Click the text below to find or hide additional information.
1. Will there be a separate progress report section required in the research plan (other than the publication list), or will the sections in the various Components serve this purpose?
Renewal applications are not to include a separate Progress Report in the Research Plan as described in the PHS 398. Instead, renewal applications are to follow FOA directions and address progress as requested in the “Performance and Applicant Experience” sections of the Components.
2. What is the UM1 NIH grant activity code?
The UM1 activity code is a research project Cooperative Agreement to support large-scale complex clinical trials with multiple components, e.g., clinical networks. The components represent a variety of supporting functions and are not independent of the research projects. Substantial Federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of an award.
3. How many HIV/AIDS Leadership Group (LG) applications does NIAID intend to fund?
The number of awards is contingent upon NIH appropriations, availability of funds in Fiscal Year (FY) 2014 and the submission of meritorious applications. For each LG FOA, NIAID anticipates funding one award each to the Leadership and Operations Center (LOC), Laboratory Center (LC) and Statistical and Data Management Center (SDMC) comprising a Leadership Group.
4. I would like to have the program for NIAID's grantsmanship workshop on July 28-29, 2012, in Washington, DC, for clinical trials units for the re-competed clinical research networks. Can you please send me the program?
The agenda for the NIAID Grantsmanship workshop in Washington, DC, is currently in development and will be made available soon. However, online registration is now available. Please continue to check for updates at Restructuring the NIAID Clinical Trials Networks.
5. NIDCR, NIMH, NINDS, and NIDA are listed as participating I/Cs in this FOA, RFA-AI-12-004. Is their contribution included in the $36.93 million for this FOA? If so, is there a specific amount these I/Cs are contributing? If not, what guidance can you provide to the applicants as to the appropriate amount of the networks scientific agenda that should be apportioned to the interests of these collaborating I/Cs?
All applications should address the Scientific Agenda outlined in the FOA in Research Priority Areas Part 2, Section 1, #3. The financial commitment of other participating NIH Institutes/Centers is reflected in the total published amount of $36.93M, but as always is contingent on the availability of funds and Programmatic priorities. This applies to all five of the HIV/AIDS Leadership Group FOAs.
6. When preparing the inclusion enrollment tables for a renewal application, should we provide data for all trials to date or only those that have opened or had changes in enrollment since the last competitive application was submitted?
The Inclusion Enrollment Report should provide data for each current trial with cumulative total accrual of subjects to date. If there is more than one study/protocol, provide a separate Inclusion Enrollment Report for each.
7. What is the primary driver for the CDISC adoption (SDMC harmonization, submission to FDA, interchange with DAIDS, etc.)?
The primary reasons for CDISC adoption include the potential requirement by the Food and Drug Administration for SDTM- formatted data submissions in the near future, and to improve our ability to effectively conduct pharmacovigilance and meta-analyses across clinical datasets.
8. What is meant by “data collection”? Do we need to collect in CDASH standards or can we map CRF/lab data to SDTM?
The use of standardized data collection with CDASH is encouraged but not required. If you plan to collect data in one format and convert to SDTM when needed, your application should characterize how your proposed process will impact the speed of data availability, costs to the grant, and accuracy of the converted data.
9. If CDASH standards are not required for data collection, at what point do we need to map to CDISC standards within a study? At first analysis? At study close-out?
Our requirement is that any data that may need to be analyzed or submitted to a regulatory authority be available in SDTM format at any point during or following the trial.
10. Do we need to standardize lab assay data (and other data that currently does not have defined data structures, e.g. behavioral data, ePRO/PRO data) across data centers? Will there be any assistance provided to the SDMCs to coordinate this?
The SDMCs will be expected to coordinate a standardized approach for any data providing additional assistance for coordination beyond the Leadership grant award itself.
11. Are there any exceptions for any data types or studies, e.g. Household-level data collected in a community randomized trial?
Our intent is for data to be readily available in SDTM format for analysis and submission to regulatory authorities. However, you may wish to propose any exceptions that you believe would be appropriate.
12. Do we need to produce ADaM datasets?
There is no requirement to produce ADaM datasets.
13. Do we need to provide technical documentation? If so, is there a required format, e.g. eCTD, or are there specifications on what should be included?
The Leadership Group RFAs request a plan on how the SDMC will collect, store, and transfer data in accordance with CDISC, and any documentation supporting these capabilities may be beneficial, but not essential.
14. What are the requirements for historical data and data from studies ongoing at initiation of new grant? Do we need to map to CDISC standards for PUDS releases?
We do not anticipate converting data from ongoing studies to CDISC format. If a determination is made to convert existing data or data from trials that are ongoing at the time of the awards, a separate funding mechanism will be used.
15. In the section "5. Leadership and Operations Center, Laboratory Center and Statistical and Data Management Center Specific Responsibilities," one of the evaluation criteria is stated as follows: “Are the plans to assure compliance with regulatory requirements for data management, including compliance with CDISC, adequate?” What regulatory requirements mandate CDISC?
No current regulatory requirements mandate use of CDISC. This statement refers to assuring compliance with a likely future regulatory requirement for use of CDISC.
16. In the "SDMC Component 2" section, the first data management requirement is that “The SDMC will also be expected to collaborate with other NIAID/DAIDS-affiliated SDMCs in the development of data elements that do not yet exist within CDISC.” Since the formal definition of new CDISC elements and, where necessary, new CDISC domains to accommodate them may require substantial medical expertise and input, what plans does NIAID/DAIDS have to provide the resources necessary to accomplish this?
The Leadership Award itself is the resource that will be provided to SDMCs to accomplish the tasks set forth in the Leadership FOAs. We do not anticipate making other specific resources available.
17. What is the NIAID/DAIDS' backup strategy for CDISC standardization if the CDISC consortium ceases to operate?
While we consider it unlikely that the CDISC consortium will cease to operate during the 7-year period of the Leadership Awards, applicants may wish to provide their proposed plans to address such a contingency.
18. For an incumbent, would an application in response to clinical trials network RFA be considered a renewal or a new application?
A current awardee of a HIV/AIDS clinical trial network has a UM-1 award with a grant number. An application in response to these RFAs, from the current PI and/or institution, would be a renewal.
19. In the FOA, Part 2, Section IV, subsection 2, regarding instructions specific to SDMC, please confirm:
(1) the Research Approach and Data Management Plans and Systems sections count toward the 30-page limit for the Research Strategy section, and
(2) the total page limit for all of Component 2 is 31 pages.
Answer: Component 2 for each linked application, Leadership and Operations Center (LOC), Laboratory Center (LC) & Statistical and Data Management Center (SDMC) allows 1 page for Specific Aims and 30 pages for Strategy for a total of 31 pages.
20. Under Section IV.2 of the RFA, applicants are instructed to send an original and three copies of the application to the Center for Scientific Review (CSR), and two additional copies to Peter Jackson with "all copies of the appendix files." Does this mean that the CSR does not get any appendix CDs? (2) Under IV.2.A-C in which the LOC, LC, and SDMC Appendix sections indicate "Five identical CDs containing all appendix material must be submitted in the same package with the application." Is the correct interpretation that the five CDs are to be sent with the two paper copies of the application to Peter Jackson? (3) Also, please verify that no paper copies of appendix materials should be submitted, regardless of the recipient.
Answer: Applicants are instructed to submit a typewritten original of the application, including the checklist, and three signed photocopies in one package to the Center for Scientific Review. In addition, two paper copies of the application along with all copies of the appendix files must be sent to Dr. Peter Jackson.
In addition to the application package submitted to CSR, two paper copies of the application and all copies of the appendix files must be sent to Dr. Peter Jackson. Five identical CDs containing all appendix material(s) must be submitted in the same package for each LOC, LC, and SDMC application. No paper copies of the appendix materials should be submitted.
Five identical CDs containing all appendix material(s) must be submitted in the same package for each LOC, LC, and SDMC application. Because the LC, LOC, and SDMC applications will be separate awards and each application will receive a separate serial number, each application type (LC, LOC, and SDMC) must be sent in a separate box.
CSR will receive three separate boxes per Network response. Each box will contain the original application and three copies of one type of application. For example, the applications for a network would arrive at CSR in three separate boxes.
Dr. Jackson will receive three separate boxes per Network response.
Each box must be complete in itself, boxes should arrive on time, boxes should not be taped together, and each box must include a cover letter that explains the contents of the box.
21. In RFA-AI-12-001 (Leadership Group for a Network on HIV/AIDS and Associated Infections in Pediatric and Maternal Populations) in Part 2, Section 1, #3, “Research Priority Areas," examples of research with the five priority areas are listed. At the end of this section (#3), under "Pharmacology, Drug Formulations and Novel Interventions," there is a paragraph on HIV-related ORAL DISEASE research, with specific areas of emphasis noted. Please confirm whether or not applicants are being asked to address this specific research area in their proposals.
Answer: All applications should address the Scientific Agenda outlined in the FOA in Research Priority Areas Part 2, Section 1-3. This applies to all five of the HIV/AIDS Leadership Group FOAs.
22. The RFA is asking for the LOC and LC components to be outlined as two separate proposals. Our Network Coordinating Center (NCC) has a role in supporting both the LOC and LC components of the network, with overlapping responsibilities. With the understanding that both the LOC and LC components are submitted through the same institution, is it acceptable to include the NCC as one unit under the LOC portion of our proposal?
Answer: A response to this FOA must include three separate, thematically-linked applications: 1) a Leadership and Operations Center (LOC) application, 2) a Laboratory Center (LC) application, and 3) a Statistical and Data Management Center (SDMC) application. An organization may submit more than once provided that the respective applications are scientifically distinct. The three separate applications can be a combination of new or renewal applications, and an eligible organization can apply for any, or all, of the three components. For proper administrative processing, each separate application must be in a separate package. Submissions that do not include the three separate, thematically linked applications will be considered non responsive to this FOA and will not be reviewed. While the three thematically linked applications will be reviewed by one, appropriately constituted scientific emphasis panel, each separate application must be complete within itself with respect to what the FOA specifies and what is to be evaluated. Each of the three separate applications, if successful, will receive a separate grant award.
23. In the NIAID application, where should an applicant integrate the HIV related oral disease research agenda as a special emphasis area identified in RFA-AI-12-001?
Answer: RFA-AI-12-001 states, “… the NIAID in collaboration with the National Institute of Dental and Craniofacial Research (NIDCR) seeks for the inclusion and implementation of an oral health research agenda, in which clinical interventions are linked to, and integrated within, the HIV/AIDS research priority areas" (see Section I, 3. Research Priority Areas). Therefore, an applicant may integrate an oral health research agenda within any appropriate NIAID research priority area(s) described in RFA-AI-12-001 (see Section IV). Applicants are reminded the RFA states: “The LG's clinical research agenda should be clearly articulated and directly related to achieving NIAID's scientific priorities,” and “Each part of the LG linked application (LOC, LC, and SDMC) is expected to demonstrate scientific leadership, effective management and efficient utilization of resources.
24. What information is requested on the cover page for each component? Is it acceptable to include a table of contents and/or an abstract on that page? Does the cover page count toward the page limit for each component?
We expect applicants to provide a cover page as an “administrative separator” between each of the components. This cover page will not count towards the page limits. Something as simple as “Component 2 – Research Agenda/Strategies” is all we expect to see.
25. In regards to the bibliography and references where "citing articles that fall under the Public Access Policy, were authored or co-authored by the applicant and arose from NIH support, provide the NIH Manuscript Submission reference number (e.g., NIHMS97531) or the PubMed Central (PMC) reference number (e.g., PMCID234567) for each article," should the applicant be defined by only the PI (or multiple PIs), key personnel, or any author cited from the applicant organization?
The applicant should be defined as the PD/PI (or multiple PD/PIs), listed in the application that have authored or co-authored any publication that falls under the NIH Public Access Policy.
26. The use of antibodies administered as products, either pre- or post-exposure, to prevent HIV acquisition (passive immunization) is not addressed as a scientific domain in any of the FOAs for Leadership Groups. Which network would have responsibility for conducting these trials?
Given the advances in the field of immunoglobulin research, there is considerable optimism regarding applications of antibody-based therapies for the prevention and treatment of HIV infection.
NIAID recognizes that antibody-based interventions have the potential for broad application within the NIH-supported HIV/AIDS Clinical Networks. Collaboration across networks should optimize unique network capabilities, such as recruiting specific populations or conducting specialized laboratory assays in order to advance the best science supporting development of unique HIV therapies, vaccines, and other prevention approaches.
The following Leadership Group (LG) lead assignments are appropriate based on scientific questions and network capabilities:
This response was published as an NIH Guide Notice, NOT-AI-12-035: Clarification on NIH HIV/AIDS Clinical Network Responsibilities for the Use of Antibody-based Therapies for the Prevention and Treatment of HIV Infection, http://grants.nih.gov/grants/guide/notice-files/NOT-AI-12-035.html.
27. In both the LG Vaccine (RFA AI-12-012) and Microbicide (RFA AI-12-008) FOAs, under the Scored Review Criteria for the LOCs, it states that “For each of the five scientific priority areas stated in Part 2, Section I-3, does the proposed research agenda have the potential to significantly advance HIV treatment, prevention and clinical care?”
However, in the Vaccine FOA there are actually nine (9) bullets, not five (5) as stated under this section as research priority areas, and in the Microbicides FOA there are actually three (3) bullets, not five (5) as stated under this section as research priority areas. Can you please clarify the number of research priority areas in the LG FOAs?
Part 2, Section 1.3 of RFA-AI-12-012, “LG for a Clinical Research Network on Vaccines to prevent HIV Infection” lists nine (9) research priority areas.
Part 2, Section 1.3 of RFA-AI-12-008, “LG for a Clinical Research Network on Microbicides to Prevent HIV Infection” lists three (3) research priority areas.
Part 2, Section 1.3 of RFA-AI-12-001, “LG for a Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations” lists five (5) research priority areas.
Part 2, Section 1.3 of RFA-AI-12-011, “LG for a Clinical Research Network on Integrated Strategies to Prevent HIV Infection” lists two (2) research priority areas.
Part 2, Section 1.3 of RFA-AI-12-004, “LG for a Clinical Research Network on Therapeutics for HIV/AIDS and HIV-associated Infections in Adults” lists four (4) research priority areas.
28. How will NIH collaborate with the clinical research networks?
Each HIV/AIDS Leadership Group will be assigned a NIAID Division of AIDS (DAIDS) Program Official(s) and Project Scientist(s). Additional NIH staff involvement will be provided to facilitate coordination of resources and activities across the Leadership Groups. External advisory groups convened by NIAID in conjunction with the LG will provide evaluation, advice, and recommendations concerning ongoing and planned research activities of the network.
29. When describing the Organizational and Governing structure, is it appropriate to list positions that will be filled and provide additional information at the JIT stage, if an award is to be made?
Assuming you are referring to Leadership and Operations Center (LOC) Component 4 (Structure and Governance) and Laboratory Center and Statistical and Data Management Center's (LC/SDMC) Component 3 (Structure and Governance):
30. Do applicants need NIAID prior approval to submit an application requesting $500,000 or more direct costs per year?
No. Applications in response to this FOA do not require prior approval to submit a request for $500,000 or more direct costs per year.
31. What are CORE Funds?
Core funds cover the expenses needed for the Leadership Group to carry out its clinical research agenda. NIAID will provide core funds to the Leadership and Operations Center (LOC), Laboratory Center (LC), and the Statistical and Data Management Center (SDMC). LG application budgets should ONLY request core funds for the LOC, LC and the SDMC. Examples include salary (including fringe benefits) for senior/key personnel and critical contributors, consultant costs, supplies, travel, equipment, and consortium costs. Core funds do not include expenses directly attributable to the development, approval, or conduct of specific clinical trials.
32. What are Protocol Funds (PF)?
PFs provide additional support to the CTU to cover protocol-related expenses attributable to protocol development, implementation or close-out of a clinical trial. For example, salary for a statistician needed to participate in protocol development is a core cost; an unanticipated increase in statistician time and effort to meet the needs of a protocol would be considered PF. Post-award, if additional funding is needed to implement and support clinical trials and/or the network's agenda these needs are to be determined in collaboration with NIAID. PFs are NOT to be included in the LG application budgets.
33. What costs should be considered LC PIF rather than LC Core? (i.e. assay supply costs, technician salary/benefits, assay specimen management, protocol peptide validation - some or all of these?)
The LC application budget needs to comprise Core costs only. It should cover senior/key personnel and other significant contributors/fringe benefits, supplies, travel, equipment, consortium costs plus related indirect and consultant costs. Further instructions and examples can be found in the PHS398 application instructions.
34. When should we expect to receive instructions on requesting LC PIF funds? How will these LC PIF funds be requested and managed? Will the LC request direction from NIH/NIAID/DAIDS?
All PIF calculations for the LG (LC/SCDMC/LOC) and CTU/CRS will occur post award and will be dependent on clinical protocol initiation. Each year, NIAID will solicit a request for PF funding and negotiations between the LG, CTU leadership, and NIAID will determine the final amount.
35. How will LC PIF costs be funded should there be a gap between the current LC award and the new PIF CORE award?
If there is a time difference between the end of current awards and the new Notice of Award, NIAID will have the ability to use a no-cost extension of current awards to ensure continuation of current studies and an orderly close-out of the appropriate activities.
36. Over the last several years the ACTG has moved toward a hybrid system of direct Protocol Funds (PF) support to the clinical research sites (awarded by NIAID to the CTUs) and additional PF in the form of sub contracts distributed by the network. The FOA states that applicants must propose one system or the other, and that a combination approach is not permitted. Is there flexibility on this point? If PF is channeled through the network, what proportion of a site's PF allocation can be provided by the network at the time subcontracts are established each year? Such advance funding will be vital to maintaining a stable personnel infrastructure at the sites.
As stated in the FOA, a proposed leadership group will need to decide on which method they will utilize for their disbursement of PF, and a combination of methods will not be permitted. This designation is limited to the annual PF distribution to the CTU and does not affect any minimal subcontract funding that a LG may negotiate with a CTU for protocol activities. More information about the structure and function of the CTUs/CRSs will be available when the CTU FOA is published in the second quarter of 2012.
37. Maximum efficiency in fiscal management of the grant is achieved when the Leadership and Operations Center (LOC) and the Laboratory Center (LC) components are awarded to the same institution (management of both grants can be centralized). If the intended LC PI is at a different institution than the LOC PI, the only way to make this work is for the LOC PI to be a co-PI on the LC component, which requires the a minimum effort of 30 percent. But, the LOC PI may already be devoting 50 percent effort.
Applications for the Leadership Group (LG) must be comprised of three separate linked UM1 applications: a Leadership and Operations Center (LOC), a Laboratory Center (LC), and a Statistical and Data Management Center (SDMC). Each of the three applications, if successful, will receive a separate grant award. Each LG segment (LOC, LC and SDMC), or grantee institution, is the funding recipient, administers the award, and is responsible for assuring compliance NIH requirements and all applicable policies, certifications, and assurances.
Co-PI is not a term that is recognized by NIH even though it is recognized by our fellow agencies. Applicants may consider either a single Program Director/Principal Investigator (PD/PI) with a co-investigator(s) or a multiple-PD/PI application if that is most appropriate. When a single PD/PI is proposed in any of the three LG applications, the PD/PI will be required to devote at least 6 person months (50 percent) effort to the project. Applications proposing Multiple PD(s)/PI(s) are permitted, but the roles and responsibilities should be clearly delineated and justified. If two or more PD(s)/PI(s) are named in any application, each PD/PI must devote at least 3.6 person months (30 percent) effort to the project.
38. Which assays should be included in PIF - primary immunogenicity, secondary immunogenicity, diagnostics (HIV, others not included in clinic costs), HLA typing, exploratory (in protocol)?
The assays associated with approved clinical protocols will be funded with PIF funding.
39. The HIV Clinical Trial network RFAs list specific dollar funding amounts for each RFA. Do these funding amounts represent a maximum as to what to budget or are they a guideline? If an application budgets in excess of the funding listed for the RFA, will it be viewed as non-responsive?
Application budgets should not exceed the total cost limit specified in Section II. Award Information of the RFA. Budget requests should remain flat throughout the entire project period. Each application's budget will be peer-reviewed and should appropriately reflect and support the science being proposed in the application. The advice of the review panel in consultation with NIAID officials will be used to determine the actual award amount. As always, the award amount contained in the notice of award is contingent upon the availability of funds and programmatic priorities.
40. Will consortium F&A costs be counted toward the total cost limit specified in the RFAs?
Consortium F&A costs are counted as part of the total costs requested in the application budget. The total costs requested should not exceed the amount specified in Section II. Award Information of the RFA.
41. Our intention is to fund the Dental and Neurology labs in direct proportion to the amount of money being provided by NIDCR and NIMH, but without knowing that amount we are unable to propose funding for those labs at this time. Should we include those labs in the budget or anticipate a supplement from NIDCR and NIMH for that purpose?
Each application's budget should appropriately reflect and support the science being proposed in the application. As always, the award amount is contingent upon the availability of funds and programmatic priorities.
42. Please confirm whether network leadership applications/budgets should include the costs associated with site community staff/representatives traveling to network annual meetings or if these expenses are to be covered by CTU budgets?
Costs associated with site community staff/representatives traveling to network annual meetings may be included in either the network leadership group or CTU application budgets, but not both, as appropriate for each network and participating CTU.
Contact information: Contact information for NIH officials is located in Section VII of each FOA.
Last Updated October 01, 2012