TRANSLATION OF TECHNOLOGIES TO DETECT ALTERATIONS IN HUMAN TUMORS Release Date: December 1, 1999 PA NUMBER: PAR-00-013 National Cancer Institute This Program Announcement (PA) replaces PAR-97-021, which was published in NIH Guide, Vol. 25, No. 44, December 20, 1996. PURPOSE The Technology Development Branch of the Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), invites Program Project grant applications (P01s) proposing the application of comprehensive molecular analysis technologies to tumor specimens to address questions of importance in clinical cancer research. This PA provides a mechanism for supporting continued refinement and application of the technologies produced under other NCI technology development initiatives. This program announcement is primarily targeted to technologies that are ready for translation to the analysis of clinical tissue specimens. NCI is aware that molecular analysis technologies are at varying stages of development and that it is unclear which technologies will best serve clinical research. This PA is targeted to those translational research projects that will benefit from a P01 structure. Investigators considering projects that do not require the P01 structure should consult with the Program Staff listed under Inquiries about other NCI initiatives supporting technology development and application. The PA encourages translational studies in which molecular analysis technologies, including nucleic acid- or protein-based technologies, will be adapted to the analysis of human clinical specimens. Application of these new or improved comprehensive technologies will allow investigators to effectively address questions in cancer diagnosis and prognosis, in selection of therapies for individual patients, and in monitoring response to therapy. The NCI’s intention is to promote an integrated team approach, where technology developers and cancer researchers will work closely together to refine and adapt technologies to develop clinically useful systems. The technical challenges of these projects are expected to require input from a diverse group of investigators, such as engineers, pathologists, molecular biologists, chemists, biologists, and informatics specialists. The process of moving the technologies forward toward clinical application will require input from clinical cancer researchers with access to clinical specimens. The goal of the program projects should be the development of integrated systems that can analyze molecular alterations in large numbers of human clinical specimens. This PA will be active for two years, up to and including the October 1, 2001 P01 receipt date. 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 Program Announcement (PA), Translation of Technologies to Detect Alterations in Human Tumors, 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, D.C. 20402-9325 (telephone 202-512-1800), or at http://odphp.osophs.dhhs.gov/pubs/hp2000. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit, and nonprofit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Applications may not be submitted by foreign institutions, however, an application from a domestic institution may include foreign components as research projects or core activities, as defined below under mechanism of support. Each application must be from a single institution but may include collaborating institutions. Collaborative projects between companies developing technologies and institutions with clinical resources and expertise are encouraged. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as Principal Investigators (PIs). MECHANISM OF SUPPORT This program announcement will use the National Institutes of Health (NIH) program project grant (P01) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The period of support for applications submitted in response to this PA may be for up to five years. This PA will be in effect for two years, up to and including the October 1, 2001 P01 receipt date. An application should be constructed using the P01 application guidelines of the NCI, which are available at http://deainfo.nci.nih.gov/awards/P01.pdf or from the NCI Referral Officer as described below under Application Procedures. The P01 mechanism is designed to support multiple, interacting projects focused on a central theme. P01s must have a minimum of three research projects and may include cores. A core is a separately budgeted component of a P01 that provides essential facilities or services to two or more of the proposed research projects. A core may not count as one of the three research projects. Collaborative funding arrangements with industry are encouraged, but detailed project descriptions must be provided even if no funds are requested for a project or core activity. P01s may support projects that are performed at multiple sites but coordinated by a single Principal Investigator at the grantee institution. An award will be made only to the PI’s institution. RESEARCH OBJECTIVES Background Recent advances in our understanding of cancer at the molecular level coupled with the on-going development of comprehensive molecular analysis technologies have great potential to change the way we diagnose and treat cancer patients. The process of developing and adapting comprehensive molecular analysis technologies for the analysis of clinical specimens is technically challenging, particularly in early-stage translational studies as attempts are made to employ the technologies to address clinical questions. Molecular analysis technologies have continued to develop rapidly since the initial release of this program announcement in December 1996. The past three years have seen an explosion in the development of microarray technologies and many other technologies for the simultaneous detection of multiple molecular alterations in tissues. These systems range from high- throughput approaches to mutation scanning to comprehensive, quantitative proteomics. The technologies have largely been developed using model systems, and most have been developed solely for the research market or for marketing to large pharmaceutical companies. Concurrently, cancer researchers have been increasingly interested in using comprehensive molecular analysis technologies to address clinical needs. This program announcement is designed to promote collaborations between clinical investigators and technology developers in the context of P01 grant applications. Research Goals and Scope This initiative invites program project (P01) grant applications proposing the continued development and adaptation of technologies for analysis of the spectrum of molecular alterations in human tumor tissues. Applications in response to this program announcement may propose to study any of a variety of technologies including comprehensive approaches to the detection of alterations in DNA, changes in patterns of gene expression at the level of both mRNA and proteins, or changes in post-translational modifications of proteins. Projects exploring relationships between alterations in genomic DNA sequence, mRNA expression level, protein expression level, or protein modification are also encouraged. This information will facilitate reaching the ultimate goal of discovering reliable molecular markers or targets for the detection, diagnosis, prognosis, and treatment of cancer. The long-term goal of this initiative is the development of integrated molecular analysis systems. Components of these systems are anticipated to include integrated technologies for specimen handling and preparation, analytical technologies, and integrated technologies for data management and analysis. However, when appropriate, projects may focus on development and adaptation of individual components of the molecular analysis system. Interdisciplinary research projects to be supported by this initiative will require collaborations between technology/instrument developers, clinicians, pathologists, basic scientists, and informatics specialists. This initiative encourages collaborations among commercial or academic organizations with appropriate genomics or proteomics programs in technology development and academic institutions with expertise and ongoing programs in cancer biology with the access to appropriate tumor tissue resources. Ideally, the program projects, through these collaborations, will result in the development of analytical systems with integrated sample handling and preparation, refined molecular analysis technologies, and informatics tools. These systems will be ready for analysis of molecular alterations in large numbers of human clinical specimens. 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 20, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994 , available on the web at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not94-100.html 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://grants.nih.gov/grants/guide/notice-files/not98-024.html LETTER OF INTENT Prospective applicants are asked to submit a letter of intent at least 60 days prior to the anticipated submission date. The letter should include 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 the program staff listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 4/98) and will be accepted on the standard P01 receipt dates of February 1, June 1, and October 1. Applications in response to this PA must be in conformance with the P01 APPLICATION GUIDELINES of the NCI (rev. 4/99), which are available via the World Wide Web at http://deainfo.nci.nih.gov/awards/P01.pdf and from the NCI Referral Officer identified under Inquiries. PHS 398 application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, e-mail: firstname.lastname@example.org. For those applicants with internet access, the 398 kit may be found at: http://grants.nih.gov/grants/forms.htm Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies in one package 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) At the time of submission, two additional copies of the application must be sent to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute 6116 Executive Boulevard, Room 8062, MSC 8239 Rockville, MD 20852 (express service) Bethesda, MD 20892-8239 The Center for Scientific Review (CSR) will not accept any application in response to the PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and responsiveness by the NCI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. 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, a process may be used by the initial review group in which all applications receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed assigned a priority score, and receive a second level review by the National Cancer Advisory Board. Review Criteria Review criteria used to evaluate P01 applications will be used in the review of these applications. Peer review of the overall scientific and technical merit emphasizes a synthesis of two major aspects: 1) review of the P01 as an integrated effort focused on a central theme and 2) review of the merit of individual research projects and core components in the context of the proposed P01. Applicants are strongly encouraged to study the evaluation criteria cited in the P01 GUIDELINES (referred to in APPLICATION PROCEDURES, http://deainfo.nci.nih.gov/awards/P01.pdf) before preparing their applications. AWARD CRITERIA Applications will compete for available funds with all other recommended applications assigned to the NCI. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Responsiveness to the goals and objectives of the PA INQUIRIES Inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Min H. Song, Ph.D. Division of Cancer Treatment and Diagnosis National Cancer Institute Executive Plaza North, Room 700 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 402-4185 FAX: (301) 402-7819 E-mail: email@example.com Direct inquiries regarding review issues to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute 6116 Executive Boulevard, Room 8062, MSC 8239 Rockville, MD 20852 (express service) Bethesda, MD 20892 - 8239 Telephone: (301) 496-3428 FAX: (301) 402-0275 E-mail: firstname.lastname@example.org Direct inquiries regarding fiscal matters to: Ms. Jill Rogers Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Rockville, MD 20852 (express mail) Bethesda, MD 20892 Telephone: (301) 496-8699 FAX: (301) 496-8601 E-mail: Rogersj@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.394, Cancer Detection and Diagnostic 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 NIH grants policies and Federal Regulations 42 CFR Parts 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The Public Health Service (PHS) strongly encourages all grant 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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