DEVELOPMENT OF NOVEL TECHNOLOGIES FOR IN VIVO IMAGING (PHASED INNOVATION AWARD) Release Date: May 29, 2001 (see replacement PAR-03-124) PA NUMBER: PAR-01-101 National Cancer Institute Letter of Intent Receipt Dates: June 11, 2001, February 11, 2002 and June 11, 2002 Application Receipt Dates: July 16, 2001, March 18, 2002, and July 16,2002 This PAR is a reissue of PAR-00-089, which was published in the NIH Guide on April 27, 2000. PURPOSE The National Cancer Institute (NCI) invites applications for the development of novel image acquisition or enhancement methods for in vivo oncology, and which incorporate limited pilot or clinical feasibility evaluations using either pre-clinical models or clinical studies. This initiative is primarily intended to facilitate the development of novel imaging technologies for early detection, screening, diagnosis or image guided treatment of cancer and to facilitate specifically limited evaluation studies to show proof of concept. Specific emphasis of this PAR is directed at (a) the development of highly innovative image acquisition and enhancement methods, including high risk/high gain research on technologies that exploit our knowledge of the molecular basis of cancer, and (b) the development of other novel imaging methods and the integration of these technologies with emerging molecular imaging methods, where appropriate, for more effective health care delivery. The primary motivation for this Program Announcement (PA) is that current technologies for the molecular analysis of disease are largely restricted to in vitro methods and need to be extended to the in vivo situation. Furthermore, the use of molecular probes or tracers for imaging molecular events in pre-clinical and clinical investigations are essential for detection of molecular changes in vivo. Developments of innovative, high-resolution imaging methods at the cellular or molecular scales are needed, with particular emphasis on identification and characterization of processes in the early formation of disease or early molecular changes during intervention or therapy. Integrations of these emerging molecular imaging methods with advances in traditional imaging methods are also required for more effective cancer investigations in vivo. This solicitation (Development of Novel Technologies for in vivo Imaging) will utilize the Phased Innovation Award Mechanism that is designed to encourage technology development. Specific features of this mechanism include: o Single submission and evaluation of both the R21 and R33 phases as one application. An R33 application also may be submitted alone. o Expedited transition from the R21 feasibility phase to the R33 development phase, based on successful completion of negotiated quantitative Milestones. o Flexible staging of feasibility (R21) and development (R33) phases. Applications from industry or industrial partnerships with other groups are encouraged. o Review of submissions by an NCI special study section, and expedited NCI program review for transition from the R21 to the R33 phase. Small businesses are encouraged to respond to the parallel PA, PAR-01- 102 (see http://grants.nih.gov/grants/guide/pa-files/PAR-01-102.html). Its objectives are identical, but it uses the Small Business Innovation Research (SBIR) and Small Business Technology Transfer Research (STTR) granting mechanisms. The same expedited review and transition from Phase I to Phase II funding apply, as do the same cost and time limits as this program announcement for Phased Innovation Awards. The National Center for Research Resources (NCRR) has recently issued a PA for Technology Development for Biomedical Applications: Phased Innovation Award (R21/R33), http://grants.nih.gov/grants/guide/pa-files/PAR-01-057.html. The NCRR phased innovation awards for medical technology developments include imaging developments that are not cancer or disease specific. BACKGROUND Significant advances in medical imaging technologies have been made over the last 25 years in such areas as magnetic resonance imaging (MRI), computed tomography (CT), nuclear medicine and ultrasound. However, these advances largely focused on structural or anatomical imaging at the organ or tissue level. Now there is a clear need and opportunity to stimulate the development and integration of novel imaging technologies that exploit our current knowledge of the genetic and molecular bases of cancer. Molecular biological discoveries have great implications for prevention, detection, and targeted therapy. Imaging technologies that can provide the same kinds of cellular and molecular information in vivo that are currently available only from techniques in vitro would be very useful. This is commonly known as in vivo molecular imaging. The need for NCI to encourage and support bioengineering and technology development by academic and industrial researchers was stressed by participants at several NIH- and NCI-supported forums over the past few years [Imaging Sciences Working Group (ISWG) July 1997; Lung Imaging Workshop: Technology Transfer, Jan 1997; Computer Aided Diagnosis and 3D Image Analysis, Oct 1998; Quantitative in-vivo Functional Imaging in Oncology, Jan 1999; Focus Group on Magnetic Resonance Spectroscopy (MRS) in Clinical Oncology, April 1999; and NIH BECON Symposium, June 1999]. The needs are to (a) promote the development of novel, high risk, high gain technologies, including continued support for their maturation and full exploitation, (b) promote system integration of technologies for targeted applications, including the development of a system prototype and small number of copies, as required, for research and clinical feasibility studies, and (c) improve technology transfer by promoting partnerships between academia and industry. Developments of novel imaging technologies usually will require multidisciplinary approaches to provide teams with broad expertise in a variety of research areas. Such varied expertise might include imaging physics, chemistry, molecular and cellular biology, informatics and biostatistics. The coordination and collaboration of investigators with the necessary variety of disciplines to demonstrate the utility and applicability of new imaging methods is encouraged. RESEARCH OBJECTIVES This initiative is primarily intended to facilitate the development of novel imaging technologies for early detection, screening, diagnosis or image guided treatment of cancer and to facilitate clinical evaluation studies of the development that are specifically limited to proof of concept. Specific emphasis of this PAR is directed at (a) developments of highly innovative image acquisition and enhancement methods, including high risk/high gain research on technologies that exploit our knowledge of the molecular basis of cancer, and (b) developments of other novel imaging methods and their integration with emerging molecular imaging methods, where appropriate, for more effective health care delivery. In particular, developments of innovative, high- resolution imaging methods at the cellular or molecular scales are needed for both pre-clinical models and clinical studies, with emphasis on identification and characterization of either the early formation of disease or early molecular changes during intervention or therapy. Methods that establish “ground truth” are required at appropriate levels of resolution to validate these emerging imaging methods. They may include the imaging of excised tissue using protocols similar to those used for imaging in vivo. Developments of probes or tracers are considered essential for detection of molecular changes in vivo to take better advantage of many technologies with potential for molecular imaging. The following objectives would make appropriate topics for proposed projects. This list is not meant to be all-inclusive. o Imaging to detect early changes. Developments of innovative high- resolution imaging methods at the cellular or molecular scales are encouraged, with a particular intent to identify and characterize pre- malignant abnormalities or other early changes, including molecular events on the path to disease. Novel solutions for in-vivo microscopic imaging systems, or microscopic implanted devices with high spatial, contrast and temporal resolution are encouraged. Similarly, developments of contrast enhancement methods and imaging probes are also encouraged. o Large scale screening applications for cancer may include, but are not limited to: development and optimization of efficient, low-cost imaging systems for rapid and automated large-scale screening with the intent of achieving significantly higher sensitivity and specificity for cancer detection are encouraged. Applications could address significant innovative improvements to current imaging methods or new emerging imaging sensors. Research topics of interest include, but are not limited to, technologies for molecular imaging, means to significantly reduce imaging time or motion effects, use of novel contrast agents or imaging probes, and use of technologies that do not involve ionizing radiation. System integration could include a variety of image processing techniques including temporal analysis of serial studies, close to real-time image processing, novel image display methods, and related imaging informatics and information reduction methods for more cost-effective solutions for screening. o Imaging for diagnosis, staging, or monitoring the effects of therapy. This initiative encourages, but is not limited to the development of novel imaging methods such as functional or molecular imaging or spectroscopy methods that would significantly improve the specificity of diagnosis of cancer, allow deterministic methods or patient-specific staging, or measure early effects of therapy. Examples of system integration would include image fusion or registration from the different modalities employed, development of software methods that would estimate the probability of malignancy or of other specific disease identification, quantitative information for monitoring the effects of therapy, and close to real-time image analysis. o Image guided biopsy (IGB), therapy (IGT), and interventional procedures. Novel approaches using imaging technologies are needed to significantly improve specificity, to identify lesion extent and microscopic involvement, and to minimize the tissue damage accompanying biopsy and therapy. Of particular interest are innovative approaches to IGB, IGT or interventional methods that include novel imaging systems that provide information at the cellular or molecular level. Examples of system integration that are of interest include, but are not limited to, navigational systems, registration methods for several imaging modalities, real-time feedback mechanisms for controlling therapy or the use of methods that are adaptive or allow patient-specific optimization of treatment and computer-assisted surgery. o The production of a limited number of systems based on the prototype may be supported to facilitate research aims that require pre-clinical or clinical investigations. Investigators anticipating this need are advised to contact program staff. MECHANISM OF SUPPORT The following are points to note about the mechanism of support and its implementation: o Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. o Awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, March 2001, available at http://grants.nih.gov/archive/grants/policy/nihgps_2001/index.htm. Hard copies are not available. Support for this program will be through the National Institutes of Health (NIH) Exploratory/Developmental Research Grant (R21) and the Exploratory/Developmental Research Grant Phase 2 (R33). The R33 is a relatively new NIH granting mechanism that provides a second phase of support to continue innovative exploratory and developmental research initiated under the R21 mechanism. Transition from the R21 to R33 phase will be expedited, and will depend on satisfactory completion of negotiated, quantitative R21 Milestones. o Under this PA, applicants can submit either a combined R21/R33 application (Phased Innovation Award application), or an R33 application alone if feasibility can be documented, as described in the APPLICATION PROCEDURES section, below. o Applications for R21 support alone will not be accepted, but may be eligible for submission under PA-01-030 (see http://grants.nih.gov/grants/guide/pa-files/PA-01-030.html). o The total project period for an application submitted in response to this PA may not exceed 4 years. Its components are limited as follows: R21, up to 2 years; R33, up to 3 years; combined R21/R33 application, up to 4 years. o For a combined R21/R33 application, the R21 phase may not exceed $100,000 direct costs per year. R21 budgets may exceed this cap to accommodate facilities and administrative costs to subcontracts to the project. The combined R21/R33 application offers two advantages over the regular application process: 1. Single submission and evaluation of both the R21 and R33 components as one application. 2. Minimal or no funding gap between the R21 and R33 budget awards. The award of R33 funds will depend upon program priorities, the availability of funds, and successful completion of negotiated, quantitative Milestones, as determined by NCI staff, who will take peer review recommendations into consideration. The R21 phase of the Phased Innovation Award must include (1) well- defined, quantifiable Milestones that will be used to judge the success of the proposed work to demonstrate the feasibility of the proposed technology development, and (2) a credible plan for the development of technology in the R33 phase. Include a separate section labeled “Milestones” at the end of the Research Plan of the R21 application. In addition to well-defined, quantifiable Milestones, include a discussion of the suitability of the proposed Milestones for assessing the success of the R21 phase, and a discussion of the implications of successful completion of these Milestones for the proposed R33 study. Examples of quantifiable milestones would be performance specifications of an imaging system, or anticipated characteristics required for suitable contrast agent performance, so that objective evaluations can be made of progress at the end of the R21 phase. Potential applicants are encouraged to access the PHS SBIR and STTR Omnibus Solicitation for information on eligibility requirements at the following website: http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, companies, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Houston Baker, Ph.D. Biomedical Imaging Program National Cancer Institute 6130 Executive Plaza, Suite 6000 Bethesda MD 20892-7412 Rockville MD 20852 (for express/courier service) Telephone: (301) 496 9531 FAX: (301) 480 3507 Email: firstname.lastname@example.org Direct inquiries regarding fiscal matters to: Kathleen J. Shino, M.B.A. Grants Administration Branch National Cancer Institute 6120 Executive Blvd, EPS 243 Bethesda MD 20892-7150 Rockville MD 20852 (for express/courier service) Telephone: (301) 846 1016 FAX: (301) 846 5720 Email: email@example.com Direct inquiries regarding review matters to: Ms. Toby Friedberg. Referral Officer National Cancer Institute 6116 Executive Boulevard, Room 8109, MSC 8236 Bethesda MD 20892-8236 Rockville MD 20852 (for overnight/courier service) Telephone: (301) 496 3428 FAX: (301) 402 0275 Email: tf12W@nih.gov LETTER OF INTENT Prospective applicants are asked to submit a Letter of Intent by the date listed at the beginning of this PA. It should provide the number and title of this program announcement, a descriptive title of the proposed research, the name, address, telephone number, and e-mail address of the Principal Investigator, and identify other key personnel and participating institutions. 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 to be sent to Dr. Houston Baker at the address listed under INQUIRIES, above. SCHEDULE Letter of Intent Receipt: June 11, 2001; February 11, 2002; June 11, 2002 Application Receipt Date: July 16, 2001; March 18, 2002; July 16, 2002 Peer Review Date: Oct-Nov, 2001; June-July, 2002; Oct-Nov, 2002 Review by National Cancer Advisory Board: February, 2002; September, 2002; February, 2003 Earliest Anticipated Start Date: March 2002; October, 2002; March 2003 APPLICATION PROCEDURES SPECIFIC INSTRUCTIONS FOR PREPARING THE COMBINED R21/R33 PHASED INNOVATION AWARD APPLICATION: Applications for R21/R33 grants are to be submitted on the grant application form PHS 398 and prepared according to the instructions provided unless specified otherwise within this section. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, 6701 Rockledge Drive, MSC 7910, Bethesda MD 20892-7910, telephone 301 435 0714, email: firstname.lastname@example.org. See also the website for PHS 398: http://grants.nih.gov/grants/funding/phs398/phs398.html The R21/R33 application must include specific aims for each phase and quantitative Milestones for the R21 component that would later help justify transition to the R33 phase. See below, Item d., "Research Design and Methods" for directions for including Milestones in the application. After funding and completion of the R21 phase, a comparison of progress with the R21 Milestones in an NCI expedited review will determine whether or not the R33 continuation grant should be awarded. Funds for R33 developments are contingent on program priorities, the availability of funds, and satisfactory completion of the negotiated Milestones. The expedited review may result in additional negotiations of award. The R21/R33 Phased Innovation Award application must be submitted as a single application, with one face page. Although it is submitted as a single application, it should be clearly organized into two phases. To provide a clear distinction between the two phases, applicants are directed to complete Sections a-d of the Research Plan twice: one write-up of Sections a-d and Milestones for the R21 phase, and Sections a-d again for the R33 phase. The Form 398 Table of Contents should be modified to show Sections a-d for each phase as well as the Milestones. There is a page limit of 25 pages for the composite a-d text (i.e., Sections a-d and Milestones for the R21 and Sections a-d for the R33 phase all must be contained within the 25-page limit). The initial review group will assign a single priority score to the combined R21/R33 application. Therefore, the clarity and completeness of the R21/R33 application with regard to the R21 feasibility Milestones and the specific goals of each phase are crucial. A weak R33 component will impact the evaluation of both phases of the R21/R33 application. Presentation of Milestones that are not sufficiently rigorous, and not quantitative, such as procedural research plans, may not permit adequate validation of the R21 feasibility studies and adversely affect reviewer opinions of the merit of the application. Page 1. Face Page of the application: Item 2. Check the box marked "YES" and type the number and title of this PA. Also indicate if the application is an R21/33 or R33. If for an R21/R33, follow the next set of instructions. If for an R33 alone, see instructions further below. Item 7a, DIRECT COSTS REQUESTED FOR INITIAL PERIOD OF SUPPORT: Insert the amount requested for first year R21 support in Item 7a. This PA does NOT use the "Modular Grant" and "Just-in-time" concepts. For the R21 phase of the combined R21/R33 application, direct costs are limited to a maximum of $100,000 per year for a maximum of two years. The award may not be used to supplement an ongoing project. The requested budget may exceed this cap to accommodate for Facilities and Administrative costs to subcontracts of the project. Item 8a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT: Insert the sum of all years of requested support for direct costs in Item 8a. For the R21 phase, direct costs requested for the proposed period may not exceed $100,000 per year for either one or two years of phase one R21 feasibility study support. The statement in item 7a above pertaining to subcontract costs also applies here. 2. Budget: The application should provide a detailed budget on Form Page 4, Initial Budget Period, for each of the initial years of the R21 and R33 phases (use two Form Page 4s, one for each phase) as well as a budget on Form Page 5 for the entire proposed period of support. Indicate on the Form pages which years are for R21 and which are for R33 support. All budgets should include written justifications for line items requested. 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. 3. Research Plan: A combined R21/R33 application should present two sets of research plans (items a through d), one of them for R21 feasibility studies, and the other for R33 developmental work. The entire Research Plan, consisting of two sets of items a through d, must fit within a 25-page limit. Item a., Specific Aims. The application must present specific aims that the applicant considers technically or scientifically appropriate for the relevant phases of the project. The PHS 398 instructions for this section of research grant applications suggest that the applicant state the hypotheses to be tested. Since the goal of this PA is the development of innovative imaging technologies, hypothesis testing per se may not be the driving force in developing such a proposal, and therefore, may not be applicable. For the R21 portion of the grant application, preliminary data are not required, although they should be included when available. Item d., Research Design and Methods. Follow the PHS 398 instructions. In addition, for the R21 phase only, the following information must be included as a final section of Item d: Applications must include a specific section labeled Milestones following the Research Design and Methods section of the R21 component of the application. Milestones are to be appropriate measures of whether the specific aims have been accomplished and proof of principle established upon completion of the R21 phase of work. Milestones should be well described, quantifiable, and technically or scientifically justified. They are not to be simply a restatement of the specific aims or be procedural in nature. A discussion of the Milestones relative to the success of the R21 phase, as well as the implications for successful completion of the Milestones for the R33 phase, should be provided. The page number of the Milestones section should be listed on the Table of Contents page. Applications lacking adequate Milestone information, as determined by the NCI program staff, will be returned to the applicant without review. SPECIFIC INSTRUCTIONS FOR PREPARATION OF THE R33 APPLICATION WHEN SUBMITTED WITHOUT THE R21 PHASE. Applications for R33 grants are to be submitted on the grant application form PHS 398 and prepared according to the instructions provided unless specified otherwise within items 1-5 below. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: email@example.com. See also the website for PHS 398: http://grants.nih.gov/grants/funding/phs398/phs398.html Face Page of the application: Item 2. Check the box marked "YES," type the number and title of this PA, and indicate R33. Budget: The application should provide a detailed budget on Form Page 4, Initial Budget Period, for the initial year of the R33 phase as well as a budget on Form Page 5 summarizing the initial year and any subsequent years (for up to three years). All budgets should include written justifications for line items requested. Research Plan: Item a., Specific Aims. The PHS 398 instructions for this section of research grant applications suggest that the applicant state the hypotheses to be tested. Because the goal of this PA is to develop innovative technologies, hypothesis testing per se may not be the driving force in developing such a proposal, and therefore, may not be applicable. Item c., Preliminary Studies/Progress report This section must document that feasibility (proof of principle) studies have been completed, and progress achieved that is equivalent to that expected through the support of an R21 project. The application must clearly describe how the exploratory/developmental work already performed is ready to scale up to an expanded developmental stage. In the event that an applicant feels that the technology is too proprietary to disclose, at a minimum the application should provide a demonstration (results) of the capabilities of the proposed technology development. Ideally, performance capabilities of the proposed technology, or quantitative performance characteristics, that may be objectively evaluated should be provided, and compared with the published literature. Item d., Research Design and Methods Follow the PHS 398 instructions. FOR ALL APPLICATIONS Clinical Trials: All clinical trials supported by any NIH Institute or Center require some form of safety monitoring plan. The method and degree of monitoring to be included in the plan should be commensurate with the degree of risk involved, 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 and in addition to the requirement for human subject study review and approval by an Institutional Review Board (IRB). For details about the Policy of the NCI for Data Safety Monitoring of Clinical Trials, see http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. For additional information, see http://grants.nih.gov/grants/guide/notice-files/not98-084.html and http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html. 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 (20817 for overnight express or courier service) At the time of submission, two additional copies of the application must be sent to: Ms. Toby Friedberg Referral Officer National Cancer Institute 6116 Executive Boulevard, Room 8109, MSC 8236 Bethesda MD 20892-8236 Rockville MD 20852 (for overnight express or courier service) Telephone: (301) 496 3428 FAX: (301) 402 0275 The Center for Scientific Review (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 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 by the CSR for completeness, and by NCI program staff for adherence to the guidelines of this PA. Applications not adhering to application instructions described above and those applications that are incomplete 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 applications will 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 Advisory Council or Board. 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 the application 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 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 judge likely to have 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. 1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will in vivo imaging technology or 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 for the targeted disease? 2. Approach. Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? What is the time frame for developing the proposed technologies, and suitability of this time frame for meeting the community's needs? How easy will it be to use the proposed technology? Are the plans adequate for the proposed technology, its integration as an effective solution for implementation, and dissemination? If industrial partnerships are proposed, how will they facilitate the development and integration of system components? 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? What additional uses can be projected for the proposed technology? 4. Investigator. Is the principal investigator appropriately trained and well suited to direct or carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? 5. Environment. Does the technical and scientific environment in which the work will be performed contribute to the probability of success? Does the proposed work take advantage of unique features of the technical and scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? Additional Considerations Milestones (for R21/R33 applications) and Proof of Principle (for R33 applications). For the R21/R33 applications, how appropriate are the proposed Milestones against which to evaluate the demonstration of feasibility for transition to the R33 development phase? For the R33 applications, how well has feasibility or proof of principle been demonstrated? For the R21/R33 Phased Innovation Award Application, the initial review group will evaluate the specific goals for each phase and the feasibility Milestones that would justify progression to the R33 phase. A single priority score will be assigned to each scored application. As with any grant application, the initial review group has the option of recommending support for a shorter duration than that requested by the applicant, and basing the final merit rating on the recommended portion of the application. This may result in a recommendation that only the R21 phase of the combined R21/R33 application be supported, based on the relative merit of the two research plans, adequacy of the milestones for determining the success of Phase I feasibility studies and capacity to provide easily assessed justification for progression to the R33 phase without further peer review. The Initial Review Group may recommend modifications to or the addition of milestones. Deletion of the R33 phase by the review panel or inadequate Milestones may affect the merit rating of the application. In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o 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. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered for award on the basis of (a) quality of the proposed project as determined by peer review; (b) availability of funds; and (c) program priority. 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 sub- populations 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 to indicate 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 UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The revisions relate to NIH defined Phase III clinical trials and require a) all applications or proposals and/or protocols to 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) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. 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 which is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators may also obtain copies of these policies from program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS All investigators proposing research involving human subjects should read the NIH policy on education in the protection of human research participants now required for all investigators, which is published in the NIH Guide for Grants and Contracts, June 5, 2000 (Revised August 25, 2000), available at the following URL address http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. A continuing education program on the protection of human participants in research is now available online at http://cme.nci.nih.gov/. 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 a 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. Reviewers are cautioned 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, Development of Novel Technologies for In Vivo Imaging (Phased Innovation Award), is related to the priority area of cancer. 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 (NCI). 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 and Federal Regulations 42 CFR 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 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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