Questions for May-July 2005:
Q: RCCs may have a number of “centers” participating in the RCC local network. Do applicants need any letters from the other institutions, e.g., from Deans, hospital administrations, IRBs? Do applicants need biosketches from any of these people?
A: Letters confirming commitment for both the protocol and the patient recruitment from all participating sites should be included in the appendix. Reviewers may judge the level commitment by the authority of the official who provides the letter. Information concerning the adequacy and strength of the local network and component parts should be described in the application.
Q: What CVs or biosketches need to be enclosed?
A: A NIH-type CV should be included for all key investigators.
Q: Is the RCC expected to include a statistician (with biosketch) in its budget or does this all reside with the coordinating center? Do applicants need biosketches for the individuals who would be participating in the two proposed projects and should the two projects include our local statisticians or will the latter also come from the coordinating center?
A: Instructions regarding the RCC budget is provided in the RFA. The investigative team required to recruit and conduct the proposed protocols should determine the percent effort and mix of expertise requested. Although expert statistical advice is essential in developing proposed protocols, it seems unlikely that such expertise would be needed to perform as a RCC.
Q: In the RCC applications, do the two proposed research protocols' budgets go within the 25 page limit for the Research Plan?
A: No, budget is not a part of the Research Plan.
Q: In the RCC applications, should there be standard Human Subjects sections detailing safety and informed consent issues for both proposed research protocols outside of the 25 page limit for the Research Plan?
A: The section dealing with human subjects is outside of the 25 page limit for the Research Plan.
Q: In the RCC applications, do statistical design and patient availability data for the proposed research protocols go within the 25 pages for the Research Plan?
A: Yes, the Research Plan should include the statistical design and description of the target population. Please note that patient availability of a RCC should be described under Resources.
Q: Where should the applicant list the patient population recruitment? Sometimes patient population is included in the Human Subjects section of R01 grants and sometimes in the body of the grant?
A: Additional information about WOMEN, CHILDREN, MINORITY RECRUITMENT can be placed in the HUMAN SUBJECTS SECTION. Networks or protocols focusing on specific patient population should include the description as part of the Research Plan.
Q: How should the 25 pages for the Research Plan be organized in reference to the usual PHS 398 R01 format as embodied in the Table of Contents page?
A: Please use the usual PHS398 format.
Q: In the RFA (Section IV, Budget Requirement for RCC Applications), the expectation is that "the cost associated with patient enrollment care will be included in the RCC budget". Assuming that an applicant for a RCC has identified a number of hospitals and private practices in the region to act as satellite centers for the RCC, can you further define what is meant by patient enrollment care?
A: There are two budgets: 1) one supporting the local infrastructure which would include personnel and 2) the other providing funds for conducting a specific protocol. Applicants should provide number of patients needed, type of patients, and cost estimates for each of the protocols enclosed with the application; it is likely that other RCCs will be needed to recruit patients into your protocol unless you can do it within your own RCC. Typically the cost of recruitment is related to having staff to enroll and follow patients. Use your protocols to project how many patients you can recruit and their related costs. The funds for actually conducting protocols are allocated in the Data Coordinating Center budget, with RCC being reimbursed from the DCC on a per patient basis. It is anticipated that the cost of screening and enrolling patients would be covered by funds supporting the local RCC infrastructure. The protocol-related material, drugs, and agents would be funded as a per patient cost in the DCC budget.
Q: In the discussion of the clinical research skills development core (Project Organization III. Clinical Research Skills Development Core), the RFA clearly states that new investigators with an active K grant can participate in the core, but may not receive salary on the Skills Development Core. This suggests that an applicant can include salary support for new investigators on the grant under the $100,000 earmarked for the core. This would be a deviation from the original 2002 description of the core referenced later in the grant (http://www.nhlbi.nih.gov/funding/policies/ntwk_skill.htm.) that states funding for new clinical investigators is neither needed nor allowable as a core cost. Funding for the new investigators needs to come from the clinical network or multicenter study (i.e. the $250,000 intended for the main study). Given the requirements of the main study, shifting the salary support to the main grant limits the ability of the applicant to support new investigators. Can it be interpreted that new investigators' salary can be supported as part of the core grant?
A: Since the clinical research skills core is intended to serve new clinical investigators who occupy positions and receive salary support from the clinical network or multicenter study, salary support for the new investigators is neither needed nor allowable as a skills core cost.
Q: What is the difference between phase 2 and phase 3 clinical trials? If an applicant is considering a multicenter effort with a novel approach to an existing, approved therapy, wouldn't this be considered a phase 3 trial?
A: The primary goal of the network is not to conduct large (thousands of patients) phase 3 trials. The focus of the Nework is on smaller trials with well defined protocols. It is, however, recognized that protocols will require participation of most network RCCs to achieve adequate enrollment as quickly as possible.
Q: Could the NHLBI clarify the meaning of “cooperative, multi-center activities”? This is listed as an application requirement.
A: The NHLBI expects that all RCCs will collaborate on the development of and be able to conduct all protocols. Any single center cannot pursue its own protocol without agreement from all other RCCs and without approval of the Steering Committee. The final scientific agenda and protocols to be conducted will be determined by the Steering Committee and NHLBI, followed by appropriate reviews by the Protocol Review Committee and DSMB.
Q: Is there a plan to establish a “specimen/tissue” bank for the network? Some of the protocols may focus on research using such materials.
A: Currently there are no funds allocated to create such bank. If a need should arise, then the steering committee would evaluate such activity and availability of funds.
Q: In planning the required clinical protocols, we are considering using both a “standard” as well as a new agent/drug in one of our protocols. Do you know if any companies are planning to supply heart failure related drugs?
A: The NHLBI has not had any contact with industry since protocols are not decided. After award of the grants, PIs from the RCCs will determine the scientific agenda and then select/develop protocols accordingly. At that time industry participants will be considered. However, having said that, if a RCC applicant includes a protocol dealing with a specific drug/agent and has had communication with a company willing to donate the drug/agent, it would be important to know. Therefore, we suggest that the applicant include a letter from company stating their intent if the protocol were selected.
Q: We will be submitting an application for the DCC in response to the above RFA. The RFA states that “The DCC will subcontract with external laboratories as needed, coordinate with suppliers of drugs, and arrange for the preparation and packaging of medications.” Because the nature and scope of the proposed research will not be determined until awards are made, we are unable to provide sufficient detail to our collaborating bioservice partner for them to accurately estimate pharmaceutical services and expenses.
Since the award mechanism will be a cooperative agreement, will NHLBI allow us to demonstrate intent to collaborate with the bioservice company, with the caveat that the cost is excluded from the budget and will be determined based upon the final selection of protocols and sites and will not exceed the cap for the DCC stated in the RFA? Otherwise, any cost estimate for these services will be very hypothetical due to all of the unknowns.
A: It is important that a DCC applicant demonstrate understanding of the likely core facilities needs and their ability to identify select and manage a core facility. However, as you suggest the actual core facilities needs will not be determined until after the program begins.
Q: It appears that applicants do not need to submit a detailed budget for the Training Core. Is that correct?
A: No, a detailed budget for an amount not to exceed $100K in direct costs is required. The budget should list personnel, travel, and other training related expenses.
Q: For the $250K direct cost RCC budget, can the applicant submit it in a modular format? i.e., named individuals with % effort, but no actual dollars?
A: No, the RFA does not state that you can use the modular budget format.
Questions for April 2005:
Q: Is there a limit on the number or the length of the documentation regarding available patients?
A: It is important to provide information to confirm patient resources in your application. This information should be detailed in Section E. Human Subjects. There is no page limit on this section.
Q: Is the focus of the RFA primarily on cutting edge therapies? Can methodological issues be studied?
A: The purpose of this Request for Applications (RFA) is to establish a Heart Failure Clinical Research Network that will accelerate research in the diagnosis and management of heart failure, in order to improve outcomes through optimal application of existing therapies and evaluation of novel therapies. As stated in the RFA, the network will focus on collaborative clinical protocols to facilitate application of emerging basic science discoveries into clinical investigations. For example, proposed protocols may evaluate cell-based treatments, treatments using novel classes of drugs such as immunomodulators, or genetic or other new biomarkers for early diagnosis and assessment of therapy. Since this RFA focuses on translation of new basic science findings, protocols focused on behavioral and lifestyle interventions, large Phase III clinical trials, or epidemiological studies are not responsive to this solicitation.
Q: Do you see a need for a histopathology core laboratory or do you contemplate such a core being solicited by the coordinating center?
A: If a protocol proposed by the RCC applicant requires central interpretation, such information and estimated cost should be included in the protocol proposal. In the event that a central laboratory is required to analyze specimens, the RCCs will be responsible for obtaining the sample(s) and the cost of obtaining them will be part of the RCCs per-patient expense. The cost of shipping, analyzing, and storage, as well as training of personnel and quality control will be the responsibility of the DCC.
Q: Do the literature references for the application count toward the page limitation?
A: Only Sections A-D of the application is included in the page limits -- the Literature Cited section is not included.
Q: Regarding budget issues, can secretarial support be part of a project application?
A: Yes, partial support of a secretary is allowable. Each regional clinical center (RCC) applicant should submit a request for a RCC budget which may include up to 1 FTE for investigator time, an additional 1 FTE for a research coordinator, and 0.5 FTE for administrative assistant. It is anticipated that half of the first year will be devoted to protocol development and staff training, with patient recruitment commencing in the second half of the first year. This should be considered in the proposed budget structure. Requests must be submitted with appropriate justification. It is anticipated that this RCC budget will include the following personnel categories: PI and Co-Investigators, Study Coordinators, Data Management Coordinator, and Secretary/Administrator. A minimum of 25% effort for the PI at each RCC is required. Appropriate effort for other key personnel, travel costs for two people to attend steering committee meetings in Bethesda, Maryland, and other travel related to Network operations (such as DSMB meetings and site visits) should be included with appropriate justification.
Q: Is the total budget of $1.25 million maximum for the entirety of the 5 years or must we be under $250,000 every year? First years would have to be considerably under $250,000 in order for the last year to not exceed $250,000.
A: For each regional clinical center (RCC), excluding the cost of implementing the proposed protocols which will be funded through the data coordinating center (DCC); direct costs may not exceed $250,000 per year. Allowable costs for the RCC are detailed in question 5 above. Remember that the cost of implementing the protocols will be funded through the DCC and is not included in your $250,000. In addition the maximum allowable direct costs for the clinical research skills development core are $100,000 per year.
Q: Can staff salaries be assigned as appropriate to the proposed protocol cost?
A: In general the RCC budget should cover personnel required for its participation network protocols and should not be included as a protocol cost.
Estimated protocol implementation costs should be based on the proposals presented in the applicant's research plan, but should not be included in the RCC budget request. A table must be included showing estimated costs per patient for conducting each proposed protocol. The budget for each protocol must be developed on a cost-per-patient basis and include all direct costs and the associated protocol facilities and administrative costs. Although the RCC budget is intended to cover the cost of personnel required to participate in network protocols, a proposed protocol might include additional staff to implement if considered necessary. Costs of drugs or laboratory tests that are not clinically indicated (i.e., are not eligible for third-party reimbursement as part of routine clinical care) should be part of the per-patient cost of conducting a protocol. Applications should clearly identify the potential source(s) for any drugs or substances (such as cell based therapies) that are being considered for clinical protocols that are currently unavailable commercially. It should be noted that funds will not be provided for the purchase of expensive medical equipment, such as echocardiographic or magnetic resonance imaging systems. It is anticipated that the cost associated with patient enrollment care will be included in the RCC budget. If any of the protocols proposed by RCC applicants include obtaining blood or tissue samples, the applicant should delineate how such specimens will be handled and analyzed. In the event that a central laboratory is required to analyze specimens, the RCCs will be responsible for obtaining the sample(s) and the cost of obtaining them will be part of the RCCs per-patient expense. The cost of shipping, analyzing, and storage, as well as training of personnel and quality control will be the responsibility of the DCC.
Q: Please clarify the allocation of the cost of the training component.
A: Applications for this program can apply for a clinical research skills development core. Costs allowable for inclusion within the $100,000 direct costs per year, over a five year period, limit for the Clinical Research Skills Development Core include: salary support for the Core Leader and other participating senior investigators and staff, travel costs for new investigators, supplies and equipment to be used in support of developmental activities, and costs for courses, seminars, workshops, and other activities directly related to the development plan. All costs requested in this Core must be justified with respect to developmental activities and may not be used to supplement the costs of research proposed in the clinical research network.
A Core is not a required component of an RCC and its absence will not disadvantage an applicant. The priority score on the Core will have no effect on the overall score of an application. If a Network application includes an application for a Core, then the Core should be mentioned in both the Abstract and the Table of Contents. Up to four additional pages may be used to describe the proposed Clinical Research Skills Development Core. The Core proposal should be inserted in the Network application at the end of the Research Plan. This text will not be counted toward the 25-page limit for the total Research Plan specified by the Form 398 instructions. Requests for Core funds should not be included in the body of Network applications as it is expected that this aspect of the Network will be supported by supplemental funds. Thus, applicants should provide a separate budget page for the Core and add the cost of the Core as a line item into the total request for funds. Applicants should read the specific requirements and other instructions for applying at http://www.nhlbi.nih.gov/funding/policies/ntwk_skill.htm.
Q: Is it proper to use part of the money for stipend for a fellow?
A: No, the clinical research skills development core should not include partial stipend support for a fellow. Please review allowable skills development core costs provided in the preceding question.
Questions for March 2005:
Q: Should protocol proposals be limited to a specific heart failure population?
A: The network is intended to have the capacity to evaluate the spectrum of disease including advanced CHF. Responsive research proposals and estimates of numbers of cases may include hospitalized patients as well as out-patients.
Q: In providing (at least) two protocols, do these protocols have to be using the same approach or can they be different?
A: Proposed protocols can stand independently, addressing specific needs in separate areas of investigation.
Q: Should protocols be simple or can they be more complex?
A: The applicant should select protocols to reflect what they consider important .and that take advantage of the proposed infrastructure of the network. It is preferable that protocols submitted NOT be restrictive requiring only a single center. Large phase III trials would not be responsive. Whether complex or simple, proposed protocols should provide study rationale and hypothesis, and detail study design, endpoints and statistical considerations with total sample size estimates, and costs. Protocols proposed should meet the time and enrollment constraints of the network.
Q: Are individual researchers to submit an application for their specific project or is the institution to submit an application defining its role as an RCC?
A: The institution should submit an application defining its role as an RCC. Sample protocol proposals are a required part of that application.
Q: Would the network consider protocols that test new devices?
A: Yes, although final protocol development and selection will be the responsibility of the Steering Committee.
Q: What is meant by a local network?
A: It is anticipated that any given institution will require the coordination of multiple services to successfully perform stipulated research. This is in addition to the internal interaction required between relevant divisions of Medicine. For example, some institutions will include participation of multiple clinical centers to gain the required number of potential participants. Others may need to work with affiliated practices or groups to assure an adequate patient participation. Such institutions will need to work closely in order to best identify eligible patients and implement protocols. A letter of agreement to document these relationships is required to demonstrate that a local network has been established to support the RCC application.
Q: Should the required two (2) protocol proposals be submitted as a part of the RCC application in the PHS 398 format, or should they be submitted separately?
A: Protocol proposals must be submitted as a part of the single RCC application in the required PHS 398 format. The application should also describe required elements of the RCC and commitment to cooperate in the network. The entire application may not exceed 25 pages. The budgetary portion of the RCC application should refer to the yearly cost of the RCC. Each of the two (2) protocol proposals should be followed by a budgetary proposal that is specific to the cost of the proposed project, recognizing that actual network protocol funds will be distributed by the DCC to the participating RCCs on a per-capita basis.
Q: How will a "region" be defined?
A: Regions will be defined both by geography and by any existing or engineered relationships that arise out of the development of local "networks".
Q: Should the two (2) protocol proposals be limited to the resources available at one RCC, or should they be proposed on a network scale?
A: In order to eliminate supposition regarding the resources available to other potential RCCs, the RFA stipulates that the two (2) proposals be written in terms of the resources available within the local "network", however, it is anticipated that proposals will be broad enough to warrant expansion to an entire network scale.
Q: Are RCC applicants required to provide all proposed services through the primary institution?
A: RCC applicants are expected to develop a local "networks" of institutions, hospitals, practice groups and others who together will be able to provide the services required to perform heart failure research.
Q: What is required in a letter of intent?
A: The letter of intent should identify a PI, the primary institution, and any associated institutions in the local “consortium”. The letter should also state whether or not the applicant will apply as an RCC or DCC. The letter should be submitted by July 19, 2005 .
Q: Can I apply for both RCC and DCC?
A: Yes, an institution can apply for both DCC and RCC as separate applications. However, the DCC must be impartial and should not be involved in recruitment of patients. Institutions that expect to apply as both an RCC and a DCC have the burden to establish a firewall between its RCC and DCC investigative teams. One of the key issues for DCC will be applicant's past experience as DCC.
Q: For proposed protocols should they be designed to be implemented in "just the applicant's RCC" or can they be designed to be implemented in more than one RCC?
A: The applicant can propose protocols which can be either conducted in one RCC or multiple RCCs. However, it is anticipated that the proposed protocols would take an advantage of multi-center collaboration. The protocol needs to have adequate information on required sample size, endpoints and their justification, power calculations and analyses.
Q: Is there just one PI or can the regional application include PI and CO-PI?
A: It is anticipated that applications would include PI and CO-PI, reflecting leadership and experience.
Q: May one institution submit two RCC applications under two different PIs?
A: Yes, although the requirements of an RCC are so extensive that it is not advised.
Last updated: July 11, 2005