APPLICATIONS OF INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER: (SBIR/STTR) INITIATIVE Release Date: May 14, 1999 PA NUMBER: PAR-99-103 P.T. National Cancer Institute Letter of Intent Receipt Dates: June 18, October 18, 1999; February 18, June 19, October 19, 2000 and February 20, 2001 Application Receipt Dates: July 21, November 21, 1999; March 21, July 21, November 21, 2000 and March 21, 2001 PURPOSE The National Cancer Institute (NCI) invites applications for research projects to evaluate the utility and pilot the application of molecular analysis technologies in studies relevant to cancer research. Molecular analysis technologies of interest include those that are entirely novel, or emerging but not currently in broad scale use, or technologies currently in use for one application or set of applications, that are being evaluated for utility for alternative applications. The Program Announcement (PA) provides support for a first phase for technology evaluation and a second phase for pilot application of the technology in a study of biological interest to cancer research. The first (evaluation) phase should include proof of principle experiments that will demonstrate the utility of the technology on samples comparable to those that will be used in the second phase study. Applicants will be expected to demonstrate the utility of all components of the process required for a fully integrated system, including sample preparation, molecular analysis assay, and data capture and analysis. The second (application) phase supports the transition of the technology optimized in the first (evaluation) phase to pilot application in a study of biological interest to cancer research. The design of the second phase study should allow the demonstration that the technology can reproducibly obtain molecular data from the selected sample type and produce information of biological interest to cancer research. Studies might appropriately target analysis of precancerous, cancerous, or metastatic cells, or host derived samples, from model cancer systems, preclinical or clinical research, or from population based research. Technologies suited for this solicitation, include those that enable the detection of alterations and instabilities of genomic DNA; measurement of expression of genes and gene products; analysis and detection of gene and or cellular products including differential expression, quantitation, post translational modification, and function of proteins; identification of exogenous infectious agents in cancer; and assaying the function or major signal transduction networks involved in cancer. Additionally, technologies that will support molecular analysis in vitro, in situ, or in vivo (by imaging or other methods) are suitable for this PA. Technologies are defined as instrumentation, techniques, devices and analytical tools (e.g., computer software) but are distinct from resources such as databases and tissue repositories. This program will utilize the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) mechanisms, but will be run in parallel with a program of identical scientific scope that will utilize the newly created Phased Technology Application Award (PAR-99-102). The SBIR and STTR applications received in response to this announcement will undergo expedited review, have the opportunity for expedited transition of successful Phase I proof of principle into an expanded technology application phase, and will be subject to cost and duration limits comparable to the parallel Phased Technology Application Award applications. This program announcement must be read in conjunction with the Omnibus Solicitation of the Public Health Service for Small Business Innovation Research Grant Applications (PHS 99-2), and the Omnibus Solicitation of the National Institutes of Health for Small Business Technology Transfer Grant Applications (PHS 99-3). All of the instructions within the Omnibus Solicitations apply with the following exceptions: Special receipt dates Initial review convened by the NCI Division of Extramural Activities Additional review considerations Opportunity for 2 years of Phase I support HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of Healthy People 2000, a PHS-led national activity for setting priority areas. This PA, Innovative Technologies for the Molecular Analysis of Cancer: SBIR/STTR Initiative, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001- 00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800), or at http://www.crisny.org/health/us/health7.html. ELIGIBILITY REQUIREMENTS Eligibility requirements for SBIR and STTR are described in the NIH Omnibus Solicitation for SBIR/STTR grant applications. As stated in the REVIEW CONSIDERATIONS section, applications submitted in response to this PA will be reviewed by one or more NCI Special Emphasis Panels convened especially for this solicitation. MECHANISM OF SUPPORT This PA will expire two years from the initial receipt date as indicated by the dates on the front of this solicitation. Responsibility for the planning, direction and execution of the proposed project will be solely that of the applicant. Awards will be administered under NIH grants policy stated in the NIH Grants Policy Statement, NIH publication 99-8 October 1998. A. FAST-TRACK APPLICATIONS. Applications may be submitted for the FAST-TRACK review option. Information on the FAST-TRACK process may be found at: http://www.nih.gov/grants/funding/sbir.htm. Applications will be accepted only on the receipt dates listed on the first page of this document. To be eligible for the FAST-TRACK option, the Phase I (R41/43) application must include well defined quantifiable milestones that will be used to judge the success of the proposed research, as well as a credible plan to apply the selected technology in a pilot study of biological interest to cancer research for the Phase II R42/44 application. The FAST-TRACK must have a section labeled Milestones at the end of the Research Plan Phase I R41/43. This section must include well-defined quantifiable milestones for completion of Phase I R41/43, a discussion of the suitability of the proposed milestones for assessing the success in Phase I R41/43, and a discussion of the implications of successful completion of these milestones on the proposed Phase II R42/R44. Applications submitted through the FAST-TRACK option are subject to the same direct cost limits per year as when submitted outside of the FAST-TRACK option: Phase I R41/43, not to exceed $100,000 per year total direct costs excluding subcontractor indirect costs; Phase II R42/44, no dollar limit. However, the total duration (Phase I plus Phase II applications) cannot exceed four years. In any case, the Phase I application cannot exceed two years duration. B. INDIVIDUAL PHASE I APPLICATIONS. Phase I applications in response to this PA will be funded as Phase I SBIR Grants R43 or STTR Grants R41 with modifications as described below. Applications for Phase I grants should be prepared following the directions for Phase I SBIR/STTR applications as described in the NIH Omnibus Solicitation. The NIH Omnibus SBIR Solicitation is available on the Internet at: http://www.nih.gov/grants/funding/sbir1/sbir.htm. The NIH OMNIBUS STTR Solicitation is available at: http://www.nih.gov/grants/funding/sttr1/toc.htm. A limited number of hard copies of the NIH Omnibus SBIR and STTR Solicitations are available from: PHS SBIR/STTR Solicitation Office 13685 Baltimore Avenue Laurel, MD 20707-5096 Telephone: 301-206-9385 FAX: (301) 206-9722 Email: a2y@cu.nih.gov Project Period and Amount of Award. Because the length of time and cost of research involving advanced technology projects often exceeds that normally awarded for SBIR/STTR grants, NCI will entertain well-justified Phase I applications with a project period up to two years and a budget not to exceed $100,000 per year direct cost (maximum of $200,000 direct costs for to 2 years excluding subcontractor indirect costs). Page Limitations. The requirements for normal Phase I applications apply (see NIH OMNIBUS Solicitation). C. INDIVIDUAL PHASE II APPLICATIONS Phase II applications in response to this PA will be awarded as Phase II SBIR Grants R44 or STTR Grants R42 with modifications as described below. Phase II applications in response to this PA will only be accepted as competing continuations of previously funded NIH Phase I SBIR/STTR awards. The Phase II application must be a logical extension of the Phase I research. Applications for Phase II awards should be prepared following the instructions for NIH Phase II SBIR/STTR applications. The Phase II SBIR instructions and application may be found on the Internet at: http://www.nih.gov/grants/funding/sbir2/index.htm. The Phase II STTR instructions and application may be found on the Internet at: http://www.nih.gov/grants/funding/sttr2/index.html Project Period and Amount of Award. Because the length of time and cost of research often exceeds that normally awarded for SBIR grants, NCI will entertain well-justified Phase II applications for this SBIR/STTR award with a project period up to three years with no budget limitation. Applications over $500,000. Although the Phase II application has no official budgetary limit, applications requesting in excess of $500,000 dollars direct costs in any single year of the grant period require prior approval before submission. Applicants who plan to submit a Phase II SBIR/STTR application requesting $500,000 or more in any year are advised that it is important that they contact program staff listed under INQUIRIES as they begin to develop plans. Applications requesting more than $500,000 received without prior staff contact may be delayed in the review process or returned to the applicant without review (NIH GUIDE, Volume 22, Number 45, December 17, 1993). BACKGROUND Rapid molecular analysis tools will expedite the molecular characterization of normal cells from precancerous, cancerous, and metastatic cells, as well as, expand our understanding of the biological basis of cancers. Comprehensive analysis of cancers at the molecular level will facilitate cancer detection and diagnosis, as well as identify new targets for therapeutic and preventative agents. The definition of the molecular alterations in cancer will require the continued development and dissemination of comprehensive molecular analysis technologies as well as identification of all of the molecular species encoded in genomes of cancer and normal cells. To this end, the NCI has established the Cancer Genome Anatomy Project (CGAP), which will put in place the research infrastructure that will allow deciphering of the molecular anatomy of a cancer cell at the DNA, RNA and protein levels. The NCI has established the Tumor Gene Index, an index identifying the genes that are expressed in normal, precancerous, and cancerous cells. This project is well under way and further information about the Index can be found at http://www.ncbi.nlm.nih.gov/ncicgap. The NCI has also begun a project to identify cancer chromosome aberrations (Cancer Chromosome Aberration Project, CCAP). The NCI has started the generation of a public repository of a standardized set of bacterial artificial chromosome (BAC) clones anchored across the whole human genome at 1 megabase intervals, for the identification of cancer chromosomal aberrations and reference points/landmarks clones for the integration of cancer chromosome aberrations and genomic data. Information on the repository and reagent access will be released on CCAP homepage (http://www.ncbi.nlm.nih.gov/). The NCI is also targeting the support for the development and dissemination to basic, preclinical, and clinical researchers of novel technologies that will allow high-throughput analysis of genetic alterations, expression of genome products, and monitoring of signal transduction pathways in cancers. A complimentary program on "Innovative Technologies for the Analysis of Cancer" to support technology development was announced in May 1998 and has recently been reissued for the next two years. This initiative, "Applications of Innovative Technologies for the Molecular Analysis of Cancer" is intended to support the demonstration that newly developed and emerging technologies have matured and are suitable for use in cancer research, followed by the initial application of these technologies in well- defined studies of biological interest to cancer research using model cancer systems, preclincial or clinical samples, or in population research. The routine use of improved molecular analysis tools will lead to a better understanding of the molecular basis of cancer, and will facilitate the identification of molecular characteristics of individuals, that influence cancer development and prognosis. Molecular analysis technologies of interest include those that will support: A more complete understanding of the biological basis of cancer. The identification of molecular variations between normal, precancerous, cancerous, and metastatic cells that can serve as targets for the detection, diagnosis, therapy, and prevention. An examination of genetic factors that influence an individual's likelihood to develop cancer or their ability to respond to external damaging agents, such as radiation and carcinogens. The molecular correlation between individuals with therapeutic or toxic responses to treatment and prevention measures and genetic factors that influence the efficacy and safety of these strategies and agents (pharmacogenomics). Identification of molecular markers in the individual that correlate with the body's response to the onset or clearance of disease and the development of biomarkers to track and even image the efficacy of therapy (therametrics) and prevention, as well as the onset of secondary cancers. Tracking of the damage to the genome from exogenous agents such as carcinogens, radiation, and existence of exogenous infectious agents resident in cancer cells. The comprehensive molecular analysis of cancer will require: High through put analysis strategies to elucidate the processing and expression of genetic material in the cell. Detection of molecular changes in the cell without preconceived ideas about which information will be most valuable to monitor. Adequate adaptations to accommodate technical issues specific to the study of cancer in vitro and in vivo, such as limited cell number, sample heterogeneity, heterogeneity of specimen types (i.e. bodily fluids and waste, tissues, cells) Adaptation of novel technologies for use in cancer research, including use on tumor specimens, in patient imaging, and in population research. Integration of sample preparation components that maintain the efficiencies of the assay system and effectively accommodate human tumor specimens. Data analysis tools for interpreting the information from highly multiplexed molecular analyses. Novel technologies for comprehensive molecular analysis are being developed. Many of these technologies have not yet been demonstrated to have utility or cost effectiveness in application to cancer model systems, cancer specimens, or in population-based research. It will be necessary to demonstrate that relevant technologies have adequate sensitivity to discriminate differences between tumors and normal tissues, and tumors of different stages. Therefore, the need exists to demonstrate the ability of emerging molecular analysis technologies to provide routine assay performance, adequate sensitivity and discrimination, and associated robust data analysis tools, that can be adapted to basic, pre- clinical, and clinical research settings for the purpose of cancer research. Translation of new in vitro technologies for the multiplexed analysis of molecular species in clinical specimens will require a multidisciplinary team approach with broad expertise in a variety of research areas. Such varied expertise, potentially including but not limited to, expertise in pathology, specimen acquisition and preparation, informatics and biostatistics exists in ongoing cancer centers and clinical trials cooperative groups. The coordination and collaboration of investigators from these various disciplines to demonstrate the utility and applicability of new analytical tools in clinical and population based studies is considered to be a high priority. Existing technologies for molecular analysis are also largely restricted to in vitro analysis. While these systems are suitable for discovery and many basic and clinical research questions, they are limited in their ability to offer information relative to molecular changes in real time and in the appropriate context of the intact cell or body. Imaging in situ or in vivo is becoming increasingly important for extending molecular analysis of early cancer formation. The application of high-resolution imaging at the cellular or molecular levels to, tissue samples, pre-clinical models, or human investigations is therefore considered to be an important extension of molecular analysis methods. Similarly, the application of molecular probes for imaging molecular events is also of interest for pre-clinical and human investigations. Finally, the use of molecular contrast enhancement techniques, such as contrast modifications of gene expression are considered critical to improve the sensitivity of detection of molecular changes in vivo. The molecular imaging methodologies proposed, including hardware and software, are specifically understood as being within the context of molecular analysis tools. They include specialized high resolution or microscopic imaging methods dedicated to detection and analysis of molecular events related to cancer formation or as applied to pre-clinical drug discovery. Improvements in these areas will bring capabilities for real time molecular analysis at whole body levels. Investigations of tumor models that do not target molecular species are not responsive to this application. Investigators are encouraged to contact NCI program staff for further information. RESEARCH OBJECTIVES The National Cancer Institute (NCI) invites applications for research projects to evaluate the utility and pilot the application of newly developed molecular analysis technologies in studies relevant to cancer research. The Program Announcement (PA) provides support for a first phase for technology evaluation and a second phase for pilot application of the technology in a study of biological interest to cancer research. The first (evaluation) phase should include proof of principle experiments that will demonstrate the utility of the technology on samples comparable to those that will be used in the second phase study. Applicants will be expected to demonstrate the utility of all components of the process required for a fully integrated system, including sample preparation, molecular analysis assay, and data capture and analysis. The second (application) phase supports the transition of the technology optimized in the first (evaluation) phase to pilot application in a study of biological interest to cancer research. The design of the second phase study should allow the demonstration that the technology can reproducibly obtain molecular data from the selected sample type and produce information of biological interest to cancer research. Studies might appropriately target analysis of precancerous, cancerous, or metastatic cells, or host derived samples, from model cancer systems, preclinical or clinical research, or from population based research. The application of new tools that support the comprehensive molecular characterization of normal, precancerous, cancerous, and metastatic cells, as well as the identification of new targets for detection, diagnosis, preventative, and therapeutic strategies, is needed to support the basic discovery process and the translation of basic discoveries to pre-clinical and clinical research. Application of improved molecular analysis technologies will also allow a more thorough examination of the variations that influence predisposition to cancer, and individual variability in response to therapeutic and prevention agents as well as the identification of exogenous infectious agents that may be associated with the development of cancer. Examples given below are not intended to be all- inclusive, but are illustrative of the types of molecular analysis capabilities that are of interest for evaluation and pilot application in response to this solicitation. --In vitro identification and characterization of sites of chromosomal aberrations, which arise from inherited or somatic alterations resulting from aging or oxidation, or exposure to radiation or carcinogens, including those that are suitable for scaling for use across whole genomes, detecting DNA adducts, detecting rare variants in mixed populations, or identifying infrequently represented mutations in mixed populations of DNA molecules. --Detection and characterization of nucleic acid sequences of novel exogenous infectious agents including viruses, bacteria or other microscopic forms of life that may be etiologic factors or co-factors in the initiation and/or progression of human cancers. New technologies are demonstrating that microorganisms may play a more important role in the initiation of malignancies than was previously appreciated. --In vitro scanning for and identification of sites of mutations and polymorphisms which reflect inherited aberrations or somatic alterations resulting from aging or oxidation, or exposure to radiation or carcinogens, including those that are suitable for scaling for screening whole genomes, detecting DNA adducts, of identifying infrequently represented mutations in mixed populations of DNA molecules. -- Highly specific and sensitive detection of specific mutations in multiplexed high through put analysis. -- Detection of mismatch and recombinational DNA repair anomalies related to cancer susceptibility, cancer progression, and drug sensitivity. -- In vitro multiplexed analysis of the expression of genes. -- Computer assisted quantitation of gene expression. -- In vitro detection of expression of proteins and their post-translationally modified forms, including technologies suitable for expansion to profiling of all proteins expressed in cells, detecting rare variants in mixed populations, and detecting protein adducts involved in chemical mutation. --Assaying the function of proteins and genetic pathways, including measurement of ligand-protein complexes and technologies for monitoring protein function of all members of a class of proteins or members of a complete genetic pathway. Translation of the utility of the technologies described above and basic research findings into tools for pre-clinical and clinical applications requires additional technological innovation with regard to sample preparation, enhanced sensitivity, and expanded data analysis tools. Of interest is the evaluation and application of technologies suitable for: -- Detection, quantification and analysis of DNA mutations and polymorphisms and functional proteins in clinical specimens (e.g., tissue, serum, plasma, nipple aspirates, bronchioalveolar lavage, sputum, urine, pancreatic juice, colonic wash, and bladder wash). --Imaging in situ or in vivo in order to extend molecular analysis to early cancer formation. The application of high-resolution imaging at the cellular or molecular levels to, tissue samples, pre-clinical models, or clinical investigations are therefore considered to be an important extension of molecular analysis methods. Similarly, the application of molecular probes for imaging molecular events is also of interest for pre-clinical and human investigations. Finally, the use of molecular contrast enhancement techniques, such as contrast modifications of gene expression are considered critical to improve the sensitivity of detection of molecular changes in vivo. The molecular imaging methodologies proposed, include hardware and software, are specifically understood as being within the context of molecular analysis tools. They include specialized high resolution or microscopic imaging methods dedicated to detection and analysis of molecular events related to cancer formation or as applied to pre-clinical drug discovery. Improvements in these areas will bring capabilities for real time molecular analysis at whole body levels. The Phase I proposal supports a first phase for technology evaluation. Applicants should describe proof of principle experiments that will demonstrate the utility of the technology. The applicant should: Demonstrate performance of the selected technology on samples comparable to those to be used in the Phase II study. Have a detailed plan to optimize and troubleshoot the technology for complete adaptation of the technology for the Phase II pilot application. Discuss how they will evaluate cost effectiveness of the technology relative to existing and competing technologies. Specifically address approaches to sample preparation, molecular analysis assays, data collection, and data management. Applicants must include in a separate section the milestones to be accomplished in the first phase of the application. Milestones are separate from specific aims. They provide a clear measure of the success of the Phase I application which is necessary to proceed to the second phase, therefore they should be clearly stated and presented in a manner that is easily quantifiable. The Phase II study is intended to support the pilot application of technology evaluated and refined in the Phase I proposal, to a study of biological interest to cancer research. Technology developers are strongly encouraged to seek collaborations with qualified cancer researchers. In the Phase II proposal the applicants should: Describe how they will assess the performance of the technology in providing useful molecular data relative to existing technologies. Provide a more refined plan detailing the questions to be asked by the study and how the forthcoming data will be translated, either directly or indirectly, into information relevant to the study of cancer. Comment in detail on the suitability of the study design (i.e., numbers, types of samples) for asking the biological questions posed by the study. This should be discussed in the context of information and data to be obtained from Phase I studies. The study design parameters (i.e., number of samples, data analysis, etc.) should be a of a scale to reflect that this is a pilot application of the technologies. Clearly define what is considered to be a high quality-sample for the technology to be used. Document a strategy for obtaining access to high-quality samples that will be needed to carry out the study. Discuss the ease of transition of the technology from the Phase I to Phase II application with respect to scaling up the technology and implications related to sample cost, availability, and sample through-put. Effective data management and analysis will be critical to the successful and productive application of the proposed technology. Therefore applications must: Address the ability to acquire, store, analyze, and extract information from data collected through the course of the study. Demonstrate capabilities to utilize databases and to perform the complex mutliplex analysis an a data acquired through the course of the study. Describe bioinformatics, other analytical systems, and approaches that will be used to interpret data obtained from the study. Applicants are encouraged to discuss potential strategies for making resulting molecular data sets available to the cancer research community in both s reviewed-publication as well as in complete electronically accessible data sets. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided 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 research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH 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 clear and compelling 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 was published in the "NIH Guide for Grants and Contracts", March 6, 1998, and is available at the following URL address: http://www.nih.gov/grants/guide/notice-files/not98-024.html As part of the scientific and technical merit evaluation of the research plan, reviewers will be instructed to address the adequacy of plans for including children as appropriate for the scientific goals of the research. LETTER OF INTENT Prospective applicants are asked to submit, by the dates listed at the beginning of this program announcement, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the PA in response to which the application may be submitted. 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 avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Jay George at the address listed under INQUIRIES. APPLICATION PROCEDURES OMNIBUS SOLICITATIONS for both the SBIR and STTR programs are available electronically through the NIH, Office of Extramural Research Small Business Funding Opportunities web site at http://www.nih.gov/grants/funding/sbir.htm. Hard copies, subject to availability, may be obtained from the PHS SBIR/STTR Solicitation Office, phone (301) 206-9385; FAX (301) 206-9722; email a2y@cu.nih.gov. Helpful information for preparation of the application can be obtained: https://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf Applications are to be submitted on the grant application form PHS 6246-1 (1/99) (SBIR) and PHS 6246-3 (STTR) (3/99) located in the back pages of the OMNIBUS SOLICITATIONS, and will be accepted at the application deadlines as indicated on the first page of this document. THE TITLE AND NUMBER OF THIS PA MUST BE TYPED IN LINE 2 ON THE FACE PAGE OF THE APPLICATION. The OMNIBUS SOLICITATIONS give the normal levels of support and period of time for SBIR and STTR Phase I and II awards. However, these award levels are guidelines and not ceilings. Therefore, larger budgets with longer periods of time may be requested if required to complete the proposed research. As stated under MECHANISM OF SUPPORT section, Phase I applications submitted in response to this PA can have a project period of up to two years and a budget not to exceed $100,000 per year direct cost excluding subcontractor indirect costs. The second year of the Phase I budget should be included on the Budget Justification page, using categorical totals if costs deviate significantly from the first year of the budget, with narrative justifications for the increase(s). If the second year simply escalates due to cost of living factors, a statement to that effect with the escalation factor should be included rather than categorical totals. Phase II applications submitted in response to this PA have no budget limitations. The total duration (Phase I and Phase II application) cannot exceed four years. An annual meeting of all investigators funded through this program will be held to share progress and research insights that may further progress in the program. Applicants should request travel funds in their budgets for the principal investigator and one additional senior investigator to attend this annual meeting. In order to apply for the FAST-TRACK option, applications for both Phase I and Phase II must be submitted together according to the instructions for FAST TRACK applications as described in the OMNIBUS SOLICITATIONS. The Phase I application must specify clear, well-defined quantifiable milestones that should be achieved prior to Phase II funding. Milestones should be located in a separate section at the end of the Research Plan of the Phase I and should be indicated in the Table of Contents. Failure to provide measurable milestones and sufficient detail may be sufficient reason for the peer review committee to exclude the Phase II application from FAST-TRACK review. If so, at a later date, the applicant may apply for Phase II support through normal application procedures. Such applications will be reviewed by a standard Study Section of the Center for Scientific Review or by a special review group convened in response to a re- issuance of this PAR, if applicable. An additional requirement of the FAST-TRACK mechanism is the Product Development Plan. The small business must submit a concise Product Development Plan (limited to five pages) as an Appendix to the Phase II application addressing the four areas described in the instructions for FAST-TRACK applications in the OMNIBUS SOLICITATIONS. In the event that an applicant feels that technology is too proprietary to disclose, applicants at a minimum should provide a demonstration (e.g., results) of the capabilities of the proposed technology. The completed original application and one legible copy must be sent or delivered to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) To expedite the review process, at the time of submission, send one additional copy of the application to: Ms. Toby Friedberg Referral Officer National Cancer Institute 6130 Executive Boulevard, Room 636a, MSC 7405 Bethesda, MD 20892-7405 Rockville, MD 20852 (for overnight/courier service) Telephone: (301) 496-3428 FAX: (301) 402-0275 Applications must be received by the receipt dates listed at the beginning of this program announcement. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the CSR for completeness and by the NCI program staff for responsiveness. Applications not adhering to application instructions described above and those applications that are incomplete or non-responsive as determined by CSR or by NCI program staff will be returned to the applicant without review. Applications that are complete and responsive to the PA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI in accordance with the review criteria stated below. As part of the initial merit review, all applicants will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit generally the top half of the applications will be discussed, assigned a priority score, and receive a second level review by the National Cancer Advisory Board (NCAB). Review Criteria. Review criteria are described in the NIH Omnibus Solicitation and are as follows: 1. The soundness and technical merit of the proposed research. (Preliminary data are not required for Phase I proposals. 2. The qualifications of the proposed principal investigator, supporting staff, and consultants. 3. The scientific, technical, or technological innovation of the proposed research. 4. The potential of the proposed research for commercial application or societal impact. 5. The appropriateness of the budget requested. 6. The adequacy and suitability of the facilities and research environment. 7. Where applicable, the adequacy of assurances detailing the proposed means for safeguarding human or animal subjects and/or (b) protecting against or minimizing any adverse effect on the environment. For Fast-Track, Phase I application should specify clear, well defined quantifiable milestones that should be achieved prior to initiating Phase II. Failure to provide clear, measurable milestones may be sufficient reason for the study section to judge the application non-competitive. In addition to the standard review criteria as described in the NIH Omnibus Solicitation, the reviewers will comment on the six following aspects of the application in their written critiques in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered by the reviewers in assigning the overall score weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority 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. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? To what degree does the technology support the needs of the targeted research community? For systems intended for clinical research the additional criteria will be considered: to what degree is the analysis system appropriate for clinical research and likely to have utility for the analysis of clinical specimens or patients? Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Milestones. How appropriate are the proposed milestones against which to evaluate the demonstration of feasibility for transition to the Phase II application? Innovation. Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? What is the throughput and cost effectiveness or expanded capabilities of the proposed technology? Investigator. Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? The initial review group will also examine: the appropriateness of the proposed project budget and duration; the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects; the provisions for the protection of human and animal subjects; and the safety of the research environment as well as the adequacy of plans for including children as appropriate for the scientific goals of the research, or justification for exclusion (see section on NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS). AWARD CRITERIA Applications will compete for available funds with all other approved SBIR and STTR applications. Funding decisions for Phase I will be based on quality of the proposed project as determined by peer review, availability of funds, and program priority. Fast-Track Phase II applications may be funded following submission of the Phase I progress report and other documents necessary for continuation. Phase II applications will be selected for funding based on the initial priority score, NCI's assessment of the Phase I progress and determination that Phase I milestones were achieved, programmatic relevance the project potential for commercial success, and the availability of funds. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Jay George Ph.D. Office of Technology and Industrial Relations National Cancer Institute 31 Center Drive, Room 11A03, MSC 2590 Bethesda, MD 20892-2590 Telephone: (301) 496-1550 FAX: (301) 496-7807 Email: jgeorge@mail.nih.gov Direct inquiries regarding fiscal matters to: Ms. Kathleen Shino National Cancer Institute Executive Plaza South, Room 243 6120 Executive Boulevard Bethesda, MD 20892-7150 Telephone: (301) 496-7800, ext. 248 FAX: (301) 496-8601 Email: shinok@gab.nci.nih.gov Direct inquiries regarding review matters to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard, Room 636 Bethesda, MD 20892-7150 Telephone: (301) 496-3428 FAX: (301) 402-0275 Email: tf12w@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.394, Cancer Detection and Diagnosis Research. Awards are made under authorization of the Sections 301 and 405 of the Public Health Service Act, as amended (42 USC 241 and 284) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 and part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke- free workplace and promote the non-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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Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
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