FLEXIBLE SYSTEM TO ADVANCE INNOVATIVE RESEARCH FOR CANCER DRUG DISCOVERY BY SMALL BUSINESSES (FLAIR) – SBIR/STTR INITIATIVE RELEASE DATE: February 25, 2003 PA NUMBER: PAR-03-074 EXPIRATION DATE: November 17, 2003, unless reissued. National Cancer Institute (NCI) (http://www.nci.nih.gov/) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.395 LETTER OF INTENT RECEIPT DATES: June 16, 2003 and October 17, 2003 APPLICATION RECEIPT DATE: July 14, 2003 and November 14, 2003 This Program Announcement (PAR) replaces PA-01-091, which was published in the NIH Guide on May 7, 2001. THIS PAR CONTAINS THE FOLLOWING INFORMATION o Purpose of the PAR o Research Objectives o Mechanisms of Support o Project Period and Amount of Award o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Receipt and Review Schedule o Required Federal Citations PURPOSE OF THIS PAR Discovery and development of new drugs and biologicals for cancer treatment, including gene therapy and drug delivery approaches, normally involve lengthy and costly projects. The multiple components of the overall process including discovery, efficacy testing, development of lead agents, toxicology and pharmacology, Investigational New Drug Application (IND) filing to the Federal Drug Administration (FDA), and clinical evaluation, may require years and several million dollars. The small business community is an active participant in the cancer therapy discovery effort. Thus it is important that their innovative ideas be supported. The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs were developed to support innovative research with a commercial intent by small businesses. This PAR provides a flexible system within the SBIR and STTR programs to accommodate the special needs of the complex discovery and development process, at least partially, from basic discovery through proof of principle demonstration in clinical trials. It is hoped that this initiative will stimulate drug discovery research efforts in the small business community. It will provide opportunity to small businesses to develop new treatments for rare cancers that are often overlooked because of small market considerations. NOTICE: This PAR must be read in conjunction with the current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, CENTERS FOR DISEASE CONTROL AND PREVENTION, and FOOD AND DRUG ADMINISTRATION FOR SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT APPLICATIONS. See https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf). All of the instructions within the SBIR/STTR Omnibus Solicitation apply with the following exceptions: o Special receipt dates o Initial review convened by the Division of Extramural Activities, National Cancer Institute (NCI) o Additional review considerations o More flexible time and budget specifications o Special provision for competitive renewal of certain R44 or R42 awards o Special provision for competitive supplements to support extended development studies including clinical trials. RESEARCH OBJECTIVES Recent advances in all branches of medical sciences provide new insight into the underlying mechanisms in malignancy and suggest new targets and approaches for the treatment and prevention of adult and pediatric cancers. For example, key growth regulatory pathways and genes mutated in cancer cells are being identified, array technology for expression of thousands of genes as well as computer-assisted evaluation of data are available, new technologies in chemistry which allow facile synthesis of millions of new chemicals, and high resolution structures of important target proteins are becoming available. NCI has made approaches for drug discovery based on these directions a high priority: see http://plan2002.cancer.gov. Translation of these new discoveries and innovations into clinical benefit for the cancer patient is essential; however, the process is lengthy and costly. Following initial discovery and lead optimization, potential drugs must undergo a series of rigorous pre-clinical evaluations that may culminate in a clinical trial. The actual procedures for this process vary somewhat with each agent to be tested, and, with innovative approaches often required for new agents, an extensive research effort may be necessary for successful development and eventual commercialization. For this PAR, the term "drug" is used broadly. It includes small molecules, biologicals, vaccines, gene therapy, or drug delivery approaches designed to make therapy more selective for cancer cells. The objective of this PAR is to provide a flexible funding mechanism with regard to budgets and time of award to support the research activities required to enable small businesses to bring their innovative efforts for drug discovery and development to clinical validation. Projects submitted in response to this PAR should be focused on discovery and development of a specific agent or class of agents. Applications devoted to topics relating more generally to drug discovery such as technology and model development without direct relevance to development of a specific agent are not appropriate. Flexibility within the PAR allows for projects to be presented at all stages of the drug discovery and development process. Projects will be evaluated on overall innovation, strength of the drug discovery approach, and probability of clinical success, with less emphasis on the nature of the specific stage proposed in the application. This latter aspect is especially important if applications are focused on later stages of the drug discovery and evaluation process that may be more routine and often considered less innovative as stand-alone projects. MECHANISM OF SUPPORT This PAR uses the SBIR and STTR mechanisms, which are set-aside programs. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing- continuation applications based on this project will compete with all SBIR/STTR applications and will be reviewed according to the customary peer review procedures. Applications that are not funded in the competition described in this PAR may be resubmitted as revised SBIR/STTR applications using the standard receipt dates for NEW applications described in the current SBIR/STTR Omnibus Solicitation. This PAR uses the just-in-time concepts. It also uses the modular budgeting format. Specifically, if you are submitting an application budget of $100,000 total costs (direct, F&A, and fee) or LESS, use the modular format and instructions as described in the current SBIR/STTR Omnibus Solicitation. Otherwise follow the instructions for non-modular research grant applications. The SBIR/STTR mechanism requires that the intent of the research be the commercialization of a product or service. Except as otherwise stated in this PAR, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, March 2001, available at https://grants.nih.gov/grants/policy/nihgps_2001. Applications may be submitted for support as Phase I STTR (R41) or Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the SBIR/STTR FAST-TRACK option as described in the SBIR/STTR Omnibus Solicitation. Phase II applications in response to this PAR 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 but not necessarily a Phase I project supported in response to this PAR. FAST-TRACK applications will benefit from expedited evaluation of progress following the Phase I feasibility study for transition to Phase II funding for expanded developmental work. Information on the FAST-TRACK process and the OMNIBUS SOLICITATION are available at: https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf. For the NCI resources available to qualified investigators in support of research, such as the compound libraries and the natural product repository, see http://dtp.nci.nih.gov. PROJECT PERIOD AND AMOUNT OF AWARD The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines of funding support and project duration periods for SBIR and STTR Phase I and Phase II awards. However, some projects are likely to require longer time periods and/or larger budgets to accomplish the proposed aims. Therefore, if adequately justified, budgets up to $300,000 total costs per year and time periods up to 2 years for Phase I and $750,000 total costs per year and up to 4 years for Phase II can be requested. Phase II applications that include support for expensive studies required for IND filing with the FDA and/or clinical trials may request up to $1 million per year total costs, but the budget must be adequately justified. For FAST-TRACK applications the total duration of Phase I plus Phase II cannot exceed 5 years. Cost-sharing arrangements are encouraged since the SBIR/STTR programs cannot support all activities that may be required to advance a material to feasibility demonstration in a clinical trial. ELIGIBLE INSTITUTIONS Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation. Only small business concerns are eligible to submit SBIR/STTR applications. A small business concern is one that, on the date of award for both Phase I and Phase II agreements, meets ALL of the criteria as described in the current SBIR/STTR Omnibus Solicitation. 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. On an SBIR application, the principal investigator must have his/her primary employment (more than 50%) with the small business at the time of award and for the duration of the project. The Principal Investigator on an STTR application may be employed with the small business concern or the participating non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PAR and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review and financial or grants management issues. Direct your questions about scientific issues to: George S. Johnson, Ph.D. Development Therapeutics Program Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, EPN 8152 Bethesda, MD 20892-7456 (For express/courier service: Rockville, MD 20852) Tel: 301-496-8783 Fax: 301-402-5200 Email: johnsong@exchange.nih.gov Direct your questions about peer review matters to: Referral Officer National Cancer Institute Division of Extramural Activities 6116 Executive Boulevard, Room 8041, MSC 8329 Bethesda, MD 20892-8329 Telephone: (301) 496-3428 FAX: (301) 402-0275 Email: ncirefof@dea.nci.nih.gov Direct your questions about financial or grants management matters to: Mr. Shane Woodward Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 6120 Executive Blvd Bethesda, MD 20892-1750 Telephone: (301) 496-8649 FAX: (301) 496-8601 Email: woodwars@mail.nih.gov LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this PAR 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 by the date listed at the beginning of this document. The letter of intent should be sent to Dr. George S. Johnson at the address provided above under WHERE TO SEND INQUIRIES. SUBMITTING AN APPLICATION The PHS 398 research grant application must be used for all competing SBIR/STTR Phase I, Phase II and Fast-Track applications (new and revised.) The PHS 398 is available at https://grants.nih.gov/grants/funding/phs398/phs398.html. Prepare your application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 398. Helpful information for advice and preparation of the application can be obtained at: https://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf. The NIH will return applications that are not submitted on the 5/2001 version of the PHS 398. For further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email: GrantsInfo@nih.gov. The SBIR/STTR OMNIBUS SOLICITATION is available electronically through the NIH, Office of Extramural Research Small Business Funding Opportunities web site: https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf. The solicitation contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. Helpful information for preparation of the application can be obtained at: https://grants.nih.gov/grants/grant_tips.htm. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: This PAR uses the modular budgeting format. Specifically, if you are submitting an application budget of $100,000 total costs (direct, F&A and fee) or less, use the modular format and instructions as described in the SBIR/STTR Omnibus Solicitation. USING THE SBIR/STTR LABEL: Attach the appropriate SBIR or STTR label to the bottom of the face page of the application (MS Word: https://grants.nih.gov/grants/funding/phs398/labels.doc or PDF: https://grants.nih.gov/grants/funding/phs398/labels.pdf). Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. THE TITLE AND NUMBER OF THIS PAR MUST BE TYPED ON LINE 2 OF THE FACE PAGE OF THE APPLICATION AND THE YES BOX MUST BE MARKED. PHASE I: Demonstration of feasibility of the innovative approach. Research should be proposed to provide sufficient information to support a future Phase II application. If two years of support are requested, the goals for the first year should be clearly stated and not simply a reiteration of specific aims. Support for the second year will be contingent upon NCI programmatic evaluation to ensure that investigators are accomplishing the goals presented. PHASE II: Continuing support for development of pre-clinical research that may include establishment of proof of principle in clinical trials. Support can be requested for pre-clinical developmental activities including pharmacology, formulation and toxicology. Innovative aspects of the research necessary to complete the projects such as development of new in vivo evaluation models that may require surrogate endpoints rather than traditional survival or tumor shrinkage models should be clearly described. Support for clinical trial evaluation to establish proof of principle (normally through Phase II development) can be requested to commence following completion of the pre-clinical activities and approval of the IND by the FDA. A plan for the clinical trial should be presented in the RESEARCH PLAN section. If clinical studies are planned in the first two years, IN THE HUMAN SUBJECTS SECTION, INCLUDE THE COMPLETE CLINICAL PROTOCOL and DATA AND SAFETY MONITORING PLAN. If it is premature to submit a complete clinical protocol, a draft protocol may be submitted. Informed consent form(s) must be included. NIH will treat as confidential any scientific, pre- clinical, clinical or formulation data and information that the sponsor deems to be proprietary and confidential. For each trial, provide a Gender and Minority Inclusion Report in the format provided in the 398 form instructions: https://grants.nih.gov/grants/funding/phs398/phs398.html. If research has not progressed to the point where a clinical protocol can be submitted with the application or by time of review but a clinical trial would be likely in later years of the Phase II award, clinical trial support should be requested in a competitive supplement at the next appropriate FLAIR receipt date. The goals and milestones for each year of support must be clearly presented. Support for years two to four, if requested, is dependent upon NCI programmatic review of progress and achievement of the proposed goals. For example, if a goal cannot be achieved such as identification of a more effective analog or demonstration of acceptable toxicity cannot be demonstrated, additional years may not be supported. This PAR encourages projects with aims focusing on later stages of drug development such as formulation and toxicology as well as clinical evaluation. However, accomplishing these aims may likely require expertise not present in the applicant small business, and a sub- contract site within the award may be required. Information on the drug development process is available: http://dtp.nci.nih.gov and http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm. Due to the complex nature of the drug development process, it is recommended that only well defined and more advanced projects be proposed for support with FAST-TRACK applications. Phase I, FAST TRACK applications must specify clear, measurable milestones that should be achieved prior to Phase II funding. Failure to provide such information in the Phase I application and/or sufficient detail in the Phase II application may be sufficient reason for the peer review committee to exclude the Phase II from consideration. If so, the applicant may apply later for Phase II support. Special provisions described in this PAR pertaining to Phase I and Phase II also apply to FAST-TRACK applications. All Phase II applications, including those submitted as a FAST-TRACK, must include a succinct Commercialization Plan. The Commercialization Plan must be included as part of the Research Plan. Refer to Phase II grant application instructions for more specific details and instructions. See https://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.pdf or https://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.doc. Potential applicants are encouraged to contact NCI program staff for guidance and to read the advice and information on the web sites. However, responsibility for planning, direction, and execution of the proposed research will be solely that of the applicant. CONSULTANT AND CONTRACTUAL COSTS: Research expertise required to obtain data for IND filing and FDA regulatory approval as well as conduct of clinical trials likely may not be available at the small business and thus will require a subcontract with an outside institution. Likewise costs for this research may exceed the normal expectations for percent of the total grant budget allocated to subcontracts. If adequately justified, applications may exceed this guideline. Resources provided for such research activity will be limited for that activity and cannot be rebudgeted. COMPETING CONTINUATION PHASE II APPLICATIONS: A competitive renewal of Phase II for up to an additional three years may be requested for current Phase II awards which have successfully discovered agents which should be considered for development to clinical trial. Research activities supported by the competing continuation award would be expected to include an extension and expansion of pre-clinical development that would be required for IND filing and FDA approval, as well as support for a clinical trial. The Phase II competing continuation should not be used to extend discovery research. All Phase II provisions stated in this PAR, including budget limitations, apply to the Phase II competitive renewal application. Since the Phase II competing continuation grant is a new funding mechanism, eligible applicants are strongly encouraged to contact their Program Director prior to submission of an application. COMPETING SUPPLEMENTS: A competing supplemental application may be submitted at the receipt dates presented on page one of this PAR to request support for a significant expansion of a project's scope, research protocol, or to add a new specific aim. Phase II awardees who wish to add research aims to obtain data required for IND filing or to conduct clinical trials are encouraged to apply for supplemental funding. Instructions for application can be found in the Omnibus SBIR/STTR Solicitation Instructions. Awardees should consult with the Program Director prior to submission of the supplement request. ADMINISTRATIVE SUPPLEMENTS: Supplements to extend a peer reviewed and funded specific aim for reasons that were unpredicted at the time of application can be requested at any time. New aims to the award cannot be added with this process. Examples appropriate for FLAIR would be, but not limited to, requirement for additional toxicity studies suggested by the FDA after the initial IND review or support for unexpected clinical trial costs. Administrative supplement requests should be discussed with and submitted to the Program Director. SENDING AN APPLICATION TO THE NIH: 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) To expedite the review process, at the time of submission, send two copies of the application to: Referral Officer National Cancer Institute 6116 Executive Blvd, Room 8041, MSC 8329 Bethesda, MD 20892-8329 Rockville, MD 20852 (for express/courier service) APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE OR THE CENTER FOR SCIENTIFIC REVIEW WILL NO LONGER BE ACCEPTED. This policy does not apply to courier deliveries (i.e. FEDEX, UPS, DHL, etc.) (https://grants.nih.gov/grants/guide/notice-files/ NOT-CA-02-002.html). This policy is published in the NIH Guide Notice https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html. RECEIPT OF APPLICATIONS: Applications must be received on or before the receipt date listed on the first page of this announcement. If an application is received after that date, it will be returned to the applicant without review. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. The Center for Scientific Research (CSR) will not accept any application in response to this PAR 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. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a PAR, it is to be prepared as a NEW application. That is the application for the PAR must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes. While the investigator may still benefit from the previous review, the PAR application is not to state explicitly how. PEER REVIEW PROCESS Upon receipt, applications will be reviewed by CSR staff for completeness and by NCI program staff for adherence to guidelines. Incomplete applications and applications not adhering to instructions described above will be returned to the applicant without further review. Applications that are complete and adhere to the guidelines of this PAR will be evaluated for scientific and technical merit and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of this PAR by an appropriate peer review group convened by the NCI, in accordance with the peer review criteria listed below. For the 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 Undergo a second level review by the National Cancer Advisory Board for those that receive a priority score. REVIEW CRITERIA The goals of NIH-sponsored research are to advance our understanding of biological systems, improve the control of disease, and enhance health. Within this framework, the specific goals of this PAR include the discovery and development of new cancer treatments within the SBIR and STTR programs. In addition to the standard review criteria described in the OMNIBUS SOLICITATION, reviewers will comment on the 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 criterion 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 highly meritorious. For example, an investigator may propose a development or testing project that alone may not be highly innovative, but is required for successful development of an innovative and potentially important agent. o Significance o Approach o Innovation o Investigator o Environment ALL SBIR/STTR APPLICATIONS 1. SIGNIFICANCE: Does the proposed project have commercial potential to lead to a marketable product or process? What may be the anticipated commercial and societal benefits of the proposed activity? 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? What is the potential clinical relevance of the research and agents proposed? 2. 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? Is it likely that the drug or vaccine can be developed in a reasonable time frame? Is the approach feasible and cost effective? For systems intended for clinical research, the following, additional criteria will be considered: to what degree is the analysis appropriate for clinical research and likely to have utility for the analysis of clinical specimens or patients? 3. INNOVATION: Does the project employ novel concepts, approaches, or methods? Are the aims original and innovative? Does the project challenge existing paradigms? Are the new drugs or vaccines or their proposed use novel? 4. INVESTIGATORS: Is the Principal Investigator capable of coordinating and managing the proposed SBIR/STTR? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers, including consultants and subcontractors (if any)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed? 5. ENVIRONMENT: Is there sufficient access to resources (e.g., equipment, facilities)? Does the scientific and technological 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? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score: PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See additional information and criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: 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 additional information and Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the required five items described under Vertebrate Animals (section f of the Research Plan instructions) will be assessed. Human Subjects: 1. Protection of Human Subjects from Research Risks - for all studies involving human subjects. See instructions and "Guidance for Preparing the Human Subjects Research Section." If an exemption is claimed, is it appropriate for the work proposed? If no exemption is claimed, are the applicant's responses to the six required points appropriate? Are human subjects placed at risk by the proposed study? If so, are the risks reasonable in relation to the anticipated benefits to the subjects and others? Are the risks reasonable in relation to the importance of the knowledge that reasonably may be expected to be gained? Are the plans proposed for the protection of human subjects adequate? 2. Inclusion of Women Plan - for clinical research only. Does the applicant propose a plan for the inclusion of both genders that will provide their appropriate representation? Does the applicant provide appropriate justification when representation is limited or absent? Does the applicant propose appropriate and acceptable plans for recruitment/outreach and retention of study participants? 3. Inclusion of Minorities Plan - for clinical research only. Does the applicant propose a plan for the inclusion of minorities that will provide their appropriate representation? Does the applicant provide appropriate justification when representation is limited or absent? Does the applicant propose appropriate and acceptable plans for recruitment/outreach and retention of study participants? 4. Inclusion of Children Plan- for all studies involving human subjects. Does the applicant describe an acceptable plan in which the representation of children of all ages (under the age of 21) is scientifically appropriate and recruitment/retention is addressed realistically? If not, does the applicant provide an appropriate justification for their exclusion? 5. Data and Safety Monitoring Plan – for clinical trials only. Does the applicant describe a Data and Safety Monitoring Plan that defines the general structure of the monitoring entity and mechanisms for reporting Adverse Events to the NIH and the IRB? Animal Welfare: If vertebrate animals are involved, are adequate plans proposed for their care and use? Are the applicant's responses to the five required points appropriate? Will the procedures be limited to those that are unavoidable in the conduct of scientifically sound research? Biohazards: Is the use of materials or procedures that are potentially hazardous to research personnel and/or the environment proposed? Is the proposed protection adequate? ADDITIONAL CONSIDERATIONS: The following items may be also be considered by reviewers but will not be included in the determination of scientific merit. BUDGET: The reasonableness of the proposed budget may be considered. For all applications, is the percent effort listed for the PI appropriate for the work proposed? On applications requesting up to $100,000 total costs, is the overall budget realistic and justified in terms of the aims and methods proposed? On applications requesting over $100,000 in total costs, is each budget category realistic and justified in terms of the aims and methods? PERIOD OF SUPPORT: The appropriateness of the requested period of support in relation to the proposed research. Phase II Application Review Criteria: In addition to the above criteria: 1. How well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity? 2. Did the applicant submit a concise Commercialization Plan [formerly Product Development Plan] that adequately addresses the four seven areas described in the Research Plan item J? 3. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan? Amended Applications In addition to the above criteria, the following criteria will be applied to revised applications. 1. Are the responses to comments from the previous SRG review adequate? 2. Are the improvements in the revised application appropriate? Phase I/Phase II Fast-Track Application Review Criteria For Phase I/Phase II Fast-Track applications, the following criteria also will be applied: 1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? 2. Did the applicant submit a concise Commercialization Plan [formerly Product Development Plan] that adequately addresses the seven areas described in the Research Plan, item J? 3. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/ STTR funding sources that would enhance the likelihood for commercialization? 4. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan? Phase I and Phase II Fast-Track applications that satisfy all of the review criteria will receive a single rating. Failure to provide clear, measurable goals may be sufficient reason for the scientific review group to exclude the Phase II application from Fast-Track review. RECEIPT AND REVIEW SCHEDULE Letter of Intent: June 16, 2003 and October 17, 2003 Application Receipt Dates: July 14, 2003 and November 14, 2003 Council Review: February 2004 and June 2004 Earliest Anticipated Award Date: April 2004 and July 2004 AWARD CRITERIA Applications submitted in response to a PAR will compete for available funds with all other recommended SBIR and STTR 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 FAST-TRACK, Phase II applications may be funded following submission of the Phase I progress report and other documents necessary for continuation. Phase II projects will be selected for funding based on the initial priority score, Program staff's assessment of the Phase I progress and determination that Phase I goals were achieved, the project's potential for commercial success, and the availability of funds. REQUIRED FEDERAL CITATIONS HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. MONITORING PLAN AND DATA AND SAFETY 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 and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: https://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: https://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 "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 (https://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 https://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 https://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 https://grants.nih.gov/grants/stem_cells.htm and at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.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 https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PAR 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 PAR 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 at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at https://grants.nih.gov/grants/policy/policy.htm. 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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