DEVELOPMENT OF NOVEL DRUG AND GENE DELIVERY SYSTEMS AND DEVICES RELEASE DATE: December 30, 2002 RFA: EB-03-011 National Institute of Biomedical Imaging and Bioengineering (NIBIB) (http://www.nibib.nih.gov) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (http://www.niddk.nih.gov/) LETTER OF INTENT RECEIPT DATE: February 25, 2003 APPLICATION RECEIPT DATE: March 25, 2003 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism(s) of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations: PURPOSE OF THIS RFA Although modern biotechnology has produced extremely sophisticated and potent therapeutic drugs and genes, many of these compounds cannot be effectively delivered using current drug and gene delivery techniques (e.g., pills, injections, and viruses). The intent of this Request for Applications (RFA) is to address the drug and gene delivery problem by encouraging the submission of innovative research proposals, using engineering principles and practice, to design, develop, and introduce novel approaches, technologies, tools, and methods that will result in new drug and gene delivery systems and devices. It is anticipated that solving problems of drug and gene delivery will involve many scientific fields, including pharmacology, biology, materials science, and electrical, chemical, mechanical, and biomedical engineering and thus teams of scientists and engineers are especially encouraged to apply. RESEARCH OBJECTIVES Intricate with the development of new drugs and treatment modalities should be the development of novel drug and gene delivery systems and devices that are designed to overcome the current problems and deficiencies associated with existing modes for systemic or localized delivery of drugs and genes such as oral, intravenous, transdermal, transmucosal, inhalation, in situ release via implants, and viral vectors. It costs an estimated $150 million to create the average new drug. Improving the effectiveness of an existing one by optimizing the delivery and dosage, minimizing side effects, and finding new therapeutic uses may be a better investment and more effective for patients than creating a brand new drug. The goal of this RFA is to encourage research to develop technologies for targeted and controlled delivery of drugs, proteins, and genes with reduced side effects and easier administration through the development of novel delivery vehicles and devices that efficiently deliver proteins, drugs and genes into cells. To accomplish the goals of this initiative, multidisciplinary collaborations among mechanical, electrical, chemical, and biomedical engineers, materials scientists, and biologist and clinicians are highly encouraged. The emphasis should be on an engineering approach, targeting design goals and specifications with systematic and quantitative analysis and prototyping, to transform drugs and/or genes into effective therapies based on the method of delivery. Topics that would be responsive to this RFA include, but are not limited to: o Further development and improvement of delivery technologies such as electroporation, iontophoresis, and ultrasound. o Use of micromachining to design and develop small devices for novel drug delivery applications such as micro- and nano-needle delivery systems and micro-and nano-particles with controlled geometry for clinically relevant delivery of drugs and genes. o Development of new, non-conventional, delivery technologies and devices that target drugs and genes to specific cell types in vivo. o Development of implantable drug delivery devices that can reduce the chance for both underdosing and overdosing, reduce the number of necessary administrations, provide more localized and better use of the active agents, and increase patient compliance. o Engineering of new drug delivery profile systems that provide optimal dosages of drugs precisely where and when they are needed and that achieve and sustain complex delivery profiles. o Development of new drug delivery matrix materials with designed or on-demand drug release mechanisms, e.g. cell or receptor specific triggering mechanisms versus hydrolytic degradation or erosion in vivo. o Novel approaches to overcome the limitations of viral vectors, in particular their relatively small capacity for therapeutic DNA, safety concerns, and difficulty in targeting to specific cell types. This should include the evaluation and development of alternative vectors based on synthetic, non-viral systems or modifications of viral systems. o New concepts and strategies for drug delivery carriers integrating targeted delivery with imaging capabilities. This may include the development of activity-dependent probes, expression pattern probes, molecular interaction probes, and single molecule reporters. In all of the areas listed above, the NIBIB is interested in the development of drug and gene delivery systems that could have broad applications to biology and/or medicine while the NIDDK is interested in applications to develop drug and gene delivery systems targeted at diseases and/or organs within the mission of NIDDK (http://www.niddk.nih.gov/welcome/mission.htm - mission), such as iron chelating agents that are not orally-effective. MECHANISM OF SUPPORT This RFA will use the NIH research grant award mechanism (R01) and the development/exploratory grant award mechanism (R21). As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. Future unsolicited, competing-continuation R01 applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures. The anticipated award date is September 30, 2003. The R01 mechanism is recommended for applications that emphasize basic discovery or cross-cutting research that addresses specific aspects of drug and gene delivery systems and devices. Research periods associated with the R01 proposals are limited to five years with no cap on budget amount. The R21 Exploratory/Developmental Award supports exploratory or developmental research aimed at proof-of-principle for high-risk projects where very little or no preliminary data is available. An R21 application can be for up to two years with a maximum budget request of $275,000 direct costs for the 2-year period and a maximum page limit of 15 pages. R21 applications are not renewable. Investigators are encouraged to use data generated from the R21 application to apply for further funding through the R01 mechanism (or other appropriate mechanisms). This RFA uses just-in-time concepts. It also uses the modular as well as the non-modular budgeting formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs (including total costs of consortium arrangements) in each year of $250,000 or less, use the modular format. Otherwise follow the instructions for non-modular research grant applications. FUNDS AVAILABLE The NIBIB intends to commit approximately $4,000,000, and the NIDDK intends to commit approximately $350,000 in FY 2003 to fund 11 to 17 new and/or competitive continuation grants in response to this RFA. An applicant may request a project period of up to 5 years for an R01 and a project period of up to 2 years for an R21. Budgets for direct costs of up to $275,000 for the 2-year period will be accepted for an R21. There is no budget limitation for R01 applications. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIBIB provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. 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 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. SPECIAL REQUIREMENTS General Clinical Research Centers: Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator should be included with the application. Grantee Meetings: Principal Investigators will be required to attend an annual meeting in the Bethesda, MD region organized by NIBIB. Investigators must include travel to this meeting as part of the budget request and state a willingness to participate in this meeting. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific/research issues to: Peter Moy, Ph.D. Program Director Division of Bioengineering National Institute of Biomedical Imaging and Bioengineering NIH/DHHS Suite 200 6707 Democracy Blvd. Bethesda, MD 20892-5469 Telephone: (301) 496-9270 Fax: (301) 480-4973 Email: moype@mail.nih.gov Maren R. Laughlin, Ph.D. Director, Metabolism Program NIDDK NIH/DHHS 6707 Democracy Blvd, Rm. 6101, MSC 5460 Bethesda, MD 20892-5460 Telephone: (301) 594-8802 Fax: (301) 480-3503 Email: laughlinm@extra.niddk.nih.gov o Direct your questions about financial or grants management matters to: Ms. Pamela Mayer Grants Management Branch Division of Extramural Activities National Institute of Biomedical Imaging and Bioengineering NIH/DHHS Suite 900 6707 Democracy Blvd. Bethesda, MD 20892 Telephone: (301) 451-4791 Fax: 301-480-4974 Email: mayerp@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 RFA 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 IC 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: Meredith D. Temple, Ph.D. Health Scientist Administrator Division of Extramural Activities National Institute of Biomedical Imaging and Bioengineering NIH/DHHS Suite 200 6707 Democracy Blvd. Bethesda, MD 20892 Telephone: (301) 451-4792 Fax: (301) 480-4973 Email: templem@mail.nih.gov SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). 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) 435-0714, Email: GrantsInfo@nih.gov. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs 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. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. 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. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. 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 the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA 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. Please Note: As of November 27, 2001, all applications and other deliveries to the Center for Scientific Review must come via courier delivery or the USPS. Applications delivered by individuals to the Center for Scientific Review will no longer be accepted. For additional information, see the NIH Guide Notice http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NIBIB. Incomplete applications will be returned to the applicant without further consideration. And, if the application is not responsive to the RFA, CSR staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the CSR in accordance with the review criteria stated below. 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 Receive a second level review by the appropriate 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 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 your study address an important problem? If the aims of your 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? (2) APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Do you acknowledge potential problem areas and consider alternative tactics? (3) INNOVATION: Does your project employ novel concepts, approaches or methods? Are the aims original and innovative? Does your project challenge existing paradigms or develop new methodologies or technologies? (4) INVESTIGATOR: Are you 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 be reviewed with respect to the following: o TEAM APPROACH: The inclusion of researchers with divergent backgrounds, for example, the partnering of an engineer, a physiologist and/or a clinician. o R21 MECHANISM ONLY: Since the R21 mechanism is intended to encourage exploratory/developmental research, proposals submitted as an R21 will be reviewed based on their high risk/high impact potential and whether or not the proposal is significantly distinct from those traditionally submitted through the R01 mechanism. For example, R21 projects designed to produce incremental advances in knowledge will not be considered. o 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. o 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) o BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: February 25, 2003 Application Receipt Date: March 25, 2003 Peer Review Date: May/June, 2003 Council Review: September, 2003 Earliest Anticipated Start Date: September 30, 2003 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS 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. 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. 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 RFA 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. 93.286 & 93.287 (NIBIB) and 93.847 & 93.849 (NIDDK) 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


H H S Department of Health
and Human Services

 
  N I H National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892