When the IRB reviews research supported by federal funds it must review the corresponding grant application. This review must ensure that all research described in the application is entirely consistent with the corresponding protocol. This procedures must also be followed when research qualifies for expedited review.

Some federal agencies, including NSF and NIH, do not require IRB review prior to the submission of a grant application. They will notify the investigator if an application is likely to be funded and require IRB approval before they make the award. There are often significant delays between the submission of a grant application and its funding; therefore, researchers may have modified their plans for using human subjects at the time of award. However, because the IRB cannot approve a protocol that deviates from the application, the investigator must submit a protocol that matches the application, as modified during the peer review process.

Subsequently, the researcher can submit an amendment to the approved protocol in order to incorporate the necessary changes. Sponsor policies will dictate which changes must be approved by the sponsor before they can be implemented.