NETWORK FOR TRANSLATIONAL RESEARCH: OPTICAL IMAGING Release Date: August 27, 2002 RFA: CA-03-002 (Reissued as RFA-CA-08-002) National Cancer Institute (NCI) (http://www.nci.nih.gov/) or (http://cancer.gov) Public Meeting of Potential Applicants: September 27, 2002 Letter of Intent Date: December 17, 2002 Application Receipt Date: January 21, 2003 THIS RFA CONTAINS THE FOLLOWING INFORMATION: o Purpose of this RFA o Research Objectives o Pre-Application Meeting o Mechanism of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Preparing and Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE The National Cancer Institute (NCI) invites applications for cooperative agreement (U54) awards to establish a Specialized Research Resource Center that will participate as a member of a network of inter-disciplinary, inter- institutional research teams for the purpose of supporting translational research in optical imaging and/or spectroscopy in vivo. The network is to be named the "Network for Translational Research: Optical Imaging" (NTROI) and will operate under the guidance of a Steering Committee (SC). The goal of this Request for Applications (RFA) is to organize a consortium with flexibility in scope, funding, and incentives to encourage inter- and intra- team collaborations on translational cancer research. The objective is to accelerate the pace of translational research by developing a consensus process to improve methods for system integration, optimization and validation of next-generation in vivo optical imaging and/or spectroscopy methods and technologies, including contrast agents. Investigators are encouraged to include in vivo molecular imaging methods that give information about molecular events in cells or the extra-cellular milieu. The research scope includes feasibility studies for the detection of pre-cancerous lesions, cancer detection and diagnosis, and measurement or prediction of response to therapy. Applications are solicited from preformed consortia, to be referred to as Teams. Approximately three such teams will be selected from applications that receive high priority scores and are most responsive to the goals of this RFA. Each team must include investigators from at least two different institutions, and the team may include investigators from academia, national laboratories, industry or intramural laboratories of the National Institutes of Health. (NIH investigators may participate in applications as investigators or collaborators, but not as principal investigators. They may not request or receive funds from this program.) Broad, multi-disciplinary teams are expected to include a variety of expertise, such as molecular biologists, chemists, physicists, optical and computer engineers, imaging scientists and physicians. Involvement of basic and clinical scientists who may not have a specific research record in cancer research, but who have the potential to provide experience crucial for the success of this network are considered important. Partnerships with industry and small business are encouraged for each team to enhance technology dissemination. RESEARCH OBJECTIVES Participants in three recent NIH sponsored workshops described new in vivo biophotonics methods applicable to the early detection, diagnosis and treatment monitoring of cancer and other diseases. The next generation of biophotonics systems, described in this RFA as in vivo optical imaging and/or spectroscopy technologies and methods, present NCI with an opportunity to promote the better prospects among them through an efficient transition from laboratory prototypes to cancer applications. Clinical applications identified in the workshops include, but are not limited to cancer of the cervix, esophagus, breast, brain, lung, prostrate and colon. Optical techniques provide unique advantages over other imaging modalities for a number of applications, particularly molecular imaging. In vivo optical measurements extend across a wide range of resolution, from molecular and cellular to tissue and organ levels. Some of these optical methods complement advances in targeted or activated optical contrast agents that may provide better sensitivity and specificity at the molecular level than other modalities. For example, they may permit deterministic methods for early cancer detection, drug discovery, and monitoring of therapy response. The identification of strong prospects among optical methods and contrast agents, and their validation and translation to cancer applications pose significant challenges, particularly for human investigations. The intent of this RFA is to establish a multi-institutional network of inter-disciplinary research teams that collectively has the breadth of expertise needed to identify the necessary approaches to validate and translate optical methods for a variety of cancer applications, using both pre-clinical models and human investigations. The following sections provide background on developments of optical contrast mechanisms and optical devices, with examples of clinical applications and kinds of validation studies anticipated under this RFA. Optical contrast mechanisms: Optical measurements of either intrinsic or extrinsic contrast yield optical signatures comprised of optical spectra or multi-spectral images. Measurement methods exploiting intrinsic (endogenous) contrast include (a) photon reflection or fluorescence of early pre-cancerous changes in cellular structure imaged by optical microscopy, (b) single point multi-spectral detectors that identify early changes in cellular structure preceding cervical, esophageal or oral cancer, (c) single point reflectance signatures to determine zones of microscopic extension of cancer, useful for interventional decisions, and (d) macroscopic changes in photon scattering and absorption detectable by optical tomography for cancer diagnosis or determining cancer risk. Extrinsic contrast agents include fluorescent and non-fluorescent dyes, which are often non-specific. Specificity is emerging with the development of new targeted agents such as fluorophore-labeled antibodies that serve a role analogous to radio-labeled agents for tumor detection and classification, or new classes of optical agents, so-called "smart agents," that use enzyme-mediated activation of fluorophores to selectively illuminate the target site. New contrast agents using near- infrared fluorophores have been shown to significantly improve target contrast-to-noise in comparison with other imaging modalities such as PET. Their use can improve upon the limited depth penetration achieved by some tissue optical measurements, including tomography. Dual-labeled probes, e.g., targeted fluorophore plus gadolinium chelates, offer the potential to improve target sampling and its classification using MR imaging to guide high- spatial-resolution fiber-optical devices. Developments of multiple optical molecular probes using nanoparticles as a platform for fluorophore support and delivery have been proposed. Imaging of more than one molecular probe could be used to measure several parameters simultaneously, for example, to image the molecular target of a drug such as tyrosine kinase inhibitor, measure a drug"s biological effect, such as apoptosis, and provide a pathological or morphomertic measure of tissue response. Optical Methods: Optical systems for imaging and spectroscopy include (a) non-invasive external methods such as time resolved diffuse optical tomography (DOT), (b) direct optical methods for accessible epithelial surfaces, or (c) minimally invasive optical fiber methods for localized in vivo tissue measurements that require some form of image guidance, including insertion of optical fibers into tissues or the use of implanted systems. External optical tomographic applications under current investigation include breast cancer imaging and small animal imaging using both intrinsic contrast and extrinsic contrast agents. Minimally invasive methods include catheter- delivered optical systems capable of confocal or multi-photon microscopy, 2D optical coherence tomography, or localized spectroscopy measurements. Among next generation optical hardware components under development are (a) new light sources, such as pulsed, ultra-fast tunable lasers, and light sources capable of multi-spectral narrow band emissions, (b) miniaturized fiber optic systems and optical systems with micro-electromechanical system (MEMS) aiming and focusing technology with signal capture by multiple optical sensors or multi-modality sensors placed at the end of a thin catheter, and (c) detectors with improved sensitivity, spectral selectivity and photon energy band width suitable for enhanced multi-spectral techniques. Another area of active development includes computer-based methods for more nearly real-time quantitative analysis, which are often essential for detection, diagnosis, or some form of intervention. These advances would allow (a) a broad range of intrinsic and extrinsic signatures to be measured, (b) 3D imaging such as 3D OCT, as opposed to point measurements, (c) greater depth penetration than is available with current optical tomographic technology, and (d) approaches to multi-spectral imaging that will allow the imaging of multiple molecular probes. An important goal of the research would be optimization of overall optical properties (photon energy characteristics) by better matching of system transmit-receive characteristics with the optical properties of molecular probes and target tissues. Clinical Investigations: Optical imaging and spectroscopy are rapidly advancing modalities in medical imaging. For example, current clinical studies using intrinsic contrast signatures, such as optical fluorescence or reflectance measurements, or extrinsic contrast afforded by optical dyes, show promise for cancer screening applications. For example, point measurements are being explored for cervical cancer screening, where comparisons of colposcopic (visual microscopic) methods with PAP smears are underway. Preliminary results show optical signature differences between colposcopically normal and abnormal regions of cervix that correlate with biological differences between normal and diseased tissue. Further advances in multi-spectral imaging devices, such as miniaturized 2D optical microscopy and 3D OCT devices, should significantly improve lesion localization, depth of tissue visualization, and tissue characterization over current methods, particularly when combined with advances in targeted and activated contrast agents. The use of endoscopes to collect optical signatures (optical biopsy) has been proposed for cancer diagnosis. The use of 2D and 3D multi-sensor systems for optical biopsy should greatly improve localization, sampling, and characterization of lesions. There is potential for optical biopsy to precisely direct the clinician to the most suspicious site or eventually supplant tissue excision for cancer diagnosis in Barrett"s esophagus, colon and lung cancer. Optical tomography is being explored currently for breast cancer characterization, using measurement of intrinsic optical signatures derived from photon scattering and absorption due to blood oxygenation levels and indocyanine green contrast agent. Preliminary data suggest sensitivities comparable to dynamic contrast-enhanced MRI methods. Advances in contrast agents to extend the capabilities of optical tomography would further improve sensitivity and specificity for cancer detection and classification. Validation Methods: Another important objective of the proposed network is validation of new optical imaging methods for specific cancer applications. Validation refers to quantitative comparisons of performance with other imaging modalities or histopathology on biopsy specimens. These validation methods would precede a clinical trial designed to demonstrate the clinical efficacy of any optical method. Since in vivo optical measurements usually preserve tissue structure, verification of optical signatures should then be possible by correlation with measurements in vitro. The latter may include biopsy and histopathological confirmation, serial imaging and/or spectroscopy of excised tissue at higher spatial resolution, micro-array analysis of tissue, or other in vivo or in vitro measurements that serve as either reference methods or gold standards. It is envisioned that investigations involving pre-cancer or cancer detection, effects of the microenvironment, or measurements of response to therapy may involve optical methods that share features, optical signatures, and analytical features in common. Validation of the observations and their interpretations will be necessary, and will extend to understanding the optical signatures that may characterize molecular pathways to disease. Validation methods are anticipated to be complex and an important challenge in successful translational research. Thus there is a critical need for NTROI investigators to explore diverse approaches to validation, and compare and share the results of their optical imaging methods, contrast agents, software implementations of their algorithms, and together develop consensus on robust methods for their validation for various cancer applications. System Development and Integration: Prototype systems often are not sufficiently robust to support independent validation studies or clinical investigations. Hence there is a critical need for the network teams to include industrial research partners to take advantage of their expertise in (a) preparing robust optical systems and contrast agents, (b) disseminating optical devices and contrast agents to the imaging research and clinical communities, and (c) experience and flexibility in development of imaging/spectroscopy acquisition and data processing protocols to provide platform independent methods, such as harmonization of acquisition and analysis methods, which may be required later for multi-center clinical trials. Objectives and Scope: A network of Specialized Research Resource Centers consisting of approximately three multi-disciplinary inter-institutional research teams will be established for the purpose of supporting translational research applied to optical imaging and spectroscopy in vivo for human and/or pre- clinical models. The network is to be named the "Network for Translational Research: Optical Imaging" (NTROI), and will operate under the guidance of a Steering Committee (SC) comprised of senior investigators from the teams and NCI program staff scientists. The goal of the RFA is to organize a consortium with flexibility in scope and funding incentives to support inter- and intra-team research collaboration to encourage translational research. The objective is to accelerate translational research by developing a consensus-based approach to improved methods for system integration, optimization, and validation of next generation optical imaging, spectroscopic methods, and contrast agents. Applications that include molecular imaging methods are encouraged. Definition of Translational Research: Translational Research in the context of this Network means the development of a consensus process and methodology to move the application of emerging optical imaging and spectroscopy methods and their intrinsic or extrinsic (agent mediated) contrast mechanisms closer to uses in clinical oncology or research with humans or animal models. The range of work may encompass system integration, optimization, validation, and development of methods and related software for analysis towards proof of feasibility. It includes a consensus approach for the development of a framework or process to encourage platform independent methods, such as harmonization of acquisition and analysis methods, which may be required later for multi-center clinical trials. It is anticipated that iterative data collection will be used to further optimize and retest system performance. It includes efforts to understand the mechanisms underlying optical signatures and the extraction of information from them as required for overall system validation. Clinical investigations specifically to demonstrate proof of feasibility or to provide feedback to improve the sensitivity and specificity of the imaging protocols are acceptable, but larger trials to establish clinical utility are beyond the scope of this RFA. The flexibility intended for NTROI teams includes the promotion of developmental projects into primary projects as they show promise and importance, and discontinuation and replacement of developmental or primary projects that are completed, or which demonstrate insufficient translational significance or progress. It is anticipated that the original teams of investigators might remain largely the same during the period of the cooperative agreement, but that lead roles among investigators may change as projects evolve or are replaced. It is expected that Teams, with Steering Committee guidance, will develop the research infrastructure and approaches necessary to sustain translational research objectives and continually develop collaborative research relationships necessary for the most effective path to completion of translations. The NTROI is expected to identify and focus on translational research that is best accomplished through research collaborations, networks and consortia. The efforts envisioned here are oriented toward proofs of feasibility, given the limitations imposed by available funding. It is therefore anticipated that as projects mature, investigators will seek independent investigator- initiated funding to carry projects beyond technical and clinical feasibility toward clinical utility. To these ends, cooperation and collaborations with other NCI funded programs are encouraged. The following list represents a partial listing of possibilities: ACRIN: American College of Radiology Imaging Network, http://www3.cancer.gov/bip/arin.htm ICMIC: In vivo Cellular and Molecular Imaging Centers and Pre-ICMICs, http://www3.cancer.gov/bip/ICMICs.htm CTEP: Cancer Therapy Evaluation Program, http://resresources.nci.nih.gov/categorydisplay.cfm?catid=7 - 21 MMHCC: Mouse Models of Human Cancers Consortium, http://web.ncifcrf.gov/researchresources/mmhcc/default.asp ERDN: Early Detection Research Network, http://www3.cancer.gov/prevention/cbrg/edrn/ SPORE: Specialized Programs of Research Excellence, http://spores.nci.nih.gov/ IMAT: Innovative Molecular Analysis Technologies, http://otir.cancer.gov/tech/imat.html A submitted application must describe a pre-formed research consortium, to be known as a Research Team. A network of approximately three such Specialized Research Resource Center teams will be formed from applications that receive high priority scores and are most responsive to the goals of the RFA. Each team must include investigators from at least two different institutions. A team may include participants from research laboratories in academia, national laboratories, large or small businesses, and/or NIH intramural research programs. NIH intramural investigators may participate in a Team application, but they must be supported by NIH intramural funds and cannot request or receive funds from this program (see special instructions under SPECIAL SUPPLEMENTAL INSTRUCTIONS FOR NIH INTRAMURAL INVESTIGATORS, CO- INVESTIGATORS, AND/OR COLLABORATORS. It is anticipated that translational research will require broad, multi- disciplinary teams. They should include representatives of fields necessary for successful completion of the proposed basic research and translational projects, and might include molecular biologists, chemists, physicists, optical and computer engineers, imaging scientists and physicians, among others. Involvement of basic and clinical scientists who may not have a specific research record in cancer research, but who have the potential to provide experience crucial for the success of this network are considered important. Each team is encouraged to include industrial partnerships formed with large or small businesses to enhance the development of technology suitable for dissemination for cancer applications for both human and pre clinical model investigations. Each application must provide a Team Description, describe an Organizational and Administrative Structure, and propose Primary Research Projects. The Organizational and Administrative Structure must include plans for how the team will initiate and select Developmental Projects for years 2-5, including recruitment of Associate Members to bring outside expertise to Primary and/or Developmental Projects. Each application must propose one or more Research Support Cores and an Administrative Core. Specifics on projects and cores are described below. The budget should consist of a Summary Budget followed by detailed individual research project and core budgets and justifications. Network members may have concurrently funded, related projects or seek additional investigator initiated funding for projects that complement the objectives of the NTROI. Primary Projects (Support: Years 1-5): Primary Projects are key to the success of the research program of a Specialized Research Resource Center, so the submitted application must provide a succinct, yet complete research plan for each one. 1. Each application must propose at least three Primary Projects. These may involve the same or different imaging methods and organ systems. 2. The Primary projects shall address at least two of the following three topical areas: (a) Basic Research: Interdisciplinary studies to improve fundamental understanding of molecular processes or cellular environment in vivo that influence the measurement, interpretation, and/or validation of optical signatures from extrinsic and/or intrinsic contrast mechanisms. (b) Optical contrast agents: Examples might include development and validation of target-based optical contrast agents or molecular probes that may be activated to improve sensitivity and/or specificity of cancer investigations, or agents for dual modality imaging. (c) Technology optimization and validation: Examples might include system integration, optimization, algorithm and software development for pre- and/or post-processing, optimization of tomographic or localized optical imaging or spectroscopy systems. As primary projects mature and their aims accomplished by translation to cancer applications, teams may terminate a primary project and replace it with a new project. Team investigators are encouraged to seek additional investigator-initiated external funding and collaborations for follow up pre– clinical or clinical studies as primary projects mature. The Steering Committee will review and advise on proposals for all primary projects. Research and Administrative Cores (Support: Years 1-5): A Research Support Core is to provide core services to at least one Primary Project and is expected to provide services for future Developmental Projects that require them. It must not duplicate any available resource facility already in place and supported by another funding mechanism, e.g., P30, P41, P01, U01, DOD, etc. However, investigators may (are encouraged) to present a proposal to augment an existing resource facility with funds and/or personnel effort in order to fulfill their needs for core resources. A Research Support Core or Cores may include, for example, (1) shared imaging and/or spectroscopic systems, perform prototype system maintenance and improvements, or related software for data analysis for small animal and/or human investigations, (2) laboratory capability for development and production of targeted and/or activated contrast agents, and/or (3) facilities for data analysis. Each Research Support Core must have its own budget and justification. An Administrative Core is to provide (1) administration and coordination among all intra-team research projects, including access for any project that requires Research Support Core services, and (2) inter-team projects coordinated through the administering team"s participation on the Steering Committee. The Administrative Core must have its own budget and justification. Developmental Project Plans (Support: Years 2-5): The application"s section on Organization and Administration must include a section that describes plans for generating developmental projects to start in years 2 and later. Do not provide descriptions of actual developmental projects, a plan for a process to identify future projects is what is required. These plans are to result in (a) feasibility studies and pilot projects that have the potential to mature into new primary projects, or (b) have potential to expand the scale and translational scope of primary projects. It is anticipated that after the formation of the NTROI that intra-team and in particular inter-team translational research scale-up of primary projects or common pilot projects would be encouraged by the Steering Committee, including access to the research resources among the teams of the overall network (NTROI). A plan for termination of unproductive Developmental Projects should be proposed. Do not provide descriptions of actual developmental projects, a plan for a process to identify future projects is what is required. Associate Members: The plans for Developmental Projects must include outreach to the academic, national laboratory, industry and small business communities to attract new collaborating researchers who would then become Associate Members of the NTROI. Outreach to Associate Members may provide, for example, access to expertise on new ideas, optical systems, probes or validation methodologies that are not available within the team. The Development Project Plan should budget approximately two-thirds of developmental funds for intra-team and inter-team developmental projects, and one-third for Associate Members. The Steering Committee will review and advise on team proposals for use of funds for Developmental Projects, including their scope, relevance to the NTROI, amount, and duration of support. Investigators gaining support for Developmental Projects will be encouraged by the Steering Committee to seek independent investigator initiated support, e.g., R01, R21, R21/R33, Fast-track SBIR, STTR, etc., as the projects mature. Budget and Related Issues: NCI will set aside approximately $3 million total costs in year 1, and $18M total costs for all 5 years for the NTROI. Average direct and total costs per Team are estimated as follows: o Primary Projects, Research and Administrative Cores: Average annual direct costs of $650 thousand (total costs of $1 million) and average direct and total costs for all 5 years of $3.25 direct, and approximately $5M total costs per funded application. o Developmental Projects: Average annual direct costs per team of $150 thousand (total costs of $225 thousand) are estimated for years 2 through 5 (not funded in year 1), with average direct and total costs for years 2-5 of $600k direct and approximately $900k total. PRE-APPLICATION MEETING A pre-application meeting for potential applicants will be organized to help communicate the goals of this RFA and answer questions. It will be held the afternoon of September 27, 2002, in Bethesda MD. Information on preliminary and final plans on venue and agenda will be emailed to interested investigators who submit contact information to Dr. Houston Baker, below. The venue and agenda also will be posted on the NCI"s Biomedical Imaging Program website, http://cancer.gov/bip. MECHANISM OF SUPPORT This RFA will use the NIH Specialized Center Cooperative Agreement (U54) award mechanism for the Network for Translational Research: Optical Imaging. With this award mechanism, each Principal Investigator of a cooperative agreement retains the primary responsibility and dominant role for planning, directing, and executing the proposed team project, maintaining active collaborations to be formed with other Specialized Research Resource Center teams competitively selected for the Network, and maintaining active participation in the Network"s Steering Committee. There is NCI staff involvement in partnership with the Principal Investigator, described in "Cooperative Agreement Terms and Conditions of Award," below. The NCI may expand or reduce the scope and direction of the Network by amendment during the course of the initial five-year period of set-aside funding, terminate it upon expiration, or extend or expand it prior to expiration by reissuing the RFA soliciting competitive applications for translational research in optical and/or other imaging technologies for oncology. It is anticipated that individual projects of a team will mature, complete aims, add new aims, end, and/or be replaced by other projects. Developments that successfully translate to clinically feasible or research-oriented instruments and methods are expected to stimulate investigator-initiated applications for clinical and basic research grants under other support mechanisms, such as the R01, R21, R21/R33, R33, R41, R42, R43, and R44. FUNDS AVAILABLE NCI intends to commit up to $3 million total costs in FY 2003 to fund approximately 3 new cooperative agreements in response to this RFA, and $3.75 million total costs in each of FY2004 through 2007, for a total commitment of $18 million. An applicant Team may request a project period of up to 5 years and a budget for direct costs of up to $1 million per year. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of NCI include support for this program, awards pursuant to this RFA are contingent upon the annual availability of funds and receipt of a sufficient number of meritorious applications. At this time, it is not known if this RFA will be reissued. NCI extramural funds are not available to fund research by NIH intramural investigators. Intramural participants must verify the availability of funding allocated from intramural sources to support their role as collaborators on a team. ELIGIBILITY Eligible Institutions: o For-profit or non-profit organizations, o Domestic or foreign organizations, o Public or private institutions, such as universities, colleges, hospitals, and laboratories, o Medical and technology research units of State and local governments, o Eligible agencies of the Federal government. (Intramural NIH scientists who are supported by intramural funds may provide Primary and Developmental Projects, and Research Support Core services to an application, or provide expertise to Network projects as Associate Members. The extramural funds set aside for this RFA are not available for support of NIH intramural research staff). A responsive application will include a minimum of two eligible institutions and present at least three Primary Projects, one Research Support Core, one Administrative Core, and plans for establishing Developmental Projects to start in year 2. Cost sharing by adding employee effort and support to an existing core facility is encouraged to reduce overall core costs and start- up time. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual from an eligible organization and who has the skills, knowledge, and resources necessary to direct and carry out the proposed research is invited to work with their organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are encouraged to apply for NIH programs. SPECIAL REQUIREMENTS In order to ensure maximal progress by the teams funded by this initiative and to realize the maximum benefit for the cancer research community and ultimately for the ongoing battle against cancer, specific obligations will be required of the funded investigators. Applicants should state in their applications the following agreements: o Their commitment to actively participate in the group activities of the proposed Network of Specialized Research Resource Centers, NTROI. o Their commitment to consider modifications of Primary Project aims to accommodate new opportunities, needs and developments by the Network as a result of progress or completion of Primary Project aims, and submit these ideas to the Steering Committee for input and advice. o Their commitment to submit proposals for Developmental Projects to review by the Steering Committee for importance and relevance to the stated goals of the proposed Network. o Their commitment to actively seek and participate in Associate Member, inter- and intra-team research collaborations as proposed by this RFA. o Their commitment to jointly publish and otherwise disseminate appropriate NTROI research findings and technological translational developments based on consensus approaches for the validation of imaging/spectroscopy methods for specific cancer applications. o Their commitment to jointly organize a NTROI public meeting in year 2 and annual meetings thereafter, based on Steering Committee recommendations. . o Their commitment to participate in organized meetings of the NTROI, conference calls, and group discussions related to encouraging inter- and intra-team collaboration. COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD The administrative and funding instrument used for this program is the NIH Specialized Center Cooperative Agreement (U54), which anticipates participation by NCI Program Staff. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the cooperative agreement awardee"s activity by involving NIH program staff in and otherwise working jointly with the award recipient in a partnership role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the Specialized Research Resource Center awardee for the project as a whole, although specific tasks and activities in conducting the studies will be shared among the awardees and the NCI Program Staff, as described below. The following terms and conditions pertaining to the scope and nature of the interaction between NCI and the investigators will be incorporated in the Notice of Grant Award. These terms will be in addition to the customary programmatic and financial negotiations that occur in the administration of grants. The terms and conditions described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74, other HHS, PHS, and NIH Grant Administration policy statements, and other NCI administrative terms of award. 1. Awardee"s Rights and Responsibilities Each Specialized Research Resource Center Awardee will have primary and lead responsibilities for its Team projects as a whole, including research design and protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, as well as collaboration with other awardees in this Network. In coordination with policy decisions of the Steering Committee, the dominant role and prime responsibility for overseeing and directing the activity of each Specialized Research Resource Center team, including assignment of duties of participating personnel, resides with its Principal Investigator. An awardee will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies, and consistent with the objectives of the NTROI Specialized Research Resource Center. An awardee has the responsibility of collaborating with other Specialized Research Resource Center teams of the NTROI and participating in its Steering Committee (described under 3. Collaborative Responsibilities). 2. NCI Program Staff Scientist Responsibilities The NCI Program Staff Scientists, consisting of the Imaging Technology Development Branch Chief and an additional scientific advisor from the Biomedical Imaging Program, will have scientific and programmatic involvement above and beyond normal stewardship in decisions and recommendations on overall project directions and allocations of all Project Funds. One staff scientist provides experience in device, algorithm and software development, and system integration. The other provides experience in cellular molecular science, imaging probe and drug development, and medical oncology. This oversight will be accomplished primarily through their participation as voting members on the NTROI Steering Committee, and secondarily through discussions with the team Principal Investigators. Specific tasks and activities in carrying out the studies will be shared among the Network Teams and may include participation by the NCI program staff scientists. NCI program staff scientists will also assist in stimulating broader NCI and NIH program interaction to accelerate the translational research efforts towards feasibility studies. NCI program staff will help identify candidate Associate Members from successful application submissions to NIH ICs or the NSF Biophotonics initiatives, including SBIR funded investigators, and encourage further interactions with other ongoing relevant NIH or other federal programs. An NCI Program Director will be assigned to perform normal programmatic stewardship and scientific administration of the cooperative agreement to be awarded. The Program Director responsible for this RFA will attend Steering Committee meetings as a non-voting observer. The NCI reserves the right to terminate or curtail an individual award in the event of insufficient progress, substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of NTROI objectives. 3. Collaborative Responsibilities Steering Committee A Steering Committee (SC) will be the main governing board for the proposed Network of Specialized Research Resource Centers (NTROI). The members of the SC will consist of three members from each of the funded teams and the two designated NCI Program staff for an anticipated total of 11 voting members. The three members from each team will include the PI and two additional co- investigators from each team, at least one of whom is from a different institution than the PI, and one of whom is a co-investigator from the team"s administrative core. Voting members from the NCI Program staff will include the Branch Chief of the Imaging Technology Development Branch and another scientific advisor from the NCI Biomedical Imaging Program. All members from teams and the two designated NCI staff will be voting members of the SC. The SC will elect one of the team principal investigators to chair this committee. The SC may include additional non-voting members, such as the Program Director responsible for scientific administration of this RFA, other NCI and NIH program staff or program staff from other federal agencies such as the FDA, NSF or NIST who would serve in advisory capacities. The Steering Committee will have primary responsibility for the overall organization of the NTROI and for coordinating research goals and resources among the teams. For example, they will review primary projects to encourage inter-and intra-team collaborations. One important role will be to develop a consensus on the best means for system integration, optimization, validation, and translation of all projects. Before the end of year 1 the Steering Committee will initiate a review process for proposals for Developmental Projects, either for pilot projects that have the potential to become new primary projects, or to expand the scale and scope of primary projects towards translational research. Developmental projects selected for funding are to have significant potential to contribute to advancing the translational research of any team in the NTROI. The SC will encourage inter-team collaborations where pooling of resources for Developmental Projects or expansion of Primary Projects would enhance or accelerate the timetable for translational research, and will actively seek new collaborators (Associate Members). The SC will develop a plan for terminating Development Projects that become unpromising or unproductive. The SC will organize an open scientific meeting in year 2 to report on progress of the NTROI, solicit input from the broader scientific community, and attract prospective Associate Members. The SC will schedule quarterly meetings and telephone conference calls as necessary for conduct of its business. The SC will schedule one annual meeting at which all NTROI team members will present their scientific progress and future plans. Each team"s Administrative Cores will share costs and effort for support of the above-described administrative activities of the SC. Each awardee is required to submit a written semi-annual report on research progress to the NCI Program Director and the NTROI SC. The SC will develop recommendations for the scope and format of these reports, which will include scientific progress, plans, and description and evaluation of the extent and progress of inter-and intra-team collaboration. Both the Steering Committee and NCI program staff will review reports. 4. Arbitration Any disagreement that may arise on scientific or programmatic matters (within the scope of the award), between award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members, one selected by the Steering Committee (with the NCI members not voting) or by the individual awardees in the event of an individual disagreement, a second member selected by NCI, and the two arbitration panel members so selected shall select a third member. This special arbitration panel will establish a procedure to arbitrate the dispute and deliver a recommendation. Its actions do not abridge the awardee"s right to appeal an adverse action that may be otherwise appealed in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. WHERE TO SEND INQUIRIES Inquiries concerning this RFA are strongly encouraged. Potential applicants may pose questions directly and/or choose to participate in a meeting for potential applicants scheduled September 27, 2002, prior to the Letter of Intent due date (December 17, 2002). Inquiries may fall into three areas: program and scientific research, peer review, and financial or grants management issues. o Direct questions about program and scientific research for the National Cancer Institute to Houston Baker, Ph.D. Program Director Imaging Technology Development Branch Biomedical Imaging Program Division of Cancer Treatment and Diagnosis National Cancer Institute EPN Room 6060 Bethesda MD 20892-7412 (or for courier service, Rockville MD 20852) Telephone: 1-301-594-9117 FAX: 1-301-480-3507 Email: firstname.lastname@example.org or Laurence P. Clarke, Ph.D. Branch Chief Imaging Technology Development Branch. Biomedical Imaging Program Division of Cancer Treatment and Diagnosis National Cancer Institute EPN Room 6054 Bethesda MD 20892-7412 (or for courier service, Rockville MD 20852) Telephone: 1-301-435-9190 FAX: 1-301-480-3507 Email: email@example.com o Direct questions about peer review issues to Referral Officer National Cancer Institute Division of Extramural Activities 6116 Executive Boulevard, Room 8041, MSC 8329 Bethesda MD 20892-8329 Telephone: 1-301-496-3428 FAX: 1-301-402-0275 Email: firstname.lastname@example.org o Direct questions about financial or grants management matters to Kelli Oster Grants Administration Branch National Cancer Institute 6120 Executive Boulevard, EPS Room 243 Bethesda MD 20892 Telephone: 1-301-496-8627 Fax: 1-301-496-8601 LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Number and title of this RFA o Descriptive title of the proposed team research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating organizations Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and plan the review. The Letter of Intent is expected by December 17, 2002. The Letter of Intent should be sent to Houston Baker, Ph.D. Biomedical Imaging Program Division of Cancer Treatment and Diagnosis National Cancer Institute EPN Room 6060 Bethesda MD 20892-7412 (or for express or courier service, Rockville MD 20852) Telephone: 1 301 594 9117 Fax: 1 301 480 3507 Email: email@example.com PREPARING AND SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). PHS 398 Forms and Instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact Grants Info, Telephone (301) 435-0714, e-mail: GrantsInfo@nih.gov. SUPPLEMENTAL INSTRUCTIONS: Preliminary Research Plan and Budget: Early in the Team"s application planning cycle, the Principal Investigator should discuss the outline plans and budget with the NCI Program Director (named above) to gain understanding of current policies, priorities, and budget environment. Face Page, Line 2. Type number, RFA: CA-03-002 and the RFA title "Network for Translational Research: Optical Imaging" on line 2 of the face page of the application form, and mark the YES box. Page 2, Key Personnel: List all key personnel, organization for each, and role on the Team. Page 3, Table of Contents: Adapt to include the Organization and Administration section, title of each Primary Project, Developmental Project Plan, each Research Support Core, and Administrative Core. Use additional pages as necessary. Appendix A, Sample Table of Contents, Guidelines for the NCI Program Project, is exemplary of the level of detail sought for a large application, although it differs in specifics from this RFA. See http://deainfo.nci.nih.gov/awards/P01.pdf#A. Budgets: The standard PHS 398 form pages 4 and 5 are to be completed for a Summary Budget, followed sequentially by budget form pages 4 and 5 for each individual research component (research projects and core activities). Use additional pages for budget justifications where necessary. The Administrative Core budget will include a share for the Network Steering Committee needs as well as the usual administrative core activities. Budgets for projects and cores from one or more collaborating institutions are listed in the section on Consortium/Contractual Arrangements in the Summary Budget, and details provided in their budgets for individual research components using Form Pages 4 and 5. Prepare separate budget pages and brief justification for Developmental Projects for years 2-5. The amount expected is $150k direct costs per year. The justification is generic because Developmental Projects are not to be submitted with the application, only plans for project identification and accrual to meet future needs and opportunities. Personnel participating in more than one project should be listed in the budget for each, showing percent effort on that project and justified in its budget justification. Percent efforts for each project should be listed by individual in the Summary Budget and then sub-totaled by individual. Provide a Table of Professional Effort, starting with the Team Principal Investigator, followed by Project and Core Leaders, and then followed by the remainder of the investigators. See Appendix B, Sample Table of Professional Effort, ibid.(http://deainfo.nci.nih.gov/awards/P01.pdf#A). o Capital Equipment: Quotes for capital equipment are not needed for application review, but will be requested prior to issuing an award. o Duplicate Equipment: The Budget for Equipment may include funds to produce one or more copies of prototype translational equipment needed for placement with another primary project or collaborating research or clinical research site. Justify the request under Equipment in the Budget Justification. Research Plan: The following adaptations of Form 398 instructions for the "Research Plan" are suggested: Large Project page limitations apply, as noted below. Applicants are urged to use fewer than the allowed number by being as concise as possible in view of the limited scope of the translational research aims for the NTROI, and to facilitate review. Team Description (10 pages): Present an overall vision for the NTROI Team, including long and short-term objectives, and how they will support the translation research as defined in this RFA. Summarize the organizational structure of the Team, concisely defining Research Components and how each will contribute to achieving the objectives of the translational effort. Briefly describe the Team"s anticipated organizational relationship with the Network, which will consist of this Team and two others. This section should provide a broad overview of the Team and its organization, reserving details for later sections. Organization and Administration (20 pages): Include organizational charts, the infrastructure, relation to the administrative structures of the host institutions (applicant and consortium/subcontracting institutions) and decision-making structure of the Team. Among appropriate components to include are the following: o Roles and responsibilities of the principal investigator, project leaders, core project directors, participating investigators/collaborators, and internal and external advisory committees. o Describe the decision-making, oversight, and communication responsibilities for each component. o Describe how projects are planned, coordinated, and evaluated. o Describe the process (plan) by which Developmental Projects for years 2 through 5 will be identified, selected, progress monitored, and promoted to a Primary Project. Include a plan for termination of unproductive Developmental Projects. Do not provide descriptions of actual developmental projects, a plan for a process to identify future projects is what is required. o Provide a tabulation of all consultants and their institutional affiliations, paid or unpaid. o Describe plans to facilitate multi-disciplinary interactions both through intra-team and inter-team collaborations, as well as collaborations from outside NTROI (Associate Members). o Describe the Applicant Institution"s commitments to support its applicant Team and consortium/subcontract component(s) of the Team. Include a description of the relationships between the Team, other departments, centers and institutes, and the institutional central administration. o Describe the Team"s anticipated relationship and intention to interact with the other teams of the NTROI. Research Projects (30 pages each): o Identify each Research Project with a number, title, and project leader, e.g., 1. Raman Optical Signatures, Jane Doe. o Research Plan Sections A-D (Specific Aims, Background and Significance, Preliminary Data and Progress, and Research Methods) must be presented within the standard 25 page limit for each Primary Project. Follow Form 398 instructions, including those for Human Subject participation and vertebrate animal use. Applicants are urged to use fewer than the allowed number of pages by being concise. o A minimum of 3 primary projects from at least two institutions must be proposed. They are key to the success of the research program of a NTROI Specialized Research Resource Center. Their evaluation will be the main focus of the review committee organized by the NCI Division of Extramural Activities. Research projects should include descriptions of how the work will support translational research for cancer. o The overall scope of the proposed primary projects must address at least two of the following three topical areas: (1) Basic Research to improve fundamental understanding, measurement, interpretation, and validation of optical signatures from extrinsic and/or intrinsic contrast mechanisms. (2) Optical contrast agents: development and validation of optical and/or multi-modality contrast agents to improve sensitivity and/or specificity of cancer investigations. (3) Technology optimization and validation, e.g., system integration, optimization, algorithm development and software methods for pre- and/or post-processing, etc. Research Support Core: o Identify each Core Project with a letter, title, and project leader, e.g., A. Ligand Labeling and Fluorophore Development Laboratory, John Doe. Each team must propose one or more Research Support Cores, each of which is to provide common support to at least one Primary Project. A Core may provide laboratory facilities, equipment and services to be shared among Research and Developmental Projects. After formation of the NTROI and its Steering Committee, arrangements may be made to provide core services to projects on other teams. Affiliations with existing Cores are encouraged to minimize duplicate costs, share resources, and reduce start-up time. Instead of a typical Research Plan, use Aims to provide a clear description of methods and services that the Core activity will provide to a Team Research Project(s) and potential future Developmental Projects. Use Background and Significance to describe the importance of the proposed services to the research project(s) and Team effort. In Progress, describe any pre-existing capabilities or preliminary data that will strengthen the proposed Core Project. Use Methods to address research activity, if any, proposed to adapt, further develop, meet research project needs, or otherwise strengthen the methods and services to be provided. Administrative Core: Each team must propose an Administrative Core to administer and facilitate (1) intra-and inter-laboratory access and coordination for meeting primary project needs among team members of the participating institutions, (2) shared Network needs for organizing, administering, and arranging representation at NTROI Steering Committee meetings, and (3) usual administrative core duties (fiscal management, clerical support, manuscript preparation, meeting organization, data management, quality control, planning, evaluation, communication within the Team and with the community external to the Team. It may include plans for internal executive committee activity, and internal and external advisory committees, including the NTROI SC). Submitted Images and Figures: Follow PHS398 instructions for submitting as appendix material original quality copies of images and figures that don"t copy well. RFA Label: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number CA-03-002 on the label. Failure to use this label could delay processing of the application such that it may not reach the review committee in time for review. The RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Sending an Application to the NIH: Submit a signed, machine printed original of the application, including the Checklist, and three signed photocopies, in one package to the Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 or Bethesda, MD 20817 (for express or courier service) At the time of submission, send two additional copies of the application to Referral Officer Division of Extramural Activities National Cancer Institute 6116 Executive Blvd., Room 8041, MSC-8329 Rockville, MD 20852 (express or courier) or Bethesda MD 20892-8329 SPECIAL SUPPLEMENTAL INSTRUCTIONS FOR NIH INTRAMURAL INVESTIGATORS, CO- INVESTIGATORS, AND/OR COLLABORATORS NIH Intramural investigators may submit a research project or core as part of a NTROI application from an extramural institution. The NIH component must use the PHS 398 application instructions and form pages (rev. 5/2001). PHS 398 Forms and Instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html. For further assistance contact Grants Info, Telephone (301) 435-0714, e-mail: GrantsInfo@nih.gov. NIH applicants must follow the PHS 398 Application Form Instructions and the modified format and content described above under PREPARING AND SUBMITTING AN APPLICATION and SUPPLEMENTAL INSTRUCTIONS, with the following modifications or clarifications: o On the Face Page, fill out only items 1., 2., 3.(leave 3c. blank), 4., 5., 6., 7a., and 8a. The remainder of the items should be left blank. The application must not be signed by either the Intramural NIH Investigator or an NIH Institute official. Do not submit pages for Other Support, Checklist, Personnel Report, or Personal Data. o An Intramural NIH investigator must obtain prior approval of his or her NIH Institute or Center Scientific Director to apply as a collaborator or participate by submitting a research project, core project or other component of a Network application, to work under the terms and conditions of this RFA, to comply with the policies of the Steering Committee, and comply with the policies of the National Cancer Institute. A copy of the Letter of IC Approval, addressed to the NCI Referral Officer, must accompany the cover letter submitted with the application. It must verify that the necessary personnel effort and resources will be made available from intramural sources to support the proposed collaborative work and Network application component. The Letter of IC Approval must provide assurance that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with PHS policy on vertebrate animal research. o The Intramural Project Leader and Extramural Principal Investigator must negotiate a project upper budget limit such that the sum of the Intramural support plus Extramural funds requested in the application does not exceed an application"s annual limit of $1,000,000 direct costs in any one year. NIH IC Scientific Director, as part of the Letter of IC Approval to Participate, must verify that no more than the negotiated upper limit to Intramural support will be allocated to the Intramural project described in the application. o All information requested on the Budget Form pages 4 and 5 should be provided, except that dollar figures must be omitted in all cases. The personnel time and effort, intramural resources available for the project, and the research environment should be carefully described (without dollar figures). The Detailed Budget for Initial Project Period page and Budget for Entire Proposed Period of Project Support (Form Pages 4 and 5) should provide the time and effort of each project participant without dollar figures. The resources available for the project and the research environment should be carefully described without dollar figures. Delivery of Applications: The National Institutes of Health and National Cancer Institute no longer accept applications hand-delivered by individuals (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html). This policy does not apply to courier deliveries (i.e., FEDEX, UPS, DHL, etc.) (http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html). Application Processing: Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it may be returned to the applicant without review. PEER REVIEW PROCESS Upon receipt, applications will be reviewed by the CSR for completeness and by the NCI program staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. Complete applications that are responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI Division of Extramural Affairs (DEA). They will be reviewed in accordance with the review criteria stated below. As part of the initial merit review, all applications will o Receive a written critique, o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the stronger half of the applications under review, will be discussed and assigned a priority score, o Those that receive a priority score will undergo a second level review by the National Cancer Advisory Board. REVIEW CRITERIA For a definition of Translational Research in the context of this proposed Network, see the subsection, Objectives and Scope, under RESEARCH OBJECTIVES of this RFA. A. Primary Research Projects Within the NTROI concept of translational research, reviewers will evaluate each of the primary research projects using the five criteria listed below. Each of the criteria will be addressed and considered by the reviewers in assigning a merit score for the project. Note that the project does not need to be strong in all categories to be judged likely to have a major translational impact and thus deserve a high merit score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) SIGNIFICANCE: Does the study address important problems in optical methods and their translation to cancer applications? What will be the effect of the proposed research on development of consensus approaches for optimization, validation and translation of optical methods for cancer applications? (2) APPROACH: Are the conceptual framework, rationale, design, methods, analyses and organizational structure adequately developed, well integrated, and appropriate to the aims of the Team? Does the application address potential problem areas and describe alternative tactics? Does the application describe efforts to include state of the art technological advances and translational research towards cancer applications? Is the experimental design adequate to achieve the proposed research and translational objectives? (3) INNOVATION: Does the application involve innovative concepts, approaches or methods that will advance the state of the art of the proposed technologies and proposed new innovative approaches for consensus in translational research likely to gain broad acceptance by the imaging community? (4) INVESTIGATOR: Are the investigators appropriately trained and well suited to carry out this collaborative work? Is the proposed work and level of effort appropriately matched by the experience of the principal investigator and the overall research team? Is there evidence that the investigators have the background, leadership and skills to collaborate and coordinate integration of basic biological sciences and clinical practices with the applied sciences and engineering required for translational research? Do they commit adequate effort? (5) ENVIRONMENT: Does the scientific, technical and intellectual environment of the team"s institutions contribute to the probability of success? Is there evidence of each institution"s support for translation of optical methods toward human or small animal investigations? B. Research Support Cores: Is the required time and talent committed to providing Research Support Core Services? Does it provide unique services (avoid duplication of existing resources)? Is it essential to the success of one or more Primary Projects (Does any project state a need for the Core"s services)? Does it provide a commitment to serve future Developmental Projects? Are plans for charge back and priority management procedures for Core services adequate? Are plans to serve investigators at the other institution(s) on the team adequate? Other NTROI teams? C. Administrative Core: Are the organizational plan, talent and time commitments adequate to provide the administrative services needed for efficient operations of the Team and its share of Steering Committee responsibilities? D. Organization and Administration: Does the organizational structure promote flexibility to adapt to progress and new opportunities? Does the structure promote development of consensus approaches to translation and validation of optical methods? Does the Developmental Project Plan appear sufficient to attract high quality intra-team and inter-team Developmental Projects, attract Developmental Projects from prospective Associate Members, help existing Primary Projects stay current with new ideas or lead to new Primary Projects, sufficient to promote expansions of Primary Project translational efforts and validations, and adequate for termination of unproductive Developmental Projects? E. Overall Application: Is there a focus on research questions best accomplished through research collaborations, networks and consortia? Will any Primary Project benefit from or need developments performed in another Primary Project or Core? Does the application show a focus on developing the research infrastructure and approaches necessary to sustain translational research objectives and continually develop collaborative research relationships necessary for finding efficient paths to completion of translations? Will the investigators produce more as a NTROI team than they would if they worked independently with separately funded projects? Is there evidence of each institution"s support for translation of optical methods toward human or small animal investigations? Does the application show a commitment by the team to cooperate and coordinate activities with all members of the NTROI? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: o PROTECTIONS: The adequacy of the proposed protection for humans, humane care and use of animals, or protection of the environment, to the extent they may be adversely affected by the project proposed in the application. o INCLUSION: The adequacy of plans to include women, racial and ethnic groups (and subgroups), and children subjects as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria included in the section on Federal Citations, below). o BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Public Meeting of Potential Applicants: September 27, 2002 Letter of Intent Receipt Date: December 17, 2002 Application Receipt Date: January 21, 2003 Peer Review Date: May/June, 2003 Council Review: September 8-10, 2003 Earliest Anticipated Start Date: September 30, 2003 AWARD CRITERIA Award criteria that will be used to make award decisions include the following: o Scientific and technical merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS DATA AND SAFETY MONITORING PLAN and DATA SAFETY AND MONITORING BOARD: Research components involving Phase I and II clinical trials must include provisions for assessment of patient eligibility and status, rigorous data management, quality assurance, and auditing procedures. It is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). Clinical trials supported or performed by NCI require special considerations. The method and degree of monitoring should be commensurate with the degree of risk involved in participation and the size and complexity of the clinical trial. Monitoring exists on a continuum from monitoring by the principal investigator/project manager or NCI program staff to a Data and Safety Monitoring Board (DSMB). These monitoring activities are distinct from the requirement for study review and approval by an Institutional review Board (IRB). For details about the Policy for the NCI for Data and Safety Monitoring of Clinical trials see: http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. For Phase I and II clinical trials, investigators must submit a general description of the data and safety-monitoring plan as part of the research application. See NIH Guide Notice on "Further Guidance on a Data and Safety Monitoring for Phase I and II Trials" for additional information: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html. Information concerning essential elements of data safety monitoring plans for clinical trials funded by the NCI is available: http://www.cancer.gov/clinical_trials/ INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates the use of an NIH definition of clinical research, updated racial and ethnic categories in compliance with the new OMB standards, clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398, and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. A continuing education program in the protection of human participants in research in now available online at: http://cme.nci.nih.gov/ HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Guidance for investigators and institutional review boards regarding research involving human embryonic stem cells, germ cells, and stem cell-derived test articles can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-044.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide the official NIH identifier(s)for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds, and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive that can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/ AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No. 93.394 and 93.395, Cancer Detection and Diagnosis Research and Cancer Treatment Research and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies described at http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
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