to participants (whether increased or decreased)
- Change to study design, randomization theme, or the data analysis plan
- Sample size reduction or increase (change in enrollment targets)
- Site addition/deletion
- Key study personnel addition/deletion
- Change of institution (include those in multisite studies)
Proposed Changes to an NCCIH-Funded Clinical Study That Are NOT a Change of Scope
Some changes to an NCCIH-approved clinical study are considered editorial or administrative updates and not a change of scope. These proposed changes do not require NCCIH approval prior to implementation.
- Typographical correction, unless the change results in a change in participant risks
- Rephrasing a sentence or section to add clarity, as long as the change does not affect the scientific intent, study design, participant risks, or study protections
- Reformatting the document, as long as the change does not affect the scientific intent, study design, participant risks, or study protections
- Address, telephone, or email changes
- Addition/deletion of non-key personnel
- Standardization of protocol language inconsistencies, as long as the change does not affect the scientific intent, study design, participant risks, or study protections
Process for Obtaining NCCIH Approval Prior to Implementation of Significant Changes
All changes representing a change of scope to NCCIH-funded clinical studies must receive NCCIH approval prior to implementation. Once NCCIH has approved the change(s), the study should seek additional approvals from the Independent Monitoring Entity (Independent Monitor, Independent Monitoring Committee, or Data and Safety Monitoring Board) and the Institutional Review Board (IRB) of record before the change can be formally implemented.
Please follow the process outlined below:
- Submit a request to the program director (PD) assigned to the NCCIH-funded grant describing the proposed change of scope and the reason(s) for seeking the significant change(s). The submission must be accompanied by a rationale, scientific impact, any power calculations, and any other supporting material (including budget implications).
- The PD will review the proposed change and rationale to assess the potential impact on scientific relevance and whether the request constitutes a change in scope from the original funded project.
- If the NCCIH PD approves the change(s), track-changed study documents are requested.
- The NCCIH PD will notify the principal investigator (PI) of any additional questions or requested revisions to the revised study documents following NCCIH review.
- In the process of reviewing the proposed clinical study changes, NCCIH may elect to elevate the oversight level assigned to the study. If the study’s oversight level is changed, additional study documents may be requested from the required templates in the NCCIH Clinical Research Toolbox.
- The NCCIH PD will provide formal approval of the significant change(s) and approve the study documents. The PI must then seek subsequent approval from the Independent Monitoring Entity and the IRB of record prior to implementing the change(s).
- For any questions about the process, please contact the assigned NCCIH PD.