Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) to Develop New Therapies for Type 1 Diabetes and Its Complications

Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) to Develop New Therapies for Type 1 Diabetes and Its Complications is sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Eye Institute (NEI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Nursing Research (NINR), National Institute of Child Health and Human Development (NICHD).

This program invites small businesses to apply cutting-edge technology to research aimed at developing new approaches to prevent, treat, and cure type 1 diabetes and its complications. This is a collaborative effort across multiple NIH institutes.

Expired RFA-DK-03-020: SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) TO DEVELOP NEW THERAPIES FOR TYPE 1 DIABETES AND ITS COMPLICATIONS This notice has expired. Check the NIH Guide for active opportunities and notices.

SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) TO DEVELOP NEW THERAPIES FOR TYPE 1 DIABETES AND ITS RELEASE DATE: August 28, 2003 RFA Number: RFA-DK-03-020 (This RFA has been reissued, see RFA-DK-05-015 ) (This RFA has been modified, see RFA-DK-05-010 ) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( http://www. niddk. nih.

gov/ ) National Eye Institute (NEI) ( http://www. nei. nih.

gov/ ) National Heart, Lung, and Blood Institute (NHLBI) ( http://www. nhlbi. nih.

gov/ ) National Institute of Allergy and Infectious Diseases (NIAID) ( http://www. niaid. nih.

gov/ ) National Institute of Neurological Disorders and Stroke (NINDS) ( http://www. ninds. nih.

gov/ ) National Institute of Nursing Research (NINR) ( http://www. ninr. nih.

gov/ ) National Institute of Child Health and Human Development (NICHD) ( http://www. nichd. nih.

gov ) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93. 847, 93. 867, 98.

837, 93. 855, 93. 853, 93.

361, 93.

865 LETTER OF INTENT RECEIPT DATE: January 19,2004 APPLICATION RECEIPT DATE: February 19, 2004 o Mechanism(s) of Support o Project Period and Amount of Award o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Receipt and Review Schedule o Required Federal Citations NOTICE: This Request for Application (RFA) 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.

The solicitation (see http://grants. nih. gov/grants/funding/sbirsttr1/index.

pdf ) contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. All of the instructions within the SBIR/STTR Omnibus Solicitation apply with the o This RFA is a one-time solicitation with the receipt date of 2/19/03.

o Upon receipt applications will be reviewed by a Special Emphasis Panel The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Eye Institute (NEI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Nursing Research (NINR), National Institute of Child Health and Human Development (NICHD) invite the small business community to apply cutting edge technology to research to develop new approaches to prevent, treat, and cure type 1 diabetes and its complications.

This RFA will utilize the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) mechanisms, but will be run in parallel with other requests for applications (RFAs) of similar scientific scope ( DK-03-015 for Innovative Partners and DK-03-001 for Bench to Bedside) that will utilize the traditional research project grant (R01), the exploratory/developmental grant (R21) or the exploratory/developmental grant phase II (R33) grant mechanisms.

RESEARCH BACKGROUND AND OBJECTIVES: Type 1 diabetes is an autoimmune disease that destroys the insulin-producing cells of the pancreas and affects an estimated one million Americans, usually with onset in childhood or young adulthood. The disease markedly impairs quality of life and shortens lifespan primarily through premature cardiovascular mortality.

Cardiovascular complications are increased four- fold compared to the general population, and type 1 diabetes is associated with numerous complications including blindness, renal failure, painful nerve disorders, and amputation.

In addition to its devastating toll in human suffering, type 1 diabetes and its complications result in significant health care expenditures for families and constitute a major societal economic Recent research progress in understanding and treating this disease has been dramatic. Researchers can now accurately identify individuals at increased risk of type 1 diabetes based on genetic tests and antibody measurements.

Clinical trials are ongoing in those with new onset disease to test new immunomodulatory agents that may have the potential to preserve residual function of the insulin producing beta cells. Clinical trials have demonstrated dramatic reductions in complications of type 1 diabetes through intensive glycemic control. However, dangerous episodes of hypoglycemia limit attempts to control blood glucose in many patients with type 1 diabetes.

Recently researchers have reported success using islet transplantation to restore lost beta cell function. However, the current immunosuppressive regimens required for transplant survival have significant immediate side effects and long term safety is uncertain.

The small business community in encouraged to contribute to the rapid progress toward developing safe and effective cell based beta cell replacement therapy, as well other new approaches to prevent, treat and cure type 1 diabetes and its macro- and micro-vascular complications.

This RFA is intended to support innovative research in the field of type 1 diabetes and its complications, conducted by small business (SBIR) and small business in partnership with academia (STTR).

Examples of projects that this announcement intends to solicit include: o Development of novel therapeutics, including beta cell replacement therapy, devices, biologics and other drugs for the treatment of type 1 diabetes and o Development of methods to increase the yield of functional and successfully transplantable islets from pancreata including the development of alternative enzymatic approaches to isolate islets and methods to increase the duration for which a pancreas can be utilized.

o Development of methods to develop replenishible sources of islet like cells or to expand the number of human islets during culture while still retaining appropriate functional islet characteristics and the ability to be successfully transplanted. o Development of pre-transplant islet testing approaches that are predictive of subsequent successful islet transplantation using functional genomics, proteomics or other methods.

o Development of methods to improve viability/function of islets prior to transplantation and the engraftment and long term function of islets after transplantation including gene transfer, encapsulation or immunoisolation, and the evaluation of alternative transplantation sites.

o Development of improved approaches to xenotransplantation as an unlimited source of islets that would reduce potential complications and enhance graft o Application of basic research in regenerative medicine to preclinical or clinical treatment of type 1 diabetes and its complications. o Application of gene therapy strategies to prevent or reverse complications.

o Development of novel approaches to immunomodulation or development of tolerance with relevance to type 1 diabetes and/or of methods to measure changes in immune status in type 1 diabetes, such as pathogenic T cell o The development of methodology or biomarkers to help understand the physiology or improve the diagnosis and treatment of type 1 diabetes and its complications (e.g. novel genetic screening methodologies, application of o The development of methods for measuring or imaging the pancreatic beta cell mass or inflammation.

o Development of methods for early detection, diagnosis and quantification of cardiovascular disease, neuropathy, retinopathy and nephropathy in type 1 o Development of non-invasive or minimally invasive methods for continuous monitoring of blood glucose and/or approaches to linkage of monitoring devices to miniaturized insulin delivery systems for the development of a "closed loop" artificial pancreas.

o Identification of biomarkers for use in clinical trials that could serve as surrogate outcomes for monitoring the progression of type 1 diabetes and/or its complications or for quantitatively assessing response to therapy to prevent or reverse disease.

o Development of high throughput assays based on biologic pathways likely involved in the pathogenesis of type 1 diabetes complications or autoimmunity that could be used to screen molecular libraries for novel therapeutic o The development of novel animal models for investigating type 1 diabetes This RFA 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. The anticipated award date is October 2004.

Applications that are not funded in the competition described in this RFA may be resubmitted as NEW SBIR/STTR applications using the standard receipt dates for NEW applications described in the current SBIR/STTR Omnibus Solicitation. This RFA uses 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. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.

nih. gov/grants/policy/nihgps_2001/part_i_1. htm .

Except as otherwise stated in this RFA, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, March 2001, available at http://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 RFA 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 RFA. 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.

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. For this RFA, budgets up to $500,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $ 1,000,000 total costs per year and up to 3 years may be requested for Phase II.

Total costs include direct costs, F&A, and fee/profit. The total funds available will be approximately $4,000,000 in FY2004. The participating institutes intend to fund 6-10 phase I, Phase II or Fast Track SBIR projects and 1-2 phase I, Phase II or Fast Track STTR projects.

Although the financial plans of the sponsoring Institutes 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 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. Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her 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 PI 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.

We encourage inquiries concerning this RFA 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 o Direct questions about scientific/research issues to: Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 685 Division of Extramural Activities Executive Plaza South, Suite 350 Cristina Rabadan-Diehl, Ph. D.

Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute E-mail: [email protected] Division of Allergy, Immunology and Transplantation Research National Institute of Allergy and Infectious Disease 6610 Rockledge Drive, Room 3027 E-mail: [email protected] National Institute of Neurological Disorders and Stroke Neuroscience Center, Room 2108 E-mail: [email protected] Office of Extramural Programs National Institute of Nursing Research 6701 Democracy Boulevard, Room 710 Telephone: (301) 594-5973 Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard; Suite 4B-11 e-mail: [email protected] o Direct questions about peer review issues to: Francisco O.

Calvo, Ph. D.

Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 o Direct questions about financial or grants management matters to: National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 708 Telephone: (301) 594-8869 Executive Plaza South, Suite 350 National Heart, Lung, and Blood Institute E-mail: [email protected] National Institute of Allergy and Infectious Disease 6610 Rockledge Drive, Room 3027 Phone: (301) 496 7104 phone E-mail: [email protected] National Institute of Neurological Disorders and Stroke Neuroscience Center, Room 3290 E-mail: [email protected] National Institute of Nursing Research 6701 Democracy Boulevard, Room 710 Telephone: (301) 594-2807 FAX: (301) 451-5651 or (301) 402-4502 Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard; Suite 4B-11 e-mail: [email protected] 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 letter of intent is to be sent to: Francisco O.

Calvo, Ph. D. Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 The PHS 398 research grant application must be used for all SBIR/STTR Phase I, Phase II and Fast-Track applications (new and revised.)

Effective October 1, 2003, applicants must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www. dunandbradstreet.

com . The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at http://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: http://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: [email protected] . SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: If you are submitting an application budget of $100,000 total costs (direct, F&A and fee) or less, you must use the modular format and instructions as described in the SBIR/STTR Omnibus Solicitation.

USING THE RFA LABEL: The RFA label available in the PHS 398 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/labels. doc or http://grants. nih.

gov/grants/funding/phs398/labels. pdf .

The title and number of this RFA must be typed on line 2 of the face page of SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 (for USPS EXPRESS or REGULAR MAIL) Bethesda, MD 20817 (for EXPRESS/COURIER NON-USPS SERVICE) At the time of submission, two additional copies of the application and five sets of appendices must be sent to: Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 APPLICATION PROCESSING: 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 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 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.

However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is the application for the RFA 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 RFA application is not to state explicitly how. Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by NIDDK. Incomplete applications will not be reviewed.

If the application is not responsive to the RFA, NIH 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 NIDDK in accordance with the review criteria stated below.

As part of the initial merit review, all applications will: 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 written critique o Receive a second level review by an appropriate national advisory council 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 within the context of the SBIR/STTR Program: ALL SBIR/STTR APPLICATIONS o Significance: Does the proposed project have commercial potential to lead to a marketable product or process?

Does this study address an important problem? What may be the anticipated commercial and societal benefits of the proposed activity? If the aims of the application are achieved, how will scientific knowledge be advanced?

Does the proposal lead to enabling technologies (e.g., instrumentation, software) for further discoveries? Will the technology have a competitive advantage over existing/alternate technologies that can meet the market needs? o Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project?

Is the proposed plan a sound approach for establishing technical and commercial feasibility? Does the applicant acknowledge potential problem areas and consider alternative strategies? Are the milestones and evaluation o Innovation: Does the project challenge existing paradigms or employ novel technologies, approaches or methodologies?

Are the aims original and o 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 o 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 RELEVANCE TO THE GOALS OF THIS RFA: Does the proposed project have the potential to open new avenues to the prevention, treatment and cure of type 1 diabetes and its complications?

For Fast Track applications, are there clear milestones that will be achieved and evaluated at the end Phase I that are directly relevant to the goals of the RFA? 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). o 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?

o 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? o 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? o 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? o 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? 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.

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: o 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?

o Did the applicant submit a concise Commercialization Plan [formerly Product Development Plan] that adequately addresses the seven areas described in the o Does the project carry a high degree of commercial potential, as described in the Commercialization Plan? In addition to the above criteria, the following criteria will be applied to o Are the responses to comments from the previous SRG review adequate?

o 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 o Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

o Did the applicant submit a concise Commercialization Plan [formerly Product Development Plan] that adequately addresses the seven areas described in the o 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 o 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.

Letter of Intent Receipt Date: January 19, 2004 Application Receipt Date: February 19, 2004 Peer Review Date: June/July 2004 Council Review: September 2004 Earliest Anticipated Start Date: October 2004 Applications submitted in response to an RFA 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 Relevance to program priorities For FAST-TRACK applications, the Phase II portion may not be funded until a Phase I final report and other documents necessary for continuation have been received and assessed by program staff that the Phase I milestones have been 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.

http://www. hhs. gov/ohrp/humansubjects/guidance/45cfr46.

htm DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III).

The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants. nih.

gov/grants/guide/notice-files/not98-084. html ). 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 ( 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 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