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Clinical and Translational Science Awards

CTSA Program Prior Approval Frequently Asked Questions

Policy

Process

Review and Approval

KL2 Scholars

Animal Subjects

TL1 Trainees


Policy

The oversight of pilot projects must follow all relevant NIH regulations and policies, including those governing the involvement of human subjects in research, and obtaining approval from the institutional review board (IRB). However, can grantee institutions use that guidance to manage this process in house, as was done in the past?

The prior management process was based on the NIH policy at that time. Since 2012, NIH has required prior approval for delayed onset of human subject studies. NCATS is required to assure compliance with the NIH policy.

Does NCATS distinguish between in vivo and ex vivo human subjects studies materials (i.e., do human cell lines or tissue repositories studies need prior approval)?

Studies involving human subjects require prior approval. The NIH Glossary defines human subjects: A living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual or obtains identifiable private information. Regulations governing the use of human subjects in research extend to use of human organs, tissues and body fluids from identifiable individuals as human subjects and to graphic, written or recorded information derived from such individuals.

Process

Does NCATS have a specific pathway through which the approval process moves?

The documentation should be submitted by the Authorized Organization Representative (AOR) to the grants management specialist and program official. At that time, a dual review begins.

Is there a service guarantee at NCATS regarding turnaround time?

In general, NCATS responds to prior approval requests within 30 days of receipt. Currently, a majority of most low -risk studies submitted with all proper documentation are being approved within 30 days.

Would it be possible to be fully transparent, so that the hubs could see exactly what the process map looks like for this process?

A process map can be shared with the CTSA Program hubs.

If NCATS does not respond within 30 days, can grantee institutions assume that the prior approval documents have been approved?

No. If you have not received a response within 30 days, please send an email reminder and request for status update to the grants management specialist and program official. If a response is not provided, please email NCATS_Grant_Inquiry@mail.nih.gov, the program official, as well as the CTSA Program director, Mary Purucker.

If the goal is to provide permission and not duplicate the IRB work, is it necessary to receive the IRB protocol and consent forms?

NIH must review all studies supported by NIH-funded grants. If there is an adverse event or negative outcome from a study, NIH maintains some responsibility as the funding agency.

If an investigator was submitting an independent grant to NIH, he/she wouldn't send the IRB protocol and consent forms; he/she would describe the project and include a human subjects protection plan. Could the list of documents be shortened?

If in the future, NCATS reaches a point where the study documentation submitted is of such quality across the consortium that there are no concerns/questions and/or denials, NCATS may consider changes to the required documentation to the extent permitted by NIH policy.

Does NCATS plan to have a Web-based submission process for the review and approval of the documents instead of submitting via email?

Yes. There is a plan for a Web-based submission process. A system has been developed that is currently undergoing alpha testing with a few CTSA Program hubs. Once the system is determined to be a more efficient and effective alternative, NCATS will open it to all CTSA hubs.

What is the average turnaround time for properly documented submissions?

Currently, most low-risk studies submitted with proper documentation are approved within 30 days.

If an investigator has a project that will include human subjects work with delayed onset (sometimes, prior work is needed, and the human subjects piece is not ready until the first part of the work is done), does he/she need prior approval before awarding either the pilot project or K awardees or only when he/she is ready to start that part of the work?

The scenario described is still considered delayed onset. Prior approval would not be required until such time that human/animal subject research is conducted. Please also ensure the project is complete and ready for submission when the prior approval request is made. Early submission of a protocol concept that lacks necessary supporting material will be returned and will lengthen the review timeline.

If an investigator is involved in a pilot program for a center funded by a different IC that has a simpler and faster process, can we use that process instead? How much flexibility do individual ICs NIH Institutes and Centers (ICs) have in the design of their process?

ICs have a limited amount of flexibility in the design of the process with all ICs following the same guiding principles as indicated in the NIH Guide notice. NCATS has reviewed the processes for several other ICs and will continue to learn from them. NCATS is a non-categorical IC. Submitted studies cover a wide range of diseases, and sometimes NCATS must invoke assistance from other ICs to ensure a proper review. Most ICs with pilot programs limit the scope, funding and number of pilot awards conducted under a single grant, helping them to streamline their review process.

Once approvals are received, can investigators retro date the pilot start date?

No.

When NCATS asks for clarification on a prior approval submission, can the principal investigator respond directly with cc to the AOR, or does the AOR need to respond?

The AOR must provide the response and/or concurrence for the response.

Does NCATS have an evaluation process for prior approval of delayed onset human subjects research to determine a typical turnaround time? Is there feedback from the CTSA Program hubs regarding the evaluation process?

NCATS is evaluating the process. The new Web-based submission process also includes a built-in tracking system to help better gauge the turnaround time. The Web-based tracking system under development is transparent for all parties involved —– NCATS staff and the CTSA hub staff.

Review and Approval

If an investigator’s project has been approved on a prior CTSA grant, but the investigator now is applying for new funding that requires "prior approval,", does the investigator have to stop study activities until the prior approval is received?

If the study was described in detail in the competing application, then additional approval is not required. If the study was not described in the competing application, then a simple request to continue the study under the new award may be submitted. This request should indicate that there is no change in the study from the prior approval. If there is a change, this must be described in detail.

Even if a CTSA Program hub has never had a prior approval rejected or questioned, sometimes the wait can be up to three months for an NIH response upon receipt of all documentation. Why are prior approvals of completed packages delayed beyond 30 days? Who do we call after 30 days?

Some studies that are more high-risk require additional reviews that could extend beyond 30 days. Additionally, submitted studies cover a wide range of diseases, and sometimes, NCATS must invoke assistance from other ICs to ensure a proper review. If a response is not provided, please email NCATS_Grant_Inquiry@mail.nih.gov, the program official, as well as the CTSA Program director, Mary Purucker.

Should a grantee institution send all the packages from the pilot awardees to NCATS in one email? What is the preferred format/method to send these files?

NCATS has no required document packaging method. However, sending more than one prior approval request in a single email can create confusion about which attachment goes with which request, thereby leading to errors, delays and returned submissions. Also, sending more than one prior approval request in a single email will increase the likelihood it will not make it through the NIH firewall.

How much flexibility does one have in packaging the documents? The number of documents and naming conventions suggested on the checklist has cause confusion and loss of documents. Can one use numeric titles and other ways of packaging?

Documents are named with standardized nomenclature to enhance storage and search functions, and all submissions for prior approval must follow these naming conventions.

Could NCATS or the Center for Leading Innovation and Collaboration (CLIC) provide guidance on submitting a successful prior approval submission, including how to avoid common pitfalls?

Yes. NCATS looks forward to working with CLIC and other interested CTSA hubs on creating such guidance.

Can grantees begin charging against federal funds for parts of the pilot project that do not involve human subjects if funding is not released until prior approval is received?

Studies that do not involve human/animal subjects do not require NCATS prior approval. Investigators at an institution may, at their own risk, begin research activities that they believe do not involve human/animal subjects while the prior approval review is in process.

Can an institution release award letters and funding to PIs whose research may be focused on animal work and on human subjects before prior approval is received?

Studies involving animal and human subjects require prior approval. Studies that do not involve human/animal subjects do not require NCATS prior approval. Institutions may, at their own risk, allow investigators to begin research activities that they believe do not involve human/animal subjects while the prior approval review is in process. In addition, investigators should not submit early scientific concepts in lieu of fully developed protocols for review. NCATS must have sufficiently developed information to conduct a substantive review of a clinical study. Incomplete or unclear submissions will be returned.

Many pilot projects have been approved by NCATS, pending IRB approval. Once the IRB approval is obtained and documents are sent to NCATS, must grantee institutions wait for NCATS to send an acknowledgment of receipt before the project can begin?

No. Once the IRB approval is submitted by the AOR, research activities may commence. Grantee institutions should receive an acknowledgement quickly, but they do not need to wait for the acknowledgement to begin research activities.

If a protocol has IRB approval, why would NIH deny approval to draw down funds based on safety/human subject risk considerations?

The NIH review process requires that the clinical study has IRB approval but may include other considerations (e.g., poor scientific justification) that may lead to lack of approval. A decision not to approve use of NIH funds involves multiple people at NCATS and may involve domain experts at other NIH ICs.

If a pilot project does not receive NIH-NCATS prior approval, is there any reason that the CTSA Program hub cannot fund the pilot from institutional funds, if available?

NCATS prior approval is required for any pilot project funded by NCATS grant funds or voluntary committed cost share designated on the Notice of Award. If the institution chooses to fund a pilot project that was not approved by NCATS, it may do so with its own funding support but may not advertise, report, publish the study, etc., as a CTSA Program-supported project.

Is institutional IRB approval always required for NCATS prior approval?

No. A prior approval request may be submitted prior to receipt of IRB approval. If NCATS approval is provided, the approval will be contingent upon the submission of the IRB approval to the NCATS grants management specialist and program official. The submission should be complete and of sufficient quality to enable substantive review by NCATS. Please ensure that the protocol and other supporting documents are as close as possible to what will be submitted for IRB review. Significant protocol revisions required by the IRB will need re-review by NCATS.

Just as IRBs streamline review based on risk, could NCATS also develop a review workflow based on risk?

The current process does take risk-level into consideration. Low-risk studies are reviewed by the program officer and clinical trials team. Higher-risk studies may undergo additional levels of review, including that of the NCATS medical monitor.

When NCATS requests clarification on submission packages, should the institution resend only the questioned/corrected documents, or should the entire package be resent?

A single document may be sent in response to a request from NCATS for clarification.

If a grantee institution uses institutional cost share funds, should it include projects funded with them in the Research Performance Progress Report (RPPR)?

Projects funded with institutional cost-share funds also require NCATS prior approval and should be reported in the RPPR.

The new NCATS submission system requires that AOR submit prior approval documents. This creates significant administrative burden and time constraints for the AOR to determine naming conventions and where files should be uploaded before uploading and submitting them. Is there a way for the system to allow investigators to fill in information and upload required documents prior to sending it to the AOR for submission? 

NCATS has received this feedback from some alpha testing sites and is working on a resolution for this process.

Is there a separate NCATS package to request prior approval for exempt human subjects studies that meet exemption categories 1–6?

There is no separate NCATS package to request prior approval for research conducted under exemption categories 1–6.

Studies that fall under Exemption 4 of 45 CFR part 46.101(b) are still human subjects research; however, if the local IRB Office notifies the grantee that the IRB determined the project is exempt from formal IRB Committee review under 45 CFR part 46.101(b) (4) (Exemption 4), then NCATS’ prior approval is not required for that research project.

While NCATS’ prior approval is not necessary for studies that an IRB determines fall under Exemption 4, the grantee does need to (1) notify NCATS of the study and (2) submit to NCATS the IRB confirmation/approval letter with the Exemption 4 determination for inclusion in the official grant file.

KL2 Scholars

Since KL2 scholars must submit a proposal for selection into the KL2 program, could CTSA Program hubs send that proposal and a human subjects plan instead of the documents that are required now?

The type of KL2 scholar research conducted is vastly different among the CTSA Program hubs. Some KL2 scholars have a small research budget and others use the pilot program for larger research projects. For this reason, NCATS cannot simply remove this requirement. NCATS is open to hearing about the concerns and attempting to find some relief for KL2 scholars who may be working directly with a mentor on another NIH-funded study. Prior approval requests must include sufficient information for NCATS to conduct a substantive review. At a minimum, such information should clearly state what is being done and who will be doing it. Submissions that include a single protocol for an individual project along with the supporting documents specific to that project are highly encouraged. Unclear or incomplete submissions will be returned.

Animal Subjects

NCATS requires prior approval for animal studies, but the documents required for animal studies are not listed. What specific documents are required?

Prior approval is required for any change in the approved use of live vertebrate animals and/or any substitution of one animal model for another. Any new study involving animal subjects that was not reviewed in the competing application, must be submitted for prior approval. The prior approval request documentation submitted should include the name of the grantee, the name of the initiating project director/principal investigator (PD/PI), the PD/PI contact information, the AOR contact information, the Vertebrate Animals Section four points, Institutional Animal Care and Use Committees approval and verification of an approved Animal Welfare Assurance.

TL1 Trainees

Is prior approval for delayed onset human subjects research required for T awardees?

Most T awardees are working on their mentors’ funded studies; and therefore, prior approval is not required. The rare exception is if a postdoctoral trainee is funded directly through the NCATS CTSA Program hub to conduct an independent research study. If this occurs, please contact the grants management specialist and program official to determine if the study requires prior approval.

Last updated: 12-06-2017
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