On August 2, 2012, the National Institutes of Health issued notices containing policy guidance on two important topics: NIH prior approval requirements for changes involving human subjects during the course of active awards and NIH prior approval requirements for awards initially submitted without definitive plans for human subjects involvement (also called Delayed Onset Awards).
For active grant awards, NIH NOT-OD-12-129 contains detailed guidance on when NIH prior approval is necessary if there are changes to human subjects involvement in an active grant. It is important to note that Changes in Scope have always required NIH prior approval. Examples of a Change in Scope in the NIH Grants Policy Statement have also always included as a Change in Scope a change from the approved involvement of human subjects, a shift of the research emphasis from one disease to another, or a clinical hold by the FDA under a study involving an IND or IDE. The August 2nd notice from NIH offers further clarification and detail.
In general, any change in research procedures that would result in an increased risk level to human subjects will require NIH prior approval. This includes:
- Any change to the study design or protocol that results in the need to change the overall human subjects designation or clinical trial designation of the grant, as follows:
- Change from non-human subjects research to human subjects research (exempt or non-exempt)
- Change from exempt to non-exempt human subjects research
- Change from “No Clinical Trial” to “Includes a Clinical Trial”
- The new inclusion of subject populations that are covered by additional regulatory protections (pregnant women, human fetuses, and neonates; prisoners; or children)
- Any change to the protocol that would result in an overall increase in risk level for subjects, including physical, psychological, financial, legal, or other risks. Examples include:
- Addition of a new study population that would be at higher risk from existing procedures;
- The addition of new study procedures that are greater than minimal risk;
- Modification of existing study procedures that increase overall risk;
- Addition of a new CS/CT intervention arm not originally proposed that is greater than minimal risk.
- New information that comes to light after a study is underway that indicates a higher level of risks to participants than previously recognized.
Principle Investigators should notify OSP prior to any such changes when such changes are contemplated or considered. (Consultation with the NIH Program Officer is also advisable in many circumstances and NIH encourages PI’s to discuss potential changes with their PO’s.) In addition, the IRB will monitor modifications to existing IRB protocols and will notify OSP if they receive any requests for amendment that involve these types of changes. However, it is important to note that the responsibility lies with the PI to comply with NIH policies. While the IRB will do its part to help, their systems are manual and may not be able to identify every applicable change.
When such changes are necessary, they must be submitted by OSP to the NIH Grants Management Specialist no later than 30 days before the proposed change. Proposed changes may be addressed in an annual progress report; however, a formal prior approval request must be submitted as a separate request prior to initiating any new human subjects activity. The materials required for such a request are detailed in NOT-OD-12-129. OSP will review each request to be sure it contains the required information and will discuss with the PI if any of the required materials are missing or incomplete.
IRB review of modification requests will continue while NIH is evaluating the request. If NIH requests additional modifications, please be aware that additional IRB review may be necessary. In all cases, no new human subjects activity may be initiated until both NIH and Emory’s IRB have approved the activity.
Similarly, NOT-OD-12-130 provides clarification on NIH prior approval requirements for awards which were submitted with the intent to conduct human subjects research, but for which definitive plans could not be included in the application. These types of awards can include single project awards in which results of pre-clinical research are needed before human subjects research can be performed, clinical research networks or consortia which add new protocols throughout the life of the award, and award mechanisms that include funds for small projects to be selected by the grantee (e.g., pilot projects).
For single project awards, requests must be submitted no later than 30 days before the proposed change. Details of what is needed for each request can be found in notice NOT-OD-12-130. As with the procedures for changes during an active award, these requests must be signed by an authorized official from OSP.
For research consortia or multi-site programs that routinely implement new human subjects research projects after award, the PI must follow the stated procedures of that consortia or group for approval of new protocols which. These procedures are determined by the funding NIH Institute or Center (IC). Review is often conducted by a defined external advisory board. PI’s must follow the instructions of the IC when preparing and submitting such requests.
For awards which include mechanisms for selecting and funding small projects (e.g., pilot projects), the institution must ensure that selected projects follow all relevant regulations and policies, including those governing human subjects research (including obtaining prior IRB approval). PI’s should also follow the IC’s guidance regarding prior approval of such individual projects and updating the status of funded projects in an annual progress report. (Such requirements are generally described in the Funding Opportunity Announcement or Notice of Grant Award.)
The notices described in this article can be found at:
NOT-OD-12-129 – http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-129.html
NOT-OD-12-130 – http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-130.html
