PTMS WILL PERMANENTLY CLOSE TO NEW SUBMISSIONS ON DECEMBER 20, 2018. WHEN USING CNS IRB GUIDANCE AND TEMPLATES, PLEASE REMEMBER THAT IRB SUBMISSIONS AFTER DECEMBER 24, 2018 WILL BE THROUGH IRIS.
This section covers documents needed for an amendment of a protocol. Please note, many of the documents listed below are not required for IRB review, but are required by other NIH offices for different purposes before a protocol can be forwarded to the CC Office of Protocol Services and receive final NIH approval. The documents are listed here as a service to investigators and because the IRB assists investigators in assembling and submitting all required documents to the Office of Protocol Services.
IRB staff determines if an amendment is eligible for expedited review based on regulatory guidance in 45 CFR 46.110 .
Not all amendment’s that meet the regulatory requirements that permit expedited review will be expedited. There may be significant changes re: vulnerable populations or other concerns that warrant sending a protocol to the full Board. The final determination of whether an amendment will be expedited is made by the IRB Chair.
IRB staff pre-review all amendment submissions for completeness and compliance. The amendment is scheduled for the next available IRB meeting of its assigned panel only after pre-review is complete. If the amendment can be expedited under a regulatory category, it will be forwarded to the IRB Chair or designee for their review.
For information on how to upload an attachment in PTMS, consider taking the PTMS training course,
or contact the PTMS liaison for PTMS-related questions.
The Amendment Application is required by NIH. The information on this form is utilized by several NIH offices and for a variety of purposes.
The Amendment Application is completed via PTMS and is launched when the PI starts a new amendment. In PTMS, the form is labeled “View Amendment & COI”. It is important to make sure the Amendment Application page is filled out completely, accurately and consistent with other submitted documents. Failure to do so will delay the review process.
The Amendment Application is self-explanatory. The Office of Human Subjects Research Protections (OHSRP) has created the
"NIH Intramural Clinical Protocol Application Glossary"
which contains instructions for completing the Amendment Application.
Directions for completing each field can also be found in PTMS by hovering the mouse over that field.
The Amendment Memo is required by the IRB. The purpose of this memo is to modify a previously approved protocol. Any change to the protocol, consent/assent forms, recruitment materials, or other associated components require an amendment. Be sure to provide a detailed rationale for each requested change.
The Amendment Memo template can be downloaded from PTMS under "IRB Forms". It is periodically updated to incorporate new regulatory reporting requirements, so it is important to download the most current version of the memo at each submission.
The Amendment Memo must be uploaded to the action’s attachments page in PTMS under the “Amendment Memorandum” heading.
For Amendment submissions, the most recently IRB approved protocol document with track changes must be uploaded to the action’s attachments page in PTMS under the “Protocol” heading. Assure that the document name has the protocol number and date and identifies it as the protocol.
For amendment submissions, the most recently IRB approved revised watermarked version of the consent and/or assent forms should be uploaded to the action’s attachments page in PTMS under the “Consent Form” heading. Assure that the document name has the protocol number and date, and identifies it as the consent form.
If no changes to the consent/assent forms are being requested with the amendment submission, upload the .pdf versions found on the
If the amendment is adding new investigators, the PI must provide documentation that they have read the protocol and agree to participate in their designated role. The documentation may consist of:
- An email from the investigator confirming their agreement. The email must clearly identify the protocol.
- An investigator can sign a hard copy of the protocol application or protocol face sheet, which can then be scanned for submission.
- The investigator can provide a signed hard-copy or electronic memo.
If an investigator on the study is an NIH employee and from an Institute other than the Institute funding the study, then documentation of that investigator’s Clinical Director’s approval for the investigator’s participation must also be obtained and submitted. For example: If an NIMH employee serves as an Associate Investigator on an NEI Protocol, then the NIMH Clinical Director’s approval must be obtained for the participation of the NIMH employee. Electronic or hard-copy documentation, as noted above, are acceptable.
Hard-copy documents should be scanned. Email notices of agreements should be saved as a document. The agreements should then be uploaded to the action’s attachments page in PTMS under the “Other” heading. The agreements from multiple investigators and CD’s can be combined into a single document for uploading.
This documentation is not required before the protocol can be reviewed by the IRB, but is required before the IRB can submit the new protocol to the Office of Protocol Services for final approval.
delineates the required training for investigators, key research personnel and others working on the protocol. If the amendment is adding new investigators, the PI is responsible for assuring and documenting completion of all required training by each individual before s/he can work on the protocol. Documentation of training by those other than the PI does not need to be uploaded into PTMS.
For information regarding training requirements, see SOP 25, "Training"
or contact OHSRP.
If the amendment changes the use of an Investigational New Drug (IND) or changes the use of device under an Investigational Device Exemption (IDE), then documentation of FDA approval must be submitted to the IRB. The IRB may request other FDA-related documents for the study.
The IRB can review the submission prior to FDA approval. The submission to the FDA can be prior to, concurrent with, or after IRB review. If FDA approval is not documented first, the IRB approval will be contingent on FDA approval. If the FDA requires changes, those changes will need to be submitted to the IRB for further review. The IRB cannot provide final approval and submit the protocol to the Office of Protocol Services for processing until FDA approval is in place and all conditions have been met.
For submission, upload FDA documents to the action’s attachments page in PTMS under the “FDA Documents” heading.
For questions regarding FDA regulated research, contact the FDA directly.
Links to FDA regulations:
If the amendment changes the use of radiation for research purposes, then approval from the Radiation Safety Committee (RSC) will need to be obtained. The IRB will need the following documentation of RSC review and approval:
- Form NIH 88-23(a): Application for Authorization to Use Radiation in Research Involving Human Subjects
- RSC Approval Memo
- Any formal correspondence with RSC (e.g., RSC stipulations stemming from review and PI response to stipulations)
For questions regarding RSC review, contact the RSC directly. Information about the RSC review can be found on their
The IRB can review the submission prior to RSC approval. The submission to the RSC can be prior to, concurrent with, or after IRB review. If RSC approval is not documented first, the IRB approval will be contingent on RSC approval. If the RSC requires changes, those changes will need to be submitted to the IRB for further review. The IRB cannot provide final approval and submit the protocol to the Office of Protocol Services for processing until RSC approval is in place.
For submission, upload RSC documents to the action’s attachment page under the “Radiation Safety Documents” heading in PTMS.
Some protocol submissions must be cleared by the Institute Deputy Ethics Counselor (DEC). The Institute Ethics Office conducts a review of the financial holdings of certain individuals listed on the protocol to determine if they have any potential financial conflicts of interest for that protocol. Investigators who have a potential conflict identified will be contacted by the DEC. The DEC will work with the PI to resolve any actual or apparent conflict.
Whether or not a protocol requires DEC Clearance, depends on whether it is a "covered research protocol" as defined in
OHSRP SOP 21.
The individuals whose financial holdings need to be reported to NIH and reviewed by the DEC are those defined as “covered individuals” in the policy. The PI and covered individuals must submit forms for the DEC clearance process. The forms are available from and submitted directly to the DEC office and are not in PTMS.
Once the DEC review is complete and any conflicts are resolved, the DEC office will provide documentation of clearance to the PI.
For more information on the DEC Clearance process: Contact the Institutes Ethics office .
Documentation of DEC Clearance should be uploaded to the attachments page in PTMS in the “Conflict of Interest Documents” section unless done automatically by the IC in PTMS.
This documentation is not required before the IRB can review the protocol, but is required before the IRB office can submit the protocol to the Office of Protocol Services for final NIH approval.
If the protocol is a multi-site study, additional information is needed for IRB review, depending on the nature of the collaboration.
Multi-Site Study and NIH is the Coordinating Site:
- Submit documentation of current IRB approval from each of the collaborating sites.
Multi-Site Study and NIH is NOT the Coordinating Site:
- Submit documentation of IRB approval, the protocol and consent form(s) from only the lead site.
Other Collaborative Study:
- Contact the IRB Office for study-specific information on required documentation, which varies based on the nature of the collaboration.
To submit documentation for a multi-site study, upload the documents to the action’s attachments page in PTMS under the “Other” heading.
Any changes to current approved materials or addition of new recruitment materials will require IRB review before they can be used. CNS
IRB guidance on recruitment material requirements is available
and must be supported by information on their planned use in the
"recruitment" section of the protocol.
To submit recruitment material, upload the documents to the action’s attachments page in PTMS under the “Other” heading.
If the amendment impacts on the scientific design of the study, the protocol must receive Institute Scientific Review approval before it can be accepted for review by an IRB. As each Institute determines their own process for scientific review, the process varies between Institutes (and sometimes between Branches within the same Institute).
Contact the Institute Clinical Director for information on the Scientific Review process.
Scientific review must be completed before the Amendment submission can be accepted for IRB review. Documentation should include:
- Scientific Review approval notification.
- Scientific Review minutes, outside reviewer reports, notifications from the Scientific Review committee, PI responses to the Scientific Review committee stipulations, etc.
For submission, the Scientific Review approval and supporting documentation are uploaded to the action’s attachments page in PTMS under the “Scientific Review Notice & Response” heading.
If the PI’s institute requires statistical review during scientific review, the documents are handled in the same manner as the scientific review documents (above), except that they are uploaded in the action’s attachments page in PTMS under the “Statistical Review Documents” heading.
If a protocol includes Non-NIH investigators, who will interact with participants and/or have access to identifiable private information, then an IRB Reliance
Agreement may be needed (see SOP 20).
The NIH Deputy Director for Intramural Research (DDIR), the Director, Office of Human Subjects Research Protections (OHSRP) and the Deputy Director, OHSRP are the only NIH officials authorized to make final decisions about entering into a Reliance Agreement. OHSRP negotiates and executes reliance agreements.
To establish a reliance agreement or determine whether an agreement is needed, contact