Questions for December 2005:
Q: Are proposals focusing on secreted cell products responsive to the RFA?
A: No, those types of proposals are not. The RFA specifically focuses on the use of healthy, functional cells (either autologous or allogeneic) to replace diseased or dysfunctional cells to treat a disease.
Questions for October 2005:
[General] [Grant Application] [Budget] [Clinical Research Skills Development Core] [Network Function] [Cell Processing] [Review]
Q: What is the definition of Cell Therapy?
A: Cell therapy is a technology that uses healthy, functional cells (either autologous or allogeneic) to replace diseased or dysfunctional cells to treat a disease. For the purposes of this RFA, cell therapy includes either transplantation of cells, modified or unmodified, or the mobilization or homing of cells to the diseased or dysfunctional area.
Q: What is a Clinical Research Network?
A: Clinical Research Network is a cooperative group of clinical research centers and a data coordinating center, whose goal is to promote the evaluation of treatment strategies. The purpose of the Cardiovascular Cell Therapy Research Network (CCTRN) is to accelerate clinical research in the use of cell-based therapies for the management of cardiovascular diseases. The network will provide the necessary infrastructure to develop, coordinate, and conduct multiple collaborative clinical protocols to facilitate application of emerging scientific discoveries into clinical investigations. Results of Network studies are expected to be widely disseminated and to provide the scientific basis for the care of affected individuals.
Q: Could you comment on the types of heart diseases that are appropriate for this program?
A: There are no restrictions on the heart diseases that may be included as long as the approach focuses on a cell-based therapy. Examples listed in the announcement include the treatment of patients with a myocardial infarction resulting in significantly depressed left ventricular function; patients with chronic heart failure undergoing left ventricular assist device placement; and angiogenic cell therapy strategies to treat patients with ischemic cardiomyopathies. Please note that proposals related to the treatment of peripheral artery disease are outside the scope of this RFA.
Q: Clinical Centers (CCs) may have other institutions or hospitals as participants in the CC. Do applicants need letters from the other institutions, e.g., from Deans, hospital administrations, Institutional Review Boards (IRBs)? Do applicants need biosketches from any of these people?
A: Letters confirming commitment for both protocol participation and potential patient recruitment from all participating sites should be included in the appendix. Reviewers may judge the level of 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 under the Research Plan.
Q: Is pre-networking with other centers prior to submission of a CC application encouraged?
A: Only collaborations necessary for a single CC application. Each CC application will be judged on its individual scientific merits, and not on pre-formed links to other potential CCs.
Q: The RFA describes funding for a five year period. If the network is successful, will it be continued beyond five years?
A: NHLBI has only recently started using networks for cardiovascular diseases, but the mechanism is more established for pulmonary disease, for example pediatric asthma, where networks have been funded for at least ten years. NHLBI views networks as an excellent mechanism for moving clinical trials forward, and if this network is successful renewal would be anticipated.
Q: What CVs or biosketches need to be enclosed?
A: A NIH-type CV should be included for all named investigators.
Q: In the CC application, should we include the standard Human Subjects sections detailing safety and informed consent issues for both proposed research protocols? Is the Human Subjects section included in the 25 page limit for the Research Plan?
A: Yes, the standard Human Subjects issues should be addressed for each of the proposed study protocols. No, the Human Subjects section is not counted as part of the 25 page limit for the Research Plan.
Q: In the CC 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. All of this information should be included in the 25 page limit. A critical element for selecting CCs is the adequacy of patient resources available. In order for reviewers to assess recruitment capacity, applicants must describe fully the cardiovascular patient population available and actual visits at their facilities during 2004. Please note that patient availability to a CC should be described under Resources. Follow the sample format and instructions on the Resources Format Page from the PHS 398 application (http://grants1.nih.gov/grants/funding/phs398/phs398.html) when completing information on resources available for the project. If there are multiple performance sites, then resources available at each site should be described.
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: Networks or protocols focusing on specific patient populations should include the description as part of the Research Plan. Additional information about WOMEN, CHILDREN, and MINORITY RECRUITMENT can be placed in the HUMAN SUBJECTS SECTION.
Q: Is there a limit on the number of pages or the length of the documentation regarding available patients?
A: It is important to provide information to confirm the ability to recruit sufficient numbers of patients in your CC application. This information should be detailed in Section E. Human Subjects. There is no page limit on this section.
Q: Do the literature references for the application count toward the page limitation?
A: Only Sections A-D of the application are included in the page limits -- the Literature Cited section is not included.
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. Rather than delineating Specific Aims, state the two proposed protocols and proceed as stated in the PHS398 instructions.
Q: Do the two proposed protocols have to use the same approach or can they be different?
A: Proposed protocols should 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 propose protocols based on what they consider important, and that take advantage of the proposed infrastructure of the network. It is preferable that protocols submitted NOT be restricted to only a single center. Phase I/II trials will be considered only. Proposed protocols should provide study rationale and hypothesis, detail study design, endpoints, statistical considerations (with total sample size estimates), and costs. Protocols should demonstrate the time and enrollment constraints of the network.
Q: Since the protocols that a CC submits may not be funded, how much detail needs to be provided in the application? Is preliminary data needed?
A: Protocols should illustrate the abilities that a site has and the expertise available. Given the space limitations, protocols are not expected to be R01 equivalents, but sufficient detail is required to show the reviewers the CC’s capabilities. Key data necessary to support the protocol feasibility should be included, as should study size calculations demonstrating that the protocol is appropriately powered to answer the problem addressed.
Q: Can an institution submit an application for the Data & Coordinating Center (DCC) and a Clinical Center?
A: Yes, the same institution may apply for both a Clinical Center and a Data Coordinating Center award, but the applications for each must be from different individuals and must be submitted separately. Awards for a Clinical Center and a Data Coordinating Center will not be made to the same principal investigator to ensure that data analysis is performed independently of data acquisition.
Q: May an institution submit two CC applications under two different PIs?
A: Yes, although the requirements of a CC are so extensive that it is not recommended.
Q: Can an application be on peripheral artery disease?
A: No, proposals to study the treatment of peripheral vascular disease are outside the scope of this RFA and will not be considered.
Q: Can NHLBI program staff help us by commenting on the broad area(s) of science covered by each of the protocols and the proposed administrative structure before submission?
A: Yes, applicants are strongly encouraged to submit to NHLBI program staff a 1-2 page proposal that describes the protocols, lists the relevant staff, and describes their plans for cell processing. This is due no later than January 27, 2006, which is 6 weeks prior to the receipt date of March 10, 2006.
Q: Would the Network consider protocols that test new delivery methods?
A: Yes, such a protocol could be part of the application, although final protocol development and selection will be the responsibility of the Steering Committee.
Q: Do researchers submit an application for their specific protocols or does the institution submit an application defining its role as a CC?
A: The institution should submit an application defining its role as a CC. Sample protocol proposals are a required part of that application.
Q: Must the overall PI of a CC be a physician?
A: Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is eligible to apply. This individual should have experience in clinical research and have knowledge in human subject recruitment, and all Federal, State, and Local regulations pertaining to human subjects in research. In most cases, this will be a physician.
Q: Can an institution outside of the United States apply?
A: Yes, institutions from Canada and Mexico are eligible to apply.
Q: Can a CC application have a subcontract to Foreign Institutions?
A: Yes, but only if the subcontract is to a Canadian or Mexican institution. Applicants for a CC may NOT subcontract to other foreign institutions.
Q: Regarding eligible institutions, are Canadian and Mexican Universities/research centers considered as “foreign”?
A: Canadian and Mexican institutions are considered to be foreign with respect to submitting an application in response to this solicitation. A foreign institution is defined as “an organization located in a country other than the United States and its territories that is subject to the laws of that country, regardless of the citizenship of the proposed PI.” This is defined in the Glossary Section of Part I of the NIH Grants Policy Statement, dated 12/03, and located on the Internet at address: http://grants1.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm#_Toc54600040.
Q: Is a letter of intent required?
A: No, but it helps the Institute staff to plan the review. Applicants are encouraged to send a letter of intent, which must be received by February 10, 2006.
Q: Can I personally deliver the application on the due date at NIH?
A: No, NIH no longer accepts applications in person; they must be either mailed or sent by one of the overnight delivery services
Q: In the RFA (Section IV, Budget Requirement for CC Applications), the expectation is that the cost associated with patient enrollment will be included in the CC budget. Can you further define what is included in patient enrollment?
A: There are two budgets for each CC application:
Q: How should we structure our budget for the first year and subsequent years of the proposal?
- The main budget supports the local infrastructure, which includes; personnel needed to maintain the CC infrastructure, travel for CC staff, and support for cell processing capabilities. The CC infrastructure provides for personnel to enroll and follow patients and it is anticipated that the cost of screening and enrolling patients would be covered by funds supporting the local CC infrastructure. This budget is submitted using the budget forms in the PHS 398 application.
- A second budget is needed to describe the costs of each of the proposed protocols, calculated on a cost-per-patient basis. This budget should be in the form of a table and include all direct costs and the associated protocol facilities and administrative costs. 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. CC applicants should provide the number of patients needed, type of patients, and cost estimates for each of the protocols proposed in the application. It is expected that other CCs will be needed to recruit patients into your protocol. Use your protocols to project how many patients you can recruit and their related costs. Once the Network is initiated, the funds for actually conducting protocols are allocated in the Data Coordinating Center (DCC) budget, with the CC being reimbursed from the DCC on a per patient basis. The patient care budget is to be included as an example only to facilitate peer review of the application.
A: It is anticipated that the first year will be devoted to protocol development and staff training, with patient recruitment commencing in the second year. This should be considered in the proposed budget structure. Requests must be submitted with appropriate justification. It is anticipated that the CC budget will include the following personnel categories: PI and Co-Investigators, Study Coordinators, Data Management Coordinator, and Secretary/Administrator. Please note that there must be a minimum total effort of 25% for the physician leadership. If there are co-investigators and a Principal Investigator, a minimum of 10% effort for each person is required. If there are no co-investigators, the Principal Investigator must have a minimum of 25% effort 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. In addition, the costs associated with cell processing must be included as part of the costs of the CC infrastructure.
Q: Is the CC expected to include a statistician (with biosketch) in its budget or does this all reside with the DCC? Do applicants need biosketches for staff participating in the two proposed protocols and should the two protocols include our local statisticians or will the latter also come from the DCC?
A: Instructions regarding the CC budget are provided in the RFA. Although expert statistical advice is essential to develop proposed protocols, it seems unlikely that such expertise would be needed to perform CC functions.
Q: In the CC application, do the budgets for the two proposed research protocols count towards the 25 page limit for the Research Plan?
A: No, because budget is not a part of the Research Plan.
Q: We will be submitting an application for the DCC. The RFA states that “The DCC will subcontract with external laboratories.” 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 core or central laboratory partner for them to accurately estimate services and expenses. Since the award mechanism will be a cooperative agreement, will the NHLBI allow us to demonstrate how we will identify and secure the necessary central lab(s) once specific protocols are approved, 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: The DCC applicant must demonstrate the capability to identify and secure necessary central laboratories or likely core facilities that will be required. The actual core facilities will be determined after the program starts, and the cost of such facilities will be determined once they are needed for a specific protocol. However, it will be necessary for DCC applicants to demonstrate the ability to secure laboratory facilities for quality control of cell processing and to budget for this laboratory.
Q: It appears that applicants do not need to submit a detailed budget for the Clinical Research Skills Development Core. Is that correct?
A: No, a detailed budget for an amount not to exceed $100,000 in direct costs is required. The budget should list personnel, travel, and other training related expenses.
Q: Can the applicant submit the $300,000 direct cost budget for a CC in a modular format? i.e., named individuals with % effort, but no actual dollars?
A: No, a categorical budget is required.
Q: Do you see a need for a histopathology or other core laboratories or do you contemplate such a core being solicited by the Data Coordinating Center?
A: A. If a protocol proposed by the CC 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 CCs will be responsible for obtaining the sample(s) and the cost of obtaining them will be part of the CCs 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: Regarding budget issues, can secretarial support be part of a CC application?
A: Yes, partial support of a secretary is allowable. Each clinical center (CC) applicant should submit a request for a CC budget, which may include up to 0.25 FTE for investigator time, an additional 1 FTE for a research coordinator, and 0.25 FTE for an administrative assistant.
Q: If the total direct cost budget for a CC is $1.5 million maximum for the entirety of the 5 years, must we budget for $300,000 in direct costs every year?
A: Clinical Center infrastructure budget costs may not exceed $300,000 direct costs per year, and include:
- There must be a minimum total effort of 25% for the physician leadership. If there are co-investigators and a Principal Investigator, a minimum of 10% effort for each person is required. If there are no co-investigators, the Principal Investigator must have a minimum of 25% effort.
- A minimum of 100% effort for a nurse coordinator. This effort can be for an individual or can be shared among two or more individuals.
- A minimum of 25% for data entry and administrative personnel.
- Travel for the Principal Investigator and the nurse coordinator to attend up to six Steering Committee (SC) meetings in Bethesda, MD, in year one, and up to three SC meeting per year thereafter. Steering Committee meetings usually are held in Bethesda, MD.
- Supplies and equipment.
- Fees to translate CCTRN protocol materials into a second language.
- Costs associated with cell isolation and processing.
- Other items as appropriate.
Note: The cost of implementing the protocols will be funded through the DCC and is not included in your $300,000, although costs of cell processing should be included in the $300,000. In addition, the maximum allowable direct costs for the clinical research skills development core are $100,000 per year.
Q: Do facilities and administrative costs of institutions under a subcontract count toward the total cost cap?
A: Yes, all costs, including facilities and administrative costs for subcontracts are considered in total costs, and count toward the total cost cap.
Q: Can staff salaries be assigned as appropriate to the proposed protocol cost?
A: In general, the CC budget should cover personnel required for its participation in network protocols and should not be included as a protocol cost. Estimated protocol implementation costs should be based on the protocols presented in the applicant's research plan, but should not be included in the CC infrastructure budget request.
Q: How do we estimate protocol costs and how are they presented in the application?
A: 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 CC 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 that are being considered for clinical protocols that are currently unavailable commercially. It should be noted that funds will not be provided to purchase expensive medical equipment, such as echocardiographic or magnetic resonance imaging systems. If any of the protocols proposed by CC 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 CCs will be responsible for obtaining the sample(s) and the cost of obtaining them will be part of the CCs per-patient expense, which will be reimbursed by the DCC. The cost of shipping, analyzing, and storage, as well as training of personnel and quality control will be the responsibility of the DCC.
Q: Should the required two protocol proposals be submitted as a part of the CC application in the PHS 398 format, or should they be submitted separately?
A: Protocol proposals must be submitted as a part of the single CC application in the required PHS 398 format. The Research Plan (Items A – D: Specific Aims, Background and Significance, Preliminary Studies/Progress Report, and Research Design and Methods), which includes the two proposed protocols may not exceed 25 pages. The budgetary portion of the CC application should refer to the yearly cost of the local infrastructure. Each of the two protocol proposals should be followed by a budgetary proposal that is specific to the cost of the proposed protocol, recognizing that actual Network protocol funds will be distributed by the DCC to the participating CCs on a per-patient basis.
Q: Cell-based therapy research can be very expensive, and the budget provided in the RFA may limit progress. How would the NHLBI view partnerships with industry?
A: Industrial partnerships would be welcomed, as long as the NHLBI requirements for 3rd party agreements can be met. However, since this is a network, the industry partner must be willing to work with all the centers and provide cells or materials to all centers in the network.
*If you wish to receive an example of a budget, please email Ms. Mary Joyce at email@example.com.
Clinical Research Skills Development Core
Q: Please clarify the allocation of the cost of the Clinical Research Skills Development Core.
A: Applicants for this program can request a clinical research skills development core. Costs allowable for inclusion within the $100,000 direct costs per year 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.
Q: How will the Clinical Skills Development Core be reviewed?
A: A Clinical Research Skills Development Core will be reviewed on its own merits and scored separately from the CC application. The Clinical Research Skills Development Core is not a required component of a CC and its absence will not disadvantage an applicant. The priority score for the Core will be determined after the review of the main CC application and the review of the Core will have no effect on the overall score of an application. If a CC application includes a request for a Skills Development 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 Clinical Skills Development Core funds should not be included in the body of the CC 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 this 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 to provide a 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.
Q: How many subjects are to be enrolled per Clinical Center?
A: The number of subjects to be enrolled per center depends on the protocols proposed, the availability of patients to be recruited, and the funds available for clinical studies. There is no prescribed minimum or maximum number of subjects to be enrolled. Epidemiologic studies or Phase III clinical trials are not responsive to this RFA. The applicant must indicate for each clinical cell therapy protocol how many patients are available in the applicant's center and how many will be required from the entire Network.
Q: Are Phase III studies also going to be supported?
A: No, Phase III protocols will not be supported in this research network.
Q: Does the Data & Coordinating Center (DCC) just disperse funds under NHLBI direction? Are they also responsible for monitoring the grant budgets of the CCs?
A: The DCC will disperse clinical dollars based on actual recruitment of patients by CCs. The DCC is not responsible for grant budget monitoring for the CCs. Grant budget monitoring remains the responsibility of the individual CCs and the NHLBI grants management staff.
Q: Will the clinical protocols proposed by the Clinical Center applicants be implemented in the Network?
A: The clinical protocols submitted in each Clinical Center application will form the basis of the review of the applications, along with other criteria noted in the RFA. Once the CCTRN is operational, the Steering Committee will determine the protocols that will be performed by the Network and prioritize them.
Q: Are CC applicants required to provide all proposed services through the primary institution?
A: CC applicants are expected to provide all proposed services. However, the applicant institution does not necessarily have to possess cell processing capabilities. These services may be contracted, but should be easily accessible. Cell isolation and preparation should not be compromised by the cell processing that is done at a location separate from the applicant institution.
Q: Will there be a uniform procedure for data sharing across centers through DCC?
A: Yes, there will be uniform data sharing across the CCTRN and the DCC will be responsible for a data collection system and manuals of operations, determining sampling and randomization schemes, and assisting in defining primary and secondary outcomes and analytical approaches for the protocols.
Q: Will the Steering Committee alter protocols?
A: The Steering Committee will evaluate and complete clinical protocols prior to their submission to the Protocol Review Committee (PRC), Data and Safety Monitoring Board (DSMB), or the Investigational Review Board (IRB).
Q: Will protocols proposed by CCs that are not funded be considered by the steering committee?
A: No, the protocols proposed by CCs which are not funded are confidential material that the SC does not have access to.
Q: Are the Protocol Review Committee (PRC) and the Data Safety and Monitoring Board (DSMB) standing committees? How often do they meet/review protocols? What is the review time?
A: The Protocol Review Committee (PRC) and the Data and Safety Monitoring Board (DSMB) will be standing committees established by the NHLBI and managed by the Data Coordinating Center. PRC meetings will be convened as necessary -- i.e. once a protocol is ready for review. The PRC will need approximately two months to review a protocol. Approval of protocols could take longer if the PRC wants additional information or raises concerns about the design of the protocol. The DSMB will meet once every six months, although there may be circumstances where it will be necessary for the DSMB to meet more frequently for a particular study. The DSMB will review studies and make recommendations immediately following the meeting, unless it is necessary to obtain additional information.
Q: Will the DCC prepare investigational new drug (IND) applications or will the DCC provide advice to a CC on how to prepare an IND application?
A: As described in the RFA, the DCC will be responsible for the submission of INDs to the FDA. The DCC will advise investigators on the format and content of the submission. The DCC will facilitate and coordinate, if necessary, communication between the FDA and investigators.
Q: Will the Clinical Center, DCC, or the NHLBI be the sponsor for a investigational new drug (IND) application to the FDA?
A: In most cases, the DCC will be the sponsor for the IND application to the FDA, although individual Clinical Center Investigators may sponsor and hold INDs. Although they may not sponsor an IND application, it is highly recommended that NHLBI program staff be involved in the FDA/investigator conference calls regarding an IND.
Q: Would it be better to have a cell production capability at the institution applying as a Clinical Center OR use the NHLBI Production Assistance for Cellular Therapies (PACT) facilities to provide this service?
A: Any facility manufacturing cells is required to manufacture clinical grade cells in a standardized manner. The DCC will be responsible for quality control of the cellular preparations, which will include characterization of the cellular products of each Clinical Center, including cell number, viability, and uniformity.
If the Center does not have the capability or access to a cell production facility the other option is to use the NHLBI PACT facilities, a resource for NHLBI investigators. However, three factors mitigate this alternative: 1) the PACT application process takes a few months and it takes time to manufacture the cells; 2) the requests for cell products may not be approved by PACT; and 3) the isolation of cells at the Clinical site, shipment to a central processing center and shipment back to the clinical site, introduces uncertainties in the cellular preparation and complicates the logistics.
If the applicant chooses to use PACT, it is important to start the application process early on.
Q: What is the relationship between the DCC and PACT on QA issues?
A: PACT is willing to communicate with the DCC on QA issues. If NHLBI creates a QA subcommittee, PACT may participate.
Q: For cell-based therapy, will both blood-derived and tissue-derived cellular therapy be considered? Will genetically modified cells be responsive?
A: Yes, a Clinical Center may address either blood-derived or tissue-derived cellular therapies, or both. Therapies which employ genetically modified cells are permitted.
Q: Are Production Assistance for Cellular Therapies (PACT) centers obligated to provide cells for CC applicants?
A: No. However, many of the criteria considered during the evaluation of a PACT product request will be addressed by either the review of the network clinical Center applications or the subsequent operating procedures of the Cardiovascular Cell Therapy Research Network. So while the PACT centers are not obligated to provide cells for the CCTRN< CCTRN Clinical centers would be in a position to submit product request applications to the current Good Manufacturing Practices (GMP) cell processing facilities that address all of the required criteria listed at the PACT internet website at http://www.pactgroup.net.
Q: What funding does PACT have?
A: PACT is funded by NHLBI as a resource to provide cells and cell products to approved NHLBI investigators; no charge is made to the investigator. PACT does not provide funding to investigators.
Q: How can I learn how to file IND? Any specific contacts at the FDA?
A: Untested, innovative cell-based therapies requiring submission of an investigational new drug (IND) application prior to commencing a Phase I safety clinical study will be evaluated by FDA's Center for Biologics Evaluation and Research in the review office of Cellular, Tissue and Gene Therapies. Information on submitting an IND application for a biological product is available online at [http://www.fda.gov/cber/ind/ind.htm]. Additionally, questions regarding IND submissions may be directed to CBER's Manufacturers Assistance and Technical Training Branch, 800-835-4709 or 301-827-1800.
Q: Can studies with human embryonic stem cells be included in the proposed protocols for Clinical center applications?
A: Research using cells lines on the NIH Human Embryonic Stem Cell Registry [http://stemcells.nih.gov/registry/index.asp] are eligible for federal funding. For use in a clinical study, a human embryonic stem cell line from this Registry would need to be qualified for this use by a series of preclinical studies that would be reviewed by the FDA. Investigators considering the use of these cell lines are encouraged to contact the FDA’s Center for Biologics Evaluation and Research (CBER) regarding the regulation of cellular therapy products.
Q: Can support for the operation of an institution's own GMP facility be included to produce stem cells?
A: Yes, if the costs are appropriate for a Clinical Center application.
Q: How will NHLBI decide which applications to fund?
A: The decision to fund will be based on three criteria: the scientific merits of the projects described within an application, the availability of funds, and program priorities. These decisions are made at two levels of review. In the first level of review, applications are evaluated for scientific merit by a tailored committee known as a Special Emphasis Panel, or SEP. This committee is composed of scientists and clinicians, like you, with demonstrated expertise in the fields related to cell-based therapy. The committee is tasked with the difficult job of stratifying the applications received and identifying those it considers to be meritorious. It does this by assigning to each, a composite score that reflects the significance of the proposed protocols, the soundness of the proposed protocols, the Clinical Center’s ability to carry out the proposed studies and patient access, and the abilities of the Clinical Center applicants to participate in the network. The committee’s critiques are incorporated into preliminary summary statements that are then made available to both the applicants and members of the National Heart, Lung, and Blood Advisory Council (NHLBAC). In addition to identifying the strengths of applications, the SEP is also asked to identify deficiencies/weaknesses of the various applications so that applicants may be given opportunity to address these, in writing, before the second, and final, level of review. The NHLBAC is composed of scientists, clinicians, and lay persons. It reviews all scored applications and makes recommendations to the Director of NHLBI regarding the scientific merits of each, as well as the applicability and validity of the first review. The final decision rests with the Director of NHLBI.
Q: Who convenes the review committee?
A: The Scientific Review Administrator (SRA) assigned to the review is responsible for selecting and recruiting the consultants that comprise the Special Emphasis Panel. For this RFA, persons working in, or familiar with cell-based therapies, will be recruited. The SRA will read all applications and select consultants based upon the aims, objectives, and keywords described in individual projects. Global areas of expertise, as well as specific project needs are also considered.
Q: My application contains color photographs of histological specimens that document how well our methods work. So that the reviewers of our application may fully appreciate this information, may I submit these as appendix materials along with my application?
A: Yes. You may include photographs, and other materials that do not copy well in black and white, into an Appendix. The guidelines for Appendices are outlined in the PHS 398 General Instructions. Please note that all photographs and plates included in the Appendix must also appear within the body of the Research Plan. If you choose to include photographs within an Appendix at the time of submission, please be sure to include 5 collated sets and, also, to include the same Appendix in the copies sent to the Review Branch. You may also be given an opportunity to submit these materials in different data formats (e.g., PDF or JPEG) and on alternative media sources (CD) under separate cover as Supplemental Materials. This is left to the discretion of the SRA handling the review.
Q: Can we resubmit our application?
A: No. Since this is a one time solicitation of applications, it will not be possible to revise and resubmit your application.
Q: What if the Clinical Center application does not score well, but my Clinical research Skills Development Core scores well? Will the Core be funded?
A: No, the award of a Clinical Research Skills Development Core is dependent on a fundable score of the Clinical Center.
Q: Will the Review Group take into account the potential for compatibility and synergy between individual CCs?
A: No, the Review Group is responsible for selecting applications containing the best science. The Review Group will, however, take into account prior participation of CCs in collaborative research. Ensuring that the CCs work together is the task of the Steering Committee and its NHLBI-appointed Chair. The long term success of the network will depend on the CCs working well together.
For further information contact:
Sonia Skarlatos, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge II Centre, Room 9158
6701 Rockledge Drive, Mail Stop 7940
Bethesda, MD 20892
Denis Buxton , Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge II Centre, Room 9188
6701 Rockledge Drive, Mail Stop 7940
Bethesda, MD 20892
Last updated: December 14, 2005