and Human Services (HHS)
EXPIRED
EXPLORATORY STUDIES IN CANCER DETECTION, DIAGNOSIS AND PROGNOSIS RELEASE DATE: October 3, 2002 PA NUMBER: PA-03-003 (This PA has been reissued, see PA-05-165) EXPIRATION DATE: September 16, 2005. National Cancer Institute (NCI) (http://www.nci.nih.gov/) This Program Announcement (PA) replaces PA-01-010, which was published in the NIH Guide on October 31, 2000. THIS PA CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanism(s) of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE OF THIS PA The Division of Cancer Treatment and Diagnosis and the Division of Cancer Prevention of the National Cancer Institute invite research grant applications from interested investigators to explore innovative strategies for the early detection of cancer, assessment of cancer prognosis or prediction of response to cancer treatment. Advances in the understanding of basic cancer biology and the development of powerful molecular technologies are leading to the identification of many new abnormalities in precancerous and cancer cells. This initiative promotes the initial evaluation of molecular or cellular characteristics in human specimens and/or the development of assays that may result in important advances in the detection, diagnosis and treatment of cancers. The objective of this Program Announcement is to encourage applications for exploratory (R21) grants from individuals who are interested in testing new ideas that are based on a sound scientific rationale and may advance progress in cancer detection and diagnosis. The R21 grant mechanism is utilized to support pilot projects or feasibility studies that may produce innovative advances in science. This Program Announcement replaces and supersedes PA-01-010, Exploratory Studies in Cancer Detection, Diagnosis and Prognosis. Investigators interested in laboratory correlative studies linked to clinical trials may also consider two additional Program Announcements from the National Cancer Institute: PA-98-099 (Correlative Studies Using Specimens from Multi-Institutional Treatment Trials) and PA-00- 047 (Quick-Trials for Novel Cancer Therapies). Exploratory studies focused on cancer imaging, including new imaging modalities, agents and analysis methods, are more appropriate for PA-01-030 (Exploratory/Developmental Grants for Diagnostic Cancer Imaging), sponsored by the NCI Biomedical Imaging Program. RESEARCH OBJECTIVES Background The National Cancer Institute is interested in the development and testing of improved methods for detecting characteristics of cancer that are useful for the clinical management of cancer patients or individuals at risk for developing cancer. Much of the work in the early stages of this development process is exploratory and descriptive, focusing on the search for molecular and cellular differences between tumors and premalignant or normal tissues. When differences are found, an attempt must be made to determine their clinical significance by correlating the changes with clinical parameters. The further development of an approach will be driven by its potential to answer clinical questions. It has been difficult for investigators to obtain support for early translational studies through the traditional research project grant(R01) mechanism. Such studies may not be sufficiently developed for a standard R01 grant application, may be more descriptive than mechanistic in nature, and may be considered high-risk. The exploratory grant (R21) mechanism is more appropriate for these investigations. We expect that results generated through these R21 grants will serve as a basis for planning futureclinical research project (R01) grant applications or NCI cooperative clinicaltrial group studies. Because the exploratory grant mechanism is designed to support innovative ideas, extensive preliminary data as evidence of feasibility are not required. However, the applicant must develop a sound research plan. The opportunity for discovery of new information about the behavior of premalignant or tumor cells in the human body and the potentialsignificance of the information to be obtained are major considerations in the evaluation. Research Goals and Scope The major goal of this initiative is to promote the initial evaluation of new molecular or cellular characteristics of premalignant cells or tumors or the development of assays that will be useful for cancer detection, diagnosis and/or prognosis. New biomarkers and laboratory assays are needed for cancer screening and risk assessment, for pathologic characterization of malignant tumors and assessment of disease prognosis, and for prediction and measurement of response to treatments, particularly with novel therapeutic or chemopreventive agents. Investigators are encouraged to pursue new clinical insights and to consider the full array of potentially informative biological characteristics of tumor cells and tissues. The investigator shouldprovide a strong rationale for proposing that a particular biomarker or assay has the potential to address a significant clinical problem. Investigators should propose innovative approaches to clinical questions or substantial improvements in existing strategies. For example, an investigator might propose to adapt and optimize an experimental assay technique for application to clinical specimens. Proof-of-principle studies might also include comparisons of assay formats (i.e., DNA-based vs. protein-based) in a clinical setting, or initial retrospective or prospective studies to correlate assay results with patient outcomes. Investigators are encouraged to employ robust techniques that could be rapidly and widely adopted. The laboratory assays must utilize human specimens. Where applicable, evidence of statistical support should be included to ensure proper correlation of laboratory measurements with clinical outcomes. This initiative is intended to support translational studies which identify promising new means for cancer detection and diagnosis and which provide the initial, critical information necessary to decide whether potential clinical utility justifies further investment. Applicants should explain the significance of the proposed research in terms of its potential for clinical application. Priority will be given to well-designed studies that will help us to differentiate those new markers and techniques that have potential clinical utility from those that do not. This Program Announcement is sponsored jointly by the Cancer Diagnosis Program and the Cancer Therapy Evaluation Program (Division of Cancer Diagnosis and Treatment) and the Cancer Biomarkers Research Group (Division of Cancer Prevention) of the National Cancer Institute. The Cancer Diagnosis Program supports research projects to develop better clinical tests to improve the assessment of cancer prognosis and guide the choice of cancer treatment. New methods are sought to refine the classification and staging of tumors, to clarify the influence of germ-line or other genetic mutations on the course of the disease, to predict the response of tumors to therapy and to monitor the recurrence of cancer. The Cancer Therapy Evaluation Program is interested in funding new mechanistic or correlative laboratory studies that are relevant toclinical studies and trials of cancer therapy and supportive care. The correlative studies must have a future clinical application such as development of new treatment strategies, predicting response to specific therapies, or selection of patients for therapies. Examples of correlative studies include, but are not limited to, analysis of predictive markers, pharmacogenetic studies, studies of drug resistance, and analysis of immune response. The Cancer Biomarkers Research Group, Division of Cancer Prevention, supports and facilitates a broad spectrum of research activities that address early development and initial validation stages of molecular biological and genetic biomarkers that can be applied in risk prediction, early detection and primary prevention of cancer. The NCI Tissue Expediter (http://www-cdp.ims.nci.nih.gov/expediter.html) can assist investigators in locating and determining appropriate human tissue resources for their research project. Applicants should remember that Federal and local regulations for the protection of human research subjects apply to the use of human tissue specimens in research, and these issues must be addressed in the application (refer to the instructions in the application kit). Additional information is available at http://www-cdp.ims.nci.nih.gov/brochure.html, and from the Office for Human Research Protections (http://www.hhs.gov/ohrp/). Applicants proposing research with human subjects must observe NIH policies regarding the inclusion of women, minorities and children (see below). MECHANISM OF SUPPORT This PA will use the NIH exploratory/developmental (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. The total project period for an application submitted in response to this PA may not exceed two years. These grants are non-renewable. Though the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $100,000 (four budget modules) per year unless the application includes consortium costs, in which case the limit is $125,000 direct costs (five budget modules) per year. This PA uses just-in-time concepts. It also uses the modular budgeting format since you are submitting an application with direct costs in each year not to exceed a maximum of $125,000. (see http://grants.nih.gov/grants/funding/modular/modular.htm). ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign o Faith-based or community based organizations INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/researchand financial or grants management issues: o Direct your questions about scientific/research issues to: Dr. James V. Tricoli Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, Room EPN 6035 Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Telephone: (301) 496-1591 FAX: (301) 402-7819 Email: [email protected] Dr. Sudhir Srivastava Cancer Biomarkers Research Group, Division of Cancer Prevention National Cancer Institute 6130 Executive Boulevard, Room EPN-330 F Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Telephone: (301) 435-1594 FAX: (301) 402-0816 Email: [email protected] Dr. Heng Xie Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, Room EPN 7009 Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Telephone: (301) 496-8866 FAX: (301) 480-4663 Email: [email protected] o Direct your questions about financial or grants management matters to: Eileen M. Natoli Grants Administration Branch National Cancer Institute 6120 Executive Blvd. EPS 243 Bethesda, MD 20892 Telephone: (301) 496-8791 Email: [email protected] SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). A letter of intent is not required and the page limits for the proposal are the same as those stipulated in the PHS 398 form. The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected]. All application instructions outlined in the PHS 398 application kit are to be followed, with the following requirements for R21 applications: 1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME" concepts, with direct costs requested in $25,000 modules, up to the total direct costs limit of $100,000 per year, unless the application includes consortium costs, in which case the limit is $125,000 direct costs per year. 2. Although preliminary data are not required for an R21 application, they may be included. 3. Sections a-d of the Research Plan of the R21 application may not exceed 25 pages, including tables and figures. 4. R21 appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism, and should not be used to circumvent the page limit for the research plan. Copies of appendix material will only be provided to the primary reviewers of the application and will not be reproduced for wider distribution. The following materials may be included in the appendix: o Up to five publications, including manuscripts (submitted or accepted for publication), abstracts, patents, or other printed materials directly relevant to the project. These may be stapled as sets. o Surveys, questionnaires, data collection instruments, and clinical protocols. These may be stapled as sets. o Original glossy photographs or color images of gels, micrographs, etc., provided that a photocopy (may be reduced in size) is also included within the 25 page limit of items a-d of the research plan. APPLICATION RECEIPT DATES: Applications submitted in response to this program announcement will be accepted at the standard application deadlines, which are available at http://grants.nih.gov/grants/dates.htm. Application deadlines are also indicated in the PHS 398 application kit. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications must be submitted in a modular grant format. The modular grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step- by-step guidance for preparing modular grants. Additional information on modular grants is available at http://grants.nih.gov/grants/funding/modular/modular.htm. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five 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) APPLICATION PROCESSING: Applications must be received by or mailed on or before the receipt dates described at http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not accept any application in response to this 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 a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique. PEER REVIEW PROCESS Applications submitted for this PA will be assigned on the basis of established PHS referral guidelines. An appropriate scientific review group convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit. 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 top 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 an appropriate advisory board or council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of your application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment The scientific review group will address and consider each of these criteria in assigning your application's overall score, weighting them as appropriate for each application. Your application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, you 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 this study address an important problem? If the aims of the application are achieved, how do they advance scientific knowledge? What will be the effect of these studies on the concepts or methods that drive this field? In this case, what is the potential for translation of basic research to clinical applications? (2) APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? This includes, where applicable, the statistical rationale for the study design and the choice of sample size. Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) INNOVATION: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to your experience level as the principal investigator and to that of other researchers (if any)? (5) ENVIRONMENT: Does the scientific environment in which your 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? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: PROTECTIONS: The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. INCLUSION: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children 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) DATA SHARING: The adequacy of the proposed plan to share data. BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended applications. 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 Relevance to program priorities REQUIRED FEDERAL CITATIONS 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. In addition, it is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring being 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 or 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 PA in a public archive, which 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 PA 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 , Cancer Detection and Diagnosis 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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