This section provides answers to frequently asked questions (FAQs) regarding DAIDS requirements for Protocol Registration Policy.
Q. What does "supported by NIAID/DAIDS" mean? Does it mean financially supported?
A. In addition to financial support, “supported” also means direct and indirect funding, other types of tangible support, such as providing lab or data management services, regulatory support, study drug supply for research activities. See the DAIDS glossary for definition of “DAIDS supported.”
Q. For studies that are supported by DAIDS but DAIDS is not the IND sponsor, are there different requirements for protocol registration?
A. Sites participating in studies where DAIDS is not the IND sponsor will be required to submit the same documents to the DAIDS Protocol Registration Office (PRO) as studies where DAIDS is the IND sponsor. The Protocol Registration algorithm defines the protocol registration requirements when DAIDS does not hold the IND but provides funding. See the algorithm associated with the Protocol Registration Policy for additional details.
Q. Is a network expected to do protocol registration when the DAIDS PRO doesn't? Is this still called Modified Protocol Registration?
A. DAIDS does not require networks to review site-specific informed consent forms (ICFs) when DAIDS does not. However, DAIDS requires protocol registration for all clinical research supported and/or sponsored by DAIDS and reviewed by DAIDS Scientific Review Committees, namely the Prevention Sciences Review Committee (PSRC) and the Clinical Sciences Review Committee (CSRC). There is no longer a modified protocol registration process.
Q. What should network sites do if they have network requirements in addition to what is required by DAIDS for protocol registration?
A. In general, it is recommended that if the networks/other groups have additional requirements for their studies, networks/other groups should develop guidance documents clearly stating the requirements sites must follow in addition to the DAIDS requirements.
Q. I'm the new Study Coordinator at my site. Could you please update the DAIDS Protocol Registration System (DPRS) so I start receiving all the necessary communications/reports?
A. Sites and new personnel should contact their DAIDS Office for Clinical Site Oversight (OCSO) representative or DAIDS program officer to initiate this process.
Q. Can my submission be expedited?
A. If you need a submission expedited, please send an email to the DAIDS PRO requesting an expedited review and the reason an expedited review is required. A determination will be made by DAIDS on a case-by-case basis.
II. Form FDA 1572/DAIDS Investigator of Record (IoR) Form
Q. How should names be listed on the Form FDA 1572/DAIDS IoR Form?
A. Sites should use the complete legal name (full first and last name) on all documents. It is recommended that site use the name that appears on legal documents (e.g., medical license, passport) on all documents.
Q. Where should sites keep original Form FDA 1572s/DAIDS IoR Forms?
A. All originals should be maintained in the regulatory files at the site.
Q. Can sub-investigators who are listed on the Form FDA 1572/DAIDS IoR Form sign the DAIDS Protocol Registration Translation Confirmation Form if the IoR is traveling and not available?
A. It is acceptable for a sub-IoR to sign the DAIDS Protocol Registration Translation Confirmation Form if this duty is delegated to a sub-IoR by the IoR.
Q. Although FDA does not require an immediate change to the Form FDA 1572 if a sub-investigator leaves the site, DAIDS does. Does that mean I still need to update the Form FDA 1572 immediately?
A. If there is any major change to the information on the current Form FDA 1572 or DAIDS IoR Form, a revised Form FDA 1572/DAIDS IoR Form must be submitted to the DAIDS PRO within 30 calendar days.
Q. Should the box marked “Curriculum Vitae” be checked always or only if CV provided for initial registration and when updated?
A. Sites should check the box if the IoR’s CV has been submitted to the DAIDS PRO with a registration submission.
Q. What if an RE/Approving Entity only reviews and approves the initial version of a protocol? Should the RE/Approving Entity be listed on the Form FDA 1572/DAIDS IoR Form? What should I do when amendments are submitted?
A. The Form FDA 1572/DAIDS IoR Form must list all IRBs/ECs/REs/Approving Entity(ies) that are responsible for the review and approval of a clinical trial at a CRS prior to the CRS initiation of the protocol. If a RE/Approving Entity is not responsible for the review of full version amendments, letters of amendment or changes to the CRS site-specific ICFs, the CRS Leader or IoR should document the IRB/EC/RE/Approving Entity procedures with a memo to the DAIDS PRO or in the DPRS when submitting registration materials.
Q. If a site submits materials stating that their local IRB approval is being performed by another IRB, does the local IRB/EC that is waiving approval need to be listed on the Form FDA 1572/DAIDS IoR Form?
A. No. The site should list only the IRB/EC that responsibilities have been delegated to on the Form FDA 1572/DAIDS IoR Form.
Q. Our main clinical site has an additional/alternate location where participants will be seen by the same study staff from the main site; should we list the name and address of both locations on the Form FDA 1572/DAIDS IoR Form?
A. Per the DAIDS Protocol Registration Manual, sites must list the names and addresses of all locations where the clinical trial will be conducted. This includes all facilities where participants will be seen and study procedures performed.
III. Curriculum Vitae (CV)
Q. Since CVs are not protocol specific, do sites have to upload it for each protocol or can it be stored in a cross-protocol manner on the DPRS?
A. Sites do not have to submit a new CV for each submission to the DAIDS PRO as long as the CV on file has a signature and date that is less than two years old.
Q. How will "expired" or "expiring" CVs be tracked, and who is responsible for obtaining renewals?
A. The DPRS will generate a report and sites will be alerted when the two-year expiration date approaches.
IV. Protocal Registration Submissions (Amendments, Letters of Amendment (LoAs), Sub-Studies)
Q. The Manual states that once a CRS has received approval from their IRB/EC and other applicable REs/Approving Entities, the amended protocol or LoA, and revised site informed consent(s) must be implemented immediately. Can you clarify what is meant by immediately? Is there a window/grace period for things such as administrative tasks or starting to have new consents signed?
A. DAIDS expects that after receiving final approval from all IRBs/ECs/REs/Approving Entity(ies), the CRS will implement approved modifications to the protocol immediately, unless the amendment or LoA states otherwise. Refer to the DAIDS Protocol Registration Manual for additional information regarding amendment and LoA implementation requirements.
Q. The DAIDS Protocol Registration policy says that sites must submit IRB/EC approvals for amendments and LOAs within 14 calendar days of final approval. Our studies are reviewed by multiple IRBs/ECs. Does the 14 days begin after receiving final approval from the ALL IRBs/ECs? Can we begin counting the 14 days beginning with the date received? Will holidays count in the 14 calendar days?
A. The 14 calendar days begin after receipt of the final written IRB/EC/RE/Approving Entity approvals from ALLIRBs/EC/RE/Approving Entities. Per the DAIDS Policy, the 14 calendar begins with the date the written documentation of ALL IRB/EC/RE/Approving Entity approvals was received by the site. Holidays will NOT be counted in the calendar days.
Q. Does the 45/75 day requirement to submit LoAs or full version protocol amendments to the local IRB/EC apply when a site is not yet registered to the study?
A. No. The requirement to submit an amended protocol is for sites that have received initial approval for a previous version from their local IRB/EC. Based on the DAIDS Protocol Registration Policy, the 45/75 day requirement is not dependent on whether a site is registered to a study but rather it is based on the date that the amendment or LoA was approved by DAIDS and distributed to sites. This does not mean that the approved amendment or LoA must be submitted and registered by the DAIDS PRO within 45/75 days. The 45/75 day requirement is the timeline for submission to the local IRB/EC only.
Q. How should sites handle protocol amendments for sub-studies? When sites submit an amendment to the DAIDS PRO for the main study, should they also submit a separate registration for the sub-study or is the approval for the sub-study assumed to be grandfathered in the parent study amendment approval?
A. Any protocol amendment (for the main study or sub-study) must be submitted as individual (separate) registration. Individual registration submission is also required for all LoA registrations.
Q. Can you provide clarification regarding the registration requirement for Continuing/Annual Reviews? Are sites required to submit IRB/EC approval of Continuing/Annual Reviews to the DAIDS PRO?
A. Sites are required to submit continuing review documentation to the DAIDS PRO within 14 calendar days after the receipt of final written documentation of IRB/EC approval.
Q. I've received a Registration with Required Corrections (RwRC) notification. Can I start using the site specific ICFs or do I have to wait until the required corrections are made and approved by the IRB/EC?
A. A RwRC Notification indicates that a site may begin using the site-specific ICFs after protocol activation by the appropriate Operations Center, Data Management/Statistical Center or DAIDS Program, if required. However, the site must make the required corrections and submit them to their IRB/EC for review and approval OR must submit justification for why the required corrections will not be made within 120 calendar days of the date the RwRC Notification was issued to the DAIDS PRO.
Q. I have already received a protocol registration notification for my English site-specific ICFs for the current version of protocol xxxx, but I just submitted revised English site-specific ICFs. Will I receive a new registration notification?
A. No, the DAIDS PRO only issues one registration notification per version/language. However, the DAIDS PRO will issue acknowledgement of receipt for the revised site-specific ICFs.
Q. I've received a disapproval notification, but I do not agree with the requested changes. What do I do?
A. If you would like DAIDS to reconsider disapproval, please submit a disapproval reversal request to the DAIDS PRO. Additional information on submitting a disapproval reversal can be found in section VI. C. ii of the DAIDS Protocol Registration Manual.
V. Site-Specific Informed Consent Form (ICF)
Q. Is there a specific format or template for the written documentation sites must provide when a site deletes or makes any substantive change to basic and/or additional elements as presented in the DAIDS-approved sample informed consent (SIC)?
A. There is no specific format or template. Examples of written documentation include but are not limited to the following:
- A memo from the Investigator of Record (IoR) or designee
- A copy of the submission letter from the site to the IRB/EC detailing the changes to the site-specific ICFs
- A copy of the letter(s) from the IRB/EC documenting queries and changes required to the site-specific ICFs
Q. Can you provide examples of “substantive change to basic and/or additional elements?”
A. Examples of these changes may include but are not limited to: deleting risks, deleting sections that are in the DAIDS-approved SIC, stating that there is compensation for research-related injury when the DAIDS-approved SIC states that there is none.
Q. What if my IRB/EC requires language in the DAIDS-approved SIC to be removed or requires language to be added to our site-specific ICFs?
A. Sites should provide a copy of the documentation from the IRB/EC requesting changes to the site-specific ICFs and/or DAIDS-approved SIC. This documentation should be provided with the site’s protocol registration submission to avoid delays or disapproval.
Q. What if there is a pregnancy consent included in the DAIDS-approved SIC, but my site only enrolls men. Am I required to submit a pregnancy consent?
A. No, only site-specific ICFs that will be used at the site are required to be submitted to the DAIDS PRO. However, the site should provide documentation stating that the ICF will not be used and why with the protocol registration submission to avoid delays or a disapproval.
Q. If my site develops a long form and concise form and we only plan to utilize the concise form, am I required to submit to submit both to the DAIDS PRO?
A. Yes, the long form and concise form should be submitted for DAIDS PRO review.
VI. Institutional Review Board/Ethics Committee (IRB/EC), Institutional Biosafety Committee (IBC) & Other Regulatory Entity (RE)/Approving Entity Approvals
Q. What does the term “REs/Approving Entity” include?
A. Any group other than the local IRB/EC who is responsible for reviewing and/or approving a clinical research protocol and site-specific ICFs prior to implementation at a site. Refer to the Definition section of the Protocol Registration Manual for additional details.
Q. What type of documentation will be accepted as proof of IRB/EC submission within 45 days?
A. Examples of appropriate documentation of the date an amended protocol/LoA and any revised site-specific ICFs were submitted to the local IRB/EC include but is not limited to
- The submission letter from the site to the IRB/EC
- A memo from the IoR or designee specifying the date of submission to the IRB/EC
Q. Are IBC approvals required for Amendments and LoAs?
A. IBC approvals for LoAs and amendments may or may not be required. If an IBC must review and approve all full version protocol amendments and LoAs prior to the implementation at a CRS, documentation of the IBC approval should be submitted to the DAIDS PRO at the time of amendment or LoA registration.
Q. If a RE/Approving Entity is not responsible for the review and approval of full version protocol amendments, LoAs, or continuing/annual reviews, will each submission for the same protocol and site require a separate statement in the comments section of the DPRS?
A. No. This is a onetime requirement per protocol/site. If documentation is submitted with the initial registration or with the first full version protocol amendment registration, the site does not need to submit documentation for any subsequent registrations for that protocol. However, if the local regulations change, the IoR for the trial is responsible for ensuring that DAIDS is aware of these changes.
VII. Translation Requirements
Q. Will time requirements for documentation submitted to the Institutional Review Board (IRB)/ Ethics Committee (EC) also apply for consents that must be translated into other languages as well?
A. Sites should submit the amended protocol and all the amended site-specific ICF(s) to their IRBs/ECs and other applicable REs/Approving Entity(ies) for review and approval as soon as possible. Per the DAIDS Protocol Registration policy, submission to the local IRB/EC must take place within 45 calendar days for U.S. sites and 75 calendar days for non-U.S. sites of the date the amendment was approved by DAIDS and distributed to the sites.
Q. At our site we will enroll English- and French-speaking subjects. Do we need to submit a back translation of the French ICFs?
A. No, if you have an IRB/EC-approved English site-specific ICF, you are not required by DAIDS to submit a back translation of the French site-specific ICF. However, some networks require back translations for all local language site-specific ICFs.
Q. What if my network requires a back translation even though we have an IRB/EC approved English site-specific ICF and DAIDS does not require a back translation?
A. You should comply with your network’s requirements regarding back translation.
Q. My site only consents participants in languages other than English. Is a back translation for each language required?
A. Yes, if there is no IRB/EC approved English site-specific ICF then a back translation is required for all other languages (with the exception of Spanish).
Q. I have already been approved for my English site-specific ICF and the IRB/EC just approved my local language site-specific ICF. Do I need to receive protocol registration notification for additional languages?
A. Yes, all site-specific ICFs in all languages are required to be submitted to the DAIDS PRO and a registration notification must be received prior to utilizing the ICF.
Q. Is a back translation for Spanish site-specific ICFs required?
A. No. However, if your network requires a back translation you should comply with your network’s requirements. A Translation Confirmation Document is NOT required for all Spanish site-specific ICFs.
Q. When is the latest point at which a site should complete deregistration?
A. Although deregistration can take place earlier, the latest that a site should deregister is after the primary analysis of the study is complete.
Q. How do we know when the primary analysis is done?
A. Sites may inquire with the protocol team.
Q. Can a site deregister if the protocol is still open at the IRB/EC?
A. Yes, after consulting with the IRB/EC, the site may deregister if all participants are off study or protocol is closed to follow up. Protocol specific safety documents will not be sent to the site. However, the monthly safety distribution report can be found on the RSC website.
Q. Will we need to file for continuing/annual review if the study is closed at the IRB/EC?
A. If a CRS closes a protocol with the IRB/EC, then it is not required to submit continuing review to the IRB/EC. If the CRS did not close the protocol with the IRB/EC then the CRS is required to submit continuing/annual review. If the CRS has not closed with the IRB/EC but has deregistered with DAIDS, the CRS does not have to submit the documentation of continuing/annual review to the DAIDS PRO but must keep it in CRS’ regulatory files at the site.