Frequently Asked Questions
Centers for Cell-Based Therapy (SCCT) for Heart, Lung, and
Blood Diseases and Data and Coordinating Center (DCC)
National Heart, Lung, and Blood Institute
May - June 2004
- What is a SCCT?
A SCCT is a multi-project grant to enable multidisciplinary basic and clinical research that is focused on clinically-relevant questions. The key new requirement in the SCCT is that at least one-half of funded projects must be clinical. As always, there must be at least three fundable projects, the Principal Investigator (PI) should be an established research scientist who will commit at least 25% of his/her time to the SCCT, and the PI must have a fundable project. All proposed projects must be designed to be completed within the five-year duration of a SCCT award.
- Where can I read about the SCCT program?
The RFA can be found in the NIH Guide for Grants and Contract’s at Internet site: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-017.html.
- Rationale for a core: Would it be better to have a cell production (cGMP) core at the applying institution OR to use one of the three NHLBI Production Assistance for Cellular Therapies (PACT) facilities, which provide this type of service? Please clarify the interactions between the Specialized Centers for Cell-based Therapy (SCCT) and the three PACT facilities.
That would depend upon the timeline and the frequency for cGMP cell products. The PACT application process takes a few months plus the time the facility would need to develop the cGMP cell process and manufacture the cell product. If a study will need several "batches" of the cell product at regular frequencies or would need products at the beginning of the award period, the PACT facility might become the limiting factor. Also, there is no guarantee that SCCT applications will be approved by PACT. SCCT applications will be reviewed in the same manner as all applications received by the PACT facilities and will be ranked by feasibility and scientific merit. The current PACT budget and the resources of the facilities will also be factors. Applicants may specify an alternate cell production facility and budget for cell processing while indicating that their Specialized Center will also apply to PACT facility.
- Can an institution submit application for the Data & Coordinating Center (DCC) only?
Yes, an institution may apply for the DCC only.
- Please describe the organization of the Data & Coordinating Center (DCC) within a program. Will the DCC be separately selected or will it be linked to a specific Specialized Center program?
The DCC will serve as a central coordinating unit, resource facility, and data repository for the Specialized Centers in the program. It will serve as the repository for funds to be released for clinical studies and will assist the Specialized Centers with the preparation of their IND applications. It is expected that prospective applicants for the DCC will have the necessary experience with the IND process as well as expertise in data management, statistical analysis, and coordinating clinical studies. Some familiarity with cell-based therapy, while helpful, is not a specific requirement. The DCC will be separately selected and will not be linked to a specific Specialized Center.
- Does a Data & Coordinating Center (DCC) need to be part of Cell Therapy RFA?
No. Each DCC application should be a complete, self-contained document and not linked to any of the SCCT applications. The DCC applications probably will be reviewed at the same meeting as the SCCT applications, but these two components of the review will be conducted independently.
- What is the role of the Data & Coordinating Center (DCC) in this program?
The duties of the DCC will include organizing meetings, arranging conference calls and establishing a web-based system to facilitate communication between, and data collection from the SCCT. In addition, the DCC will be expected to play a major role in the preclinical and clinical activities of the SCCT. In the first two years, during the preclinical studies phase, the DCC will work with the Steering Committee to establish the general organization and structure of the program; assess availability of existing cell-based therapy databases, define and develop a web-based catalog to facilitate the collection and sharing of cell-based therapy data, initiate preclinical data collection, and implement a data quality program. The DCC will also provide statistical, regulatory, and data management support, as needed, for the development of Phase I /II clinical studies. It is anticipated that protocol development will be led by each specialized center. During the clinical phase of the program (years’ three through five), the DCC will continue to support the above preclinical activities. In addition, the DCC will implement web-based data collection and data quality programs for clinical studies, collect and report adverse events as required by NHLBI and federal regulatory bodies, and provide data monitoring reports to NHLBI oversight committees and other federal organizations as needed.
- How are supplementary resources treated within a program, particularly for SBIR applications? New application priority scores will not be available in advance of a program a score?
Pending applications, including SBIR applications, will be listed as such on the "Other Support" pages. Alternate plans should be discussed in the research plan for the application, describing alternate plans for proceeding if supplement funds or resources do not become available.
- Does the Small Business Innovation Research (SBIR) extension have to be a direct extension of ongoing work or can it be “similar”?
The SBIR extension or Phase II competing continuation award would represent a continuation of support for research and development of previous work funded by the original Phase II grant (see http://grants.nih.gov/grants/guide/pa-files/PA-04-028.html). If new work is to be proposed, a new small business application can be submitted (see http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).
- Was a second date added because certain centers could not attend today?
A second date was added so that more investigators would be able to attend one of the two pre-submission meetings (see http://grants2.nih.gov/grants/guide/notice-files/NOT-HL-04-113.html).
- Do programs need projects in each area of NHLBI, heart, lung and blood? If so, what level of programmatic interaction/theme will be required?
. However, Specialized Centers are encouraged to include projects addressing more than one therapeutic area. Basic projects should be related to clinical projects and overall the Specialized Center should demonstrate an integrated program of research.
- Can the focus of the application be genetically engineered cells?
Studies that exclusively focus on gene therapy or gene transfer, rather than cellular therapy, are outside of the scope of this announcement. However, projects that focused on a cell-based therapy and that include genetically engineered cells can be submitted. Early in planning process and well before the application receipt deadline, applicants are strongly encouraged to contact NHLBI program officer to discuss proposed projects.
- What about T cell or dendritic cell-based therapies?
Novel cell-based therapies for replacement and/or regeneration of a hematopoietic cell lineage (e.g., red cells or platelets) or system (e.g., immune) will be responsive.
- How many subjects to be enrolled per specialized center? Is web-based data entry mandatory? Are paper Case Report Forms (CRFs) allowed?
The number of subjects to be enrolled per center is dependent on the projects 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. However, it is not intended that epidemiologic studies or Phase III clinical trials be performed within the context of these specialized centers. As stated in the RFA “Applicants for the Data & Coordinating Center (DCC) should …. develop and implement a web-based system to coordinate SCCT center activities.” However, this does not mean that web-based data entry is mandatory. Applicants should propose data collection and maintenance activities for the Centers based on their experience and the requirements of their program.
- Phase I and II study support is described. Are Phase III studies also going to be supported?
No, Phase III studies are considered unresponsive to this announcement and will not be supported in these Specialized Centers.
- For cell-based therapy, will both blood-derived and tissue-derived cellular therapy be considered?
Yes, a Specialized Center may address either blood-derived or tissue-derived cellular therapies, or both.
- Are Production Assistance for Cellular Therapies (PACT) centers obligated to provide cells for SCCT?
No. However, many of the criteria considered during the evaluation of a PACT product request will be addressed by either the review of the SCCT applications or the subsequent operating procedures of the SCCT. So while the PACT centers are not obligated to provide cells for the Specialized Centers, SCCT Centers would be in position to submit product request applications to the current Good Manufacturing Practices (cGMP) cell processing facilities that address all of the required criteria listed at the PACT Internet website at http://spitfire.emmes.com/study/scac/products/products.htm.
- Would it be appropriate to link other grants (particularly PPGs) to the SCCT proposal?
It is important to link to other existing programs where possible. Cost savings and benefits to the SCCT program should be described in the application to demonstrate opportunities for leveraging scientific and budget resources.
- Regarding appropriate scope: Would a project involving establishing pancreatic islets and the resulting revascularization be appropriate?
Projects should focus on clinical and basic scientific issues related to diseases and disorders relevant to the mission of the NHLBI. A project involving establishing pancreatic islets may be included if it affects the cardiovascular complication of diabetes. Studies of cell-based revascularization would be responsive if directed at coronary artery disease or peripheral artery disease.
- How can I learn how to file IND? Any specific contacts at the FDA?
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.
- Regarding program interaction: Do basic science projects have to interact thematically with clinical science projects? Is a cell therapy interaction sufficient? i.e. Can you have a cardiac stem cells basic project and a T cell clinical project?
In general, reviewers will look for genuine and mutually supportive scientific interactions between the projects. These interactions should produce a significant enhancement of the quality and productivity of the projects in comparison to what would occur if they were performed outside of the Specialized Center. The nature of these interactions and how they will improve the program and the individual projects should be described clearly in the application. As stated in the RFA on page 11, "...interactions between clinical and basic scientists are expected to strengthen the research, enhance the translation of fundamental research findings to the clinical setting, and identify new research directions. Translation of findings from basic to clinical studies is an important focus of the SCCT program…". Furthermore, "…each awarded SCCT must consist of three or more projects, all of which are directly related to the overall clinical focus of the SCCT." Under Review Criteria on page 18, the RFA states "Collaborative interaction between clinical and basic research components...and plans for transfer of potential findings from basic to clinical studies."
- Would the Specialized Center for Cell-based Therapy (SCCT) support more than one disease targets in the same center? For example: heart regeneration and lung regeneration.
Yes. A Specialized Center is encouraged to be multidisciplinary and can include projects involving more than one disease are of interest to NHLBI.
- Would a plasticity project involving skin, as proof of principle in the clinical wound healing area be acceptable or would this not fit the guidelines? This is basic work and clinical work on marrow converting to skin. We already have basic work and clinical protocols.
In general, this area of investigation has involved use of dermal or other skin fibroblasts to generate more skin. These types of studies would not be considered in this RFA targeted to heart, lung, and blood disorders. Nevertheless, there may be extenuating circumstances and investigators are encouraged to discuss individual project proposals with Program Staff at NHLBI.
- Do you seek highly interdisciplinary centers or more highly focused-single disease-type centers?
Either. The RFA encourages investigators to submit applications including more than one disease area, but this is not a requirement.
- Can the principal investigator or PI of a Specialized Center lead a basic research project or must the P.I. direct a clinical research project?
Yes, the PI can lead a basic research project, but he or she must work closely with the leaders of the clinical projects to assure translation.
- Can one clinical project involve mesenchymal stem cells (MSC) for “bone” repair?
Yes, but only if prior studies show that the bone repair is directly related to the treatment of heart, lung, or blood diseases.
- Will Specialized Centers (SCCT) using other NHLBI resources (e.g., Programs of Excellence in Gene Therapy (PEGT) or Production Assistance of Cellular Therapy (PACT) ) be favored?
While applicants are encouraged to utilize available NHLBI and other resources at their Specialized Centers, applications including the use of NHLBI resource programs will not be given special consideration.
- Can studies with human embryonic stem cells be included in a Specialized Center (SCCT)? Can clinical studies using human embryonic stem cells be included in a clinical study in a Specialized Center (SCCT)?
Research using cells lines on the NIH Human Embryonic Stem Cell Registry [http://stemcells.nih.gov/registry/index.asp] are eligible for federal funding and may be included in a Specialized Center program. 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.
- Can support for the operation of an institution's own GMP facility be included to produce stem cells?
Yes, if the costs are appropriate for the project(s) in the SCCT application.
- What is an expected timeline for the development of an IND application to proceed from preclinical studies to clinical studies?
Specialized Centers can propose preclinical studies in the first or in the first and second year. The IND should be developed during this time so that clinical studies begin no later than the beginning of the third year of the program. A pre-IND meeting(s) should be held with FDA to discuss milestones for filing IND.
- Could you comment on the types of lung diseases that are appropriate for this program?
There are no restrictions on the lung diseases that may be included as long as the approach focuses on a cell-based therapy. Examples listed in the announcement include acute lung injury reactions and degenerative lung diseases, such as emphysema, pulmonary or alveolar hypoplasia, or pulmonary fibrosis. However, other lung disease areas may be proposed and investigators are encouraged to contact program staff to discuss their proposals.
- Regarding collaborative SBIR applications - Does it have the same deadline or follow SBIR dates? Is it reviewed by the same section as the SCCT? Is the budget considered part of the total SCCT budget? Should the SBIR application cite this RFA?
The SBIR applications follow SBIR receipt dates, will be reviewed separately, and the budget is separate. The SCCT and SBIR applications can cite each other and indicate potential synergy if both are successful, however, the applications should also indicate contingency plans if the other is not successful.
- Can program personnel help us reviewing broad area of each of the projects before submission?
Yes. Applicants are strongly encouraged to submit to NHLBI program staff a 1-2 page proposal describing the projects and cores, listing the project leaders, and describing the synergy between the projects and cores.
- If a project has both basic science and clinical components, will the project be categorized as basic or as clinical?
Applicants must identify each project as clinical or basic, depending upon the major emphasis of that project. NHLBI staff will review SCCT applications to determine if the basic and clinical projects are appropriate for the program. Applicants are strongly encouraged to contact NHLBI program staff regarding whether projects are appropriate as basic or clinical prior to submitting their applications."
- Are there any priorities set for the project focused on particular organs/ tissue? That is, blood, heart, lungs, vascular?
No. All areas of interest to NHLBI will be considered.
- Can synergies between basic and clinical research occur within a project?
Yes. Synergy between basic and clinical research is strongly encouraged within and across projects.
- Are clinical projects proposed by one Specialized Center implemented at the other Specialized Centers? Can they be?
The clinical projects proposed at one Specialized Center should be designed for implementation at that Center, however, the Steering Committee with representatives from all Specialized Centers can consider this possibility.
- Will there be a uniform procedure for data sharing across centers through DCC? What needs to be stated in application regarding data sharing plan?
Yes, the DCC will collect preclinical and clinical data for the benefit of all Specialized Centers and the program. The applicant should state their willingness to share data is described in RFA.
- Is there a priority or a disadvantage to be more than 50% clinical?
No predetermined priority. Applicants are encouraged to submit a 1-2 page proposal to program and to obtain comments on this type of proposal.
- If a "clinical" project fails to go into patients by year 2, and was required for 50% clinical, what happens?
In order to be selected as a Specialized Center, an applicant must demonstrate to the review panel that the clinical projects proposed can begin clinical studies by the beginning of year 3. However, it is realized that other factors could intervene while the studies are being carried out. For example, if the FDA places a regulatory hold on all new cell-based therapies while
additional safety studies are carried out, then all SCCT clinical studies could be delayed .
- In a Specialized Center 50% of the projects must be at the primary applying organization. Does this also relate to funding levels?
The level of funding associated with these projects must be appropriate for the proposed work, but needed not satisfy a particular percentage.
- Does the Data & Coordinating Center (DCC) just disperse funds under NHLBI direction?
Are they also responsible for grant budget monitoring?
The DCC will disperse clinical dollars, however, the DCC is not responsible for grant budget monitoring. Grant budget monitoring remains the responsibility of the NHLBI grants staff.
- Do indirect costs of institutions under a subcontract count toward the $2.3 million total cost cap?
Yes, All costs including Indirect costs for subcontracts are considered in total costs, and count toward the total cost cap.
- What is the format of the application? P01 with introduction?
The format of the Specialized Center application differs from a program project grant or P01. Applicants are to use the detailed instructions for completing the application posted on the NHLBI website at [http://www.nhlbi.nih.gov/funding/inits/index.htm] under RFA-HL-04-017. Applicants for a Data & Coordinating Center should use the format for a research project grant or R01 grant and should use the instructions on the NIH website for the PHS Form 398 found at
- The SCCT application begins with a section describing the Program Introduction and Statement of Objectives including the theme of the proposed Center. How long can this first section be?
The first section described on "Program Introduction and Statement of Objectives" should not exceed a 10-page limit.
- For clinical protocols submitted with initial proposal, must they be in the 25-page "project" or in the appendix?
The clinical protocol must be described within the 25-page limit for the research project so that the review panel can understand and evaluate the clinical study. Additional details consisting of well-established and routine procedures and a copy of the clinical protocol may be included in the appendix; however, the 25-page project description will serve as the basis for the review.
- Must an overall PI of a SCCT be a physician?
No. However, the PI should be experienced and knowledgeable in clinical research, including human subject recruitment and all rules and regulations governing the participation of human subjects in research.
- Can an investigator be the PI for more than two projects?
Yes, but the investigator must devote the required effort (20% for each project leader; 25% for the overall SCCT PI).
- Can a project be headed by an individual who is K08 funded? Can junior investigators serve as a project PI? Is prior R01 funding necessary?
While not a requirement, most project leaders with the appropriate experience are likely to have already received R01 grants or other similar support. Investigators are encouraged to contact program officers to discuss their qualifications.
- How much emphasis will be placed on a hypothesis, since if the projects are entering phase I trials, the outcomes of the original hypothesis are already known or proven?
The review criteria of Specialized Centers are listed in the RFA. While hypothesis-driven research will be important component of the Specialized Centers, the criteria differ from that of an individual R01 grant.
- Can Institutional Review Board (IRB) approval of a clinical trial be "pending" at the time of submission, for a project where one year of preclinical studies will be done first? (Assuming that human subjects approval is in place for the research).
An application with a proposed clinical study, which is preceded by a preclinical phase, will require protocol evaluation by the Specialized Center for Cell-based (SCCT) Steering Committee, protocol review by the NHLBI Protocol Review Committee (PRC) and the NHLBI SCCT Data and Safety Monitoring Committee, and institutional review board (IRB) approval.
- Can applications be submitted with "pending" IRB applications?
Yes. An approved IRB is not required at the time of submission.
- Should the Institutional Review Board (IRB) submission be done at the time of application?
IRB submission is not required at the time of application. However, IRB submission–pending or approved–at the time of application would be needed for a clinical study scheduled to occur during the first year of the program. Under this circumstance, protocol and informed consent review may be provided by the NHLBI-constituted Peer Review Group rather than the NHLBI SCCT Protocol Review Committee (PRC). An IRB-approved clinical study acceptable to the Peer Review Group will, however, require SCCT Steering Committee and NHLBI SCCT Data and Safety Monitoring Board (DSMB) approval before the trial can be instituted.
- Will review of resources factor into the review of the application? That is, if SBIR is not funded will it reflect negatively on review of SCCT?
The availability of resources will be factored into the evaluation of applications, however, it is realized that not all resources will be in place at the time the application is submitted. Where resources are involved, the application should indicate the status of the resources required and include related letters of support. If the resources or grants to generate resources have not yet been finalized or approved, alternate plans to obtain the resources should be described in the application.
- Can an institution outside of the United States apply?
No, but an individual project or parts of a project could be from a non-US institution.
- Regarding eligible institutions, are Canadian Universities/research centers considered as “foreign”?
Canadian 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.
- What is a clinical project?
A clinical project is one in which the project investigators have direct contact with patients having the disease or condition of interest. Normal healthy subjects may be included, but only in combination with patients. In studies involving the use of human specimens, the investigators must have direct interaction with the patient from whom the specimen is obtained and relate the research results to the patient status or outcome for this to be considered a clinical project. It is intended that the requirement for investigator interaction with the study participants will eliminate research involving archived tissue.
- An investigator can obtain samples from patients enrolled in a clinical treatment trial being conducted by industry in order to measure pathogenic markers that will be evaluated with respect to individual patient outcome. Does this qualify as a clinical project?
No. If the investigators are not involved as a site in the clinical study, this would not be considered a clinical project. The SCCT investigators must interact directly with the participants in a study.
- Can a project involving studies of non-human primates and/or other animals AND patients qualify as a clinical project?
Yes, but the primary focus of the project must be clinical.
- Can an institution collaborate with other institution(s) in order to obtain sufficient patients to perform meaningful clinical studies?
Yes; the usual subcontracting requirements apply.
- Can an R01 be submitted simultaneously for research proposed in one of the projects in a SCCT application?
No. This is possible for program project grant, but can not be done for a SCCT application.
- Can my institution submit two applications for the same SCCT program?
Yes, however each SCCT application must have a different PI and a different set of investigators.
- Is a letter of intent required?
No, but it helps the Institute staff to plan the review. If you intend to submit an application, check the information in the RFAs for the due dates and addresses.
- Can I personally deliver the application on the due date at NIH?
No, NIH no longer accepts applications in person; they must be either mailed or sent by one of the overnight delivery services.
- Will the steering committee alter approved protocols?
The Steering Committee will be responsible for evaluating clinical protocols prior to their submission to the Protocol Review Committee (PRC), Data and Safety Monitoring Board (DSMB), or the Investigational Review Board (IRB).
- 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?
The Protocol Review Committee (PRC) and the Data and Safety Monitoring Board (DSMB) will be standing committees established by the NHLBI, managed by the Data Coordinating Center. Meetings of the PRC will be convened as necessary, i.e. once a protocol is ready for review. The review of protocols by the PRC should be of the order of approximately 2 months. 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.
- If applications are weak, will three centers still be awarded? Are 3 centers guaranteed?
Specialized Center and Data & Coordinating Center awards will only be issued if strong applications are received.
- Will the DCC prepare investigational new drug (IND) applications for Specialized Center clinical studies or will the DCC provide advice with a Specialized Centers on how to prepare an IND application?
As described in the announcement, each Specialized Center must have a well-delineated organizational structure and administrative mechanism to support protocol development. It is anticipated that the center’s administrative support will be responsible for the submission of INDs to the FDA. The DCC will advise investigators on the format and content of the submission and may also assist with the preparation of the submission. The DCC will facilitate and coordinate, if necessary, communication between the FDA and investigators.
- Will the Specialized Center or the NHLBI be the sponsor for IND application to the FDA?
In most cases, the Specialized Center will be the sponsor for the IND application to the FDA.
- Is this a one shot RFA, or do you anticipate an ongoing initiative for new centers in future years?
Each NHLBI SCCT and DCC program is limited to 10 years of support. Under this policy, a given SCCT or DCC grant is awarded for a 5-year project period following an open competition. Only one 5-year competing renewal is permitted, for a total of 10 years of support. Applications for the second competition period will be limited to centers that received awards.
- Will preclinical data from centers be shared so they are available as supporting data for multiple Investigational New Drug applications (INDs)?
Yes. A high level of cooperation is expected among the participants to further the development of new cell-based therapies by the Program. The Specialized Centers and the DCC will be managed as a Cooperative Agreement by NHLBI, where the DCC will function as a clearing house for preclinical information available in a common data base for access by investigators within this Program only.
- Will there be a database to accrue clinical outcomes lifelong to address patient safety and benefit?
The Data & Coordinating will collect preclinical and clinical data for the Specialized Centers in this program. A long term database has not yet been established for the new area of cell-based therapy.
- After the clinical protocol is evaluated by the advisory committee, does NHLBI have resources to provide help with IND?
The SCCT should include administrative support that will prepare the IND application(s). The Data & Coordinating Center will assist the Specialized Centers with IND applications, however, it is the Specialized Centers responsibility to prepare the application.
- Will follow-up of all patients for a long term be needed? That is, is follow-up of greater than 10 years needed?
It is possible that the FDA will require long-term follow up, however, the requirements for new cell-based therapies remain to be established.
Last updated: August 18, 2004