**OMB No. 0990-0115\
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PHS 2009-1**

**SOLICITATION OF**

**THE NATIONAL INSTITUTES OF HEALTH AND**

**THE CENTERS FOR DISEASE CONTROL**

**AND PREVENTION**

**FOR**

> SMALL
>
> BUSINESS INNOVATION
>
> RESEARCH

CONTRACT PROPOSALS

Internet: <http://grants.nih.gov/grants/funding/sbir.htm>

Table of Contents

[**Part I Instructions for Preparing and Submitting a Proposal
1**](#part-i-instructions-for-preparing-and-submitting-a-proposal)

[1. PROGRAM DESCRIPTION 1](#program-description)

[1.1 Purpose of Solicitation 1](#purpose-of-solicitation)

[1.2 Three Phase Program 1](#three-phase-program)

[1.3 Awarding Components 2](#awarding-components)

[National Institutes of Health (NIH)
2](#national-institutes-of-health-nih)

[Centers for Disease Control and Prevention (CDC)
3](#centers-for-disease-control-and-prevention-cdc)

[1.4 SBIR Program Eligibility 3](#sbir-program-eligibility)

[2. AGENCY CONTACT FOR INFORMATION 4](#agency-contact-for-information)

[3. DEFINITIONS 5](#definitions)

[4. Phase I PROPOSAL PREPARATION INSTRUCTIONS AND REQUIREMENTS
12](#phase-i-proposal-preparation-instructions-and-requirements)

[4.1 Limitations on Length of Proposal
12](#limitations-on-length-of-proposal)

[4.2 Technical Proposal Format and Content Requirements
12](#technical-proposal-format-and-content-requirements)

[4.2.1 Technical Proposal Cover Sheet 12](#__RefHeading___Toc205616377)

[4.2.2 Abstract of Research Plan 13](#__RefHeading___Toc205616378)

[4.2.3 Research Plan 13](#__RefHeading___Toc205616379)

[4.2.4 Current Awards and Pending Proposals/Applications
14](#__RefHeading___Toc205616380)

[4.2.5 Prior SBIR Phase II Awards 15](#__RefHeading___Toc205616381)

[4.2.6 Proposed Cost Breakdown 15](#__RefHeading___Toc205616382)

[4.2.7 Streamlining the Contracting Process
16](#__RefHeading___Toc205616383)

[4.2.8 Requirement for Adequate Assurance of Protection of Human
Subjects 16](#__RefHeading___Toc205616384)

[4.2.9 Requirement for Adequate Assurance of Compliance with the PHS
Policy on\
Humane Care and Use of Laboratory Animals
17](#__RefHeading___Toc205616385)

[4.3 Limitations on Use of Appropriated Funds
18](#limitations-on-use-of-appropriated-funds)

[5. "Fast-Track" Initiative 20](#fast-track-initiative)

[6. Fast-Track Phase II Proposal Preparation Instructions and\
Requirements
20](#fast-track-phase-ii-proposal-preparation-instructions-and-requirements)

[6.1 Limitations on Length of Proposal
20](#limitations-on-length-of-proposal-1)

[6.2 Technical Proposal Format and Content Requirements
21](#technical-proposal-format-and-content-requirements-1)

[6.3 Business Proposal Format and Content Requirements
24](#business-proposal-format-and-content-requirements)

[7. METHOD OF SELECTION AND EVALUATION CRITERIA
24](#method-of-selection-and-evaluation-criteria)

[7.1 Evaluation Process 24](#evaluation-process)

[7.2 Technical Evaluation Criteria 25](#technical-evaluation-criteria)

[7.3 Proposal Debriefing 26](#proposal-debriefing)

[7.4 Award Decisions 26](#award-decisions)

[8. CONSIDERATIONS 26](#considerations)

[8.1 Awards 26](#awards)

[8.2 Monthly Progress Report 27](#monthly-progress-report)

[8.3 Final Report 28](#final-report)

[8.4 Payment 28](#payment)

[8.5 Limited Rights Information and Data
28](#limited-rights-information-and-data)

[8.6 Performance of Research and Analytical Work
31](#performance-of-research-and-analytical-work)

[Clauses That Apply to Contracts *NOT* Exceeding \$100,000
31](#clauses-that-apply-to-contracts-not-exceeding-100000)

[Clauses That Apply to Contracts Exceeding \$100,000
31](#clauses-that-apply-to-contracts-exceeding-100000)

[8.7 Additional Information 32](#additional-information)

[9. INSTRUCTIONS FOR PROPOSAL SUBMISSION
32](#instructions-for-proposal-submission)

[9.1 Receipt Date 32](#receipt-date)

[9.2 Number of Copies 33](#number-of-copies)

[9.3 Binding and Packaging of Proposal
33](#binding-and-packaging-of-proposal)

[10. Contracting Officers and Addresses for Mailing or Delivery of\
Proposals
33](#contracting-officers-and-addresses-for-mailing-or-delivery-of-proposals)

[10.1 National Institutes of Health (NIH)
33](#national-institutes-of-health-nih-1)

[National Cancer Institute (NCI) 33](#national-cancer-institute-nci)

[National Center for Research Resources (NCRR)
34](#national-center-for-research-resources-ncrr)

[National Heart, Lung, and Blood Institute (NHLBI)
34](#national-heart-lung-and-blood-institute-nhlbi)

[National Institute on Alcohol Abuse and Alcoholism (NIAAA)
34](#national-institute-on-alcohol-abuse-and-alcoholism-niaaa)

[National Institute of Allergy and Infectious Diseases (NIAID)
35](#national-institute-of-allergy-and-infectious-diseases-niaid)

[National Institute on Drug Abuse (NIDA)
35](#national-institute-on-drug-abuse-nida)

[National Institute of Mental Health (NIMH)
35](#national-institute-of-mental-health-nimh)

[10.2 Centers for Disease Control and Prevention (CDC)
36](#centers-for-disease-control-and-prevention-cdc-1)

[National Center on Birth Defects and Developmental Disabilities
(NCBDDD)
36](#national-center-on-birth-defects-and-developmental-disabilities-ncbddd)

[National Center for Chronic Disease Prevention and Health Promotion
(NCCDPHP)
36](#national-center-for-chronic-disease-prevention-and-health-promotion-nccdphp)

[Immunization Safety Office (ISO) 36](#immunization-safety-office-iso)

[National Center for Immunization and Respiratory Diseases (NCIRD)
37](#national-center-for-immunization-and-respiratory-diseases-ncird)

[11. SCIENTIFIC AND TECHNICAL INFORMATION SOURCES
37](#scientific-and-technical-information-sources)

[12. RESEARCH TOPICS 37](#research-topics)

[NATIONAL INSTITUTES OF HEALTH 37](#__RefHeading___Toc205616427)

[National Cancer Institute (NCI) 37](#__RefHeading___Toc205616428)

[229 Development of Molecular Pharmacodynamic Assays for Targeted
Therapies 38](#__RefHeading___Toc205616429)

[249 System to Analyze and Support Biomarker Research and Development\
Strategies 40](#__RefHeading___Toc205616430)

[255 Development of Anticancer Agents 42](#__RefHeading___Toc205616431)

[256 Innovative Methods for Manufacturing Safe, Effective Cancer
Therapeutics 43](#__RefHeading___Toc205616432)

[257 Biopsy Instruments and Devices that Preserve Molecular Profiles in
Tumors 44](#__RefHeading___Toc205616433)

[258 Innovative Strategies to Protect Radiosensitive Organs and
Structures\
During Radiation Therapy 46](#__RefHeading___Toc205616434)

[259 Quantitative Tissue Imaging For Clinical Diagnosis and Treatment
48](#__RefHeading___Toc205616435)

[260 High Level Programming Language to Expedite Development of User
Interfaces 49](#__RefHeading___Toc205616436)

[261 Mobile Computing for Consumer-centered Cancer Prevention and
Control 51](#__RefHeading___Toc205616437)

[262 Health Information Technology to Facilitate Patient-centered
Communication\
in Cancer-related Care 53](#__RefHeading___Toc205616438)

[263 Antibody Array for Cancer Detection and Diagnosis
55](#__RefHeading___Toc205616439)

[264 Novel and Improved Methods for Detecting Epigenetic Modifications
56](#__RefHeading___Toc205616440)

[265 Development of shRNA Library Screening Technology for
Cancer-Related\
Targets 58](#__RefHeading___Toc205616441)

[266 Nanotechnology Imaging and Sensing Platforms for Improved Diagnosis
of\
Cancer 59](#__RefHeading___Toc205616442)

[267 Multifunctional Therapeutics Based on Nanotechnology
61](#__RefHeading___Toc205616443)

[268 Novel Antibody Epitope Mapping Technologies
62](#__RefHeading___Toc205616444)

[269 Development of Novel Protein Expression Technologies for
Glycosylated\
Cancer Related Proteins 64](#__RefHeading___Toc205616445)

[270 Peptide Aptamers: New Tools to Capture and Study Protein
Interactions in\
Lieu of Immunological Reagents 65](#__RefHeading___Toc205616446)

[National Center for Research Resources (NCRR)
67](#__RefHeading___Toc205616447)

[012 Visualizing Biomedical Research Characteristics
67](#__RefHeading___Toc205616448)

[National Heart, Lung, and Blood Institute (NHLBI)
69](#__RefHeading___Toc205616449)

[035 Ultrasonic Wave Transmitter, Transmission Line and Receiver for\
Interventional MR 69](#__RefHeading___Toc205616450)

[040 Nanoprobes for Non-Invasive Detection of Atherosclerotic Plaques
69](#__RefHeading___Toc205616451)

[043 Development of Pathogen Inactivation Technologies for Blood
Components 70](#__RefHeading___Toc205616452)

[044 Development of Cell-based Bioassays Using Induced Pluripotent Stem
(iPS)\
Cell Lines 71](#__RefHeading___Toc205616453)

[045 Development of Novel Formulations for Iron Chelators to Treat Iron\
Overload in Patients on Transfusion Therapy
71](#__RefHeading___Toc205616454)

[046 Multiplexed Assay Platforms for Protein Biomarkers of
Cardiovascular\
Disease 72](#__RefHeading___Toc205616455)

[047 Transcatheter Ablation Devices for Arrhythmia Treatment
72](#__RefHeading___Toc205616456)

[048 Developing Novel Anticoagulants and Synthetic Heparins
73](#__RefHeading___Toc205616457)

[049 Development of Gene Transfer Approaches for Correction of Genetic\
Blood Diseases 73](#__RefHeading___Toc205616458)

[050 Wireless Communications Systems for Magnetic Resonance Imaging
(MRI)\
Guided Surgery 74](#__RefHeading___Toc205616459)

[National Institute on Alcohol Abuse and Alcoholism (NIAAA)
74](#__RefHeading___Toc205616460)

[034 Simple, Low-Cost, Onsite Biomarker Test Kits for
Alcohol-Associated\
Disorders 74](#__RefHeading___Toc205616461)

[035 Biological Sample Repository for Alcohol Research
75](#__RefHeading___Toc205616462)

[036 Identification of miRNAs as Biomarkers for Alcohol-Induced
Disorders 75](#__RefHeading___Toc205616463)

[National Institute of allergy and infectious diseases (NIAID)
76](#__RefHeading___Toc205616464)

[017 Clinical Sample Collection and Processing Technologies for
Infectious\
Disease Diagnostics 76](#__RefHeading___Toc205616465)

[National Institute on Drug Abuse (NIDA)
77](#__RefHeading___Toc205616466)

[099 Innovative Technologies to Support Economic Research in the Drug
Abuse\
Treatment System 77](#__RefHeading___Toc205616467)

[100 Instrument Development 77](#__RefHeading___Toc205616468)

[101 Rapid Assessment Tools of Sexual and Drug Use Risk Behaviors
78](#__RefHeading___Toc205616469)

[102 Electronic Drug Abuse Treatment Referral Systems for Physicians
78](#__RefHeading___Toc205616470)

[103 Virtual Reality Simulations to Train Caregivers/Providers
79](#__RefHeading___Toc205616471)

[104 Improvement of Reliability and Validity of Reporting of Sensitive
Data 79](#__RefHeading___Toc205616472)

[105 Development of Therapeutic Agents for Substance Use Disorders
79](#__RefHeading___Toc205616473)

[106 Pharmaceutical Approaches for Development of Pharmacotherapies for\
Drug Addiction 80](#__RefHeading___Toc205616474)

[107 Design and Synthesis of Treatment Agents for Drug Abuse
81](#__RefHeading___Toc205616475)

[108 Repository for Substance Abuse Brain Imaging Data (SBIR/STTR)
81](#__RefHeading___Toc205616476)

[109 Web Based Cognitive/Neuropsychological Testing for Substance Abuse
82](#__RefHeading___Toc205616477)

[110 Development of Science Education Materials or Programs
82](#__RefHeading___Toc205616478)

[111 Screening, Characterization and Validation Assays for Protein
Capture\
Reagents 83](#__RefHeading___Toc205616479)

[112 Tool Development for New or Improved Capture Reagents
83](#__RefHeading___Toc205616480)

[National Institute of Mental Health (NIMH)
84](#__RefHeading___Toc205616481)

[061 Home-Based Lithium Level Testing for Bipolar Patients
84](#__RefHeading___Toc205616482)

[Centers for Disease Control and Prevention (CDC)
84](#__RefHeading___Toc205616483)

[National Center on Birth Defects and Developmental Disabilities
(NCBDDD) 84](#__RefHeading___Toc205616484)

[008 Development of Website with Modules for Study Participants and
Fellow\
Researchers 85](#__RefHeading___Toc205616485)

[009 Development of a Publication Database and Information Retrieval
System with Announcement Feature 85](#__RefHeading___Toc205616486)

[010 Development of Standardized Evaluation Software for Blood Disorder
Public\
Health Surveillance Systems 86](#__RefHeading___Toc205616487)

[011 Animated Software depicting Iron Out of Balance
86](#__RefHeading___Toc205616488)

[012 Development and Evaluation of Web-based Applications Using
Emerging\
Technologies and New Media 87](#__RefHeading___Toc205616489)

[013 Application of Gaming Technology to Communicate Health Messages
and\
Promote Healthy Living among Persons with Disabilities
87](#__RefHeading___Toc205616490)

[014 Use of Cutting-edge Technology to Communicate with and Educate
Health\
Care Professionals about Birth Defects, Developmental Disabilities and\
Ways to Improve the Health and Wellness of Persons with Disabilities
88](#__RefHeading___Toc205616491)

[National Center for Chronic Disease Prevention and Health Promotion
(NCCDPHP) 88](#__RefHeading___Toc205616492)

[028 Inexpensive, Portable, User-friendly Calibration of Aneroid and
Electronic\
Blood Pressure Devices 89](#__RefHeading___Toc205616493)

[029 Dynamic Health Promotion Decision Making for Preconception Health
and\
Healthcare 90](#__RefHeading___Toc205616494)

[030 Development and Evaluation of a Quality and Affordable
Electric-Assist\
Bicycle for Commuting 91](#__RefHeading___Toc205616495)

[Immunization Safety Office 91](#__RefHeading___Toc205616496)

[006 Novel or Enhanced Technology for Vaccination Delivery and
Immunization\
Programs 92](#__RefHeading___Toc205616497)

[National Center for Immunization and Respiratory Diseases (NCIRD)
92](#__RefHeading___Toc205616498)

[001 Novel Methods for Detecting Viruses in Clinical Samples
92](#__RefHeading___Toc205616499)

[part II human subjects Research Guidance and Information Supplement
94](#part-ii-human-subjects-research-guidance-and-information-supplement)

[1. Introduction 94](#introduction)

[2. Scenarios 94](#scenarios)

[3. Instructions for Preparing the Section on Protection of Human
Subjects
96](#instructions-for-preparing-the-section-on-protection-of-human-subjects)

[4. Instructions Pertaining to Non-Exempt Human Subjects Research
100](#instructions-pertaining-to-non-exempt-human-subjects-research)

[4.1 Protection of Human Subjects 100](#protection-of-human-subjects)

[4.1.1 Risks to Human Subjects 100](#risks-to-human-subjects)

[4.1.2 Adequacy of Protection Against Risks
101](#adequacy-of-protection-against-risks)

[4.1.3 Potential Benefits of the Proposed Research to Human Subjects and
Others
102](#potential-benefits-of-the-proposed-research-to-human-subjects-and-others)

[4.1.4 Importance of the Knowledge to be Gained
102](#importance-of-the-knowledge-to-be-gained)

[4.1.5 Data and Safety Monitoring Plan
102](#data-and-safety-monitoring-plan)

[4.1.6 ClinicalTrials.gov Requirements
103](#clinicaltrials.gov-requirements)

[4.2 Inclusion of Women and Minorities
103](#inclusion-of-women-and-minorities)

[4.2.1 Additional Instructions and Requirements When NIH-Defined Phase
III Clinical\
Trials Are Proposed
105](#additional-instructions-and-requirements-when-nih-defined-phase-iii-clinical-trials-are-proposed)

[4.3 Instructions for Completing the Targeted/Planned Enrollment Tables
for\
Reporting Race and Ethnicity Data for Subjects in Clinical Research
105](#instructions-for-completing-the-targetedplanned-enrollment-tables-for-reporting-race-and-ethnicity-data-for-subjects-in-clinical-research)

[4.4 Inclusion of Children 107](#inclusion-of-children)

[5. Human Subjects Research Policy 108](#human-subjects-research-policy)

[5.1 Protection of Human Subjects 108](#protection-of-human-subjects-1)

[5.2 Vulnerable Populations 109](#vulnerable-populations)

[5.3 Data and Safety Monitoring Plans for Clinical Trials
110](#data-and-safety-monitoring-plans-for-clinical-trials)

[5.4 IRB Approval 110](#irb-approval)

[5.5 Required Education in the Protection of Human Research Participants
110](#required-education-in-the-protection-of-human-research-participants)

[5.6 NIH Policy on the Inclusion of Women and Minorities in Clinical
Research
111](#nih-policy-on-the-inclusion-of-women-and-minorities-in-clinical-research)

[5.7 NIH Policy on Inclusion of Children
111](#nih-policy-on-inclusion-of-children)

[5.8 NIH Policy on Reporting Race and Ethnicity Data: Subjects in
Clinical Research
111](#nih-policy-on-reporting-race-and-ethnicity-data-subjects-in-clinical-research)

[5.9 Research on Transplantation of Human Fetal Tissue
112](#research-on-transplantation-of-human-fetal-tissue)

[5.10 Research Using Human Embryonic Stem Cells
112](#research-using-human-embryonic-stem-cells)

[5.11 ClinicalTrials.gov Requirements
113](#clinicaltrials.gov-requirements-1)

Appendix A --- PROPOSAL COVER SHEET - use for Phase I proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)

APPENDIX B --- ABSTRACT OF RESEARCH PLAN - use for Phase I, Phase II,
and Fast-Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)

APPENDIX C --- PRICING PROPOSAL - use for Phase I, Phase II and
Fast-Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)

Appendix D --- Phase II Technical Proposal Cover Sheet - use for Phase
II and Fast-Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.pdf)

Appendix E --- Statement of Work Sample Format - use for Phase II and
Fast-Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.pdf)

Appendix F --- Summary of Related Activities - use for Phase II and
Fast- Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.pdf)

Appendix G --- Proposal Summary and Data Record - use for Phase II and
Fast-Track Proposals\
[MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc)\
[PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf)

The Appendices noted above are in Microsoft Word and Adobe Acrobat
Reader fillable format.

NOTE: Other software packages for completing these proposals may be
available from other sources; however, it is essential that the type
size and format specifications are met or the proposal may be returned
without review.

DISCLAIMER: Reference to these software packages neither constitutes nor
should be inferred to be an endorsement or recommendation of any
product, service, or enterprise by the National Institutes of Health,
any other agency of the United States Government, or any employee of the
United States Government. No warranties are stated or implied.

U. S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH AND THE CENTERS FOR
DISEASE CONTROL AND PREVENTION FOR\
SMALL BUSINESS INNOVATION RESEARCH\
CONTRACT PROPOSALS

# Part I [Instructions for Preparing and Submitting a Proposal](#PartI)

# 1. PROGRAM DESCRIPTION

## 1.1 Purpose of Solicitation

The National Institutes of Health (NIH) and the Centers for Disease
Control and Prevention (CDC) invite small business concerns to submit
research proposals under this Small Business Innovation Research (SBIR)
Contract Solicitation. Firms with the capability to conduct research and
development (R&D) in any of the health related topic areas described in
[Section 12](#research-topics), and to commercialize the results of that
R&D, are encouraged to participate.

*This solicitation is for Phase I contract proposals and also for Phase
I/Phase II Fast-Track contract proposals (see specific topics listed in*
[Section 12](#research-topics) *and awarding components identified as
accepting Fast-Track proposals).*

Included are instructions for offerors to prepare contract proposals, a
description of the proposal review process, and some conditions of a
contract award. **Contract proposals will be accepted only if they
respond specifically to a research topic within this solicitation (see
Section 12 "Research Topics").** Otherwise, proposals will be returned
to the offeror(s) without evaluation.

To apply for an SBIR GRANT rather than an SBIR CONTRACT, use the Omnibus
Solicitation of the NIH, CDC, and FDA for Small Business Innovation
Research Applications
(<http://grants.nih.gov/grants/guide/pa-files/PA-08-050.html>).

The objectives of the SBIR program include stimulating technological
innovation in the private sector, strengthening the role of small
business in meeting Federal R/R&D needs, increasing private sector
commercialization of innovations developed through Federal SBIR R&D,
increasing small business participation in Federal R&D, and fostering
and encouraging participation by socially and economically disadvantaged
small business concerns and women-owned small business concerns in the
SBIR program.

The Federal SBIR program is authorized under Public Laws 97-219, 99-443,
102-564, and 106-554. The basic design of the NIH/CDC SBIR program is in
accordance with the Small Business Administration (SBA) SBIR Program
Policy Directive, 2002. This SBIR Contract solicitation strives to
encourage scientific and technical innovation in areas specifically
identified by the NIH/CDC awarding components shown in Section I.3. The
guidelines presented in this solicitation reflect the flexibility
provided in the Policy Directive to encourage proposals based on
scientific and technical approaches most likely to yield results
important to the NIH/CDC and to the private sector.

## 1.2 Three Phase Program

The SBIR program consists of three separate phases:

The objective of Phase I is to determine the scientific or technical
feasibility and commercial merit of the proposed research or R&D efforts
and the quality of performance of the small business concern, prior to
providing further Federal support in Phase II. Phase I awards normally
may not exceed \$100,000 for direct costs, indirect costs, and profit
(fixed fee) for a period normally not to exceed 6 months.

The objective of Phase II is to continue the research or R&D efforts
initiated in Phase I. Funding shall be based on the results of Phase I
and the scientific and technical merit and commercial potential of the
Phase II proposal. Phase II awards normally may not exceed \$750,000 for
direct costs, indirect costs, and profit (fixed fee) for a period
normally not to exceed two years. *Phase II proposals may only be
submitted upon the request of the Contracting Officer, if not submitted
concurrently with the initial Phase I proposal under the Fast-Track
procedure (described in Section 5).* *Only one Phase II award may result
from a single Phase I SBIR contract.*

The objective of Phase III, where appropriate, is for the small business
concern to pursue with non-SBIR funds the commercialization objectives
resulting from the outcomes of the research or R&D funded in Phases I
and II. Phase III may involve follow-on, non-SBIR funded R&D or
production contracts for products or processes intended for use by the
U.S. Government.

The competition for SBIR Phase I and Phase II awards satisfies any
competition requirement of the Armed Services Procurement Act, the
Federal Property and Administrative Services Act, and the competition in
Contracting Act. Therefore, an agency that wishes to fund an SBIR Phase
III project is not required to conduct another competition in order to
satisfy those statutory provisions. As a result, in conducting actions
relative to a Phase III SBIR award, it is sufficient to state for
purposes of a Justification and Approval pursuant to FAR 6.302-5 that
the project is a SBIR Phase III award that is derived from, extends, or
logically concludes efforts performed under prior SBIR funding
agreements and is authorized under 10 U.S.C. 2304(b)(2) or 41 U.S.C.
253(b)(2).

The NIH is interested in developing products and services via the SBIR
program that improve the health of the American people. In its
commitment to also support President Bush\'s [Executive Order 13329
(http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2004/pdf/04-4436.pdf)](http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2004/pdf/04-4436.pdf),
encouraging innovation in manufacturing-related research and
development, NIH seeks, through the SBIR program, biomedical research
related to advanced processing, manufacturing processes, equipment and
systems; or manufacturing workforce skills and protection. This
solicitation includes some topic areas that are considered relevant to
manufacturing-related R&D. Additional information will be posted on the
[NIH Small Business Research Funding Opportunities Web site
(http://grants.nih.gov/grants/funding/sbir.htm)](http://grants.nih.gov/grants/funding/sbir.htm)
and in the [NIH Guide for Grants and Contracts
(http://grants.nih.gov/grants/guide/index.html)](http://grants.nih.gov/grants/guide/index.html)
as it becomes available. Small businesses may be interested in reading a
U.S. Department of Commerce 2004 report, [\"Manufacturing in America: A
Comprehensive Strategy to Address the Challenges to U.S. Manufacturers\"
(http://www.commerce.gov/opa/press/Secretary_Evans/2004_Releases/ManufacturingReport/DOC_MFG_Report_Complete.pdf)](http://www.commerce.gov/opa/press/Secretary_Evans/2004_Releases/ManufacturingReport/DOC_MFG_Report_Complete.pdf).

## 1.3 Awarding Components

The following awarding components are participating in this SBIR
Solicitation for Contract Proposals.

### National Institutes of Health (NIH)

-   National Cancer Institute (NCI)

-   National Center for Research Resources (NCRR)

-   National Heart, Lung, and Blood Institute (NHLBI)

-   National Institute on Alcohol Abuse and Alcoholism (NIAAA)

-   National Institute of Allergy and Infectious Diseases (NIAID)

-   National Institute on Drug Abuse (NIDA)

-   National Institute of Mental Health (NIMH)

### Centers for Disease Control and Prevention (CDC)

-   National Center on Birth Defects and Developmental Disabilities
    (NCBDDD)

-   National Center for Chronic Disease Prevention and Health Promotion
    (NCCDPHP)

-   Immunization Safety Office (ISO)

## 1.4 SBIR Program Eligibility

***Organizational Criteria:*** Each organization submitting a proposal
under the SBIR program must qualify as a small business concern as
defined in [Section 3](#small_business_concern). In determining whether
an offeror is a small business concern, an assessment will be made of
several factors, including whether or not it is independently owned and
operated and whether or not it is an affiliate of a larger organization
whose employees, when added to those of the offeror organization, exceed
500. In conducting this assessment, all appropriate factors will be
considered, including common ownership, common management, and
contractual relationships.

In accordance with 13 C.F.R. 121.103, affiliation exists when "... one
concern controls or has the power to control the other ... control may
be affirmative or negative, ...it does not matter whether control is
exercised, so long as the power to control exists." One of the
circumstances that would lead to a finding that an organization is
controlling or has the power to control another organization involves
sharing common office space and/or employees and/or other facilities
(e.g., laboratory space). 13 C.F.R. 121.103 also states that control or
the power to control exists when "... key employees of one concern
organize a new concern ... and serve as its officers, directors,
principal stockholders, and/or key employees; and one concern is
furnishing or will furnish the other concern with subcontracts,
financial or technical assistance, and/or other facilities, whether for
a fee or otherwise."

Joint ventures and limited partnerships are eligible provided the entity
created qualifies as a small business concern as defined in [Section
3](#small_business_concern) of this solicitation.

*If it appears that an offeror does not meet eligibility requirements,
the NIH/CDC will request an eligibility determination of the
organization from the cognizant SBA Government Contracting Area Office.
The evaluation of the proposal for scientific merit will be deferred
until the SBA provides a determination*.

***Project Director/Principal Investigator Criteria.*** The primary
employment of the Project Director/Principal Investigator (PD/PI) must
be with the offeror at the time of contract award and during the conduct
of the proposed project. The PD/PI is the single individual designated
in the proposal with responsibility for the scientific and technical
direction of the project. Primary employment means that *more than one
half of the PD/PI's time* is spent in the employ of the small business
concern. *Primary employment with a small business concern precludes
full-time employment at another organization*.

In the event that the PD/PI: (1) is a less-than-full-time employee of
the small business, (2) is concurrently employed by another
organization, or (3) gives the appearance of being concurrently employed
by another organization, whether for a paid or unpaid position, at the
time of submission of the proposal, *it is essential that documentation
be submitted with the proposal to verify his/her eligibility*. If the
PD/PI also is employed or appears to be employed by an organization
other than the offeror (e.g., a university, a nonprofit research
institute, or another company), a letter must be provided by the
*non-offeror organization* confirming that the PD/PI will, if awarded an
SBIR contract, become a less-than-half-time employee of such
organization and will remain so for the duration of the SBIR project. If
the PD/PI is employed by a university, the Dean\'s Office must provide
such a letter. If the PD/PI is employed by another for-profit
organization, the corporate official must sign the letter. This
documentation is required for every proposal that is submitted, even one
that is a revision of a previously submitted proposal.

***Multiple Principal Investigators.*** Offerors may propose a multiple
Project Director/Principal Investigator (PD/PI) model to direct the
project or program to be supported by the contract. The multiple PD/PI
model is intended to supplement, and not replace, the traditional single
PI model. Ultimately, the decision to submit a proposal using the
multiple PD/PI versus single PD/PI is the decision of the investigators
and their organizations. The decision whether to employ multiple PDs/PIs
should be consistent with and justified by the scientific goals of the
project.

The offeror organization may designate multiple individuals as principal
investigators (PD/PIs) who share the authority and responsibility for
leading and directing the project, intellectually and logistically. When
multiple principal investigators are named, each is responsible and
accountable to the offeror organization, or as appropriate, to a
collaborating organization for the proper conduct of the project or
program including the submission of all required reports. The presence
of more than one PD/PI on a proposal or award diminishes neither the
responsibility nor the accountability of any individual PD/PI.

***For Multiple PD/PI proposals:*** The first PI listed must be
affiliated with the applicant small business concern organization
submitting the proposal and will serve as the **Contact PD/PI**. For
both SBIR Phase I and SBIR Phase II, the *primary employment of the
"Contact PD/PI" must be with the small business concern at the time of
award and during the conduct of the proposed project.*

***Performance Site Criteria.*** For both Phase I and Phase II, the
research or R&D project activity *must be performed in its entirety in
the United States (see* [Part I, Section 3.
Definitions](#United_States)*)*.

Access to special facilities or equipment in another organization is
permitted (as in cases where the SBIR awardee has entered into a
subcontractual agreement with another institution for a specific,
limited portion of the research project). However, research space
occupied by an SBIR contractor organization must be space that is
available to and under the control of the SBIR contractor for the
conduct of its portion of the project. Where there is indication of
sharing of common employees, a determination will be made on a
case-by-case basis of whether or not such sharing constitutes control or
the power to control.

Whenever a proposed SBIR project is to be conducted in facilities other
than those of the offeror, a letter must be submitted *with* the
proposal stating that leasing/rental arrangements have been negotiated
for appropriate research space (i.e., space that will be available to
and under the control of the SBIR contractor organization).

This letter must be signed by an *authorized official of the
organization whose facilities are to be used for the SBIR project.* It
also must include a description of the facilities and, if appropriate,
equipment that will be leased/rented to the offeror organization.

***Market Research.*** *The NIH/CDC will not support any market research
under the SBIR program*. Neither will it support studies of the
literature that will lead to a new or expanded statement of work.
Literature searches where the commercial product is a database are
acceptable.

For purposes of the SBIR program, "market research" is the systematic
gathering, recording, computing, and analyzing of data about problems
relating to the sale and distribution of the subject of the research
project. It includes various types of research, such as the size of
potential market and potential sales volume, the identification of
consumers most apt to purchase the products, and the advertising media
most likely to stimulate their purchases. However, "market research"
does not include activities under a research plan or protocol that
require a survey of the public as part of the objective of the project
to determine the impact of the subject of the research on the behavior
of individuals.

# 2. AGENCY CONTACT FOR INFORMATION

***Web Site.*** The NIH SBIR/STTR Web Site at
<http://grants.nih.gov/grants/funding/sbir.htm> offers electronic access
to SBIR solicitations, abstracts of ongoing SBIR projects, the latest
updates on the SBIR program, hyperlinks to sources of business
assistance, and other useful information.

***Technical Questions about Solicitation Topics or Contract
Administration.*** Technical questions about a particular contract topic
and general questions on the administration of an SBIR contract should
be directed to the appropriate contracting officer listed in [Section
10. Contracting Officers and Addresses for Mailing and Delivery of
Proposals](#contracting-officers-and-addresses-for-mailing-or-delivery-of-proposals).

***General Questions about the NIH SBIR Program***

Ms. Jo Anne Goodnight

NIH SBIR/STTR Program Coordinator

6705 Rockledge Drive

Rockledge I, Room 3540

Bethesda, MD 20892-7963

Phone: 301-435-2688 Fax: 301-480-0146

Email: <sbir@od.nih.gov>

Ms. Kay Etzler

NIH SBIR/STTR Program Analyst

6705 Rockledge Drive

Rockledge I, Room 3535

Bethesda, MD 20892-7963

Phone: 301-435-2713 Fax: 301-480-0146

Email: <sbir@od.nih.gov>

***General Questions about the CDC SBIR Program***

Dr. Denise Burton

Office of Public Health Research (OPHR)

Office of the Chief Science Officer

Phone: 404-639-4641

Email: <DBurton2@cdc.gov>

Mr. Jerald O'Hara

Office of Public Health Research (OPHR)

Office of the Chief Science Officer

Phone: 404-639-4796

Email: <JOHara@cdc.gov>

***Listserv.*** The NIH maintains a ListServ e-mail broadcast service.
To stay in touch with SBIR opportunities and receive notices about
upcoming conferences and solicitations, subscribe by sending an email to
<LISTSERV@LIST.NIH.GOV> with the following text in the message body:
subscribe listname your name, where listname is the name of the list you
wish to subscribe to, and your name is your name. (LISTSERV will get
your e-mail address from the "From:" address of your e-mail message.)

# 3. DEFINITIONS

***A******ffiliate.*** This term has the same meaning as set forth in 13
C.F.R. Part 121 -- Small Business Size Regulations, §121.103, *"How does
the SBA determine affiliation?"*
([http://www.washingtonwatchdog.org/documents/cfr/title13/part121.html#121.103](http://www.washingtonwatchdog.org/documents/cfr/title13/part121.html%23121.103))

***Autopsy Materials.*** The use of autopsy materials is governed by
applicable Federal, state and local law and is not directly regulated by
45 CFR Part 46.

***C***[]{#child .anchor}***hild.*** The NIH Policy on Inclusion of
Children defines a child as an individual under the age of 21 years. The
intent of the NIH policy is to provide the opportunity for children to
participate in research studies when there is a sound scientific
rationale for including them, and their participation benefits children
and is appropriate under existing Federal guidelines. Thus, children
must be included in NIH conducted or supported clinical research unless
there are scientific or ethical reasons not to include them.

DHHS Regulations (45 C.F.R. Part 46, Subpart D, Sec.401-409
([http://www.hhs.gov/ohrp/humansubjects/
guidance/45cfr46.htm#subpartd](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd)))
provide additional protections for children involved as subjects in
research, based on this definition: \"Children are persons who have not
attained the legal age for consent to treatments or procedures involved
in research, under the applicable law of the jurisdiction in which the
research will be conducted.\" Generally, state laws define what
constitutes a "child." Consequently, the age at which a child\'s own
consent is required and sufficient to participate in research will vary
according to state law. For example, some states consider a person age
18 to be an adult and therefore one who can provide consent without
parental permission.

[]{#clinical_research .anchor}***Clinical Research.*** NIH defines human
clinical research as research with human subjects that is:\
*(1)* Patient-Oriented Research.\
Research conducted with human subjects (or on material of human origin
such as tissues, specimens and cognitive phenomena) for which an
investigator (or colleague) directly interacts with human subjects.
Excluded from this definition are *in vitro* studies that utilize human
tissues that cannot be linked to a living individual. Patient-oriented
research includes: (a) mechanisms of human disease, (b) therapeutic
interventions, (c) clinical trials, or (d) development of new
technologies.

*(2)* Epidemiologic and Behavioral Studies.

*(3)* Outcomes Research and Health Services Research.

Studies falling under Exemption 4 for human subjects research are not
considered clinical research by this definition.

[]{#clinical_trial .anchor}***Clinical Trial.*** The NIH defines a
clinical trial as a prospective biomedical or behavioral research study
of human subjects that is designed to answer specific questions about
biomedical or behavioral interventions (drugs, treatments, devices, or
new ways of using known drugs, treatments, or devices).

Clinical trials are used to determine whether new biomedical or
behavioral interventions are safe, efficacious, and effective.

Behavioral human subjects research involving an intervention to modify
behavior (diet, physical activity, cognitive therapy, etc.) fits this
definition of a clinical trial.

Human subjects research to develop or evaluate clinical laboratory tests
(e.g. imaging or molecular diagnostic tests) might be considered to be a
clinical trial if the test will be used for medical decision making for
the subject or the test itself imposes more than minimal risk for
subjects.

Biomedical clinical trials of experimental drug, treatment, device or
behavioral intervention may proceed through four phases:

-   *Phase I* clinical trials test a new biomedical intervention in a
    small group of people (e.g., 20-80) for the first time to evaluate
    safety (e.g., to determine a safe dosage range and to identify side
    effects).

-   *Phase II* clinical trials study the biomedical or behavioral
    intervention in a larger group of people (several hundred) to
    determine efficacy and to further evaluate its safety.

-   *Phase III* studies investigate the efficacy of the biomedical or
    behavioral intervention in large groups of human subjects (from
    several hundred to several thousand) by comparing the intervention
    to other standard or experimental interventions as well as to
    monitor adverse effects, and to collect information that will allow
    the intervention to be used safely.

-   *Phase IV* studies are conducted after the intervention has been
    marketed. These studies are designed to monitor effectiveness of the
    approved intervention in the general population and to collect
    information about any adverse effects associated with widespread
    use.

-   []{#Human_Subjects_Defs_NIH_PhaseIII .anchor}*NIH-Defined Phase III
    Clinical Trial*. An NIH-defined Phase III clinical trial is a
    broadly based prospective Phase III clinical investigation, usually
    involving several hundred or more human subjects, for the purpose of
    evaluating an experimental intervention in comparison with a
    standard or control intervention or comparing two or more existing
    treatments. Often the aim of such investigation is to provide
    evidence leading to a scientific basis for consideration of a change
    in health policy or standard of care. The definition includes
    pharmacologic, non-pharmacologic, and behavioral interventions given
    for disease prevention, prophylaxis, diagnosis, or therapy.
    Community trials and other population-based intervention trials are
    also included.

***Coded.*** With respect to private information or human biological
specimens, *coded* means that:

\(1\) identifying information (such as name or social security number)
that would enable the investigator to readily ascertain the identity of
the individual to whom the private information or specimens pertain has
been replaced with a number, letter, symbol or combination thereof
(i.e., the code); and

\(2\) a key to decipher the code exists, enabling linkage of the
identifying information with the private information or specimens.

Research that involves only coded private information/data or coded
human biological specimens may not constitute human subjects research
under the DHHS human subjects regulations (45 CFR 46) if:

-   the specimens and/or information/data are not obtained from an
    interaction/intervention with the subject specifically for the
    research; and

-   the investigator(s) cannot readily ascertain the identity of the
    individual(s) to whom the coded private information or specimens
    pertain (e.g., the researcher\'s access to subject identities is
    prohibited).

Individuals who provide coded information or specimens for proposed
research and who also collaborate on the research involving such
information or specimens are considered to be involved in the conduct of
human subjects research.

(See the following guidance from the Office for Human Research
Protections (OHRP) for additional information and examples:
<http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf>.)

***Commercialization.*** The process of developing markets and producing
and delivering products for sale (whether by the originating party or by
others). As used here, commercialization includes both government and
private sector markets.

***C******onsultant.*** An individual who provides professional advice
or services for a fee, but normally not as an employee of the engaging
party. In unusual situations, an individual may be both a consultant and
an employee of the same party, receiving compensation for some services
as a consultant and for other work as a salaried employee. To prevent
apparent or actual conflicts of interest, grantees and consultants must
establish written guidelines indicating the conditions of payment of
consulting fees. Consultants may also include firms that provide paid
professional advice or services.

***Contract.*** An award instrument establishing a binding legal
procurement relationship between a funding agency and the recipient,
obligating the latter to furnish an end product or service and binding
the agency to provide payment therefore.

***Data and Safety Monitoring Plan.*** NIH requires a data and safety
monitoring plan for each clinical trial that will provide oversight and
monitoring to ensure the safety of participants and the validity and
integrity of the data. The level of monitoring should be commensurate
with the risks and the size and complexity of the clinical trial. A
detailed data and safety monitoring plan must be submitted to the
applicant's IRB and subsequently to the funding IC for approval prior to
the accrual of human subjects. The reporting of Adverse Events must be
reported to the IRB, the NIH funding Institute or Center, and other
required entities. This policy requirement is in addition to any
monitoring requirements imposed by 45 CFR Part 46
([http://www.hhs.gov/ohrp/humansubjects/guidance/
45cfr46.htm](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)).

***Data and Safety Monitoring Board (DSMB).*** NIH requires the
establishment of a Data and Safety Monitoring Board (DSMB) for
multi-site clinical trials involving interventions that entail potential
risk to the participants, *and generally for Phase III clinical trials*.

***Essentially Equivalent Work.*** This term is meant to identify
"scientific overlap," which occurs when: (1) substantially the same
research is proposed for funding in more than one contract proposal or
grant application submitted to the same Federal agency; OR (2)
substantially the same research is submitted to two or more different
Federal agencies for review and funding consideration; OR (3) a specific
research objective and the research design for accomplishing that
objective are the same or closely related in two or more proposals or
awards, regardless of the funding source.

[]{#Human_Subjects_exempt .anchor}***Exemptions.*** The six categories
of research exempt from the DHHS human subject regulations are:

***Exemption 1:*** Research conducted in established or commonly
accepted educational settings, involving normal educational practices,
such as (i) research on regular and special education instructional
strategies, or (ii) research on the effectiveness of or the comparison
among instructional techniques, curricula, or classroom management
methods.

[]{#Human_Subjects_Exemption2 .anchor}***Exemption 2:*** Research
involving the use of educational tests (cognitive, diagnostic, aptitude,
achievement), survey procedures, interview procedures, or observation of
public behavior, unless:

\(i\) information obtained is recorded in such a manner that human
subjects can be identified directly or through identifiers linked to the
subjects and (ii) any disclosure of the human subjects\' responses
outside the research could reasonably place the subjects at risk of
criminal or civil liability or be damaging to the subjects\' financial
standing, employability, or reputation.

> Exemption 2 for research involving survey or interview procedures or
> observation of public behavior, does not apply to research with
> children (see 45 CFR Part 46, Subpart D
> ([http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#
> subpartd](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd))),
> except for research involving observations of public behavior when the
> investigator(s) do not participate in the activities being observed.

***Exemption 3:*** Research involving the use of educational tests
(cognitive, diagnostic, aptitude, achievement), survey procedures,
interview procedures, or observation of public behavior that is not
exempt under paragraph (b)(2) of this section if: (i) the human subjects
are elected or appointed public officials or candidates for public
office; or (ii) Federal statute(s) require(s) without exception that the
confidentiality of the personally identifiable information will be
maintained throughout the research and thereafter.

***Exemption 4:*** Research involving the collection or study of
existing data, documents, records, pathological specimens, or diagnostic
specimens, if these sources are publicly available or if the information
is recorded by the investigator in such a manner that subjects cannot be
identified, directly or through identifiers linked to the subjects.

The humans subjects regulations decision charts
(<http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm>) of
the Office of Human Research Protection (OHRP) will determine whether
the research falls under the human subjects regulations and if so,
whether it meets the criteria for Exemption 4. The NIH Office of
Extramural Research website also contains information that is helpful
for determining whether human subjects research meets the criteria for
Exemption 4. See <http://grants.nih.gov/grants/policy/hs/index.htm>.

> Research that meets the criteria for Exemption 4 is not considered
> "clinical research" as defined by NIH. Therefore the NIH policies for
> inclusion of women, minorities and children in clinical research, and
> targeted/planned enrollment tables, do not apply to research projects
> covered by Exemption 4.

***Exemption 5:*** Research and demonstration projects that are
conducted by or subject to the approval of Department or Agency heads
and that are designed to study, evaluate, or otherwise examine: (i)
public benefit or service programs (ii) procedures for obtaining
benefits or services under those programs (iii) possible changes in or
alternatives to those programs or procedures or (iv) possible changes in
methods or levels of payment for benefits or services under those
programs.

***Exemption 6:*** Taste and food quality evaluation and consumer
acceptance studies (i) if wholesome foods without additives are consumed
or (ii) if a food is consumed that contains a food ingredient at or
below the level and for a use found to be safe, or agricultural,
chemical, or environmental contaminant at or below the level found to be
safe, by the Food and Drug Administration or approved by the
Environmental Protection Agency or the Food Safety and Inspection
Service of the U.S. Department of Agriculture.

***Feasibility.*** The extent to which a study or project may be done
practically and successfully.

***Funding Agreement.*** Any grant, contract, or cooperative agreement
entered into between any Federal agency and any small business concern
for the performance of experimental, developmental, or research work,
including products or services, funded in whole or in part by the
Federal Government.

***Gender.*** Refers to the classification of research subjects into
either or both of two categories: women and men. In some cases,
representation is unknown, because gender composition cannot be
accurately determined (e.g., pooled blood samples or stored specimens
without gender designation).

[]{#human_subjects_research .anchor}***Human Subjects.*** The DHHS
regulations "Protection of Human Subjects" ([45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm),
administered by OHRP) define a human subject as a living individual
about whom an investigator conducting research obtains:

-   data through *intervention* or *interaction* with the individual or

-   identifiable *private information*

***Individually Identifiable Private Information.*** According to its
guidance for use of coded specimens, OHRP generally considers private
information or specimens to be *individually identifiable* as defined at
45 CFR 46.102(f) when they can be linked to specific individuals by the
investigator(s) either directly or indirectly through *coding* systems.
Conversely, OHRP considers private information or specimens not to be
individually identifiable when they cannot be linked to specific
individuals by the investigator(s) either directly or indirectly through
coding systems.

***Innovation.*** Something new or improved, including research for: (1)
development of new technologies, (2) refinement of existing
technologies, or (3) development of new applications for existing
technologies. For the purposes of PHS programs, an example of
"innovation" would be new medical or biological products, for improved
value, efficiency, or costs.

***Intellectual Property.*** The separate and distinct types of
intangible property that are referred to collectively as "intellectual
property," including but not limited to: patents, trademarks,
copyrights, trade secrets, SBIR technical data (as defined in this
section), ideas, designs, know-how, business, technical and research
methods, and other types of intangible business assets, and including
all types of intangible assets either proposed or generated by an SBC as
a result of its participation in the SBIR program.

***Intervention*** includes both physical procedures by which data are
gathered (for example, venipuncture) and manipulations of the subject or
the subject\'s environment that are performed for research purposes. (45
CFR 46.102(f)).

***Interaction*** includes communication or interpersonal contact
between investigator and subject. (45 CFR 46.102(f)).

***Investigator.*** The OHRP considers the term investigator to include
anyone involved in conducting the research. OHRP does not consider the
act of solely providing coded private information or specimens (for
example, by a tissue repository) to constitute involvement in the
conduct of the research. However, if the individuals who provide *coded*
information or specimens also collaborate on other activities related to
the conduct of the research with the investigators who receive such
information or specimens, they will be considered to be involved in the
conduct of the research. (See OHRP's [2004 Coded Specimen Guidance
(http://www.hhs.gov/ohrp/humansubjects/
guidance/cdebiol.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.htm).)

***Joint Venture.*** An association of concerns with interests in any
degree or proportion by way of contract, express or implied, consorting
to engage in and carry out a single specific business venture for joint
profit, for which purpose they combine their efforts, property, money,
skill, or knowledge, but not on a continuing or permanent basis for
conducting business generally. A joint venture is viewed as a business
entity in determining power to control its management.

For additional information, see
<http://www.sba.gov/library/cfrs/13cfr121.html>.

***Manufacturing-related R&D as a result of Executive Order 13329.***
Encompasses improvements in existing methods or processes, or wholly new
processes, machines or systems. Four main areas include:

1\. *Unit process level technologies* that create or improve
manufacturing processes including:

-   fundamental improvements in existing manufacturing processes that
    deliver substantial productivity, quality, or environmental
    benefits.

-   development of new manufacturing processes, including new materials,
    coatings, methods, and associated practices.

2\. *Machine level technologies* that create or improve manufacturing
equipment, including:

-   improvements in capital equipment that create increased capability
    (such as accuracy or repeatability), increased capacity (through
    productivity improvements or cost reduction), or increased
    environmental efficiency (safety, energy efficiency, environmental
    impact).

-   new apparatus and equipment for manufacturing, including additive
    and subtractive manufacturing, deformation and molding, assembly and
    test, semiconductor fabrication, and nanotechnology.

3\. *Systems level technologies* for innovation in the manufacturing
enterprise, including:

-   advances in controls, sensors, networks, and other information
    technologies that improve the quality and productivity of
    manufacturing cells, lines, systems, and facilities.

-   innovation in extended enterprise functions critical to
    manufacturing, such as quality systems, resource management, supply
    change integration, and distribution, scheduling and tracking.

-   technologies that enable integrated and collaborative product and
    process development, including computer-aided and expert systems for
    design, tolerancing, process and materials selection, life-cycle
    cost estimation, rapid prototyping, and tooling.

4\. *Environment or societal level technologies* that improve workforce
abilities, productivity, and manufacturing competitiveness, including:

-   technologies for improved workforce health and safety, such as human
    factors and ergonomics.

-   technologies that aid and improve workforce manufacturing skill and
    technical excellence, such as educational systems incorporating
    improved manufacturing knowledge and instructional methods.

***Obtains.*** In its guidance for use of coded specimens, OHRP has
determined that under the definition of human subject at 45 CFR
46.102(f), *obtaining* identifiable private information or identifiable
specimens for research purposes constitutes human subjects research.
*Obtaining* means receiving or accessing identifiable private
information or identifiable specimens for research purposes. OHRP
interprets *obtaining* to include an investigator's use, study, or
analysis for research purposes of *identifiable private information* or
identifiable specimens already in the possession of the investigator.

***Principal Investigator, Program Director, or Project Director
(PD/PI).*** The individual(s) designated by the offeror organization to
have the appropriate level of authority and responsibility to direct the
project or program to be supported by the award.

***Private information*** includes information about behavior that
occurs in a context in which an individual can reasonably expect that no
observation or recording is taking place, and information that has been
provided for specific purposes by an individual and that the individual
can reasonably expect will not be made public (for example, a medical
record). Private information must be *individually identifiable* (i.e.,
the identity of the subject is or may readily be ascertained by the
investigator or associated with the information) in order for obtaining
the information to constitute research involving human subjects. (45 CFR
46.102(f))

***Prototype.*** A model of something to be further developed that
includes designs, protocols, questionnaires, software, devices, etc.

***Research or Research and Development (R/R&D).*** Any activity that
is:

-   A systematic, intensive study directed toward greater knowledge or
    understanding of the subject studied.

-   A systematic study directed specifically toward applying new
    knowledge to meet a recognized need.

-   A systematic application of knowledge toward the production of
    useful materials, devices, and systems or methods, including design,
    development, and improvement of prototypes and new processes to meet
    specific requirements.

***SBIR Technical Data.*** All data generated during the performance of
an SBIR award.

***SBIR Technical Data Rights.*** The rights a small business concern
obtains in data generated during the performance of any SBIR Phase I,
Phase II, or Phase III award that an awardee delivers to the Government
during or upon completion of a Federally-funded project, and to which
the Government receives a license.

***Senior/Key Personnel.*** The PD/PI and other individuals who
contribute to the scientific development or execution of the project in
a substantive, measurable way, whether or not salaries or compensation
are requested.

Typically, these individuals have doctoral or other professional
degrees, although individuals at the masters or baccalaureate level may
be considered if their involvement meets the definition of Senior/Key
Personnel. Consultants should also be included if they meet the
definition of Senior/Key Personnel. Senior/Key Personnel must devote
measurable effort to the project whether or not salaries are
requested\--"zero percent" effort or "as needed" are not acceptable
levels for those designated as Senior/Key Personnel.

***Significant Difference.*** For purposes of NIH policy, a "significant
difference" is a difference that is of clinical or public health
importance, based on substantial scientific data. This definition
differs from the commonly used "statistically significant difference,"
which refers to the event that, for a given set of data, the statistical
test for a difference between the effects in two groups achieves
statistical significance. Statistical significance depends upon the
amount of information in the data set. With a very large amount of
information, one could find a statistically significant, but clinically
small difference that is of very little clinical importance. Conversely,
with less information one could find a large difference of potential
importance that is not statistically significant.

[]{#small_business_concern .anchor}***Small Business Concern***. A small
business concern is one that, at the time of award of Phase I and Phase
II, meets *all* of the following criteria:

1\. Is independently owned and operated, is not dominant in the field of
operation in which it is proposing, has its principal place of business
located in the United States, and is organized for profit.

2\. Is at least 51% owned and controlled by either: (a) one or more
natural persons (individuals who are citizens of, or permanent resident
aliens in, the United States); or (b) another for-profit business
concern that is itself at least 51% owned and controlled by one or more
natural persons (individuals who are citizens of, or permanent resident
aliens in, the United States)(See 13 CFR 121.105 (defining "business
concern")).

3\. Has, including its affiliates, *a number of employees not exceeding
500*, and meets the other regulatory requirements found in 13 CFR Part
121. Business concerns, other than investment companies licensed, or
state development companies qualifying under the Small Business
Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one
another when either directly or indirectly, (a) one concern controls or
has the power to control the other; or (b) a third-party/parties
controls or has the power to control both.

Control can be exercised through common ownership, common management,
and contractual relationships. The term \"affiliates\" is defined in
greater detail in 13 C.F.R. 121, as is the process for calculating
"number of employees."

Business concerns include, but are not limited to, any individual (sole
proprietorship), partnership, corporation, joint venture, association,
or cooperative. Further information may be obtained by contacting the
Small Business Administration Size District Office at
<http://sba.gov/size>.

***S******ocially and Economically Disadvantaged Individual.*** A member
of any of the following groups: Black Americans; Hispanic Americans;
Native Americans; Asian-Pacific Americans; Subcontinent Asian Americans;
other groups designated from time to time by the Small Business
Administration (SBA) to be socially disadvantaged; or any other
individual found to be socially and economically disadvantaged by SBA
pursuant to Section 8(a) of the Small Business Act, 15 U.S.C. 637(a).

***Socially and Economically Disadvantaged Small Business Concern.*** A
socially and economically disadvantaged small business concern is one
that is at least 51% owned by (a) an Indian tribe or a native Hawaiian
organization, or (b) one or more socially and economically disadvantaged
individuals; **and** whose management and daily business operations are
controlled by one or more socially and economically disadvantaged
individuals.

***Subcontract.*** Any agreement, other than one involving an
employer-employee relationship, entered into by a Federal Government
prime contractor calling for supplies or services required solely for
the performance of the prime contract or another subcontract.

[]{#United_States .anchor}***United States.*** The 50 states,
territories and possessions of the U.S., Commonwealth of Puerto Rico,
Trust Territory of the Pacific Islands, and District of Columbia.

***W******omen-Owned Small Business Concern.*** A small business concern
that is at least 51% owned by a woman or women who also control and
operate it. "Control" in this context means exercising the power to make
policy decisions. "Operate" in this context means being actively
involved in the day-to-day management.

# 4. Phase I PROPOSAL PREPARATION INSTRUCTIONS AND REQUIREMENTS

## 4.1 Limitations on Length of Proposal

SBIR Phase I proposals must not exceed 25 single-sided, single-spaced
pages, including the cover sheet, abstract, cost breakdown, and all
enclosures or attachments. Pages should be of standard size (8 l/2" X
11"), and you should use an Arial, Helvetica, Palatino Linotype or
Georgia typeface and a font size of 11 points or larger. Excluded from
the 25-pages are cover letters, Human Subjects Research and Vertebrate
Animal information, letters of commitment from collaborators and
consultants and letters to determine eligibility, and, if applicable,
the list of prior SBIR Phase II awards (see Section 4.2). Unless
specifically solicited by a Contracting Officer, no other appendices or
attachments may be submitted, and if submitted, they will not be
considered in the evaluation of scientific and technical merit.
Proposals in excess of the page limitation shall not be considered for
review or award.

## 4.2 Technical Proposal Format and Content Requirements

[]{#__RefHeading___Toc205616377 .anchor}**4.2.1 Technical Proposal Cover
Sheet** - Complete the form identified as Appendix A ([MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)),
and use it as the first page of the proposal. *No other cover sheet
should be used*.

If submitting a proposal reflecting Multiple Project Directors/Principal
Investigators (PDs/PIs), the individual designated as the Contact PI
should be entered here.

-   ***Topic Number.*** Provide the appropriate numerical designator of
    the research topic for which your proposal is being submitted. If
    your proposal is responsive to a subtopic, provide both the topic
    and subtopic numbers. (A numerical or alphabetical designator
    precedes each topic and subtopic.)

-   ***Project Title.*** Select a title that reflects the substance of
    the project. Do not use the title of the topic that appears in the
    solicitation.

[]{#__RefHeading___Toc205616378 .anchor}**4.2.2 Abstract of Research
Plan** - Complete the form identified as Appendix B ([MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)),
and insert it as the second page of each proposal. Do not include any
proprietary information as abstracts of successful proposals will be
published by NIH. The abstract should include a brief description of the
problem or opportunity, specific aims, and a description of the effort.
Summarize anticipated results and potential commercial applications of
the proposed research.

Include at the end of the Abstract a brief description (two or three
sentences) of the relevance of this research to **public** health. In
this description, be succinct and use plain language that can be
understood by a general, lay audience.

[]{#__RefHeading___Toc205616379 .anchor}**4.2.3 Research Plan**

Beginning on page three of the proposal, discuss in the order indicated
the following elements:

a\. ***Identification and Significance of the Problem or Opportunity.***
Provide a clear statement of the specific technical problem or
opportunity addressed.

b\. ***Technical Objectives.*** State the specific objectives of the
Phase I effort, including the technical questions it will try to answer
to determine the feasibility of the proposed approach.

*c. **Work Plan.*** Provide an explicit, detailed plan for the Phase I
R&D to be carried out, including the experimental design, procedures,
and protocols to be used. Address how the objectives will be met and the
questions stated in Item b above. Discuss in detail the methods to be
used to achieve each objective or task. The plan should indicate what is
planned, how, when, and where the work will be carried out, a schedule
of major events, the final product to be delivered, and the completion
date of the effort. The Phase I effort should determine the technical
feasibility of the proposed concept. For specific guidance and
instructions related to Human Subjects research, please see the section
entitled, "[Human Subjects Research and Protection from
Risk](#human-subjects-research-and-protection-from-risk)" and the
"[Human Subjects Research Guidance and Information
Supplement](#part-ii-human-subjects-research-guidance-and-information-supplement)."

d\. ***Related Research or R&D.*** Describe significant research
activities directly related to the proposed effort, including any
conducted by the Project Director/Principal Investigator (PD/PI), the
proposing firm, consultants, or others. Describe how these activities
interface with the proposed project and discuss any planned coordination
with outside sources. *The PD/PI must persuade reviewers of his or her
awareness of recent significant research or R&D conducted by others in
the same scientific field*.

e\. ***Relationship with Future R&D.***

1\. State the anticipated results of the proposed approach, assuming
project success.

2\. Discuss the significance of the Phase I effort in providing a
foundation for the Phase II R/R&D effort.

f\. ***Potential Commercial Applications.*** Describe why the proposed
project is deemed to have potential commercial applications (for use by
the Federal Government and/or private sector markets.) Describe the
market as it currently exists and how your product may enter and compete
in this market. Include the potential barriers to market entry and how
you expect to overcome them.

g\. ***Key Personnel and Bibliography of Directly Related Work.***
Identify key personnel, including their directly related education,
experience, and bibliographic information. Where resumes are extensive,
focus on summaries of the most relevant experience or publications.
*Provide dates and places of employment* and some information about the
nature of each position or professional experience. Resumes must
identify the current or most recent position.

***Multiple PD/PI Leadership Plan.*** For proposals designating multiple
PDs/PIs, a leadership plan must be included. A rationale for choosing a
multiple PD/PI approach should be described. The governance and
organizational structure of the leadership team and the research project
should be described, including communication plans, process for making
decisions on scientific direction, and procedures for resolving
conflicts. The roles and administrative, technical, and scientific
responsibilities for the project or program should be delineated for the
PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to
specific components of the project or the individual PDs/PIs should be
delineated in the Leadership Plan. In the event of an award, the
requested allocations may be reflected in Contract Award.

h\. ***Subcontractors/Consultants.*** Involvement of a university or
other subcontractors or consultants in the project may be appropriate
and is permitted. If such involvement is intended, it should be
described in detail and identified in the cost proposal. In addition,
supported by appropriate letters from each individual confirming his/her
role in the project must be included. A minimum of two-thirds of the
research and/or analytical work in Phase I, as measured by direct and
indirect costs, must be carried out by the proposing firm, unless
otherwise approved in writing by the contracting officer.

i\. ***Facilities and Equipment.*** Indicate where the proposed research
will be conducted. *One of the performance sites must be the offeror
organization*. Describe the facilities to be used; identify the
location; and briefly indicate their capacities, pertinent capabilities,
relative proximity, and extent of availability to the project. Include
clinical, computer, and office facilities of the offeror and those of
any other performance sites to be used in the project.

> Whenever a proposed SBIR project is to be conducted in facilities
> other than those of the offeror, a letter must be submitted *with* the
> proposal stating that leasing/rental arrangements have been negotiated
> for appropriate research space (i.e., space that will be available to
> and under the control of the SBIR contractor organization).
>
> This letter must be signed by an *authorized official of the
> organization whose facilities are to be used for the SBIR project.* It
> also must include a description of the facilities and, if appropriate,
> equipment that will be leased/rented to the offeror organization.

List the most important equipment items already available for this
project, noting location and pertinent capabilities of each.

Any equipment and products purchased with Government funds shall be
American-made, to the extent possible.

*Title to Equipment.* Title to equipment purchased with Government
funding by the SBIR awardee in relation to project performance vests
upon acquisition in the Federal Government. However, the Government may
transfer such title to an SBIR awardee upon expiration of the project
where the transfer would be more cost-effective than recovery of the
property.

Any research proposal involving the collection of information, such as
surveys or interviews, of 10 or more public respondents will require
clearance by the U.S. Office of Management and Budget. Therefore, it is
not practical to propose such an activity for Phase I, which normally
has only a six-month duration.

[]{#__RefHeading___Toc205616380 .anchor}**4.2.4 Current Awards and
Pending Proposals/Applications**

A small business concern may not submit both a contract proposal and a
grant application for essentially the same project to the same or
different awarding component(s) of the NIH/CDC. The only exception would
be the submission of a grant application after a contract proposal has
been evaluated and is no longer being considered for award. A firm that
receives a Phase I SBIR contract may submit a Phase II grant application
and vice versa.

A Phase I contractor may submit a Phase II contract proposal only if
invited by an NIH Contracting Officer.

While it is permissible, with proposal notification, to submit identical
proposals or proposals containing a significant amount of essentially
equivalent work (as defined in this solicitation) for consideration
under numerous Federal program solicitations, it is unlawful to enter
into contracts or grants requiring essentially equivalent effort.\
\
If there is any question concerning this, it must be disclosed to the
soliciting agency or agencies before award.

If a firm elects to submit identical proposals or proposals containing a
significant amount of essentially equivalent work under other Federal
program solicitations, include a statement in each such proposal
indicating the information requested in items 1-10 set forth below.

In addition, provide the information requested in items 1-10 on (a)
active funding through contracts, grants, and cooperative agreements
from public or private sponsors; (b) contract proposals and grant and
cooperative agreement applications pending review or funding; and (c)
contract proposals and grant and cooperative agreement applications
about to be submitted.

a\. Name and address of the funding source.

b\. Type of award (contract, grant, cooperative agreement) and
identifying number.

c\. Title of research project.

d\. Name and title of Principal Investigator(s) or Project Manager(s).

e\. Hours per week on the project by the Principal Investigator(s) or
Project Manager(s).

f\. Annual costs proposed or awarded.

g\. Entire period of support.

h\. Date of proposal/application submission or date of award.

i\. Title, number, and date of solicitations under which proposals or
applications were submitted or awards received.

j\. The specific applicable research topic for each SBIR proposal or
application submitted or award received. *Specifically identify those
projects that are SBIR*.

[]{#__RefHeading___Toc205616381 .anchor}**4.2.5 Prior SBIR Phase II
Awards**

If the small business concern has received more than 15 Phase II awards
in the prior 5 fiscal years, submit name of awarding agency, date of
award, funding agreement number, amount, topic or subtopic title,
follow-on agreement amount, source, and date of commitment and current
commercialization status for each Phase II.

*This information must be submitted with the proposal, but is excluded
from the 25-page limitation.*

[]{#__RefHeading___Toc205616382 .anchor}**4.2.6 Proposed Cost
Breakdown**

Complete the form identified as Appendix C (Contract Pricing Proposal)
([MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)).
The cost breakdown should appear as the last section of the proposal.
*If some items on this form do not apply to the proposed project, they
need not be completed*.

-   Under "Government Solicitation No.," enter "PHS 2009-1."

-   If supplies are proposed, provide the quantities and the price per
    unit.

-   Under "Direct Labor," *list all key personnel by name*. Support
    personnel may be consolidated into categories or labor classes,
    e.g., research assistants or data processing clerks.

-   Cost for travel funds must be justified and related to the needs of
    the project. If travel is proposed, provide the following details on
    "Exhibit A -- Supporting Schedule": destination(s); duration of
    trip(s); number of travelers; and cost per trip, broken down by cost
    elements, e.g., airfare, lodging, and meals.

-   If consultants are proposed, provide name(s), rate(s), and number of
    hours/days.

-   If a subcontract is proposed, provide the same type of detailed cost
    breakdown as required for Appendix C. *Also provide a copy of the
    subcontractual agreement*.

-   Use "Exhibit A -- Supporting Schedule" to itemize and justify all
    major cost elements. If more space is needed, use Page 3 of Appendix
    C.

-   *Normally, at least two-thirds or 67% of the entire research or
    analytical effort must be carried out by the offeror*, i.e.,
    subcontracts for portions of the scientific/technical effort and
    consultant fees normally may not exceed 33% of the total cost
    breakdown.

[]{#__RefHeading___Toc205616383 .anchor}**4.2.7 Streamlining the
Contracting Process**

With the Federal Acquisition Streamlining Act of 1994 and the Federal
Acquisition Reform Act of 1996, a number of terms and conditions that
previously applied to contracts under \$100,000 are no longer
applicable. Under the SBIR program, Phase I awards, which normally may
not exceed \$100,000, will reflect the streamlined contract document.

The NIH uses special *"just in time" procedures* that are designed to
reduce the administrative burden on offerors without compromising the
information needed during the initial evaluation of proposals. Certain
documents that would previously have been required for submission with
the Phase II proposal will be requested at a later stage in the
evaluation process. The following documentation is part of the "just in
time" procedures and offerors who elect to submit proposals under the
*"Fast-Track" initiative* below are not required to submit this
documentation with their initial Phase II business proposal:

-   ***Travel Policy.*** The offeror\'s written travel policy.

-   ***Annual Financial Report.*** The offeror\'s most recent annual
    financial report.

-   ***Total Compensation Plan.*** Salary and fringe benefits of
    professional employees under service contracts.

-   ***Data Substantiating the Costs and Prices Proposed.*** That is,
    payroll documentation, vendor quotes, invoice prices, etc.

[]{#__RefHeading___Toc205616384 .anchor}**4.2.8 Requirement for Adequate
Assurance of Protection of Human Subjects**

The DHHS regulations for the Protection of Human Subjects, 45 C.F.R. 46
(as amended), provide a systematic means, based on established ethical
principles, to safeguard the rights and welfare of individuals who
participate as subjects in research activities supported or conducted by
the DHHS. *The requirement is that an approved assurance of compliance
with the regulations must be on file with the Office for Human Research
Protections (OHRP), DHHS (*<http://www.hhs.gov/ohrp>*) before a DHHS
award can be made.*

Neither an Institutional Review Board (IRB) review nor an OHRP-approved
Assurance is required at the time the proposal is submitted or at the
time that the proposals are peer reviewed.

### Human Subjects Research and Protection from Risk

##### Instructions and Required Information

*This information must be submitted with the proposal, but is excluded
from the 25-page limitation*.

Create a section heading entitled "**Human Subjects Research**." Place
it immediately following the "Research Plan" section of the proposal.

In the Human Subjects Research section, you must provide sufficient
information for reviewers to determine that the proposed research meets
(1) the requirements of the DHHS regulations to protect human subjects
from research risks ([45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)),
(2) the requirements of NIH policies for data and safety monitoring of
clinical trials, and (3) the requirements of NIH policies on inclusion
of women, minorities, and children.

Provided in the [Human Subjects Research Guidance and Information
Supplement](#part-ii-human-subjects-research-guidance-and-information-supplement)
are six possible research scenarios, and links to the instructions for
providing information on human subjects protection information and the
inclusion of women, minorities, and children specific to each scenario.
All research will fall into one of these six scenarios. Determine which
scenario the proposed research falls into, then go to the specific
instructions applicable to that scenario in Section 3 of the Supplement.
Where appropriate, Section 3 provides instructions on addressing the
Inclusion of Women and Minorities, the Targeted/Planned Enrollment
Table, and the Inclusion of Children. All definitions related to human
subjects research are linked to text found in Part I, Section 3,
Definitions. Section 5 of this Part includes descriptions of and links
to the DHHS Human Subjects Protections regulations and NIH policies that
apply to clinical research.

Much of the information on the protection of human subjects that you are
required to provide in this section is identical to information that
will be required for IRB review.

[]{#__RefHeading___Toc205616385 .anchor}**4.2.9 Requirement for Adequate
Assurance of Compliance with the PHS Policy on Humane Care and Use of
Laboratory Animals**

##### Instructions and Required Information

*This information must be submitted with the proposal, but is excluded
from the 25-page limitation*.

Create a section heading entitled **"Vertebrate Animals."** Place it
immediately following the "Research Plan" section of the proposal (or
after Human Subjects Research section, if applicable).

Under the Vertebrate Animals heading, address the following five points.
In addition, when research involving vertebrate animals will take place
at collaborating site(s) or other performance site(s), provide this
information before discussing the five points. Although no specific page
limitation applies to this section of the proposal, be succinct.

1\. Provide a detailed description of the proposed use of the animals in
the work outlined in the Research Design and Methods section. Identify
the species, strains, ages, sex, and numbers of animals to be used in
the proposed work.

2\. Justify the use of animals, the choice of species, and the numbers
to be used. If animals are in short supply, costly, or to be used in
large numbers, provide an additional rationale for their selection and
numbers.

3\. Provide information on the veterinary care of the animals involved.

4\. Describe the procedures for ensuring that discomfort, distress,
pain, and injury will be limited to that which is unavoidable in the
conduct of scientifically sound research. Describe the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining
devices, where appropriate, to minimize discomfort, distress, pain, and
injury.

5\. Describe any method of euthanasia to be used and the reasons for its
selection. State whether this method is consistent with the
recommendations of the Panel on Euthanasia of the American Veterinary
Medical Association. If not, present a justification for not following
the recommendations.

###### Guidance and Additional Instructions

NIH no longer requires Institutional Animal Care and Use Committee
approval of the proposed research before NIH peer review of a proposal
([http://grants.nih.gov/
grants/guide/notice-files/NOT-OD-02-064.html](http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-064.html)).

In August, 2002 NIH announced an IACUC "just-in-time" process for
applications submitted for the October 1, 2002 deadline or other
deadlines where the applications had a May/June 2003 Council review. The
PHS policy requirement that no award may be made without an approved
Assurance and without verification of IACUC approval remains in effect.
The new policy gave institutions flexibility in the timing of IACUC
review relative to the submission of a proposal and the verification of
IACUC review. The policy does not require that IACUC approval be
deferred. Institutional officials retain the discretion to require IACUC
approval prior to NIH peer review in circumstances of their choosing if
deemed necessary. As part of the NIH peer review process, the scientific
review group will continue to address the adequacy of animal usage and
protections in the review of a proposal and will continue to raise any
concerns about animal welfare issues. Verification of IACUC approval
will be required in a "just-in-time" fashion prior to award.

The PHS *Policy on Humane Care and Use of Laboratory Animals* requires
that offeror organizations proposing to use vertebrate animals file a
written Animal Welfare Assurance with the Office of Laboratory Animal
Welfare (OLAW), establishing appropriate policies and procedures to
ensure the humane care and use of live vertebrate animals involved in
research activities supported by the PHS. The PHS policy stipulates that
an offeror organization, whether domestic or foreign, bears
responsibility for the humane care and use of animals in PHS-supported
research activities. This policy implements and supplements the *U.S.
Government Principles for the Utilization and Care of Vertebrate Animals
Used in Testing, Research, and Training* and requires that institutions
use the *Guide for the Care and Use of Laboratory Animals* as a basis
for developing and implementing an institutional animal care and use
program. This policy does not affect applicable state or local laws or
regulations that impose more stringent standards for the care and use of
laboratory animals. All institutions are required to comply, as
applicable, with the Animal Welfare Act as amended (7 USC 2131 et sec.)
and other Federal statutes and regulations relating to animals. These
documents are available from the Office of Laboratory Animal Welfare,
National Institutes of Health, Bethesda, MD 20892, (301) 496-7163.

The PHS Policy defines "animal" as "any live, vertebrate animal used or
intended for use in research, research training, experimentation or
biological testing or for related purposes."

No PHS award for research involving vertebrate animals will be made to
an offeror organization unless that organization is operating in
accordance with an approved Animal Welfare Assurance and provides
verification that the IACUC has reviewed and approved the proposed
activity in accordance with the PHS policy. Proposals may be referred by
the PHS back to the IACUC for further review in the case of apparent or
potential violations of the PHS policy. No award to an individual will
be made unless that individual is affiliated with an assured
organization that accepts responsibility for compliance with the PHS
policy. Foreign offeror organizations applying for PHS awards for
activities involving vertebrate animals are required to comply with PHS
policy or provide evidence that acceptable standards for the humane care
and use of animals will be met.

## 4.3 Limitations on Use of Appropriated Funds

The Department of Health and Human Services Appropriation Act for Fiscal
Year 2008 (Public Law 110-161), limits the use of appropriated funds on
NIH grant, cooperative agreement, and contract awards for Fiscal Year
2008, as specified below. It is anticipated that these statutory
provisions will continue in subsequent fiscal years.

### Salary Rate Limitation

Public Law 110-161 restricts the use of Federal funds to pay the direct
salary of an individual under an NIH grant, cooperative agreement, or
applicable contract, at a rate in excess of Executive Schedule, Level I
of the Federal Executive Pay scale. The salary rate limitation also
applies to individuals proposed under subcontracts; however, it does not
apply to consultants. The legislation also does not apply to firm fixed
price contracts. Effective January 1, 2008, the Executive Level I salary
is \$191,300 per year.

### Anti-Lobbying (for contracts exceeding \$100,000)

\"(a) No part of any appropriation contained in this Act shall be used,
other than for normal and recognized executive-legislative
relationships, for publicity or propaganda purposes, for the
preparation, distribution, or use of any kit, pamphlet, booklet,
publication, radio, television, or video presentation designed to
support or defeat legislation pending before the Congress or any State
legislature, except in presentation to the Congress or any State
legislature itself. (b) No part of any appropriation contained in this
Act shall be used to pay the salary or expenses of any grant or contract
recipient, or agent acting for such recipient, related to any activity
designed to influence legislation or appropriations pending before the
Congress or any State legislature.\"

### Restriction on Distribution of Sterile Needles 

\"Notwithstanding any other provision of this Act, no funds appropriated
under this Act shall be used to carry out any program of distributing
sterile needles or syringes for the hypodermic injection of any illegal
drug.\"

### Acknowledgment of Federal Funding 

\"When issuing statements, press releases, requests for proposals, bid
solicitations and other documents describing projects or programs funded
in whole or in part with Federal money, all grantees receiving Federal
funds included in this Act, including but not limited to State and local
governments and recipients of Federal research grants, shall clearly
state: (1) the percentage of the total costs of the program or project
which will be financed with Federal money; (2) the dollar amount of
Federal funds for the project or program; and (3) percentage and dollar
amount of the total costs of the project or program that will be
financed by non-governmental sources.\"

### Restriction on Abortions 

"(a) None of the funds appropriated under this Act, and none of the
funds in any trust fund to which funds are appropriated in this Act,
shall be expended for any abortion."

### Ban on Funding of Human Embryo Research 

"(a) None of the funds made available in this Act may be used for: (1)
the creation of a human embryo or embryos for research purposes; or (2)
research in which a human embryo or embryos are destroyed, discarded, or
knowingly subjected to risk of injury or death greater than that allowed
for research on fetuses in utero under 45 CFR 46.204(b) (2) and section
498(b) of the Public Health Service Act (42 U.S.C. 289g(b)). (b) For
purposes of this section, the term "human embryo or embryos" includes
any organism, not protected as a human subject under 45 CFR 46 as of the
date of the enactment of this Act, that is derived by fertilization,
parthenogenesis, cloning, or any other means from one or more human
gametes or human diploid cells."

### Limitation on Use of Funds for Promotion of Legalization of Controlled Substances 

\"(a) None of the funds made available in this Act may be used for any
activity that promotes the legalization of any drug or other substance
included in schedule I of the schedules of controlled substances
established by section 202 of the Controlled Substances Act (21
U.S.C.812). (b) The limitation in subsection (a) shall not apply when
there is significant medical evidence of a therapeutic advantage to the
use of such drug or other substance or that federally sponsored clinical
trials are being conducted to determine therapeutic advantage.\"

### NIH Public Access Requirement

"The Director of the National Institutes of Health shall require that
all investigators funded by the NIH submit or have submitted for them to
the National Library of Medicine's PubMed Central an electronic version
of their final, peer-reviewed manuscripts upon acceptance for
publication, to be made publicly available no later than 12 months after
the official date of publication: *Provided,* that the NIH shall
implement the policy in a manner consistent with copyright law." \
Further information on the implementation of NIH's Public Access
Requirement is available in NIH Guide Notice [NOT-OD-08-033
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)](http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
published on January 11, 2008.

### Dissemination of False or Deliberately Misleading Scientific Information

"None of the funds made available in this Act may be used to disseminate
scientific information that is deliberately false or misleading."\
While this mandate has not been included in past appropriations acts, it
is similar to existing requirements concerning research integrity,
fraud, and false claims, and as such, NIH does not expect this new
requirement to impact significantly the business practices at most
institutions. Grantees and contractors are advised to review their
implementation of the PHS Policies on Research Misconduct contained in
42 CFR Part 93 and the Civil False Claims Act (31 U.S.C. 3729(a)),
Criminal False Claims Act (18 U.S.C. 287 and 1001), and Program Fraud
and Civil Remedies Act (31 U.S.C. 3801 et seq.).

### Restriction on Employment of Unauthorized Alien Workers

"None of the funds in this Act may be used to employ workers described
in section 274A(h)(3) of the Immigration and Nationality Act." \
While this mandate has not been included in past appropriations acts, it
is similar to existing requirements contained in the Immigration and
Nationality Act (18 U.S.C. 1324a), and as such, NIH does not expect this
new requirement to impact significantly the business practices at most
institutions. Grantees and contractors are advised to review their
current hiring and employment practices to ensure compliance.

# 5. "Fast-Track" Initiative

### (Applicable Only to Proposals Submitted to NIH)

The "Fast-Track" initiative is a parallel review option available to
those small business concerns (offeror organizations) whose proposals
satisfy additional criteria that enhance the probability of the
project\'s commercial success. This initiative is applicable only to NIH
and only if an awarding component indicates it is accepting Fast-Track
proposals for a particular topic. (Refer to [Section 12. "Research
Topics](#research-topics)," for notation.)

The Fast-Track initiative is an opportunity for small business concerns
to submit both a Phase I and Phase II proposal for concurrent peer
review. This initiative also has the potential to minimize any funding
gap between Phase I and Phase II.

Phase I and Phase II are considered separate funding agreements under
the Fast-Track Initiative. Therefore, Phase I Fast-Track awardees must
recertify that they meet all of the eligibility criteria for an SBIR
award prior to issuance of the Phase II award.

### Fast-Track Proposal Process

To identify the proposals as Fast-Track, check the box marked "Yes" next
to the words "Fast-Track Proposal" shown on the Phase I Proposal Cover
Sheet, Appendix A ([MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/
ContractAppendixA.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)).

The small business concern must submit both a Phase I and a Phase II
proposal for concurrent initial peer review and evaluation. The
Fast-Track proposal must consist of the following parts:

1\. ***Phase I Proposal.*** Prepared in accordance with Section 4. Phase
I Proposal Preparation Instructions and Requirements, and addressing all
factors stated in the evaluation criteria (Section VII) for Phase I
proposals.

2\. ***Phase II Proposal.*** Prepared in accordance with Section 6,
Fast-Track Phase II Proposal Preparation Instructions and Requirements
and addressing all factors stated in the evaluation criteria (Section 7)
for Phase II proposals.

3\. **Commercialization Plan.** Prepared in accordance with instructions
in Section 6.2.

The Phase I and Phase II proposals are separate proposals and will be
scored individually.

Fast-Track Phase II proposals may be funded following submission of the
Phase I final report, and a determination that the Phase I objectives
were met, feasibility was demonstrated, and funds are available.

# 6. Fast-Track Phase II Proposal Preparation Instructions and Requirements

## 6.1 Limitations on Length of Proposal

SBIR Phase II proposals generally should not exceed a total of 150
single-spaced pages, including all enclosures and attachments. Pages
should be of standard size (8 1/2" x 11") and you should use an Arial,
Helvetica, Palatino Linotype or Georgia typeface and a font size of 11
points or larger. Excluded from the page limitation are cover letters
and letters from collaborators and consultants.

## 6.2 Technical Proposal Format and Content Requirements

1\. **Phase II Technical Proposal Cover Sheet** - Use Appendix D ([MS
Word (http://grants.nih.gov/grants/
funding/SBIRContract/ContractAppendixD.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.doc)
\| [PDF (http://grants.nih.gov/grants/funding/SBIRContract/
ContractAppendixD.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.pdf)).

2\. **Table of Contents**

3\. **Abstract of the Research Plan** - Use Appendix B ([MS Word
(http://grants.nih.gov/grants/funding/
SBIRContract/ContractAppendixB.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc)
\| [PDF (http://grants.nih.gov/grants/funding/SBIRContract/
ContractAppendixB.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)).
State the broad, long-term objectives and specific aims. Do not include
any proprietary information. Briefly and concisely describe the research
design and methods for achieving these goals.

4\. **Anticipated Results of Phase I Effort** - Briefly discuss and
summarize the objectives of your Phase I effort, the research activities
to be carried out, and the anticipated results.

5\. **Research Plan**

a\. *Detailed Approach and Methodology* - provide an explicit detailed
description of the Phase II approach. This section should be the major
portion of the proposal and must clearly show advancement in the project
appropriate for Phase II. Indicate not only what is planned, but also
how and where the work will be carried out. List all tasks in a logical
sequence to precisely describe what is expected of the contractor in
performance of the work. Tasks should contain detail to (1) establish
parameters for the project; (2) keep the effort focused on meeting the
objectives; (3) describe end products and deliverables; and (4) describe
periodic/final reports required to monitor work progress under the
contract. Offerors using [Human Subjects](#__RefHeading___Toc205616384)
or [Vertebrate Animals](#__RefHeading___Toc205616385) in their research
should refer to the specific instructions provided in this solicitation.

b\. *Personnel* - List by name, title, department and organization, the
extent of commitment to this Phase II effort, and detail each person's
qualifications and role in the project. *Provide resumes for all key
staff members,* describing directly related education, experience, and
relevant publications. Describe in detail any involvement of
subcontractors or consultants, and *provide resumes for all key
subcontractor staff. Also, include letters of commitment with proposed
consultants confirming the extent of involvement and hourly/daily rate.*

c\. *Resources* - List/describe all equipment, facilities and other
resources available for this project, including the offeror's clinical,
computer and office facilities/equipment at any other performance site
that will be involved in this project. Briefly state their capacities,
relative proximity and extent of availability to this effort. *(Any
equipment specifically proposed as a cost to the contract must be
justified in this section as well as detailed in the budget. Equipment
and products purchased with Government funds shall be American-made, to
the extent possible. Title to the equipment will vest in the
Government.)*

d\. *Other considerations* - Provide a brief narrative of any unique
arrangements, safety procedures in place, animal welfare issues, human
subjects, etc. Note: If the research plan includes the use of human
subjects or animals, refer to paragraphs [Sections 4.2.8 and
4.2.9](#__RefHeading___Toc205616384) of this solicitation for further
guidance.

*Multiple PD/PI Leadership* Plan. For proposals designating multiple
PDs/PIs, a leadership plan must be included. A rationale for choosing a
multiple PD/PI approach should be described. The governance and
organizational structure of the leadership team and the research project
should be described, including communication plans, process for making
decisions on scientific direction, and procedures for resolving
conflicts. The roles and administrative, technical, and scientific
responsibilities for the project or program should be delineated for the
PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to
specific components of the project or the individual PDs/PIs should be
delineated in the Leadership Plan. In the event of an award, the
requested allocations may be reflected in Contract Award.

*Resource Sharing Plan(s).* NIH considers the sharing of unique research
resources developed through NIH-sponsored research an important means to
enhance the value and further the advancement of the research. When
resources have been developed with NIH funds and the associated research
findings published or provided to NIH, it is important that they be made
readily available for research purposes to qualified individuals within
the scientific community. If the final data/resources are not amenable
to sharing, this must be explained in the application. See
<http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm>.

1\. *Data Sharing Plan*: Offerors seeking \$500,000 or more in direct
costs in any year are expected to include a brief 1-paragraph
description of how final research data will be shared, or explain why
data-sharing is not possible (for example human subject concerns, the
Small Business Innovation Development Act provisions, etc.). See
[Data-Sharing Policy (http://grants.nih.gov/grants/
policy/data_sharing/)](http://grants.nih.gov/grants/policy/data_sharing/)
or <http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html>.

2\. *Sharing Model Organisms*: Regardless of the amount requested, all
proposals where the development of model organisms is anticipated are
expected to include a description of a specific plan for sharing and
distributing unique model organisms or state appropriate reasons why
such sharing is restricted or not possible. See [Sharing Model Organisms
Policy (http://grants.nih.gov/grants/policy/model_organism/
index.htm)](http://grants.nih.gov/grants/policy/model_organism/index.htm),
and [NIH Guide NOT-OD-04-042
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html)](http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html).

3\. *Genome Wide Association Studies (GWAS)*: Regardless of the amount
requested, offerors seeking funding for a genome-wide association study
are expected to provide a plan for submission of GWAS data to the
NIH-designated GWAS data repository, or an appropriate explanation why
submission to the repository is not possible. GWAS is defined as any
study of genetic variation across the entire genome that is designed to
identify genetic associations with observable traits (such as blood
pressure or weight) or the presence or absence of a disease or
condition. For further information see Policy for Sharing of Data
Obtained in NIH Supported or Conducted Genome-Wide Association Studies,
[NIH Guide NOT-OD-07-088
(http://www.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html)](http://www.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html),
and <http://grants.nih.gov/grants/gwas>.

e\. *Appendices*

\(1\) **Work Statement** -- The Contracting Officer may require the
offeror to develop a Statement of Work similar in format to the sample
in Appendix E ([MS Word (http://grants.nih.gov/grants/funding/
SBIRContract/ContractAppendixE.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.doc)
\| [PDF (http://grants.nih.gov/grants/funding/SBIRContract/
ContractAppendixE.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.pdf)).
Create this from your detailed approach and methodology. It will be
incorporated into the final contract document. Do not include
proprietary information.

\(2\) **Commercialization Plan** -- Required for the Phase II portion of
ALL Fast-Track proposals.

The Phase II portion of Fast-Track proposals must include a succinct
Commercialization Plan. The Commercialization Plan is limited to *15
pages*. Be succinct. There is no requirement for offerors to use the
maximum allowable pages allotted to the Commercialization Plan.

Create a section entitled, "Commercialization Plan," and provide a
description in each of the following areas:

a\. ***Value of the SBIR Project, Expected Outcomes, and Impact.***
Describe, in layperson\'s terms, the proposed project and its key
technology objectives. Clarify the need addressed, specifying weaknesses
in the current approaches to meet this need. In addition, describe the
commercial applications of the research and the innovation inherent in
this proposal. Be sure to also specify the potential societal,
educational, and scientific benefits of this work. Explain the
non-commercial impacts to the overall significance of the project.
Explain how the SBIR project integrates with the overall business plan
of the company.

b\. ***Company.*** Give a brief description of your company including
corporate objectives, core competencies, present size (annual sales
level and number and types of employees), history of previous Federal
and non-Federal funding, regulatory experience, and subsequent
commercialization, and any current products/services that have
significant sales. Include a short description of the origins of the
company. Indicate your vision for the future, how you will grow/maintain
a sustainable business entity, and how you will meet critical management
functions as your company evolves from a small technology R&D business
to a successful commercial entity.

c\. ***Market, Customer, and Competition.*** Describe the market and/or
market segments you are targeting and provide a brief profile of the
potential customer. Tell what significant advantages your innovation
will bring to the market, e.g., better performance, lower cost, faster,
more efficient or effective, new capability. Explain the hurdles you
will have to overcome in order to gain market/customer acceptance of
your innovation.

Describe any strategic alliances, partnerships, or licensing agreements
you have in place to get FDA approval (if required) and to market and
sell your product.

Briefly describe your marketing and sales strategy. Give an overview of
the current competitive landscape and any potential competitors over the
next several years. (*It is very important that you understand and know
the competition*.)

d\. ***Intellectual Property (IP) Protection.*** Describe how you are
going to protect the IP that results from your innovation. Also note
other actions you may consider taking that will constitute at least a
temporal barrier to others aiming to provide a solution similar to
yours.

e\. ***Finance Plan.*** Describe the necessary financing you will
require, and when it will be required, as well as your plans to raise
the requisite financing to launch your innovation into Phase III and
begin the revenue stream. Plans for this financing stage may be
demonstrated in one or more of the following ways:

-   Letter of commitment of funding.

-   Letter of intent or evidence of negotiations to provide funding,
    should the Phase II project be successful and the market need still
    exist.

-   Letter of support for the project and/or some in-kind commitment,
    e.g., to test or evaluate the innovation.

-   Specific steps you are going to take to secure Phase III funding.

f\. ***Production and Marketing Plan.*** Describe how the production of
your product/service will occur (e.g., in-house manufacturing, contract
manufacturing). Describe the steps you will take to market and sell your
product/service. For example, explain plans for licensing, internet
sales, etc.

g\. ***Revenue Stream.*** Explain how you plan to generate a revenue
stream for your company should this project be a success. Examples of
revenue stream generation include, but are not limited to, manufacture
and direct sales, sales through value added resellers or other
distributors, joint venture, licensing, service. Describe how your
staffing will change to meet your revenue expectations.

Offerors are *encouraged to seek commitment(s) of funds and/or resources
from an investor or partner organization for commercialization* of the
product(s) or service(s) resulting from the SBIR contract.

Your Phase III funding may be from any of a number of different sources
including, but not limited to: SBIR firm itself; private investors or
"angels"; venture capital firms; investment companies; joint ventures;
R&D limited partnerships; strategic alliances; research contracts; sales
of prototypes (built as part of this project); public offering; state
finance programs; non SBIR-funded R&D or production commitments from a
Federal agency with the intention that the results will be used by the
United States government; or other industrial firms.

Fast-Track proposals that do not contain all parts described above will
be redirected for Phase I consideration only.

6\. **Summary of Related Activities** - Use Appendix F ([MS Word
(http://grants.nih.gov/grants/funding/
SBIRContract/ContractAppendixF.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.doc)
\| [PDF (http://grants.nih.gov/grants/funding/SBIRContract/
ContractAppendixF.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.pdf)).

7\. **Number of Copies** - Submit an original and 9 copies.

## 6.3 Business Proposal Format and Content Requirements

1\. **Cover Page** - Use NIH Form 2043, Proposal Summary and Data
Record, Appendix G ([MS Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf)).

2\. **Proposed Cost Breakdown** -- **For Phase I**, use Appendix C ([MS
Word
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc)
\| [PDF
(http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)](http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)).
Explain the basis for all costs and submit documentation to support all
proposed costs. Prepare a separate Appendix C for each year of the
contract and a summary of the entire project. **For Phase II
Fast-Track**, use Appendix C. Delete the fringe benefit costs, indirect
costs and fee. Prepare a separate Appendix C for each year of the
contract and a summary of the entire project.

3\. **Number of Copies** - Submit an original and 4 copies.

# 7. METHOD OF SELECTION AND EVALUATION CRITERIA

All Phase I and Fast-Track proposals will be evaluated and judged on a
competitive basis. Using the technical evaluation criteria in Section
7.1, a panel of scientists, consisting primarily of nongovernment
experts knowledgeable in the disciplines or fields under review, will
evaluate proposals to determine the most promising technical and
scientific approaches. Each proposal will be judged on its own merit.
The Agency is under no obligation to fund any proposal or any specific
number of proposals in a given topic. It also may elect to fund several
or none of the proposed approaches to the same topic or subtopic.

## 7.1 Evaluation Process

Your proposal will be peer reviewed by a panel of scientists selected
for their competence in relevant scientific and technical fields. Each
peer review panel will be responsible for evaluating proposals for
scientific and technical merit. When relevant, reviewers will be
instructed to comment on the reasonableness of the following Resource
Sharing Plans, or the rationale for not sharing the following types of
resources. However, reviewers will not factor the proposed resource
sharing plan(s) into the determination of scientific merit or priority
score. Program staff within the funding organization will be responsible
for monitoring the data sharing policy

-   Data Sharing Plan
    \[<http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm>\]

-   Sharing Model Organisms
    \[<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html>\]

-   Genome Wide Association Studies (GWAS)
    \[<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html>\].

The peer review panel provides a rating, makes specific recommendations
related to the scope, direction and/or conduct of the proposed research,
and for those proposals recommended for award, may provide a commentary
about the funding level, labor mix, duration of the proposed contract
project, vertebrate animal and human subject research issues. The
Institute program staff of the awarding component will conduct a second
level of review. Recommendations of the peer review panel and program
staff are based on judgments about not only the technical merit of the
proposed research but also its relevance and potential contributions to
the mission and programs of the awarding component and commercial
potential. A Phase I or Fast-Track contract may be awarded only if the
corresponding proposal has been recommended as technically acceptable by
the peer review panel. *Funding for any/all acceptable proposals is not
guaranteed.*

## 7.2 Technical Evaluation Criteria

In considering the technical merit of each proposal, the following
factors will be assessed:

+------------------------------------------------------------+---------+
| Factors for Phase I Proposals                              | Weight  |
+============================================================+=========+
| 1\. The soundness and technical merit of the proposed      | 40%     |
| approach and identification of clear measurable goals      |         |
| (milestones) to be achieved during Phase I.                |         |
|                                                            |         |
| For proposals designating multiple PDs/PIs, is the         |         |
| leadership approach, including the designated roles and    |         |
| responsibilities, governance, and organizational           |         |
| structure, consistent with and justified by the aims of    |         |
| the project and the expertise of each of the PDs/PIs?      |         |
|                                                            |         |
| (*Preliminary data are not required for Phase I            |         |
| proposals*.)                                               |         |
+------------------------------------------------------------+---------+
| 2\. The qualifications of the proposed PDs/PIs, supporting | 20%     |
| staff, and consultants.                                    |         |
+------------------------------------------------------------+---------+
| 3\. The potential of the proposed research for             | 15%     |
| technological innovation.                                  |         |
+------------------------------------------------------------+---------+
| 4\. The potential of the proposed research for commercial  | 15%     |
| application.                                               |         |
|                                                            |         |
| The commercial potential of a proposal will be assessed    |         |
| using the following criteria:                              |         |
|                                                            |         |
| a\. Whether the outcome of the proposed research activity  |         |
| will likely lead to a marketable product or process.       |         |
|                                                            |         |
| b\. The offeror's discussion of the potential barriers to  |         |
| entry and the competitive market landscape.                |         |
+------------------------------------------------------------+---------+
| 5\. The adequacy and suitability of the facilities and     | 10%     |
| research environment.                                      |         |
+------------------------------------------------------------+---------+

+------------------------------------------------------------+---------+
| Factors for Phase II Proposals                             | Weight  |
+============================================================+=========+
| 1\. The scientific/technical merit of the proposed         | 30%     |
| research, including adequacy of the approach and           |         |
| methodology, and identification of clear, measurable goals |         |
| to be achieved during Phase II.                            |         |
|                                                            |         |
| For proposals designating multiple PDs/PIs, is the         |         |
| leadership approach, including the designated roles and    |         |
| responsibilities, governance, and organizational           |         |
| structure, consistent with and justified by the aims of    |         |
| the project and the expertise of each of the PDs/PIs?      |         |
+------------------------------------------------------------+---------+
| 2\. The potential of the proposed research for             | 30%     |
| commercialization, as documented in the offeror's          |         |
| Commercialization Plan and evidenced by (a) the offeror's  |         |
| record of successfully commercializing its prior SBIR/STTR |         |
| or other research projects, (b) commitments of additional  |         |
| investment during Phase II and Phase III from private      |         |
| sector or other non-SBIR funding sources, and (c) any      |         |
| other indicators of commercial potential for the proposed  |         |
| research.                                                  |         |
+------------------------------------------------------------+---------+
| 3\. The qualifications of the proposed PDs/PIs, supporting | 25%     |
| staff and consultants.                                     |         |
+------------------------------------------------------------+---------+
| 4\. The adequacy and suitability of the facilities and     | 15%     |
| research environment.                                      |         |
+------------------------------------------------------------+---------+

## 7.3 Proposal Debriefing

Offerors will be notified promptly in writing if their proposals are no
longer being considered for award. Offerors may request a debriefing by
submitting a written request to the Contracting Officer within three
days of receipt of the notification. Untimely requests may be
accommodated at the Government's discretion.

## 7.4 Award Decisions

For proposals recommended for award, the awarding component considers
the following:

1\. Ratings resulting from the scientific/technical evaluation process;

2\. Areas of high program relevance;

3\. Program balance (i.e., balance among areas of research); and

4\. Availability of funds.

The agency is not under any obligation to fund any proposal or make any
specific number of contract awards in a given research topic area. The
agency may also elect to fund several or none of the proposals received
within a given topic area. The SBIR contract projects do not require
establishing a competitive range or requesting final proposal revisions
before reaching source selection decisions.

# 8. CONSIDERATIONS

## 8.1 Awards

1\. The award instrument will be a contract.

2\. A profit or fixed fee may be included in the proposal, as specified
in Federal Acquisition Regulation (FAR) Part 15.404-4. The fee will be
negotiated as an element of the potential total contract amount over and
above allowable costs.

3\. Phase I awards will be firm fixed price contracts. Normally, Phase
II awards will be cost-plus-fixed-fee contracts.

4\. Normally, Phase I contracts may not exceed \$100,000. Phase II
contracts normally may not exceed \$750,000---including direct costs,
indirect costs, and negotiated fixed fee.

5\. Cost-sharing is permitted for proposals under this solicitation;
however, cost sharing is not required nor will it be an evaluation
factor in the consideration of your proposal. Cost-sharing is an
explicit arrangement under which the contractor bears some of the burden
of reasonable, allocable, and allowable contract cost. If cost-sharing
is proposed, it should be reflected in your budget summary.

Approximate number of Phase I contract awards:

+---------------------------------+--------+--------------------------+
| Awarding Components             | No. of | Estimated Time of Award  |
|                                 | Awards |                          |
+=================================+========+==========================+
| **National Institutes of Health | 52-70  | Scientific and Technical |
| (NIH)\                          |        | Merit Review:\           |
| **National Cancer Institute     |        | May 2009                 |
| (NCI)                           |        |                          |
|                                 |        | Anticipated Award Date:  |
|                                 |        | July 2009                |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 6      | Scientific and Technical |
| (NIH)\                          |        | Merit Review:\           |
| **National Center for Research  |        | February 2009            |
| Resources (NCRR)                |        |                          |
|                                 |        | Anticipated Award Date:  |
|                                 |        | June 2009                |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 26     | Scientific and Technical |
| (NIH)\                          |        | Merit Review:            |
| **National Heart, Lung, and     |        | February-April 2009      |
| Blood Institute (NHLBI)         |        |                          |
|                                 |        | Anticipated Award Date:  |
|                                 |        | July-Sept 2009           |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 4-9    | Scientific and Technical |
| (NIH)\                          |        | Merit Review: March 2009 |
| **National Institute on Alcohol |        |                          |
| Abuse and Alcoholism (NIAAA)    |        | Anticipated Award Date:  |
|                                 |        | June-Sept 2009           |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 1-6    | Scientific and Technical |
| (NIH)\                          |        | Merit Review: March 2009 |
| **National Institute of Allergy |        |                          |
| and Infectious Diseases (NIAID) |        | Anticipated Award Date:  |
|                                 |        | June 2009                |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 14-19  | Scientific and Technical |
| (NIH)\                          |        | Merit Review: March 2009 |
| **National Institute on Drug    |        |                          |
| Abuse (NIDA)                    |        | Anticipated Award Date:  |
|                                 |        | August 2009              |
+---------------------------------+--------+--------------------------+
| **National Institutes of Health | 3      | Scientific and Technical |
| (NIH)\                          |        | Merit Review: January    |
| **National Institute of Mental  |        | 2009                     |
| Health (NIMH)                   |        |                          |
|                                 |        | Anticipated Award Date:  |
|                                 |        | May 2009                 |
+---------------------------------+--------+--------------------------+
| **Centers for Disease Control   | 4      | Scientific and Technical |
| and Prevention (CDC)\           |        | Merit Review: February   |
| **National Center on Birth      |        | 2009                     |
| Defects and Developmental       |        |                          |
| Disabilities (NCBDDD)           |        | Anticipated Award Date:  |
|                                 |        | May 2009                 |
+---------------------------------+--------+--------------------------+
| **Centers for Disease Control   | 7      | Scientific and Technical |
| and Prevention (CDC)\           |        | Merit Review: February   |
| **National Center for Chronic   |        | 2009                     |
| Disease Prevention and Health   |        |                          |
| Promotion (NCCDPHP)             |        | Anticipated Award Date:  |
|                                 |        | May 2009                 |
+---------------------------------+--------+--------------------------+
| **Centers for Disease Control   | 9      | Scientific and Technical |
| and Prevention (CDC)\           |        | Merit Review: February   |
| **Immunization Safety Office    |        | 2009                     |
| (ISO)                           |        |                          |
|                                 |        | Anticipated Award Date:  |
|                                 |        | May 2009                 |
+---------------------------------+--------+--------------------------+
| **Centers for Disease Control   | 1      | Scientific and Technical |
| and Prevention (CDC)\           |        | Merit Review: February   |
| **National Center for           |        | 2009                     |
| Immunization and Respiratory    |        |                          |
| Diseases (NCIRD)                |        | Anticipated Award Date:  |
|                                 |        | May 2009                 |
+---------------------------------+--------+--------------------------+

## 8.2 Monthly Progress Report

Contractors will be required to submit a monthly progress report during
Phase I along with their invoice. Phase II reports will be required at
intervals stipulated in the terms and conditions of award.

## 8.3 Final Report

A final report is required of all Phase I and Phase II contractors. It
should include a detailed description of the project objectives, the
activities that were carried out, and the results obtained. **An
original and two copies** of this report must be submitted as directed
by the Contracting Officer not later than the expiration date of the
Phase I contract.

Each Phase II "Fast-Track" contractor must submit semi-annual progress
reports. A final report is required no later than the expiration date of
the Phase II contract. *All reports must be submitted as specified in
the contract or as directed by the Contracting Officer.*

## 8.4 Payment

The Government shall make payments, including invoice and contract
financing payments, by electronic funds transfer (EFT). As a condition
to any payment, the contractor is required to register in the Central
Contractor Registration (CCR) database before the award of a contract.
The registration site for the CCR is
[http://www.ccr.gov](http://www.ccr.gov/).

Payments on Phase I contracts may be made on a monthly advance basis.
Invoices/financing requests submitted for costs incurred under Phase II
cost reimbursement contracts will be on a monthly basis unless otherwise
authorized by the contracting officer.

## 8.5 Limited Rights Information and Data

***Proprietary Information.*** Information contained in unsuccessful
proposals will remain the property of the offeror. The Government,
however, may retain copies of all proposals. Public release of
information in any proposal will be subject to existing statutory and
regulatory requirements.

The Department of Health and Human Services (DHHS) recognizes that, in
responding to this solicitation, offerors may submit information that
they do not want used or disclosed for any purpose other than for
evaluation. Such data might include trade secrets, technical data, and
business data (such as commercial information, financial information,
and cost and pricing data). The use or disclosure of such information
may be restricted if offerors identify it and the Freedom of Information
Act (FOIA) does not require its release. For information to be
protected, offerors must identify in the Notice of Proprietary
Information (on the Proposal Cover Sheet) the page(s) on which such
information appears. Any other Notice may be unacceptable to the
Government and may constitute grounds for removing the proposal from
further consideration without assuming any liability for inadvertent
disclosure.

Unless disclosure is required by the FOIA, as determined by FOI
officials of the DHHS, data contained in those portions of a proposal
that have been identified as containing restricted information, in
accordance with the Notice of Proprietary Information, shall not be used
or disclosed except for evaluation purposes.

The DHHS may not be able to withhold data that has been requested
pursuant to the FOIA, and the DHHS FOI officials must make that
determination. The Government is not liable for disclosure if the DHHS
has determined that disclosure is required by the FOIA.

If a contract is awarded to the offeror as a result of, or in connection
with, the submission of a proposal, the Government shall have the right
to use or disclose the data to the extent provided by law. Proposals not
resulting in a contract remain subject to the FOIA.

***Rights to Data Developed Under SBIR Funding Agreement.*** Rights to
data, including software developed under the terms of any funding
agreement resulting from a contract proposal submitted in response to
this solicitation, shall remain with the awardee. However, the
Government shall have the limited right to use such data for Government
purposes only.

\(1\) Each agency must refrain from disclosing SBIR technical data to
outside the Government (except reviewers) and especially to competitors
of the Small Business Concern (SBC), or from using the information to
produce future technical procurement specifications that could harm the
SBC that discovered and developed the innovation.

\(2\) SBIR agencies must protect from disclosure and non-governmental
use all SBIR technical data developed from work performed under an SBIR
funding agreement for a period of not less than four years from delivery
of the last deliverable under that agreement (either Phase I, Phase II,
or Federally-funded SBIR Phase III) unless, subject to paragraph (3)of
this section, the agency obtains permission to disclose such SBIR
technical data from the awardee or SBIR offeror. Agencies are released
from obligation to protect SBIR data upon expiration of the protection
period except that any such data that is also protected and referenced
under a subsequent SBIR award must remain protected through the
protection period of that subsequent SBIR award. For example, if a Phase
III award is issued within or after the Phase II data rights protection
period and the Phase III award refers to and protects data developed and
protected under the Phase II award, then that data must continue to be
protected through the Phase III protection period. Agencies have
discretion to adopt a protection period longer than four years. The
Government retains a royalty-free license for Government use of any
technical data delivered under an SBIR award, whether patented or not.
This section does not apply to program evaluation.

\(3\) SBIR technical data rights apply to all SBIR awards, including
subcontracts to such awards, that fall within the statutory definition
of Phase I, II, or III of the SBIR program, as described in Section 4 of
the SBIR Policy Directive, dated September 24, 2002. The scope and
extent of the SBIR technical data rights applicable to Federally-funded
Phase III awards is identical to the SBIR data rights applicable to
Phases I and II SBIR awards. The data rights protection period lapses
only: (i) Upon expiration of the protection period applicable to the
SBIR award, or (ii) by agreement between the awardee and the agency.

***Copyrights.*** The awardee may normally copyright and publish
(consistent with appropriate national security considerations, if any)
material developed with PHS support. The awarding component receives a
royalty-free license for the Federal Government and requires that each
publication contain an acknowledgement of agency support and disclaimer
statement, as appropriate. An acknowledgement shall be to the effect
that: \"This publication was made possible by contract number
\_\_\_\_\_\_\_\_ from (DHHS awarding component)\" or \"The project
described was supported by contract number \_\_\_\_\_\_\_\_ from (DHHS
awarding component).\"

***Patents.*** Small business concerns normally retain the principal
worldwide patent rights to any invention developed with Government
support. Under existing regulations, 37 CFR 401, the Government receives
a royalty-free license for Federal Government use, reserves the right to
require the patent-holder to license others in certain circumstances,
and requires that anyone exclusively licensed to sell the invention in
the United States must normally manufacture it substantially in the
United States.

To the extent authorized by 35 U.S.C. 205, the Government will not make
public any information disclosing a Government-supported invention for a
four year period to allow the awardee a reasonable time to file a patent
application, nor will the Government release any information that is
part of a patent application.

Inquiries or information about additional requirements imposed by 37
C.F.R. 401 should be obtained from local counsel or from:

Office of Policy for Extramural\
Research Administration,\
Division of Extramural Inventions and\
Technology Resources,\
National Institutes of Health (NIH)\
6705 Rockledge Drive, MSC 7980\
Bethesda, MD 20892-7980\
Phone: (301) 435-0679\
Fax: (301) 480-0272\
Email: <jpkim@nih.gov>

*Inventions must be reported promptly*---within two months of the
inventor's initial report to the contractor organization---to the
Division of Extramural Inventions and Technology Resources, NIH, at the
address above. This should be done prior to any publication or
presentation of the invention at an open meeting, since failure to
report at the appropriate time is a violation of 35 USC 202, and may
result in loss of the rights of the small business concern, inventor,
and Federal Government in the invention. All foreign patent rights are
immediately lost upon publication or other public disclosure unless a
United States patent application is already on file. In addition,
statutes preclude obtaining valid United States patent protection after
one year from the date of a publication that discloses the invention.

Awardees are encouraged to submit reports electronically using
Interagency Edison ([http://www.iedison.gov](http://www.iedison.gov/)).
Information from these reports is retained by the NIH as confidential
and submission does not constitute any public disclosure. Failure to
report as described at 37 CFR Section 401.14 is a violation of 35 U.S.C.
202 and may result in loss of the rights of the recipient organization.
In addition to fulfilling reporting requirements, Edison notifies the
user of future time sensitive deadlines with enough lead-time to avoid
the possibility of loss of patent rights due to administrative
oversight. Edison can accommodate the invention reporting need of all
organizations. For additional information about this invention reporting
and tracking system, visit the Edison home page cited above or contact
Edison via email at <Edison@od.nih.gov.>

***Resource Sharing Plan(s).*** NIH considers the sharing of unique
research resources developed through NIH-sponsored research an important
means to enhance the value of, and advance research. When resources have
been developed with NIH funds and the associated research findings
published or provided to NIH, it is important that they be made readily
available for research purposes to qualified individuals within the
scientific community. If the final data/resources are not amenable to
sharing, this must be explained in the Resource Sharing section of the
proposal. See
<http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm>.

 (a) *Data Sharing Plan*: Investigators seeking \$500,000 or more in
direct costs in any year are expected to include a brief 1-paragraph
description of how final research data will be shared, or explain why
data-sharing is not possible (for example human subject concerns, the
Small Business Innovation Development Act provisions, etc.) Offerors are
encouraged to discuss data-sharing plans with their program contact. See
[Data-Sharing Policy
(http://grants.nih.gov/grants/policy/data_sharing/)](http://grants.nih.gov/grants/policy/data_sharing/)
or [http://grants.nih.gov/grants/guide/
notice-files/NOT-OD-03-032.html](http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).

\(b\) *Sharing Model Organisms*: Regardless of the amount requested, all
proposals where the development of model organisms is anticipated are
expected to include a description of a specific plan for sharing and
distributing unique model organisms and related resources, or state
appropriate reasons why such sharing is restricted or not possible. See
[Sharing Model Organisms Policy
(lhttp://grants.nih.gov/grants/policy/model_organism/index.htm)](lhttp://grants.nih.gov/grants/policy/model_organism/index.htm),
and [NIH Guide NOT-OD-04-042
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html)](http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html).

*(c) Genome Wide Association Studies (*G*WAS):* Regardless of the amount
requested, offerors seeking funding for a genome-*w*ide association
study are expected to provide a plan for submission of GWAS data to the
NIH-designated GWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible.  A
genome-wide association study is defined as any study of genetic
variation across the entire genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight)
or the presence or absence of a disease or condition.  For further
information see Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, [NIH Guide NOT-OD-07-088
(http://www.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html)](http://www.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html),
and <http://grants.nih.gov/grants/gwas/>.

***Royalties.*** If royalties exceed \$1,500, you must provide the
following information on a separate page for each separate royalty or
license fee:

1\. Name and address of licensor.

2\. Date of license agreement.

3\. Patent numbers.

4\. Patent application serial numbers, or other basis on which the
royalty is payable.

5\. Brief description (including any part or model number of each
contract item or component on which the royalty is payable).

6\. Percentage or dollar rate of royalty per unit.

7\. Unit price of contract item.

8\. Number of units.

9\. Total dollar amount of royalties.

10\. If specifically requested by the Contracting Officer, a copy of the
current license agreement and identification of applicable claims of
specific patents (see FAR 27.204 and 31.205-37).

## 8.6 Performance of Research and Analytical Work

*In Phase I projects*, normally a minimum of two-thirds or 67% of the
research or analytical effort must be performed by the small business
concern.

*In Phase II projects*, normally a minimum of one-half or 50% of the
research or analytical effort must be performed by the small business
concern.

The Contracting Officer must approve deviations from these requirements
in writing.

***Contractor Commitments.*** Upon entering into a contract, the
contractor agrees, in accordance with the terms and conditions of the
contract, to accept certain legal commitments embodied in the clauses of
Phase I and Phase II contracts. The following list illustrates the types
of clauses to which a contractor is bound. This list is not exhaustive.
Copies of complete terms and conditions are available upon request.

### Clauses That Apply to Contracts *NOT* Exceeding \$100,000

1\. ***Standards of Work.*** Work performed under the contract must
conform to high professional standards.

2\. ***Inspection.*** Work performed under the contract is subject to
Government inspection and evaluation at all times.

3\. ***Termination for Convenience.*** The Government may terminate the
contract at any time for convenience if it deems termination to be in
its best interest, in which case the contractor will be compensated for
work performed and for reasonable termination costs.

4\. ***Disputes.*** Any dispute concerning the contract that cannot be
resolved by agreement shall be decided by the contracting officer with
right of appeal.

5\. ***Equal Opportunity.*** The contractor will not discriminate
against any employee or applicant for employment because of race, color,
religion, sex, or national origin.

6\. ***Affirmative Action for Veterans.*** The contractor will not
discriminate against any employee or applicant for employment because he
or she is a disabled veteran or veteran of the Vietnam era.

7\. ***Affirmative Action for Handicapped.*** The contractor will not
discriminate against any employee or applicant for employment because he
or she is physically or mentally handicapped.

8\. ***Gratuities.*** The Government may terminate the contract if any
gratuities have been offered to any representative of the Government to
secure the contract.

9\. ***American-made Equipment and Products.*** When purchasing
equipment or products under an SBIR contract award, the contractor shall
purchase only American-made items whenever possible.

### Clauses That Apply to Contracts Exceeding \$100,000

*In addition to the foregoing clauses, the following clauses apply to
contracts expected to exceed \$100,000*.

10\. ***Examination of Records.*** The Comptroller General (or a duly
authorized representative) shall have the right to examine any directly
pertinent records of the contractor involving transactions related to
this contract.

11\. ***Default.*** The Government may terminate the contract for
default if the contractor fails to perform the work described in the
contract and such failure is not the result of excusable delays.

12\. ***Contract Work Hours.*** The contractor may not require an
employee to work more than eight hours a day or forty hours a week
unless the employee is compensated accordingly (i.e., overtime pay).

13\. ***Covenant Against Contingent Fees.*** No person or agency has
been employed to solicit or secure the contract upon an understanding
for compensation except bona fide employees or commercial agencies
maintained by the contractor for the purpose of securing business.

14\. ***Patent Infringement.*** The contractor shall report each notice
or claim of patent infringement based on the performance of the
contract.

## 8.7 Additional Information

1\. This solicitation is intended for informational purposes and
reflects current planning. If there is any inconsistency between the
information contained herein and the terms of any resulting SBIR
contract, the terms of the contract are controlling.

2\. Prior to award of an SBIR contract, the Government may request the
offeror to submit certain organizational, management, personnel and
financial information to assure responsibility of the offeror to receive
an award.

3\. The Government is not responsible for any expenditures of the
offeror in advance and in anticipation of an award. In a cost
reimbursement contract, reimbursement of costs by the Government may be
made only on the basis of costs incurred by the contractor after award
and during performance.

4\. This solicitation is not an offer by the Government and does not
obligate the Government to make any specific number of awards. Awards
under this program are contingent upon the scientific/technical merit of
proposals and the availability of funds.

5\. The SBIR contract program is not intended as a mechanism to invite
unsolicited proposals. Unsolicited SBIR contract proposals shall not be
accepted under the SBIR program in either Phase I or Phase II.

6\. If an award is made pursuant to a proposal submitted in response to
this SBIR solicitation, the contractor will be required to certify that
he or she has not previously been, nor is currently being, paid for
essentially equivalent work by any agency of the Federal Government.

7\. Prior to award of a contract, the contractor will be required to
provide a Data Universal Numbering System (DUNS) number. A DUNS number
may be obtained immediately, at no charge, by calling Dun and Bradstreet
at 1-866-705-5711 or via the Internet at
<https://eupdate.dnb.com/requestoptions/government/ccrreg/>. The
contractor must also Number range CHAPTERbe registered in the Central
Contractor Registry (CCR) prior to award of a contract. Registration can
be made via the Internet at Number range
CHAPTER[http://www.ccr.gov](http://www.ccr.gov/).

# 9. INSTRUCTIONS FOR PROPOSAL SUBMISSION

## 9.1 Receipt Date

The deadline for receipt of all contract proposals submitted in response
to this solicitation is:\
5:00 p.m., Eastern Time\
Monday, November 3, 2008

Any proposal, modification or revision received at the offices
designated below after the exact time specified for receipt is "late"
and will not be considered unless it is received before award is made,
and

1\. There is acceptable evidence to establish that it was received at
the Government installation designated for receipt of offers and was
under the Government's control prior to the time set for receipt of
offers; or

2\. It is the only proposal received.

Acceptable evidence to establish the time of receipt at the Government
installation includes the time/date stamp of that installation on the
proposal wrapper, other documentary evidence of receipt maintained by
the installation, or oral testimony or statements of Government
personnel.

If an emergency or unanticipated event interrupts normal Government
processes so that proposals cannot be received at the office designated
for receipt of proposals by the exact time specified in the
solicitation, and urgent Government requirements preclude amendment of
the solicitation, the time specified for receipt of proposals will be
deemed to be extended to the same time of day specified in the
solicitation on the first work day on which normal Government processes
resume.

Proposals may be withdrawn by written notice received at any time before
award. Notwithstanding above, a proposal received after the date and
time specified for receipt may be considered if it offers significant
cost or technical advantages to the Government and it was received
before proposals were distributed for evaluation, or within 5 calendar
days after the exact time specified for receipt, whichever is earlier.

Note: Modifications or revisions to proposals that result in the
proposal exceeding the stated page limitations will not be considered.

## 9.2 Number of Copies

*For Phase I, submit the original and 5 copies of each proposal. The
Principal Investigator and a corporate official authorized to bind the
offeror must sign the original*. The 5 copies of the proposal may be
photocopies of the original.

For Fast-Track Phase II, submit the original and 9 copies.

For Phase I and Fast-Track Phase II business proposals, submit an
original and 4 copies.

## 9.3 Binding and Packaging of Proposal

Send all copies of a proposal in the same package. Do not use special
bindings or covers. Staple the pages in the upper left corner of each
proposal.

# 10. Contracting Officers and Addresses for Mailing or Delivery of Proposals

Any small business concern that intends to submit an SBIR contract
proposal under this solicitation should provide the appropriate
contracting officer(s) with early, written notice of its intent, giving
its name, address, telephone, email, and topic number(s). If a topic is
modified or canceled before this solicitation closes, only those
companies that have expressed such intent will be notified.

## 10.1 National Institutes of Health (NIH)

### National Cancer Institute (NCI)

Ms. Mary Landi-O'Leary

Phone: (301) 435-3807

Fax: (301) 480-0309

Email: <ml186r@nih.gov>

Proposals to the NCI, if mailed through the U.S. Postal Service, must be
addressed as follows:

Ms. Mary Landi-O'Leary

Contracting Officer

Office of Acquisitions

National Cancer Institute

6120 Executive Blvd., EPS, Room 6044

Bethesda, MD 20892-7193 \*

\**Change the city to Rockville and the zip code to 20852 if
hand-delivered or delivered by an overnight service to the NCI*.

### National Center for Research Resources (NCRR)

Mr. John Taylor

Phone: (301) 435-0327

Fax: (301) 480-3338

E-mail: <taylorjc@nhlbi.nih.gov>

Proposals to the NCRR, if mailed through the U.S. Postal Service, must
be addressed as follows:

Review Branch

Division of Extramural Affairs

National Heart, Lung, and Blood Institute

6701 Rockledge Drive

Room 7091

Bethesda, MD 20892-7924 \*

*\*Change the zip code to 20817 if hand-delivered or delivered by an
express or other courier service to the NHLBI.*

### National Heart, Lung, and Blood Institute (NHLBI)

Mr. John Taylor

Phone: (301) 435-0327

Fax: (301) 480-3338

E-mail: <taylorjc@nhlbi.nih.gov>

Proposals to the NHLBI, if mailed through the U.S. Postal Service, must
be addressed as follows:

Review Branch

Division of Extramural Affairs

National Heart, Lung, and Blood Institute

6701 Rockledge Drive

Room 7091

Bethesda, MD 20892-7924 \*

*\*Change the zip code to 20817 if hand-delivered or delivered by an
express or other courier service to the NHLBI.*

### National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Mr. Matthew Packard

Phone: (301) 443-3041

Fax: (301) 443-3891

Email: <packardm@mail.nih.gov>

Proposals to the NIAAA must be mailed or delivered to:

Mr. Matthew Packard

Chief, NIAAA Contracts Management Branch

NIDDK Office of Acquisitions

5635 Fishers Lane, Room 3019

Bethesda, MD 20892-9304 \*

*\*Change the city to Rockville, MD and the zip code to 20852 if
hand-delivered or delivered by an overnight service to the NIAAA.*

### National Institute of Allergy and Infectious Diseases (NIAID)

Ms. Barbara Shadrick

Phone: (301) 496-7288

Fax: (301) 402-0972

Email: <bs92y@nh.gov>

Proposals to the NIAID, if mailed through the U.S. Postal Service, must
be addressed as follows:

Ms. Barbara Shadrick

Contracting Officer, MIDRCB-B

OA, DEA, NIAID

6007B Rockledge Dr., Room 3214

Bethesda, MD 20892-7612 \*

\**Change the city to North Bethesda, MD and the zip code to 20817 if
hand-delivered or delivered by an overnight service to the NIAID*.

### National Institute on Drug Abuse (NIDA)

Mr. Craig Sager

Phone: (301) 443-6677

Fax: (301) 443-7595

Email: <cs591t@nih.gov>

Proposals to the NIDA must be mailed or delivered to:

Mr. Craig Sager

Contracting Officer

NIDA R&D Contracts Management Branch

Neurosciences Office of Acquisition

6101 Executive Boulevard

Room 260, MSC 8402

Bethesda, MD 20892-8402 \*

\**Change the city to Rockville and the zip code to 20852 if
hand-delivered or delivered by an overnight service to the NIDA*.

### National Institute of Mental Health (NIMH)

Ms. Suzanne Stinson

Phone: (301) 443-2696

Fax: (301) 443-0501

Email: <sstinson@mail.nih.gov>

Proposals mailed to the NIMH must be addressed to:

Ms. Stephanie Powell

Contract Specialist

Contracts Management Branch

National Institute of Mental Health

6001 Executive Boulevard

Room 8154, MSC 9661

Bethesda, MD 20892-9661\*

\**Change the city to Rockville and the zip code to 20852 if
hand-delivered or delivered by an overnight service to the NIMH*.

## 10.2 Centers for Disease Control and Prevention (CDC)

For general administrative SBIR program questions, contact:

Dr. Denise Burton

Office of Public Health Research (OPHR)

Office of the Chief Science Officer

Phone: (404) 639-4641

Email: <DBurton2@cdc.gov>

Mr. Jerald O'Hara

Office of Public Health Research (OPHR)

Office of the Chief Science Officer

Phone: (404) 639-4796

Email: <JOHara@cdc.gov>

### National Center on Birth Defects and Developmental Disabilities (NCBDDD)

### National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

Mrs. Theresa Routh-Murphy

Contracting Officer, NCBDDD/CDC

Phone: (770) 488-2713

Fax: (770) 488-2778

Email: <TNR3@cdc.gov>

Proposals to the NCBDDD or NCCDPHP must be mailed or delivered to:

Mrs. Theresa Routh-Murphy

Contracting Officer

CDC Procurement and Grants Office

2920 Brandywine Road, MS-E09

Atlanta, GA 30341

### Immunization Safety Office (ISO)

Mr. Alan Sims

Phone: (770) 488-2896

Fax: (770) 488-2670

Email: [auy0@cdc.gov](mailto:auy02@cdc.gov)

Proposals to ISO must be mailed or delivered to:

Mr. Alan Sims

Contract & Grants Management Specialist

Centers for Disease Control and Prevention (CDC) Acquisition and
Assistance,

Branch B, Team IV

2920 Brandywine Road

Atlanta, GA 30341

### National Center for Immunization and Respiratory Diseases (NCIRD)

Mr. Paul Rota

Phone: (404) 639-4181

Fax: (404) 639-4187

Email: <prota@cdc.gov>

Proposals to NCIRD must be mailed or delivered to:

Mr. Paul Rota

Centers for Disease Control and Prevention

Mailstop C-22

Building 18, Rm 5-131

1600 Clifton Rd

Atlanta, GA, USA 30333

# 11. SCIENTIFIC AND TECHNICAL INFORMATION SOURCES

Health science research literature is available at academic and health
science libraries throughout the United States. Information retrieval
services are available at these libraries and Regional Medical Libraries
through a network supported by the National Library of Medicine. To find
a Regional Medical Library in your area, visit <http://nnlm.gov/> or
contact the Office of Communication and Public Liaison at
<publicinfo@nlm.nih.gov>, (301) 496-6308.

Other sources that provide technology search and/or document services
include the organizations listed below. They should be contacted
directly for service and cost information.

National Technical Information Service

1-800-553-6847

[http://www.ntis.gov](http://www.ntis.gov/)

National Technology Transfer Center

Wheeling Jesuit College

1-800-678-6882

<http://www.nttc.edu/>

Regional Technology Transfer Centers

1-800-472-6785

<http://www.ctc.org/NewFiles/RTTCs.html>

# 12. RESEARCH TOPICS

[]{#__RefHeading___Toc205616427 .anchor}NATIONAL INSTITUTES OF HEALTH

[]{#__RefHeading___Toc205616428 .anchor}National Cancer Institute (NCI)

The NCI is the Federal Government's principal agency established to
conduct and support cancer research, training, health information
dissemination, and other related programs. As the effector of the
National Cancer Program, the NCI supports a comprehensive approach to
the problems of cancer through intensive investigation in the cause,
diagnosis, prevention, early detection, treatment, rehabilitation from
cancer, and the continuing care of cancer patients and families of
cancer patients. To speed the translation of research results into
widespread applications, the National Cancer Act of 1971 authorized a
cancer control program to demonstrate and communicate to both the
medical community and the general public the latest advances in cancer
prevention and management.

SBIR Phase I and Phase II awards may not exceed the limits for total
costs (direct costs, facilities and administrative (F&A)/indirect costs,
and fee) listed under each topic area.

Phase II proposals may only be submitted upon the request of the NCI
Contracting Officer, if not submitted concurrently with the initial
Phase I proposal under the Fast-Track procedure (described in Section
5). Unless the Fast-Track option is specifically allowed as stated
within the topic areas below, applicants are requested to submit only
Phase I proposals in response to this solicitation.

**NCI Phase II Bridge Award**

The National Cancer Institute would like to provide notice of a novel
funding mechanism entitled the SBIR Phase II Bridge Award. This notice
is for informational purposes only and is not a call for Phase IIB
Bridge Award proposals. This informational notice does not commit the
government to the development of a Phase IIB Bridge Award mechanism for,
or making such awards to, contract awardees.

Successful transition of SBIR research and technology development into
the commercial marketplace is not easy and SBIR Phase II awardees often
encounter challenges, including significant ones in regulatory affairs,
raising capital, licensure, and production, as they try to advance their
projects towards commercialization. The NCI views the SBIR program as a
long term effort and in order to help address these difficult issues, it
has developed the SBIR Phase IIB Bridge Award under the grants
mechanism. The specific requirements for the Phase IIB Bridge Award are
described in the full RFA announcement
(<http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-08-021.html>).

The Phase IIB Bridge Award is meant to provide additional funding of up
to \$3M and up to three additional years to assist promising small
business concerns with the challenges of commercialization. The NCI
anticipates expanding this program in the future to also include
awardees funded under the SBIR contract mechanism.

It is anticipated that the Phase IIB Bridge Award program will be open
to contractors who successfully complete a Phase I award as a result of
this solicitation, and who are subsequently awarded a Phase II contract
(or have an exercised Phase II option under a Fast-Track contract). NIH
SBIR Phase II contractors who satisfy the above requirements may be able
to apply for a Phase IIB Bridge Award under a future Phase IIB Bridge
Award grant/cooperative agreement funding opportunity announcement
(FOA), if they meet the eligibility requirements detailed therein.
Selection decisions for a Phase IIB award will be based both on
scientific/technical merit as well as business/commercialization
potential.

**NCI Topics:**

This solicitation invites Phase I (and in certain topics Fast Track)
proposals in the following areas:

[]{#__RefHeading___Toc205616429 .anchor}229 Development of Molecular
Pharmacodynamic Assays for Targeted Therapies

Number of anticipated awards: 4-6

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

The NCI requests that qualified small businesses submit proposals to
develop pharmacodynamic assays for measuring a number of high-priority
molecular targets. (For a list of the targets of interest to NCI, please
see: <http://sbir.cancer.gov/>). The short term goal of this contract is
to develop new rigorous, validated assays to measure molecular-level
response to treatment in conjunction with preclinical development of new
candidate therapeutic agents. These assays should measure modulation of
molecular targets upon treatment with investigational anticancer
therapeutics and support pharmacodynamic studies in animal models and in
human tumor and surrogate tissue samples. Real-time assays that could be
used to rapidly assess response to treatment in the clinic in
conjunction with a clinical trial are highly desirable. Ideally, these
assays should also have a known correspondence to tumor modulation in
animal efficacy models for the same target. Standard operating
Procedures (SOPs) for these assays must be developed and be provided to
the NCI along with all supporting data. (To view sample SOPs, please
see: <http://sbir.cancer.gov/>.) Small businesses may also submit
proposals for the development of assays that measure molecular targets
relevant to oncology therapeutics development which have been identified
by the small business.

Project goals: The long term goal of this contract is to provide a
mechanism to develop a series of molecular pharmacodynamic assays to
allow clinical target validation for a wide array of cancer therapeutics
to determine earlier in the drug development process if the intended
target is modulated and whether this corresponds to either tumor stasis
or regression. In addition to the assay itself, the contract recipient
will develop and provide to the NCI SOPs that have been fully qualified
or validated with human tumor/tissue samples. In addition, the goal is
for companies to extend this work into developing research kits or
diagnostic agents to stratify patients for clinical trial selection or
to evaluate response to new therapeutic agents.

The goal of the NCI SBIR program is to fund small businesses to develop
commercially viable products that advance the research and development
needs of the Institute. The NCI Strategic Plan identifies validating
molecular targets for cancer prognosis, metastasis, treatment response
and cancer progression as a strategic priority (Strategy 4.2). Part of
this strategy includes creating a library of validated molecular target
assays in order to advance broad development of targeted anti-tumor
agents. Grant mechanisms thus far have not been an effective method of
developing these assays, as they have little publication value. Market
analysis indicates that pharmacodynamic assay development is a valuable
first step for eventual commercialization of cancer diagnostics and
laboratory assays, in addition to serving the needs of cancer
therapeutic development.

Two different tracks will be considered:

Track 1 will focus on the development of pharmacodynamic assays for
measuring a number of high priority molecular targets. (For a list of
the molecular targets of high priority to NCI, please see
<http://sbir.cancer.gov/>.) This list of molecular targets is being
actively pursued by NCI's researchers; thus assays developed under this
topic will be good candidates for beta testing at NCI laboratories and
clinics. The NCI will determine and periodically re-prioritize the list
of molecular targets to be addressed in subsequent years based on the
needs of both intramural and extramural investigators.

For Track 2 small businesses are invited to submit proposals for the
development of assays that measure molecular targets relevant to
oncology therapeutics development which have been identified by the
small business.

All proposals will be reviewed by NCI, and overall priority will be
given to proposals to develop pharmacodynamic assays of high priority to
NCI. Both tracks will have the following deliverables.

Phase I Activities and expected deliverables:

-   Develop a research pharmacodynamic assay for the molecular target
    described.

-   Characterize assay reproducibility, variability and accuracy.

-   Deliver to NCI the SOP of the research pharmacodynamic assay for the
    molecular target described.

Phase II Activities and expected deliverables:

-   Develop a qualified or validated molecular pharmacodynamic assay for
    the target described. The assay should be applicable in the clinical
    setting.

-   Perform studies to characterize the correlation between the
    resulting assay in tumor versus surrogate tissues (e.g. blood,
    serum), if applicable.

-   Perform studies to characterize the correlation between the
    resulting assay in human versus animal tissues.

-   Make available to NCI all SOPs for this assay.

[]{#__RefHeading___Toc205616430 .anchor}249 System to Analyze and
Support Biomarker Research and Development Strategies

Number of anticipated awards: 3-4

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$750,000

Summary:

Because of the rapid expansion of the worldwide biomarker research data
in volume and breadth, there is a critical need for integrating all of
these data within a knowledge management system that supports automated
review and evaluation of current research and development efforts,
particularly within the context of all cancer research and therapeutic
and diagnostic product development. Such a system permits rapid
identification and decision-making to allocate resources where they can
most efficiently be used to enhance product development. Thus, the
objective of this project is to expand the present methodology of
biomarker research data analysis and strategic planning using a system
that allows review and analysis of biomarker research and development
projects as they relate to available worldwide data.

Project Goals:

The system would permit rapid identification and correlations of
parameters of interest to the users' senior scientific staff, while
simultaneously providing high-efficiency development pathways for
program areas of interest. The system should incorporate parameters
allowing evaluation of methods/assays, tissue and disease specificities,
clinical applications, and regulatory and clinical development status.
The system when fully developed may be applied over a broad range of
technologies such as genomics and proteomics, imaging modalities,
immunohistochemistry, and histopathology. Also, when fully developed,
the system should be usable by the private sector (e.g., pharma,
biotech, diagnostics industries, etc.) and the public sector (e.g., NCI
programs such as Developmental Therapeutics, SPOREs, EDRN, Cancer
Imaging, OBQI, PACCT, NTROI, and intramural and extramural
investigator-initiated research). Potential offerors can propose
projects to comprehensively include all relevant cancer-related
biomarkers or specific subsets (e.g., toxicity biomarkers) under a
relational database system.

An example application would be selection of a biomarker of a molecular
target (e.g., a mutated tyrosine kinase), all published drugs/chemicals
that interact with the target, all cancer target organs that have the
biomarker and in what incidence, stage(s) of cancer progression where
the biomarker is found, existing assays to measure the biomarker and
their states of development and use, toxicity associated with biomarker
modulation, etc.

System Requirements:

The core of the system will be a database cataloging and classifying the
biomarker research projects with links to the original data sources. The
remainder of the system will be tools (reports and algorithms) for
summarizing, analyzing, and integrating the data with other sources.
Multiple parameters describing the biomarkers cited shall be extracted
into the database―e.g., biomarker name, clinical use, cancer target
organ (clinical and nonclinical), specimen source, technology/assay
methodology and/or assay target, biological process related to
neoplastic progression (e.g., angiogenesis, proliferation, apoptosis),
signaling pathway, drug or other intervention used in study (as
appropriate), biomarker category (e.g., prognostic, predictive, risk,
drug effect), disease stage, study population demographics, and phase of
clinical study. The database shall be fully searchable (for individual
records and categories of data) on all these parameters. The database
shall be capable of supporting a large base of concurrent users via a
user friendly, web-based user interface.

The database and other components of the system shall be built with open
source code compatible with current industry and NCICB standards (e.g.,
J2EE, ANSI compliant SQL and Eclipse). Since NCI has invested
substantially in developing informatics for cancer-specific uses, where
possible, applications previously developed by NCICB should be
leveraged. For example, applications developed for the Cancer
Bioinformatics Grid (caBIG) should be considered, and the system should
be integrated with caBIG applications, if appropriate. The system should
be fully integrated with the NCI Enterprise Vocabulary System (EVS) and
should use EVS terminology (and should comply with NCI's Cancer Data
Standards Repository (caDSR) metadata standards, using NCI approved
Common Data Elements where appropriate). However, the system developed
should be compatible with other users' specific requirements.

System and user documentation shall be provided, quality control
procedures shall be developed and applied to maintenance of the system,
and quality assurance audits shall be carried out periodically. The
project shall also include organization and administration of technical
and scientific advisory groups involved in the design and implementation
of the system.

Phase I activities and expected deliverables:

-   Review a large, representative sample of relevant biomarker data and
    literature to develop an overall biomarker research program analysis
    and support model. Determine what, if any, algorithms exist to
    convert present research portfolio databases (electronic, manual,
    and hybrid) into an integrated automated knowledge management system
    that fulfills strategic research and business planning requirements
    for multiple users.

-   Determine what, if any commercial software products exist that may
    serve as a platform for the proposed research program analysis and
    support tool. For example, the proposed product might be best
    developed as an add-on to an existing portfolio management package.

-   Convene a focus group of senior scientists to solicit input on the
    scientific content and functionality required for the proposed
    product.

-   Evaluate the availability of research data in the world-wide
    scientific literature with respect to the desired selection and
    measurement parameters. Identify problems with comparability and
    availability of research and administrative data over time and as
    collected by different systems.

-   Develop a statement of functional requirements and user interface
    requirements for the product.

-   Develop a prototype of the system using a representative sample of
    biomarkers.

-   Include funds to present Phase I findings and system design.

Phase II activities and expected deliverables:

-   Conduct a formal use study of the software with representative users
    to evaluate the prototype system developed in Phase I. Enhance and
    modify the prototype's functionality and user interface based on
    this feedback.

-   Complete two iterations of the tracking program software, including
    technical documentation of the system and a training manual.
    Documentation of the system design, business procedures (SOPs), data
    sources, data extraction guidelines and evaluation criteria shall be
    prepared. An indexed/searchable User Guide describing data sources,
    data parameters, evaluation criteria, and system functionality
    (e.g., searching, report generation and linking to data sources)
    shall be prepared. SOPs shall include quality control procedures for
    data entry (e.g., data edit checks).

-   Develop and implement a project plan for populating, updating, and
    maintaining the biomarkers database.

-   Develop evaluation measures.

-   Demonstrate the flexibility of design that would permit updating the
    software as new biomarkers, research modalities, treatments, data
    formats, or other parameters of interest are added.

-   Documentation of the database design, business procedures (SOPs),
    data sources, data extraction guidelines and evaluation criteria
    shall be prepared on implementation of the database and shall be
    updated annually. An indexed/searchable User Guide describing data
    sources, data parameters, evaluation criteria, and database
    functionality (e.g., searching, report generation and linking to
    data sources) shall be prepared and loaded on the database website.
    SOPs shall include quality control procedures for data entry (e.g.,
    data edit checks).

-   Identify Phase II barriers to evaluating the impact of the software
    and resolutions to these barriers.

-   In the first six months of the first year of the contract, provide
    the program and contract officers with a letter of commercial
    interest to either purchase or subscribe to the system once it is
    created.

-   In the first six months of the second year of the contract, provide
    the program and contract officers with a letter of commercial
    commitment based on the successful outcome of the Phase II. It is
    anticipated that potential customers would be the NCI, NIH, and
    others in the public sector; and pharma, biotech, diagnostics
    industry, clinical laboratory industry, and others in the private
    sector.

[]{#__RefHeading___Toc205616431 .anchor}255 Development of Anticancer
Agents

Number of anticipated awards: 7

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,500,000

Summary:

The short term goal of this SBIR contract topic is to support small
businesses that are developing candidate therapeutic agents of interest.
Work scope may include animal efficacy testing, structure activity
relationships (SAR), medicinal chemistry, formulation, production of GMP
bulk drug and clinical product, as well as pharmacokinetic,
pharmacodynamic, and toxicological studies. These data will establish
the rationale for continued development of the experimental therapeutic
agent to the point of filing an Investigational New Drug Application
(IND)
(<http://www.fda.gov/cder/Regulatory/applications/ind_page_1.htm>).
Successful projects will also be eligible for further development at
NCI, including early-stage clinical trials via the Joint DCTD-CCR Early
Therapeutic Development Program. Companies should submit proposals for
the development of agents that are in mid to late pre-clinical
development (expected time to clinic 1-3 years). The development plan,
targeted to oncologic indications, will be reviewed by NCI.

Project goals:

The goal of the NCI SBIR program is to fund small businesses to develop
commercially viable products that advance the research and development
that ultimately benefit cancer patients. The NCI Strategic Plan
identifies integrating clinical trial structures to expedite
identification of the most promising treatment opportunities and rapid
execution of the necessary clinical trials as a strategic priority
(Strategy 4.5). Part of this strategy includes creating an integrated
infrastructure to accelerate the implementation of high-priority
clinical trials. The long term goal of this contract is to enable a
small business to bring a fully developed cancer therapeutic agent to
the clinic and eventually to the market.

Recipient companies will benefit in several ways:

-   If appropriate, NCI will provide assistance to the small business in
    its development of an IND-directed development plan. Assistance
    might include assistance in study design and identification of
    necessary studies that would be appropriate for filing of an IND.

-   Potential for further collaboration with NCI
    inventors/investigators.

-   Potential for an early-stage clinical development partnership with
    NCI upon project completion.

Phase I activities and expected deliverables:

-   Specific activities will range from SAR and medicinal chemistry to
    animal toxicology and pharmacology, depending on the agent selected
    for development.

-   Mutually agreed-upon development plan that describes in detail the
    experiments necessary to file an IND or an exploratory IND.

-   Demonstrate ability to deliver results for the initial set of
    experiments (project-specific, according to the development plan
    above).

Phase II activities and expected deliverables:

-   Complete all experiments according to the development plan (can be
    re-evaluated if needed).

-   If warranted, provide sufficient data to file an IND or an
    exploratory IND for the candidate therapeutic agent in question
    (oncologic indications).

-   Demonstrate the ability to produce a sufficient amount of clinical
    grade materials suitable for an early clinical trial (according to
    FDA's Exploratory IND guidance)
    <http://www.fda.gov/cder/guidance/7086fnl.htm>.

-   A comprehensive IP and development plan, outlining how the small
    business will develop and commercialize the subject therapeutic
    agent. If relevant, finalize clinical co-development agreement with
    NCI.

[]{#__RefHeading___Toc205616432 .anchor}256 Innovative Methods for
Manufacturing Safe, Effective Cancer Therapeutics

Number of anticipated awards: 2

(Fast-Track proposals will not be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

Summary:

The NIH Roadmap Initiative for Medical Research emphasizes the
importance of translational activities that bridge the gap between
laboratory research and medical product development. At the same time,
the FDA has identified a growing gap between the rapid advances in drug
discovery and the number of regulatory approvals for new drugs. One
aspect of translational research that is frequently overlooked is the
significance of the transition from a lab-scale production process to an
industrial-scale manufacturing process. Many product failures are
attributed to inadequate product design, characterization, scale-up and
manufacturing. The potential for recent advances in basic and
translational research cannot be fully realized without technological
research targeting improved methods for production of safe and effective
drugs.

A primary roadblock in the development of new cancer therapeutics is the
lack of well-defined manufacturing processes for production of high
quality, safe and effective pharmaceutical-grade reagents. Production
failures increase both the cost and time required to bring a drug to
market and often result in missed opportunities to evaluate promising
new approaches. Expensive toxicology studies and clinical trial results
are often brought into question during regulatory review for failure to
demonstrate reliable, reproducible methods of production or for
inadequate characterization of the agent used in the study. Production
lot failures that occur during manufacturing or product testing
significantly increase production costs and time-to-market. Innovative,
state-of-the art technologies are critical to cost-effective, regulatory
compliant pharmaceutical manufacturing at the commercial-scale.

The use of standardized approaches to product characterization,
specifications, testing strategies, manufacturing processes, stability
evaluation and reference standards leads to more rapid, cost-effective
drug development and a higher level of regulatory success. Achieving
this level of standardization for cancer therapeutics requires specific,
pragmatic scientific research directed at modernizing the product
production process.

Project Goals:

Effective use of science and engineering principles during the
development of a drug can improve both the efficiency and reliability of
the manufacturing process and the quality of the final product. The
purpose of this initiative is to facilitate the development of
innovative methods that improve and modernize the medical product
manufacturing process for biologic drugs for cancer treatment. The focus
of this research includes:

1\) Development of innovative methods for more rapid and efficient
production of biologics by designing, optimizing and monitoring the
manufacturing process including new applications of in-line or on-line
process analyzers providing multi-variate data to improve the efficiency
of process controls and determination of production end-points.

2\) Development of formulation design and stability testing strategies
that collect information on multiple attributes with minimal sample
preparation.

3\) Development of methods and reagents to more efficiently assess
factors related to the ultimate product quality, safety and efficacy of
biologics.

These projects may include but are not limited to development of new or
improved manufacturing methods including 1) application of new
technologies for monitoring and improving process efficiency 2)
development and standardization of new methods to predict and detect
safety problems during manufacturing 3) development of tools for product
testing including development of in vitro assays and new animal models
4) development and production of reference standards and reagents
required for GMP manufacturing of a specific product type. The proposed
projects must be conducted in compliance with FDA Guidelines for
manufacturing biotherapeutics
([http://www.FDA.gov](http://www.fda.gov/)). The long-term goal of this
initiative is to provide the tools necessary for efficient and
high-quality manufacturing of novel therapies in the emerging field of
cancer biologics.

Phase I Activities and expected deliverables: Phase I will involve novel
inventions related to improvements in manufacturing processes, in vitro
or in vivo assay systems for evaluating the safety and efficacy of a
product or class of products, or development of reference standards and
reagents required for GMP production of a class of products. Examples of
phase I activities and deliverables:

-   Scientific data demonstrating the feasibility of the manufacturing
    improvement or assay.

-   Scientific data demonstrating the proposed scalability of the
    manufacturing improvement.

-   Beta-testing of the manufacturing improvement.

-   Qualification of the assay including, but not limited to:
    identification of reference standards, system suitability criteria,
    reproducibility, matrix effects, robustness.

Phase II Activities and expected deliverables: Phase II activities will
include validation of novel process improvements in manufacturing or
production of reference standards, reagents and novel assays systems
identified in Phase I. The deliverable for a Phase II project will be a
process or product that applies new technology to medical product
development. Examples of phase II activities and deliverables:

-   Prototype with detailed specifications for hardware/software
    manufacturing improvements.

-   Full validation of process improvements.

-   Full validation of novel assays or assay improvements including, but
    not limited to: system suitability, reproducibility, matrix effects,
    robustness.

-   Standard operating procedures for each assay.

[]{#__RefHeading___Toc205616433 .anchor}257 Biopsy Instruments and
Devices that Preserve Molecular Profiles in Tumors

Number of anticipated awards: 2-3

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$250,000; Phase II: \$2,000,000

Summary:

Molecular medicine holds much promise for advancing cancer diagnosis and
treatment, if biomarkers, molecular targets and drug effects on these
targets can be accurately assessed in tumor nodules in the viscera. The
amount and function of molecular drug targets within signal transduction
pathways are often regulated by rapid enzymatic reactions in response to
physiological stimuli. Biopsies play a central role in assessing
biomarkers and molecular targets in solid tumors, but conventional
practices and medications used by surgeons and interventional
radiologists necessarily perturb the tumor environment and thereby
induce extraneous and confounding molecular responses to tissue trauma,
vascular changes, hypoxia, anesthetics, etc. Expeditious processing of
the biopsy specimen using snap freezing or rapid fixation are
ineffective for preventing many rapid enzymatic modifications, because
time frames of biopsy procedures are much longer than that of the
enzymatic reactions. Thus, there is a need to develop clinical devices,
instruments and approaches suitable for clinical practice that stabilize
molecular profiles in visceral tumor lesions during the procedure, and
prevent molecular response to the procedure. The diagnostics market
includes devices for needle cryobiopsy of breast lesions that freeze the
tissue in situ before sampling, but the needle size is too large for
percutaneous image-guided biopsy of visceral sites. Although unlikely to
improve routine diagnostic biopsies, innovative approaches for tumor
biopsy that preserve the molecular profile will create an entirely new
diagnostic area and market in molecular therapeutics, which will not
only facilitate pharmacodynamic assessment of targeted therapeutics but
also enable individualized molecular therapy of solid tumors based on
accurate information about signal transduction pathways, molecular drug
targets and biomarkers.

Project goals:

The short-term goal of the project is the identification of technical
strategies with potential for stabilizing the molecular profile of
cancerous lesions in visceral tissue sites during clinical biopsy
procedures. The long-term goals of the project are the design and
development of operational prototype instruments/devices required to
practice the innovative biopsy approach; the demonstration of the
operational success of the innovative approach when applied to visceral
lesions of solid tumors in model systems; and the evaluation of the
potential superiority of the innovative biopsy approach over
conventional surgical and radiological procedures for assessing highly
dynamic molecular profiles that are associated with a high degree of
instability during conventional biopsy procedures. The project scope
includes advancements in biopsy technologies and approaches from any
medical discipline performing biopsy procedures (surgery, radiology,
dermatology, etc.) that improve the fidelity of molecular assessment of
visceral tumor lesions. Reaching these goals on the basis of
experimental evidence will mark a major advance in the ability to
accurately assess the molecular profile of solid tumor lesions of the
viscera and the functional status of their molecular targets during
early clinical trials of experimental therapeutics. If successful, this
project will improve the accuracy of biomarker assessment for diagnosis
and prognosis and the information available about the pharmacodynamics
and molecular efficacy of targeted drug therapy.

Phase I proposal should identify a technical strategy for preventing
changes in molecular status during solid tumor biopsy and articulate its
rationale and critical principles of operation. It is expected that the
company will establish regulatory requirements for clearing the proposed
instrument of device through the FDA prior to submitting the proposal.
Research plan should contain quantifiable, testable feasibility
milestones.

Phase I activities and expected deliverables:

-   Generate scientific data indicating that the innovative biopsy
    procedure stabilizes a biochemical process or reaction, or a
    functional molecular status, that is unstable during conventional
    surgical or needle biopsy procedures.

-   Provide a description of the technical strategy underlying the
    innovative biopsy approach, the critical operating principles and
    the experimental design for testing if feasibility has been
    achieved.

-   Provide a summary report of the results proving the feasibility of
    the innovative biopsy approach in tumor lesions of the viscera.

-   Produce histochemical, biomarker, and/or other pharmacodynamic data
    that demonstrate that the innovative biopsy approach stabilizes a
    biochemical or molecular endpoint that is unstable during
    conventional biopsy procedures.

-   Engage and obtain feedback from potential customers and users
    guiding the development of the product.

Phase II activities and expected deliverables:

-   Design of clinic-ready device using FDA-compliant design processes.

-   Production of a clinic-ready system and R&D activities to support
    integration of such system in clinical practice.

-   Specify or develop assay for assessing molecular preservation which
    is suitable to be a general quality control indicator of molecular
    stabilization in clinical specimens.

-   Design and conduct comparative studies of the innovative biopsy
    approach and instrument, and surgical and/or conventional needle
    biopsy of visceral lesions of a solid tumor model in animals, using
    validated assays.

-   Provide results of the comparative study of the innovative and
    conventional biopsy approaches in the animal model, using validated
    assays

-   Generate scientific publication regarding system performance
    oriented at the end user (surgeon, interventional radiologist,
    oncologist, pathologist, etc)

-   Provide instrument data sheet and written instructions for the
    operation of any prototype biopsy device or instrument and the
    procedure for performing the innovative biopsy with quality control
    measures.

[]{#__RefHeading___Toc205616434 .anchor}258 Innovative Strategies to
Protect Radiosensitive Organs and Structures During Radiation Therapy

Number of anticipated awards: 3-5

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$200,000; Phase II: \$1,000,000

Summary:

Radiation therapy is an essential tool in the cancer treatment arsenal.
More than one million patients undergo radiation therapy in the US each
year, and recent improvements in instrumentation have increased the
clinical utility of this treatment modality. Despite significant
progress, there are still situations where patient/organ motion limits
the dose that can be safely delivered to the tumor without damaging
adjacent radiosensitive organs such as bladder, heart, spinal cord and
others. There have been significant recent advances in this area,
examples of which include development of implantable markers and
electromagnetic localization systems, introduction of respiratory
gating, advances in image-guided radiation therapy, growth in
availability of proton/heavy ion radiotherapy, brachytherapy, and
others. However in certain clinical situations damage to the adjacent
tissues, and resulting complications, could be further reduced enhancing
the efficacy of therapy, if better knowledge of radiation dose
distribution could be obtained and organ motion during the radiation
delivery better controlled. This contract solicitation seeks to
stimulate research, development, and commercialization of innovative
devices and methodologies designed to protect radiosensitive organs and
structures during radiation delivery.

Project goals:

The short-term goal of the project is to perform proof-of-principle
technical feasibility demonstration of innovative strategies for
protection of critical organs and structures through methods or
procedures enacted prior to, during, or following the radiation
delivery. These strategies may include, but are not limited to
innovative devices, methods, phantoms, software, imaging systems, etc to
assist in this goal. The long-term goal of the project is to generate
scientific evidence regarding the safety and efficacy of the method and
to bring the strategy to the clinic.

It is expected that the proposed innovation is driven by clinical need,
therefore, in addition to standard proposal components; the contract
proposal should contain specific discussion of:

1\. Evidence of an existing clinical problem which is addressed by the
proposed method.

2\. Analysis of competitive methods to address the same problem and
explanation of competitive advantages of proposed system.

3\. Quantitative estimate of number of patient cases where the strategy
will help to deliver better result per typical clinical site. This
evaluation should be supported by literature, letters from radiation
oncologists, radiologists, medical physicists, or other qualified
specialists. It is expected that the company will establish regulatory
requirements for clearing the proposed system through the FDA prior to
submitting the proposal.

Research should be proposed with quantifiable, testable feasibility
milestones.

Phase I Activities and Expected Deliverables:

Phase I activities should support the technical feasibility of the
innovative approach. Specific activities and deliverables during Phase I
should include:

-   Design of a prototype system implementing the proposed method.

-   Development or procurement of an appropriate phantom or model
    necessary to evaluate the performance of the proposed system

-   Validation of the prototype system with the phantom or model

Documentation providing description of the prototype system design,
validation protocol, and testing results should be provided to NCI as
part of Phase I progress report.

Phase II Activities and Expected Deliverables:

Phase II activities should support introduction of the device into
clinical practice. Where cooperation of other equipment manufacturers is
critical for implementation of proposed methodology, company should
provide evidence of such cooperation (through partnering arrangement,
collaboration, or other letters of intent).Specific activities and
deliverables during Phase II should include:

-   Design of clinic-ready device using FDA-compliant design process

-   Scientific studies of system performance as required by the FDA for
    submitting IDE, 510(k), PMA, or other appropriate regulatory
    pathway. (Studies may include phantom testing, animal testing,
    clinical testing, etc)

-   Production of a clinic-ready system and R&D activities to support
    integration of such system in clinical practice.

-   Submission of scientific publication regarding system performance
    oriented at the end user (radiation oncologist, medical physicist,
    etc).

Data sheet detailing performance of developed system should be provided
to NCI as part of Phase II progress report.

[]{#__RefHeading___Toc205616435 .anchor}259 Quantitative Tissue Imaging
For Clinical Diagnosis and Treatment

Number of anticipated awards: 4-6

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

Summary:

This SBIR announcement solicits submissions of proposals from small
businesses interested in developing automated assays to identify and
quantify subsets of specific cells in tumor biopsy tissue. An automated
cell-based assay could become an important alternative to approaches
based on genetic, epigenetic or proteomic profiles that focus on
molecular features of tumor tissue to predict response to therapy. These
methods are often slow, complicated, and may fail to detect small
populations of specific cells within tumors such as cancer stem cells,
or host immune or stromal cells whose presence may determine the
clinical outcome of a treatment.

Assays designed to measure quantitatively the presence of cell
subpopulations may be easier to perform on tissue biopsies than those
that measure profiles of all the molecules in extracts of tissues. In
addition, monitoring the presence of specific cells within tumor
biopsies may provide a more accurate assessment of treatment response
than molecular profiles of extracts of small biopsies. This will enable
the use of specifically identified cell subsets as therapeutic targets
and potentially open new avenues to monitor therapeutic response. These
objectives are consistent with several NCI strategic goals in molecular
medicine, nanotechnology and development of novel therapeutics.

This initiative is intended to stimulate and fund development of
rigorous, validated automated assays to measure cells in tumor tissues
based on the application of current state of the art image acquisition
and quantitative analysis. The cell types may be cancer stem cells, host
immune, stromal, endothelial or other cells (please see :
[http://sbir.cancer.gov](http://sbir.cancer.gov/)/ for examples).
Initial development may involve use of preclinical models but the intent
of this initiative is for the development of clinically useful assays.
Deployment of the new assays may be via a central laboratory service or
distribution of equipment and specific kits to clinical laboratories.
Validation of analytical performance of the assay will be required by an
alternative technology. Offerors may submit proposals that will measure
cellular subsets of their own choosing that are alternatives to the
foregoing suggestions, so long as they remain relevant to oncology
therapeutics development.

Project goals:

The short term goal of this contract is to develop rigorous, validated
assays to measure cell subsets present within neoplastic tissue that may
be predictive or prognostic markers. The focus of this solicitation is
development of automated image acquisition and quantitative analysis in
real time of cell populations in tissues collected in accordance with
guidelines provided by the Office of Biorepositories and Biospecimen
Research (OBBR, please see
[http://biospecimens.cancer.gov](http://biospecimens.cancer.gov/)/). The
assay design can be aimed to provide either a service by a clinical
laboratory or a kit with equipment, supplies and Standard Operating
Procedure (SOP) for end users. For either choice, an SOP for the assay
must be developed and provided to the NCI. Validation data from a second
technology that confirms the quantitative measurements of the specified
cell subsets (e.g., by flow cytometry or functional assay) must be
provided to the NCI. Small business respondents may submit proposals to
develop assays of their own invention or those they have identified in
the literature as the company has appropriate rights to commercialize
the technology.

The long term goal of contracts under this RFP is the development of a
series of imaging assays for cell-based markers that provide prognostic,
predictive or therapeutic response information on clinical tissue
biopsies of potential value to clinical practice. Any successes would
support the goal of the NCI SBIR program to fund small businesses
developing commercially viable products that improve public health and
well being. Specifically, strategic priorities 4.1-3 and 4.5 of the NCI
Strategic Plan identify efforts to validate biomarkers and targets for
cancer prognosis, metastasis, treatment response and cancer progression,
and their integration into clinical trials.

Market analysis indicates that developments of quantitative imaging
assays are valuable first steps to eventual commercialization of cancer
diagnostic and laboratory assays. It is expected that companies will
apply their assay service or kit developments to the task of patient
stratification for clinical trial selection and/or to predict or
evaluate response to new therapeutic agents.

Phase I activities and expected deliverables:

1\. Develop an automated quantitative imaging assay for a defined
cellular subset in a preclinical model that is consistent with the
current DICOM standard. The NCI is interested in a specific list of
candidate cells (please see http://sbir.cancer.gov/ for this list of
candidates). The identification of each cell type is expected to require
simultaneous measurement with two or more analyte-specific reagents. The
imaging assay must demonstrate adequate accuracy in both fresh and
formalin-fixed tissues. The SBIR contract recipient must deliver SOPs
for specimen collection, processing and stability of the cell subset
under the conditions of the imaging assay.

2\. The SBIR contract recipient must deliver data that demonstrate
research assay reproducibility, variability and accuracy in a
preclinical model and that show consistency with the current DICOM
standard and assay SOPs.

3\. The SBIR recipient must confirm the quantitative analysis in the
first deliverable with a second technology that assesses phenotype or
function of the cell of interest. This validation should also involve
both fresh and formalin-fixed tissues. The data for this validation must
be presented to the NCI.

4\. The SBIR recipient must demonstrate acceptable real-time assay
performance in preclinical model tissue such that assay results will be
generated within 3 -- 5 days of initiating tissue analysis.

5\. Research should be proposed with quantifiable, testable feasibility
milestones.

Phase II activities and expected deliverables:

1\. Provide data to NCI that validates the automated quantitative
imaging assay from Phase I for the cell subset in clinical samples with
a second technology that measures the subset phenotypically and/or
functionally. This is expected to require analysis of normal and
malignant tissues that are both fresh and formalin-fixed to enable
parallel confirmation of phenotype and/or function. The assay must be
applicable in the clinical laboratory setting as well as in its intended
use and conform to current DICOM standards. The assay may be distributed
as either a service by a central laboratory or as a kit with equipment,
supplies and SOPs when fully developed and validated.

2\. Provide data to NCI from studies performed to characterize the
correlation between the resulting assay in tumor versus surrogate
tissues (e.g. blood, serum), if applicable.

3\. Provide the SOP for specimen collection and processing and of the
imaging assay for the cell subset with the exception of proprietary
information.

[]{#__RefHeading___Toc205616436 .anchor}260 High Level Programming
Language to Expedite Development of User Interfaces

Number of anticipated awards: 1-2

(Fast-Track proposals will not be accepted.)

Budget (total costs): Phase I: \$200,000; Phase II: \$750,000

Summary:

The development of new statistical methodology represents a key
component of biomedical research as we face increasingly varied
challenges such as optimizing the design of randomized controlled trials
(RCT's), exploring high dimensional genetic data, and applying data
mining techniques for pharmaco-surveillance of large administrative data
bases. A recent workshop held by the NCI entitled, "Barriers to the
Development of User-Friendly, Well-Tested Software for Cutting Edge
Statistical Methodology", identified the cost of development of user
interfaces as a major impediment to the speed with which new statistical
methods become usable by the broader audience of biomedical researchers.
The development of statistical methodology and associated software goes
through phases. In the earliest phase, a statistical calculation engine
is created (with no interface) to be used primarily by the developers of
the methodology and other research level statisticians. In a second
phase, the efficiency of the calculation engine is improved and a basic
interface is developed so that end users may apply the method in various
types of applications and test the practical usefulness of the
methodology. In a third phase, the programming of the calculation engine
is further enhanced by professional programmers, a full blown interface
is developed, and/or the methodology is incorporated into well developed
statistical packages (e.g. SAS, STATA, SPSS).

Project Goals:

The goal of this solicitation is to develop a high level programming
language which could be used directly by statisticians to develop user
interfaces in the 2nd phase of the development of statistical
methodology. The user interface would have to be readily accessible to a
broad audience (e.g. EXCEL), and the product should be able to connect
the interface with the most commonly used languages for the development
of statistical calculation engines (e.g. R, C++, Proc IML in SAS,
Gauss). The product could be written in various languages (e.g. Visual
Basic for Applications - VBA) but would have to be easy to learn and use
for those not formally trained as programmers. Since biomedical
researchers other than statisticians often face the same problem of
linking a calculation engine to a user interface (e.g. risk
communication tools, patient decision making tools, policy evaluation
tools), an important aspect of phase I of development will be to assess
the broader market for this tool.

Phase I Activities and Expected Deliverables:

-   Develop a basic prototype user interface programming language with
    limited features (e.g. fixed length inputs and outputs).

-   Test the usability of the system by demonstrating the development of
    a basic user interface for one statistical and one non-statistical
    application. The user interfaces should be programmed by the
    developers of the calculation engines.

-   Convene focus groups or conduct interviews with potential end-users
    to determine the acceptability of the system contents, format, etc.

-   Document the ease of use of the system based on these applications.

-   Identify potential target audiences beyond statisticians.

-   Develop suggested features of a full-blown system.

-   Demonstrate the system at statistical and/or non-statistical
    conferences.

-   Provide monthly reports.

-   Develop a working prototype of the system.

-   Include travel funds to present Phase I findings and demonstrate
    product prototype to an NCI Evaluation Panel.

    Phase II Activities and Expected Deliverables:

-   Develop a full featured high level programming language as proposed
    in Phase I.

-   Develop a well written user manual for the product.

-   Develop a working group of interested users of the product comprised
    of both statisticians and non-statisticians. Seek guidance from this
    working group on a regular basis about usability, flexibility and
    features of the product both from the developer and end-user points
    of view.

-   Test out the programming language with groups of experienced and
    non-experienced users for feedback and modifications to the product.

-   Produce quarterly reports summarizing how the development of the
    product is being guided by the user group.

-   Identify Phase II barriers and resolutions.

-   In the first year of the contract, provide the program and contract
    officers with a letter(s) of commercial interest.

-   In the second year of the contract, provide the program and contract
    officers with a letter(s) of commercial commitment.

-   Include \$30,000 in the budget for evaluation of the system at the
    NCI Evaluation Lab.

-   Provide a final report summarizing the product, it features, and
    potential user groups.

-   Include sufficient travel funds for the P.I. to participate in an
    NCI/DCCPS SBIR Showcase.

-   Prepare at least one manuscript describing the development and
    evaluation of the product for publication in a peer-reviewed
    scientific journal.

-   Submit final Phase II report in the template provided by the NCI
    program officer.

[]{#__RefHeading___Toc205616437 .anchor}261 Mobile Computing for
Consumer-centered Cancer Prevention and Control

Number of anticipated awards: 1-2

(Fast-Track proposals will not be accepted.)

Budget: Phase I: \$200,000; Phase II: \$1,000,000

Summary:

The evolution of the geo-spatial web
(<http://en.wikipedia.org/wiki/Geoweb>) combined with the convergence of
computers and mobile phones into "smart phone" technologies will allow
for geo-positioning capabilities that can deliver real-time context
specific health-related information to consumers. Devices such as these
will have applications that capitalize on existing geo-spatial databases
describing the environment, similar to current GPS navigation devices or
web-based mapping services used for personal cartography. Other
potential applications include range and orientation-sensing, and health
monitoring capability with wearable sensors, as projected by the Centers
for Disease Control and Prevention and the Institute for the Future
(<http://www.iftf.org/taxonomy/term/44>).

With annual savings estimated to be over \$77 billion dollars (RAND
Health IT Report:
<http://rand.org/pubs/research_briefs/RB9136/index1.html>)
public-private collaboratives such as the American Health Information
Community 2.0, are striving to develop shared standards, ontologies, and
systems to integrate health and bio-medical information at a "cells to
society" level that includes population data and personal health
records. In this regard, one of the challenges in developing next
generation mobile device applications for health promotion and
communication lies in their ability to effectively integrate formal and
informal geo-spatial, behavioral, psychosocial, and biomedical data and
metadata for consumer-facing applications. For example, mobile devices
providing real-time dietary/nutrition information triggered by
geo-spatial location, such as walking into a restaurant, entails
potential integration of geographic, dietary behavior, and biomedical
information.

Through this integration of data from multiple sources, mobile 'smart
phones' have the potential to transform cancer control and prevention
through applications for cancer communication, health promotion,
surveillance, treatment, clinical trials and health systems research.
Such a device could serve both communication (multi-directional, between
consumers, providers, and scientists) and real-time data capture
(geo-spatial, environmental, biomedical sensor, and behavioral)
purposes. Examples of applications include health coaching for smoking
cessation, sun-safety reminders triggered by UV sensors, automated
mapping of walking/running/bike paths based on location and tailored
physical activity goals, portable assessment of patient/caregiver
self-care, location-based health risks/hazards, and monitoring symptoms
and behaviors of patients in treatment and follow-up.

Project Goals:

The National Cancer Institute (NCI) promotes the use of state-of-the-art
mobile technology to support products and applications that 1) are
needed by professionals or the public to reduce cancer risk or improve
the quality of life of cancer survivors; 2) help fill gaps in research;
3) resolve barriers to use so that products can be used effectively in a
variety of settings including medical and community-based contexts; and
4) improve communication behaviors between health care professionals,
researchers, and patients/care-givers in cancer-related matters.

Short-term goals include development of a prototype mobile device (i.e,
smart phones or other appropriate electronic devices) or enhancement of
existing mobile devices through software and/or hardware devices that
are ideally interoperable with current widely used standards. This
mobile device should be able to usefully integrate behavioral,
psychosocial, and/or biomedical data with real-time geo-spatial
information for cancer control and prevention-related health
communication, health promotion, surveillance, and/or treatment. The
development process should emphasize principles of user-centered design.
Another goal could be to develop applications for groups at higher risk
of cancer, namely racial-ethnic minorities, socio-economically
disadvantaged groups, and low literate populations. Interdisciplinary
collaborations (e.g., behavioral researchers, computer scientists,
nutrition specialists, exercise physiologists, health disparities
scientists, etc.) are highly recommended to move the field forward in an
integrative manner.

Long-term goals include evaluation and refinement of the mobile device
with robust data interoperability across geo-spatial, behavioral,
psychosocial, and/or biomedical datasets, potentially including linkages
to information stored in electronic/personal health record (EHR/PHR)
systems.

Phase I Activities and Expected Deliverables:

-   Develop a fully functional prototype of an electronic mobile "smart
    phone" device or software and/or hardware attachments for existing
    mobile devices that can integrate behavioral, psychosocial, and/or
    biomedical data with real-time geo-spatial information for cancer
    control and prevention-related health communication, health
    promotion, surveillance, and/or treatment.

-   Convene focus groups or conduct interviews with potential end-users
    of the device to determine if the system contents, format, etc. are
    appropriate for ease of use.

-   Develop real-time or information feedback options to the user in all
    developed mobile device applications/tools.

-   Develop the ability for the device to operate in both online and
    offline environments (i.e., disconnected from network) when
    appropriate.

-   Provide outlines for an operation manual and primer for
    consumer-level and scientific/research applications/tools when
    appropriate.

-   Develop software designs and specifications, where applicable.

-   Include in the proposals, letters of agreement from organizations
    participating in Phase I feasibility testing and evaluation.

-   Provide monthly progress reports.

-   Include funds in budget to present Phase I findings and demonstrate
    the final prototype to an NCI Evaluation Panel.

    Phase II Activities and Expected Deliverables:

-   Develop and beta-test a mobile "smart phone" device or software
    application and/or hardware attachment for existing mobile devices
    with individuals from different population groups, and with
    researchers.

-   Evaluate and refine the device and related applications/tools based
    on user feedback.

-   Develop the final mobile "smart phone" device, applications/tools,
    and documentation where applicable.

-   Develop related operations manuals and primers, addressing both
    technical implementation and social/cultural change management.

-   In the first year of the contract, provide the program and contract
    officers with a letter(s) of commercial interest.

-   In the second year of the contract, provide the program and contract
    officers with a letter(s) of commercial commitment.

-   Provide quarterly progress reports.

-   Include \$30,000 in the budget for evaluation of the mobile "smart
    phone" device at NCI's Evaluation Lab.

-   Present final research findings and demonstrate the final product at
    an NCI/DCCPS sponsored Product Showcase.

-   Develop at least one article describing the development and
    evaluation of the mobile "smart phone" device and related
    applications/tools that is suitable for publication in scientific
    venues.

-   Submit final report in the template provided by the NCI program
    officer.

[]{#__RefHeading___Toc205616438 .anchor}262 Health Information
Technology to Facilitate Patient-centered Communication in
Cancer-related Care

Number of anticipated awards: 1-2

(Fast-Track proposals will not be accepted.)

Budget: Phase I: \$150,000; Phase II: \$750,000

Summary:

The 2001 Institute of Medicine (IOM) report titled "Crossing the Quality
Chasm" cited a need to make care "patient-centered". To achieve that end
physicians and organizations who are delivering care must begin to see
medical care from the patient perspective. As outlined in a recent NCI
report on Patient-Centered Communication (2007), "patient-centeredness"
is a multi-dimensional concept that goes beyond the notion of
satisfaction. Care for cancer patients can be described as a series of
visits, an aggregated experience often called episodes of care. Those
episodes might include a short series of visits to attend to an acute
illness or multiple visits and hospitalizations to deal with chronic
life-threatening conditions. Information technology (IT) that could
begin to integrate cancer-related care during episodes of care in a
patient-centered manner addresses DHHS and IOM priorities for
electronic/personal health records and healthcare quality improvement.
As suggested by the industry-standard Health Information and Management
Systems Society (HIMSS;
[http://www.himss.org](http://www.himss.org/ASP/index.asp)), developing
electronic tools and applications that support patient-centeredness in
clinician-patient communication is a fast growing market area.

Consequently, the goal of this topic is to encourage the development of
novel technology-based solutions that will assist clinicians in
accomplishing key functions of patient-centered communication in cancer
care: fostering relationships, exchanging information, responding to
emotions, enabling patient self-management, managing uncertainty, and
making decisions. Potential applications could be targeted to any
specific problem or domain of cancer treatment---e.g., specific
treatments for particular malignancies---but would need to address all
of the key functions of patient-centered communication in an integrative
manner. For example, clinical decision support tools and applications to
improve care coordination and follow-up; the emphasis is on solutions
that successfully address the multiple domains of patient-centeredness
in patient-clinician communication. Such technology could interact with
the health system, primary care providers, and oncologists to remind
patients when they were scheduled to see a physician, help them schedule
when they needed to, provide access to information relevant to those
visits, and even guide the patient to the office. A patient-centered
development process to develop information technology that could provide
these and other functions patients identify as critical to their care is
the focus of this topic.

Project Goals:

The major goal of this project is to create patient-centered clinical
applications in primary care and oncology designed to improve patient
empowerment through improved access to crucial decision-making
information.

Phase I Activities and Expected Deliverables:

-   Develop a system prototype that registers referrals, appointments,
    and all patient-provider and provider-provider communication
    throughout the coordination of the diagnostic process. This system
    could include the software application for a handheld device and/or
    telephone, and the relevant software to link with existing
    electronic health records. The application should also solve the
    problem of how to link the electronic health records of two separate
    medical offices with each other and the patient.

-   Develop a software prototype that includes a real time visual
    simulation of the coordination process with alerts, reminders and
    other signals that support the patient's progress and information
    needs, while clarifying the accountability of individual team
    members, and assuring the integrity of the entire coordination
    effort.

-   Develop a program that is capable of integrating into a larger
    system of home based coordinated cancer care (ideally a ubiquitous
    system with minimal patient burden); avoid redundant documentation.

-   Review the VA/NCI cancer care coordination model, other coordination
    protocols and relevant literature to develop an overall cancer
    coordination process model.

-   Establish a team or set of teams that includes providers in FQHCs
    who will conduct cancer care coordination during the diagnostic
    process.

-   Conduct interviews with team members and selected community
    participants to develop a set of use case scenarios (from first
    abnormality (abnormal screening test or symptomatic presentation in
    a physician's office through diagnosis for one cancer type) that
    will serve as the basis of the coordination simulation software
    program.

-   Convene focus groups or conduct interviews with potential end-users
    of the system to determine if the system contents, format, etc. are
    appropriate for ease of use.

-   Provide a report detailing the coordination tracking program design,
    including theoretical and methodological bases for the evaluation.

-   Provide a set of use case scenarios that have been approved by
    members of the team for tracking.

-   Develop a working prototype of the cancer care coordination tracking
    program.

-   Include in the proposal, letters of agreement from organizations
    participating in Phase I feasibility testing and evaluation.

-   Include funds in the budget to present Phase I findings and
    demonstrate the final prototype to an NCI Evaluation Panel.

    Phase II Activities and Expected Deliverables:

-   Complete 2 iterations of the tracking program software, including
    technical documentation of the system and a training manual.

-   Develop evaluation and outcome measures.

-   Evaluate and refine the program based upon user feedback.

-   Integrate the tracking program into telehealth monitoring,
    electronic patient record, and viable personal health record
    systems.

-   Test and evaluate the complete system serving cancer patients and
    their care coordination team using process and outcome measures as
    described above.

    System Requirements include:

1\) Embedding the tracking software into a home telehealth monitoring
and reporting system based upon the VA/NCI model of home centered
coordinated cancer care; this could involve partnering or licensing with
other vendors or developers of these components.

2\) Integrating the home centered coordinated cancer care system into a
community's existing IT infrastructure using the IT interoperability
standards offered by The U.S. Department of Health and Human Services
([www.hhs.gov/healthit](http://www.hhs.gov/healthit)). Eligible
communities are those that have been funded by The Foundation for
eHealth Initiative which provides seed funding and support to
multi-stakeholder collaboratives within communities (both geographic and
non-geographic) who are using electronic health information exchanges
(HIE) and other information technology tools to drive improvements in
healthcare quality, safety, and efficiency
([www.ehealthinitiative.org](http://www.ehealthinitiative.org/)).

3\) Evaluating the system in a real community setting, according to
cost, quality of care, quality of life and access outcome measures in
addition to the community's own health and IT standards. Community
members should be included in the research and development team from the
beginning of the research and development project.

In the first year of the contract, provide the program and contract
officers with a letter (s) of commercial interest.

In the second year of the contract, provide the program and contract
officers with a letter (s) of commercial commitment.

Include \$30,000 in the budget for evaluation of the product at NCI's
Evaluation Lab.

Present final research findings and demonstrate the final product at an
NCI/DCCPS sponsored Product Showcase.

Prepare at least one manuscript describing the development and
evaluation of the system for publication in a peer-reviewed scientific
journal.

[]{#__RefHeading___Toc205616439 .anchor}263 Antibody Array for Cancer
Detection and Diagnosis

Number of anticipated awards: 3-5

(Fast-Track proposals will not be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

Summary:

The purpose of this initiative is to provide support for the development
of high throughput antibody arrays for quantitative analysis of multiple
biomarkers for cancer detection, diagnosis and prognosis. These arrays
may include antibodies based on the applicant\'s own research and/or
knowledge of the literature. The selected applicants will develop
microarrays, the chemistry of which may be based on nanotechnology
and/or microfluidics. Applicants should focus initial development on the
diagnosis and detection of prostate, breast, lung, colon, and other
major epithelial cancers. In Phase II, the antibody microarray developed
in Phase I will be validated under a plan developed with the NCI project
officer.

Project Goals:

The specific objectives are:

-   Prepare and purify biomarker-specific antibodies in the form of
    recombinant antibodies or monoclonal antibodies (mAb) and construct
    arrays;

-   Develop and/or improve methodologies for quantitative measurements
    of the bound antigens on Ab microarrays;

-   Perform analytical validation, e.g., test the reproducibility,
    sensitivity, specificity and dynamic range of detection.

    Currently, there is no single marker or a combination of biomarkers
    that has sufficient sensitivity and specificity to detect and
    diagnose early stage cancer. However, recent developments in gene
    and proteomic profiling of precancerous and cancerous lesions
    suggest that a combination or a patterns of markers may be used to
    distinguish between cancer and non-cancer with high sensitivity and
    specificity (95-100%). Innovative technologies, such as
    microfluidics and nanotechnology, combined with antibody arrays are
    likely to provide a reliable, sensitive and quantitative detection
    tool for measuring differentially expressed biomarkers from a
    limited amount of sample (20ul or less of serum). The involvement of
    small businesses through the SBIR contract mechanism will strengthen
    NCI's efforts in the development, validation and commercialization
    of biomarkers for cancer detection, diagnosis and prognosis.

    Phase I Activities and Expected Deliverables:

    Relevant biomarkers could be selected from published literature.

-   Establish the proof of principle

-   Develop an antibody microarray for detection of 3 biomarkers using
    innovative technologies

-   Demonstrate that the tiled antibodies perform as well or better than
    a conventional ELISA in the detection of these biomarkers in serum
    from cancer patients

    Phase II Activities and expected deliverables:

-   Develop antibody microarrays with a capability to simultaneously
    detect and measure the concentration of 30-50 biomarkers.

-   Develop SOPs for antibody microarray assays utilizing limited
    amounts of sample.

-   Validate antibody microarrays for performance including sensitivity,
    specificity and dynamic range of the assay.

-   Produce and test up to 1000 microarrays with samples from normal and
    case subjects

[]{#__RefHeading___Toc205616440 .anchor}264 Novel and Improved Methods
for Detecting Epigenetic Modifications

Number of anticipated awards: 2-3

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

Summary:

Epigenetic markers have shown promise for early detection and diagnosis
of cancerous lesions. However, it is unlikely that any single epigenetic
marker has sufficient sensitivity and specificity to accurately and
reliably detect early cancers, or to predict cancer risk and
progression. Also, methods used to measure epigenetic modifications need
to be improved to increase specificity, sensitivity, reproducibility,
and throughput. For example, most methods to measure CpG methylation at
specific sites require bisulfite treatment, which is time consuming and
can result in incomplete conversion of cytosines to uracils, leading to
fluctuations in methylation measurements and poor accuracy. Assays,
methods and arrays or chips need to be developed to integrate and
improve the ability to detect epigenetic modifications as a non-invasive
approach for early cancer detection, risk assessment, diagnosis,
prognosis, and clinical response. Responses to this solicitation may
include assays for epigenetic modifications such as CpG methylation,
histone modification, as well as others.

Project Goals:

The purpose of this initiative is to solicit small businesses to develop
innovative and improved assays, methods, or chips for detecting
epigenetic modifications applicable for clinical assessment of
epigenetic markers of cancer. This SBIR contract solicitation
encourages: (1) development of new methods for methylation detection
that do not require bisulfite treatment or increase the conversion rate
of cytosine to uracil by bisulfite; (2) development of chips for high
throughput detection of epigenetic modifications; and (3) development of
more sensitive techniques that allow for epigenetic modifications to be
measured in small volumes of bodily fluids such as sera or sputum. Most
current methods require large volumes, making them unsuitable for use
with these bodily fluids and hence for use in early cancer detection and
diagnosis.

Phase I activities and expected deliverables:

Develop innovative and improved epigenetic modification detection
methods or increase analytical sensitivity to allow for measurement of
modifications in low abundance;

-   Demonstrate proof of principle for the development of the assay,
    method or chip;

-   Establish a panel of epigenetic cancer markers of interest to be
    used in testing the assay, method or chip;

-   Demonstrate feasibility by testing a panel of 5 to 10 target
    epigenetic markers;

-   Test the usefulness of these methods using DNA extracted from cell
    lines or clinical samples;

-   Obtain input from potential customers and the clinical community in
    preparation for developing a comprehensive commercialization plan
    for the assay, method or chip.

    Phase II activities and expected deliverables:

    Refine and analytically validate the assays, methods, or chips to
    test accuracy, sensitivity, precision, and dynamic range.

-   Provide data comparing the assay, method or chip to previous widely
    used assays detailing improvements in accuracy, sensitivity,
    precision, dynamic range, throughput and sample size;

-   Use these assays, methods, or chips to characterize more than 30
    epigenetic markers;

-   Clinically validate the sensitivities and specificities of assays
    and methods using appropriate clinical samples;

-   Generate a scientific publication regarding assay or method
    performance targeted to the end user audience.

[]{#__RefHeading___Toc205616441 .anchor}265 Development of shRNA Library
Screening Technology for Cancer-Related Targets

Number of anticipated awards: 1

(Fast-Track proposals will not be accepted.)

Budget: Phase I: \$150,000; Phase II: \$1,000,000

Summary:

The goal of this SBIR contract topic is to develop improved shRNA
screening technologies for identification of molecular components of
pathways in cancer. An shRNA library will be used to inhibit expression
of every gene in the genome which will determine whether a given gene
product is required for a specific process in cells. To allow for high
throughput, stable and transient transduction of the shRNAs using a wide
variety of dividing and non-dividing cells, a lentiviral vector should
be employed. Cellular readouts of protein expression and degradation
such as fluorescently tagged fusion constructs should be used in the
screening system. The selected offeror should then adapt the cellular
readout to a rapid throughput system that can be screened against the
shRNA library. Phase I will involve development of a rapid throughput
system for transduction of shRNAs into a dividing and non-dividing cells
and validation for a limited number of target transcripts. Phase II will
adapt this transduction system to both human and mouse shRNA libraries
that include sequences targeting multiple regions of all annotated
genes. The output of this screening system will be information on
candidate gene products that participate in the pathway being examined.

Project Goals:

To determine whether a given gene product is involved in a molecular
pathway shRNAs can be designed that specifically degrade the given
message. The shRNA approach can also be used to identify new components
of a pathway by individually blocking each product of the genome. For
example, to identify factors that are involved in the pathway to Mcl-1
protein expression in cancer cells, an shRNA library could be screened
for factors that interfere with Mcl-1 expression. When Mcl-1 is fused
with GFP, the proteosomal degradation of Mcl-1 also extinguishes GFP
fluorescence. Thus, a cancer cell transfected with Mcl-1-GFP would
fluoresce unless it harbors shRNA that destabilizes the message or
enhances degradation of the protein in the cancer cell. Conversely, a
growth factor dependent cell line transfected with Mcl-1-GFP would, in
the absence of growth factor, lose fluorescence unless it harbors an
shRNA that protects Mcl-1. The latter could, for example identify an E3
ubiquitin ligase that specifically targets Mcl-1 degradation, or it
could identify any component upstream of the E3. Like Mcl-1, levels of
p27^kip1^ are regulated by ubiquitination and proteasomal degradation.
The mechanisms of the specific targeting of p27^kip1^ in cancer cells
are unclear, and these pathways could be explored using p27^kip1^-GFP
and the shRNA library. Both such screenings require development of an
shRNA screening mechanism amenable to individually testing a large
number of clones (60,000 or more). Some shRNA libraries are commercially
available and are being improved, the goal being to knock down all known
genes by about 75% on average, to assure a detectable biological effect.
Application of these libraries in a suitably large scale arrayed
screening mechanism is currently unavailable. The NCI aims to stimulate
development of this technology to advance cancer research. It is hoped
that the selected offeror would move to provide this valuable technology
as a fee for service to investigators in academic as well as
pharmaceutical and biotechnology industries.

NCI encourages offerors to consider including appropriate shRNA clones
to study the MCL-1 and P27^kip1^ protein and their role in both human
chronic lymphocytic leukemia (CLL) line and an untransformed murine T
lymphocyte line that is dependent on interleukin 7 for survival and
proliferation. Offerors may also assume in their proposals that NCI
investigators will make fluorescent cellular readout systems and these
cell types available for the development of the shRNA screening system.
**Please Note:** Ultimately the choice of gene targets, cellular readout
proteins and cell types will be at the discretion of the offeror.
However, in all cases selected targets, cellular readouts and cell types
must be relevant to cancer biology. Technical merit of each proposal
will be determined based on the offeror's ability to execute on the
deliverables listed below.

In summary the selected offeror must:

-   Develop a high throughput infection and screening system.

-   Acquire or develop lentiviral shRNA libraries that cover all
    expressed human and mouse genes.

-   Apply screening to a cell readout system, such as a fluorescent
    signal.

-   Identify candidate gene products.

    All inventions conceived or first actually reduced to practice by
    the selected offerors under this contract will be the property of
    the selected offeror in accordance with the Bayh-Dole Act (35 USC
    Section 200, et.). It is intended that data and information related
    to the development of the high throughput shRNA screening platform
    developed by the contractor be the core of the SBIR endeavor and
    subject to the FAR Clause 52.227-20 Rights in Data-SBIR Program.
    Output screening data including gene targets are explicitly excluded
    as SBIR Data pursuant to FAR Clause 52.227-20, and such data will be
    subject to FAR Clause 52.227-14 Rights in Data-General. It is
    intended that these screening data and gene target clones delivered
    to NCI by the contractor be shared with the research community as
    appropriate and consistent with the Principles of Recipients of NIH
    Research Grants and Contracts on Obtaining and Disseminating
    Biomedical Research Resources. Intellectual property discovered
    jointly by the selected biotech company and any NCI investigators
    will be jointly owned by the biotech company and NCI consistent with
    the contract terms.

    Phase I activities and expected deliverables:

1\. Array and apply shRNAs in lentiviral vectors to knocking down
cellular targets. This delivery system must be amenable to scaleup to
about 60,000 clones in Phase II.

2\. Determine the efficacy of gene silencing for \~100 gene targets,
with a depth of coverage of at least 3 shRNAs per transcript, following
lentivirus transduction of standard epithelial cell line(s) plus at
least one cell line of lymphocyte origin. Efficacy for all shRNAs will
be determined at the RNA or protein level.

Phase II activities and expected deliverables: (For projects that
continue into phase II additional materials may be made available
through negotiations with the Contracting Officer and the Contracting
Officers Technical Representative.)

1\. Scale up all deliverable from Phase I to whole genome levels (human
and mouse).

2\. Complete high throughput screens of whole genome shRNAs (human and
mouse) against cellular targets with fluorescent readouts.

3\. Construct, acquire or purchase human and mouse specific shRNA
libraries corresponding to 4,000 to 7,000 gene targets (all RefSeqs
including transcript variants) in lentiviral-based vectors screening
purposes. The depth of coverage will be 3 to 8 shRNAs per transcript.

4\. Generate lentiviral stocks for the 4,000 to 7,000 gene target shRNA
library in a fully arrayed format.

5\. Conduct two pilot, fully arrayed, shRNA mediated RNAi screens using
the whole genome libraries.

[]{#__RefHeading___Toc205616442 .anchor}266 Nanotechnology Imaging and
Sensing Platforms for Improved Diagnosis of Cancer

Number of anticipated awards: 3-5

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$200,000; Phase II: \$1,000,000

Summary:

Nanotechnology involves the design, synthesis, and manipulation of
materials at the nanoscale to take advantage of novel material
properties (e.g. large surface to volume ratio, increased conductivity,
enhanced imaging contrast, etc.) that are not normally present in
conventional bulk length scales. These properties render nanomaterials
as ideal candidates for imaging, sensing, and detecting purposes.
Further functionalization can be achieved by conjugating biological
ligands (e.g. oligonucleotides, short peptide sequences, antibodies,
etc.) that can serve to achieve specific targeting of
cells/tissues/organs or specific capturing of genomic/proteomic
candidate biomarkers.

For several types of cancer, the primary cause of poor survival is late
detection, almost often after the disease has spread to distant sites.
For example, most melanomas that are found without evidence of
metastasis can be cured with surgical resection. In contrast, patients
with advanced or metastatic melanoma, the prognosis is poor (a 5-year
survival of 5-10%). Consequently, efforts are currently being made to
develop new diagnostic solutions comprising of imaging and/or monitoring
of prognostic biomarkers.

To accelerate such efforts, the National Cancer Institute (NCI) requests
proposals for the development of commercially-viable
nanotechnology-based imaging agents and/or sensing platforms that will
ultimately assist and improve current clinical protocols of cancer
detection and diagnosis.

Project Goals:

The goal of the project is to develop nano-enabled platforms that can
provide increased resolution both spatially, and more importantly,
temporally, in detecting cancer that would ultimately offer clinicians a
way to maximize the chance of positive clinical prognosis. The platforms
can be used for early detection/imaging of initial onset of disease, or
be used as post-treatment monitoring to detect/image recurrence of
disease. Strategies can also include screening assays that provide a
better mechanistic understanding of metastasis which can help develop
better therapies and further improve patient outcome. As current drug
development continues to rely mainly on reductions in overall size of
tumors, many validated compounds may not work on metastatic disease.
Novel imaging and sensing diagnostic nanoplatforms could also be used,
in a preclinical setting, both for high throughput screening assays to
locate new metastasis-directed compound and for validating the new
compounds either in vitro, in situ, or ultimately, in vivo.

Potential relevant imaging and sensing nanoplatforms could include, but
are not limited to:

1\) Imaging and Sensing Nanoparticles; Examples: Fluorescent agents
(quantum dots, quantum rods, etc.); medical imaging agents (MR, CT,
SPECT, PET, etc.); in vivo sensors (FRET sensors, biologically-activated
systems, etc). Potential Applications: Use of agents as secondary-tags
to improve existing in vitro/ex vivo assays; Detecting smaller lesions
and/or better delineation of tumor margins with traditional clinical
imaging modalities (MR, CT, PET, etc.) before, during, and after
interventions (resection, chemotherapy, etc.); Novel in vivo sensors to
monitor cancer biology-related activities (enzymes, cleaved peptides,
etc.).

2\) Nano-enabled Sensing Platforms; Examples: Use of functionalized
nanomaterials (nanowires, nanotubes, nano-cantilevers, etc.) to build
sensing platforms with optical or electrical output. Potential
Applications: Novel platforms that would enhance sensitivity/specificity
of existing candidate biomarker detection and validation; Sensing of
tumor metastasis and/or recurrence post-treatment.

3\) High throughput Screening Nanoplatforms; Examples: Single or
combinations of nanotechnologies (nanopatterning, imaging agent, sensing
platform, microfluidics) for assay development. Applications: Locating
novel cancer biomarkers that may be undetectable using traditional
assays; detecting cellular changes using nano-sensors to screen for
novel therapeutic agents.

Given the diversity of potential applications discussed above, submitted
proposals should place emphasis on the specific nanotechnology-enabling
component of the proposed platform. Research should be proposed with
quantifiable, testable feasibility milestones.

Phase I Activities and Expected Deliverables

Platform design:

-   Development of sensing/imaging methodology

-   Demonstration of unique spatial/temporal capabilities enabled by
    nanotechnology

-   Proof of concept experiments

-   Benchmarking experiments against conventional methodologies

First-stage validation of design in relevant preclinical samples as
listed below,

-   Medical imaging agents: In vivo small animal efficacy studies

-   Sensing platforms: Candidate biomarkers in serum-free samples

-   High throughput imaging and screening assays: Non-primary cell lines
    and/or tissue samples

-   Successful completion of benchmarking experiments demonstrating a
    minimum of 2x improvement against conventional methodologies

Phase II Activities and Expected Deliverables

-   Second-stage validation of design for potential clinical adaptation

-   Medical imaging agents: In vivo small animal toxicology studies that
    can be used for regulatory filing purposes

-   Sensing platforms: Candidate biomarkers in patient samples

-   High throughput imaging and screening assays: primary cells and/or
    tissues obtained from patients

-   Submitted regulatory application (for example IDE, IND, etc.) to
    obtain necessary approval for clinical validation.

[]{#__RefHeading___Toc205616443 .anchor}267 Multifunctional Therapeutics
Based on Nanotechnology

Number of anticipated awards: 3-5

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$200,000; Phase II: \$1,200,000

Summary:

Nanoscale devices carrying therapeutic payloads and delivered within
close proximity of the tumor in vivo can play a significant role in
increasing the effectiveness of the treatment while decreasing severity
of side effects. Such techniques would be highly relevant, particularly,
for organs that are difficult to access because of a variety of
biological barriers, including those developed by tumors. For example,
nanoparticles are capable of crossing the blood-brain barrier due to
their small size and thus are an excellent candidate for non-invasive
treatment of brain tumors.

Multifunctional nanoscale devices, which are currently emerging, allow
for a combination of diagnostic or imaging agent with a therapeutic and
even a reporter of therapeutic efficacy in the same nanodevice package.
In conjunction with the development of these devices, local targeting
techniques are emerging. This process can utilize epitopes expressed on
specific signatures of tumor cells or other cellular markers of
biological processes such as angiogenic and apoptotic pathways. In
molecular oncology, this is potentially useful as a general approach
since it allows for targeting of multiple cancers or even more broadly
for targeting of multiple diseases. For instance, there are already
examples of multi-functional nanoparticles that target vascular
peptides, growth factor receptors, transmembrane proteins such as ion
channels, and are utilized for both cancer and cardiovascular disease
recognition.

To accelerate such efforts, the National Cancer Institute (NCI) requests
proposals for the development of commercially-viable
nanotechnology-based multifunctional therapeutics, designed to deliver
chemotherapeutics to cancerous cells while sparing normal, healthy
tissue, leading to increased therapeutic index and improved patient
outcomes.

Project Goals:

The goal of this project is to develop an in vivo nanodevice-based
delivery platform with improved efficacy as compared to currently used
treatments. For example, such devices can take the form of
multi-functional targeted nanoparticles or multi-chamber chips carrying
encapsulated drugs. Further, the devices may also utilize imaging agents
for a combination of therapeutic and diagnostic modalities that aim to
provide real-time feedback and monitoring of therapy. The devices can be
administered orally, intravenously, or can be implanted. They may
include, but are not limited to the following:

-   Novel therapeutic nanodevices;

-   Novel tumor targeting and concentrations schemes;

-   Novel drug loading and releasing schemes;

-   Novel nanodevices which are able to cross the blood-brain barrier.

Phase I activities and expected deliverables:

-   Fabrication techniques resulting in the manufacturing of nanodevices
    with good reproducibility should be developed. The novel use of
    existing particles acquired from commercial manufacturers will also
    be considered under this program.

-   *In vitro* (cell culture) demonstration of drug efficacy.

-   Proof-of-concept small animal studies showing improved therapeutic
    efficacy as compared to the use of free drug.

Phase II activities and expected deliverables:

-   Demonstration of targeting (multiple biomarkers) and concentration
    techniques for a specific organ/disease.

-   *In vivo* small animal drug efficacy demonstration (at least 60 day
    study with statistically relevant number of animals) utilizing an
    appropriate animal model.

-   Long term toxicity studies (biodistribution and bioelimination for
    IV administered nanodevices and biocompatibility for implanted
    devices).

-   Nanodevice manufacturing and scale-up activities.

-   IND-enabling studies carried out in a suitable pre-clinical
    environment.

-   Initiation of large animal studies.

Fast-Track justification:

While not necessary for all grantees, there are specific situations
where fast-track funding would be appropriate. Fast-track combines Phase
I and Phase II projects into one submission and allows for a faster
transition between the phases. If there is a significant amount of
preliminary data, or proof of concept demonstration already exists, this
approach may result in a faster rate of technology development. A
fast-track proposal requires inclusion of quantitative and specific
deliverables in the Phase I portion of the application.

Before Phase II funding is awarded, a progress report towards meeting of
the Phase I milestones must be received. Only upon successful evaluation
of this report by the contracting officer will Phase II funding be
approved.

[]{#__RefHeading___Toc205616444 .anchor}268 Novel Antibody Epitope
Mapping Technologies

Number of anticipated awards: 4

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$750,000

Summary:

The purpose of this initiative is to provide support for the development
of novel epitope mapping technologies. Epitope Mapping encompasses all
the major methods for the identification and definition of epitopes. The
ability to characterize the epitope of an antibody on its target protein
is now being extensively employed to develop new therapeutics and
biomarkers. This epitope information can help researchers to understand
the \"mechanism of action\" of an antibody, to predict the potential
cross-reactivity and connecting a SNP polymorphism to a specific protein
structure. In addition, epitope mapping has been used as a powerful tool
for rational drug design. Studies have revealed that while off-rate is
an important factor in determining antibody potency, it is not the
critical factor. Antibodies can recognize a linear string of amino
acids, but they frequently bind to discontinuous/conformational epitopes
(i.e. amino acids in a protein sequence that are brought together in the
three-dimensional protein fold but are disparate in its linear
sequence). Therefore the quality of antibodies results from the fine
specificity of the molecular interactions, rather than simple binding
parameters. A number of computational algorithms are now available for
mapping conformational discontinuous epitopes. Additionally, various
methods namely use of synthetic peptides, expression cloning, site
directed mutagenesis and protein footprinting have also been used for
epitope mapping.

Specifically, the NCI is interested in proposals that focus on the
development of novel, fast, reliable and economical epitope mapping
techniques. Proposals should explicitly describe how the proposed
technology/system will develop and characterize monoclonal antibody
epitope mapping.

Project Goals:

Information about the epitopes of proteins recognized by antibodies is
important for their use as biological or diagnostic tools as well as for
understanding molecular recognition events. The information about
Ab-antigen interactions gained from epitope mapping can be utilized in
two important ways: either by using engineered Abs as bait for the
detection of antigens in biologic samples; or by using recombinant
proteins as diagnostic tools for the presence of Abs produced in an
immune response. The purpose of this project is to stimulate the
development of novel, fast, reliable and economical monoclonal antibody
epitope mapping technologies including mass spectrometry (MS) based
methods.

Offerors are encouraged to coordinate and pursue selected monoclonal Abs
developed by the Clinical Cancer Proteomics community. These Abs are
being generated from biomarkers listed in the following reference: Malu
Polanski and N. Leigh Anderson. (2006) "A List of Candidate Cancer
Biomarkers for Targeted Proteomics." Biomarker Insights 2:1-48.

Phase I Activities and Expected Deliverables

-   Demonstrate the feasibility of the innovative monoclonal Ab epitope
    mapping method (including MS-based techniques).

-   Produce an initial product prototype in working with the Clinical
    Proteomic Technologies Initiative community.

-   Demonstrate that epitope mapping method can be made reproducibly and
    economically.

-   Epitope map at least 10 monoclonal Abs (offerors are encouraged to
    select targets in coordination with the Clinical Cancer Proteomics
    community).

-   Functionally characterize the mapped epitopes e.g. demonstrate which
    amino acids are critical for binding.

-   Present findings to NCI program staff.

-   Research should be proposed with quantitative feasibility
    milestones.

Phase II Activities and Expected Deliverables

-   Implement strategy and project plan for a fully functional novel,
    fast, reliable and economical epitope mapping technology.
    Achievement of such criteria could be derived by comparison with
    existing technologies.

-   Epitope map at least 100 monoclonal Abs (targets to be selected in
    coordination with the Clinical Cancer Proteomics community).

-   Functionally characterize the mapped epitopes e.g. demonstrate which
    amino acids are critical for binding.

-   Work with the Clinical Proteomics community to integrate platform
    into the technology assessment programs and greater scientific
    community.

-   Research should be proposed with quantitative feasibility
    milestones.

[]{#__RefHeading___Toc205616445 .anchor}269 Development of Novel Protein
Expression Technologies for Glycosylated Cancer Related Proteins

Number of anticipated awards: 4

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$750,000

Summary:

The purpose of this initiative is to provide support for the development
of novel technologies for the expression of cancer-related glycosylated
proteins. Many proteins become post-translationally modified (PTM)
during the "secretory process" which involves of a journey from their
site of synthesis in the rough endoplasmic reticulum (ER), through the
Golgi apparatus and then to various cellular and extracellular
destinations. Various covalent modifications often occur, either during
or after assembly of the polypeptide chain, that are indispensable for
the activity of these proteins. Knowledge of these modifications is
extremely important because they may alter the proteins' physical and
chemical properties, folding, conformation distribution, stability,
activity, and consequently, function. Moreover, the modification itself
can act as an added functional group. Examples of the biological effects
of protein modifications include glycosylation, phosphorylation,
acetylation, and amidation. Of these, the most complex procedure,
involving several enzymes, is glycosylation. Hence, glycoproteins are
the most diverse group of biological compounds that are ubiquitous
constituents of almost all living organisms. A given glycoprotein may
contain N-linked (asparagine-linked) oligosaccharide chains only,
O-linked (threonine- or serine-linked) oligosaccharide chains only, or
both. The carbohydrate units of glycoproteins exhibit considerable
variation in size and structure ranging from mono- or disaccharide- to a
branched oligosaccharide composed of as many as 20 monosaccharide
residues. Consequently, the analysis of proteins and their
post-translational modifications is particularly important for the study
of cancer, neurodegenerative diseases, heart disease and diabetes.

Specifically, the NCI is interested in proposals that focus on the
development of glycosylated human proteins. Proposals should explicitly
describe how the proposed technology/system will develop/express,
isolate and characterize the glycosylated proteins.

Project Goals:

Increasing demand for recombinant glycosylated proteins has focused
research on techniques for improving protein expression and controlling
post-translational processing. The purpose of this project is to
stimulate the development on all aspects of glycosylated protein
expression including novel cell systems, expression vectors, and culture
conditions. Glycosylated proteins selected for production are to entail
low abundance cancer-related proteins from bodily fluids preferably
developed in coordination with the Clinical Proteomics community.
Furthermore, these glycosylated proteins must be made available as a
resource to the greater scientific community.

Offerors are encouraged to coordinate selection of analytes with the
Clinical Proteomics Technologies for Cancer community during Phase I.
Targets for Phase II are to be selected in coordination with this
community from glycosylated biomarker candidates listed in the following
reference: Malu Polanski and N. Leigh Anderson. (2006) "A List of
Candidate Cancer Biomarkers for Targeted Proteomics." Biomarker Insights
2:1-48.

Phase I Activities and Expected Deliverables

-   Demonstration of feasibility of the innovative glycosylated protein
    development approach.

-   Produce an initial glycosylated protein production prototype.

-   Produce evidence that the glycosylated proteins are well
    characterized (preferably using MS-based techniques).

-   Demonstrate that glycosylated proteins can be made reproducibly and
    economically.

-   Generate at least 10 glycosylated targets (offerors are encouraged
    to select targets in coordination with the Clinical Proteomic
    Technologies for Cancer community).

-   Research should be proposed with quantitative feasibility
    milestones.

Phase II Activities and Expected Deliverables

-   Generate at least 100 glycosylated targets (to be selected in
    coordination with the Clinical Proteomic Technologies for Cancer
    community)

-   Glycosylated proteins are to be well characterized (preferably using
    MS-based techniques).

-   Work with the Clinical Proteomic Technologies for Cancer community
    to integrate glycosylated proteins into the technology assessment
    programs and greater scientific community.

-   Research should be proposed with quantitative feasibility
    milestones.

[]{#__RefHeading___Toc205616446 .anchor}270 Peptide Aptamers: New Tools
to Capture and Study Protein Interactions in Lieu of Immunological
Reagents

Number of anticipated awards: 4

(Fast-Track proposals will be accepted.)

Budget: Phase I: \$150,000; Phase II: \$750,000

Summary:

The purpose of this initiative is to provide support for the development
of peptide aptamers that can be used instead of antibodies for
immunological uses. The Production of polyclonal and monoclonal
antibodies is now well established and many of the antibodies are
commercially available. Yet, man antibodies remain poorly characterized
and suboptimal across multiple applications. In addition, polyclonal
antibodies are typically not a renewable resource. Moreover, the
specificity of a monoclonal antibody against a target of interest there
is not guaranteed, nor is there any certainty as to whether or not a
monoclonal will work in the needed assay, or can be used in combination
with other antibodies due to an antibody's large size and subsequent
competition for overlapping binding domains. Furthermore, the high costs
associated with producing even small quantities of monoclonal antibodies
represent a large barrier towards cost-effective reagents and resources
for proteomic technology research and clinical adaptation. The goal of
this project is to develop reproducible, highly qualified/characterized
peptide aptamers as alternative protein capture reagents for the cancer
research community. Peptide aptamers are most commonly used as
disrupters of protein--protein interactions in vivo, but the flexibility
of protein engineering means that peptide aptamers can be turned into
tools for virtually any type of biological study. For example, peptide
aptamers can provide a basis for the development of novel diagnostic and
therapeutic strategies, with implications for a broad variety of
different disease entities including cancer. The development of these
affinity capture reagents will be done in coordination with NCI's
Clinical Proteomic Technologies for Cancer and be targeted to a list of
purified recombinant proteins being constructed and characterized
through this initiative.

Project Goals:

NCI is interested in proposals that focus on developing peptide aptamers
as alternative affinity capture reagents that can effectively compete
against antibody technologies in terms of protein recognition, binding
affinity, and detection and can be reproducibly produced in a
cost-effective and efficient manner. Furthermore, these capture reagents
must pass performance characterization criteria and be made available as
a resource to the scientific community.

The peptide aptamers are required to demonstrate equivalent or improved
performance to other affinity-based platforms. It is expected that
peptide aptamers have dissociation constants that are comparable to or
better than antibodies and can be used in the same way as antibodies.
Suggested choices of performance applications that could be validated
include immunoblot, and immunoprecipitation. In addition, other
considerations include the actual binding epitope, and application in
multiplex platforms such as microarrays. While it is expected that
initial development and quality assurance/quality control costs may be
comparable to that of monoclonal antibodies, it is intended that
production costs of these renewable reagents will be significantly
lower.

Offerors are encouraged to coordinate selection of analytes with the
Clinical Proteomics Technologies for Cancer community during Phase I.
Targets for Phase II are to be selected in coordination with this
community included in the following reference: Malu Polanski and N.
Leigh Anderson. (2006) "A List of Candidate Cancer Biomarkers for
Targeted Proteomics." Biomarker Insights 2:1-48.

Phase I Activities and Expected Deliverables

Demonstrate feasibility of the innovative method for peptide aptamer
production

-   Work with the clinical proteomics community and private and public
    sectors to identify appropriate minimum characterization
    criteria/validation assays

-   Generate peptide aptamers to at least 10 protein targets and
    demonstrate equivalent or improved performance to other
    affinity-based platforms

-   Demonstrate that peptide aptamers have improved cost effectiveness
    and throughput capabilities in production compared to antibodies

-   Present findings to NCI program staff

-   Research should be proposed with quantitative feasibility milestones

Phase II Activities and Expected Deliverables

-   Implement strategy and project plan for a fully functional peptide
    aptamer reagent development platform for at least 100 protein
    targets. The reagents should be able to capture the target of
    interest from complex biological mixtures such as blood, plasma, or
    tissue.

-   Test performance criteria against other affinity platforms

-   Work with the cancer clinical proteomics community to integrate the
    platform into the technology assessment programs and greater
    scientific community.

-   Research should be proposed with quantitative feasibility
    milestones.

[]{#__RefHeading___Toc205616447 .anchor}National Center for Research
Resources (NCRR)

The National Center for Research Resources (NCRR) provides clinical and
translational researchers with the training and tools they need to
understand, detect, treat, and prevent a wide range of diseases. This
support enables discoveries that begin at a molecular and cellular
level, move to animal-based studies, and then are translated to
patient-oriented clinical research, resulting in cures and treatments
for both common and rare diseases. NCRR connects researchers with one
another, as well as with patients and communities across the Nation, to
harness the power of shared resources and research.

This solicitation invites proposals in the following areas.

[]{#__RefHeading___Toc205616448 .anchor}012 Visualizing Biomedical
Research Characteristics

(Fast-Track proposals will be accepted.)

Biomedical research can be characterized in a multitude of ways.
Publications, grant applications, progress reports, funding,
experimental approach, specific aims, collaborations, scientific
networks, organizations and people with specific expertise, as well as
many other factors reflect the complex activity of biomedical research.
These elements are interlinked and often are represented by large
volumes of data. For example, thousands of papers are produced weekly.
To make sense of these data and to aid in seeing the big picture, new
methods are needed. Visualization has proven to be useful for extracting
information from abundant data. There is a variety of visualization
techniques based on well-developed scientific principles. They enable us
to identify patterns and relationships and provide other useful
information, especially for the process of making decisions. NCRR
invites SBIR proposals that will facilitate the introduction of
visualization technology into the management of a research portfolio.

**Main requirements:**

The outcome of this contract is expected to be software that assists in
exploring multidimensional textual data, understanding complex concepts,
and portfolio analysis. The software must

-   meaningfully visualize massive amounts of data from potentially
    diverse data sources

-   enable data exploration, change of displayed dimensions, and viewing
    at different levels of details (zooming in and out)

-   be able to identify and work with complex dimensions, i.e., not
    necessarily linear combinations of a number of data elements. The
    applicants are encouraged to apply the elements of principal
    component analysis (PCA) for identifying meaningful combinations of
    data elements and research characteristics

-   have transparent, validated, and well-documented protocols for all
    steps of data processing (cleansing, filtering, analysis,
    visualization, etc.)

-   have source code available

-   be accompanied by documentation of data processing algorithms, data
    accuracy, precision, and other features necessary for the most
    accurate basis to interpret the produced visualization

-   have Application Programming Interface (API) that does not require
    programming skills

-   take advantage of high-resolution display screens

**Deliverables**

-   Phase 1 should produce meaningful visualizations of a test
    dataset(s), e.g., a subset of publications in a particular domain
    from PubMed, that address some sample areas below and demonstrate
    \"proof of concept\" for the Phase 2 deliverable

-   Phase 2 deliverable is web-enabled software that can be used for
    multidimensional data exploration and portfolio analysis

**Sample areas of interest to NCRR**

-   Distribution of funding among various scientific domains,
    institutions, types of grantees

-   Evolution of scientific domains, collaborations, and concepts

-   Landscape of science where a location and interconnectivity of an
    entity (scientist, organization, paper, or concept) can be
    identified

-   Scientific forecasts

-   Pathways for translating Discovery into Innovation

-   Success factors for translational research, e.g., infrastructure,
    people, funding

-   Visualization of cross-discipline evolution pathways for people,
    concepts, etc

-   Clinical and Translational Science Awards (CTSA) domain, subjects,
    and networks

-   Productive career pathways, e.g., those leading to significant
    awards

-   Visual thesaurus of scientific domain fingerprints or other complex
    concepts

-   Map of existing standards and their applicability and usefulness for
    specific tasks and environments, which may assist in choosing one or
    a combination for a project

-   Visualization that enables meaningful exploration of
    high-dimensional data

-   Map of NCRR-related entities, activities, funding, networks, etc.
    that represent online knowledge resource for the researchers

**Visualization implementation**

Various visualization techniques can be used. Examples of visualizations
can be found at [http://www.scimaps.org](http://www.scimaps.org/) and
include

-   knowledge/domain/concept maps

-   innovative ways to display complex concepts

-   collaborations and other networks

**Data sources**

The analysis should be done using a number of various data sources,
e.g., journal publications, conference proceedings, and NIH databases.
The identification of appropriate sources is determined by the offeror.
The choices must be justified, analyzed, and well documented with
advantages and limitations of every source.

**Other project clarifications**

The offerors are encouraged to utilize the multiple principal
investigator option to bring in experts from academia
<http://grants.nih.gov/grants/multi_pi/>.

[]{#__RefHeading___Toc205616449 .anchor}National Heart, Lung, and Blood
Institute (NHLBI)

The NHLBI plans, conducts, fosters, and supports an integrated and
coordinated program of basic research, clinical investigation, and
trials, observational studies, and demonstration and education projects.
The Institute's mission includes studies related to the causes,
prevention, diagnosis, and treatment of heart, blood vessel, lung,
blood, sleep disorders, and blood resources management. Studies are
conducted in its own laboratories and by other scientific institutions
and individuals supported by research grants and contracts. The NHLBI
SBIR program fosters basic, applied, and clinical research on all
product and service development related to the mission of the NHLBI.

This solicitation invites proposals in the following areas.

[]{#__RefHeading___Toc205616450 .anchor}035 Ultrasonic Wave Transmitter,
Transmission Line and Receiver for Interventional MR

(Fast-Track proposals will be accepted.)

At the present time, signals from electronically active devices used
within an MR scanner are transmitted out of the scanner on coaxial
cables. This includes signals from \"marker\" coils on interventional
devices such as catheters and guidewires. These long transmission lines
couple with the transmitted RF which can potentially cause heating in
the patient. If the conductor length can be made lower than a quarter of
the transmitting wavelength, the heating problem can be eliminated; but,
this length is approximately 30 cm within the body and the average
length of intravascular catheters is about 1 meter. A non-conductive
transmission line was designed to carry RF signals to eliminate this
heating problem. In this design, a conductive coil at the distal tip of
the catheter receives RF signals emitted by the tissue. The received
signal reaches the micro piezoelectric transducer (MPT) and the MPT
converts the RF signal into an ultrasonic wave. A custom designed
acoustic wave guide transmits the signal until it reaches the proximal
end of the catheter. At this point another MPT receives the ultrasonic
wave and converts it back to an electronic RF wave, and after
amplification of the signal it reaches the scanner receiver for MR image
reconstruction. This will be the first application of ultrasonic waves
to visualize interventional MRI catheters. The most challenging part of
this project is miniaturizing the technology to fit inside a 0.035"
outer-diameter catheter. To manufacture the first prototype, we need
acoustic transducers, transducer electrodes and custom designed acoustic
wave guide defined by using photolithographic techniques.

The Phase I application should provide proof of concept for conversion
of the RF signal to acoustical domain, and transmission of the
acoustical signal in a wave-guide. In this phase, available materials
will also be evaluated in terms of performance and efficiency. Iterative
designs will consider available materials and fabrication methods that
may be suitable for later phases. The electrodes on the transducer will
be patterned using microelectromechanics techniques such as
photolithography. Tools will be developed to align and attach the
transducers and the wave-guide. Phase I will yield a functional
prototype.

The Phase II application will translate the Phase I findings into a
clinical grade device. The wave-guide will be similar to the final
product in terms of acoustical properties. The whole device will be
composed of two transducers, an acoustic wave-guide and a low noise
amplifier. The project includes in vitro and in vivo testing.

[]{#__RefHeading___Toc205616451 .anchor}040 Nanoprobes for Non-Invasive
Detection of Atherosclerotic Plaques

(Fast-Track proposals will be accepted.)

Coronary heart disease is a major cause of death and disability in the
U.S. and other industrialized societies. The underlying cause, in most
cases, is the development of atherosclerotic lesions in the coronary
arteries. The atherosclerotic lesion progresses largely in a clinically
silent and asymptomatic manner to form plaques that severely block the
coronary arteries. Many of these plaques are prone to rupture resulting
in acute coronary thrombosis and myocardial infarction.

Many of the factors involved in the atherosclerotic process have been
identified and a complex interaction exists between the cellular
entities involved in the atherosclerotic process. Endothelial cells,
smooth muscle cells, platelets, leukocytes are all involved in the
formation of an atherosclerotic lesion. Plaque erosion, stenosis, and
hemorrhage are thought to be important in plaque rupture as are force
imbalances within the plaque and acute changes in intraluminal coronary
pressure. Currently, a significant limitation to early detection is the
unavailability of non-invasive imaging modalities for the detection of a
developing plaque, a plaque prone to rupture, or a plaque that is
stable.

The goal of this proposal is to develop nanoprobes for non-invasive or
minimally invasive visualization/detection of a developing
atherosclerotic plaque and its characteristics. Early detection of
atherosclerotic plaques would be extremely useful in risk assessment and
appropriate targeting of preventive measures. Further, early detection
and characterization of atherosclerotic plaques susceptible to rupture
may decrease morbidity and mortality.

Phase I applications should address initial development and feasibility
testing of novel technologies for plaque detection and Phase II
applications should be focused on completing the development of the
technology for incorporation into the clinic. The work is expected to
include in vitro and in vivo studies to demonstrate effectiveness.

[]{#__RefHeading___Toc205616452 .anchor}043 Development of Pathogen
Inactivation Technologies for Blood Components

(Fast-Track proposals will be accepted.)

Great strides have been made over the past 25 years greatly improving
the safety of the nation's blood supply. Current blood donor screening
and laboratory testing has drastically reduced the risks of acquiring
infectious disease through blood transfusion. However, the potential for
new, emerging infectious agents entering the blood supply continues to
be a serious concern of the blood banking community. Pathogen
inactivation of blood and blood components provides an additional layer
of protection from such agents. The effectiveness of pathogen
inactivation technology is best exemplified with the virtual elimination
of certain infectious agents from manufactured plasma derivatives. Since
1985, there have been no transmissions of human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) by U.S.
licensed plasma derivatives. However, because of the labile nature of
red blood cells and platelets, these technologies are far too harsh for
use with cellular blood components. During the past several years, new
technologies have been developed and evaluated in clinical studies
offering hope that blood components can also be treated to destroy the
infectivity of a wide array of microbial agents without significantly
reducing the component's therapeutic effectiveness. These technologies
include leukoreduction of blood, photochemical treatment of platelets or
plasma with ultraviolet light and psoralen compounds, and various
chemical treatments of red blood cells which may or may not involve
irradiation with ultraviolet or visible light. Some of these
technologies have been shown to reduce infectivity in a wide array of
infectious agents. While much progress has occurred in the development
of these technologies in recent years, there is still no U.S. licensed
pathogen inactivation process for cellular blood components. There is a
need to evaluate other new, promising compounds and procedures. It does
not appear that any one inactivation technology will be effective in
treating all classes of agents (e.g., viruses, bacteria, protozoa,
prions). It is likely that a combination of techniques that remove
and/or inactivate agents will be needed. These technologies are
generally sophisticated and costly. They probably will be utilized by
the developed world if found to be safe and effective. However, because
of costs they will be out of reach for resource-poor countries where
blood-borne agents are highly prevalent and laboratory screening
irregular or nonexistent. In such settings, the availability of simple,
cost-effective inactivation procedures could save millions of lives.
This solicitation encourages research leading to the development of
pathogen inactivation procedures for blood components, particularly red
blood cells and platelets, although work on plasma components would also
be responsive to this solicitation. Research on the development of
simple, low cost procedures for use by less practiced laboratory
personnel in the developing world would also be responsive and is highly
encouraged.

The Phase I application shall focus on studies that provide proof of
concept that the pathogen inactivation procedure is capable of reducing
the infectivity of infectious agents in the blood component(s) while
maintaining the function of the component at an acceptable therapeutic
level. The inactivation kinetics of the infectious agents being studied
shall be determined. The effect of the procedure on the viability of the
blood component shall be determined using a variety of different
approaches depending on the component such as flow cytometry studies to
determine the extent of platelet activation, platelet aggregation
studies or assays for the red cell storage lesion (e.g., extracellular
potassium leakage).

Phase II studies will extend the efforts of the Phase I studies and
shall focus on in vitro and in vivo studies and scale-up of the process
and prototype device including ancillary equipment such as blood bags.
Studies shall include the use of human blood in quantities comparable to
those amounts to be treated in the blood bank. In vivo studies shall be
designed to demonstrate acceptable product performance as predetermined
by FDA regulations (RBC) or by agreement with FDA staff (platelets). The
array of infectious agents to be tested can be expanded in this phase.
The therapeutic effectiveness of the component shall be investigated.
Safety studies of the treated component shall be conducted and shall
include toxicity, reproductive toxicity, and mutagenic and carcinogenic
potential.

[]{#__RefHeading___Toc205616453 .anchor}044 Development of Cell-based
Bioassays Using Induced Pluripotent Stem (iPS) Cell Lines

(Fast-Track proposals will be accepted.)

Recent new technology enabling the production of induced Pluripotent
Stem (iPS) cell lines has created significant opportunities for the
development of new cell lines for use as cell-based bioassays such as in
screening assays. The technology provides the means to expand the iPS
cell lines to the numbers needed for bioassay applications and will
enable the derivation of cell lines with specific phenotypic or genetic
characteristics uniquely suited to specific assay requirements. Thus,
iPS cell lines represent an excellent substitute for improving upon
cell-based assays currently carried out with existing lines or limited
supplies of primary cells. Basic research studies are needed to obtain
sufficient quantities of the iPS cell line to test their suitability and
for comparison to existing assay methods. And fundamental research to
improve upon the methods used for iPS cell derivation will accelerate
all commercial opportunities. The availability of the initial iPS
cell-based assays will benefit those investigators utilizing these assay
tools in their research as well as serve as prototypes for investigators
who may wish to develop new bioassays using iPS cell lines.

The goal of this solicitation is the development and production of new
bioassays based on iPS cell technology to be used for research purposes
and to be made available to the scientific community. The assays may be
designed for basic research applications and potentially with future
clinical assays. The derivation and expansion of the cell lines must be
well defined and produced under appropriate manufacturing practices and
quality control. The cell-based bioassay must be developed and validated
including the use of existing assays as comparators. The successful
applicant must develop a production plan to commercialize the assay.

Phase I proposals should focus on the development of a
well-characterized iPS cell line and bioassay for research applications.
Investigations in this phase will involve laboratory research and early
scale-up studies.

Phase II proposals shall focus on scale-up and production of a bioassay
for distribution. Assay validation will be required.

[]{#__RefHeading___Toc205616454 .anchor}045 Development of Novel
Formulations for Iron Chelators to Treat Iron Overload in Patients on
Transfusion Therapy

(Fast-Track proposals will be accepted.)

Inherited disease of anemia, such as sickle cell disease, the
thalassemias and aplastic anemia often require chronic transfusion
therapy in order to sustain life or prevent devastating events such as
stroke. The administration of repetitive transfusions, however,
increases the levels of iron in the body, which, if not removed, causes
toxicity to the organs where it is deposited. Traditionally, excess iron
is removed from the body through the use of iron chelating molecules.
For many years the primary iron chelator used to treat iron overload has
been deferoxamine. Although an excellent chelator, it must be delivered
intravenously through a slow infusion pump over many hours. This
procedure is both time consuming and uncomfortable for the patient often
leading to a lack of compliance. More recently, other iron chelators,
that can be taken orally, have been developed. While these chelators are
more convenient to take, they have their own side effects which may not
make them beneficial to all patients**.**

The goal of this solicitation is to develop novel formulations or
modifications of existing iron chelators that will provide effective
chelation, while at the same time offer a more convenient therapy
regimen with minimal side effects. Novel formulations may include
liposomal or other encapsulation methods, attachment to target molecules
that facilitate homing to organs, or coating with inert molecules.
Changes in formulation to reduce rapid metabolism or reduce adverse side
effects should be considered.

Phase I proposals should focus on the use of these formulations in
animal models to demonstrate proof of principle.

Phase II proposal should involve the development of a well-defined
formulation produced under good manufacturing practices (GMP), be
uniform from lot to lot and be certified under quality control. The
proposal should focus also on scale up and production for future Phase I
clinical study.

[]{#__RefHeading___Toc205616455 .anchor}046 Multiplexed Assay Platforms
for Protein Biomarkers of Cardiovascular Disease

(Fast-Track proposals will be accepted.)

Proteomic technologies have the potential to identify and quantify novel
proteins in the plasma that can function as biomarkers of the presence
or severity of clinical disease states and hold great promise for
clinical use. Multiplex arrays that simultaneously measure multiple
protein markers are useful in disease screening, assessing disease
severity, and prognosis. They economize on time, cost, sample
consumption, and reagent volumes while increasing sample throughput
relative to single protein measurement. The information provided by a
single protein marker is limited and a multimarker approach is more
useful in deriving information about the diverse physiologic pathways
that contribute to diseases activity.

Antibody based enzyme-linked immunoassays have been adapted for
multiplex biomarker assessment and different multiplex platforms
relevant to the cardiovascular disease spectrum are being developed for
research purposes. However, they are plagued with lack of sensitivity
and reproducibility, high variability and correlation of variances, and
non-specific binding. The goal of this proposal is to develop multiplex
assay platforms specific for cardiovascular diseases that overcome the
above limitations. These platforms can be antibody or other protein
capture method based but must be scalable and amenable to high
throughput formats.

Phase I applications should address initial development and feasibility
testing of the multiplex platforms and Phase II applications should be
focused on completing the development of the technology for
incorporation into the clinic.

[]{#__RefHeading___Toc205616456 .anchor}047 Transcatheter Ablation
Devices for Arrhythmia Treatment

(Fast-Track proposals will be accepted.)

Cardiac arrhythmias represent a major public health burden associated
with a high degree of morbidity and mortality. Among the arrhythmias,
atrial fibrillation is the most common form of sustained cardiac
arrhythmia, and its occurrence which increases with age leads to
increased risks for heart disease and stroke. In the United States,
there are over 2 million adults diagnosed with atrial fibrillation,
affecting about 4% of the population over 60 years of age and
contributing to approximately 75,000 strokes per year.

Cardiac transcatheter ablation is an important component of the
available therapies for atrial fibrillation, particularly in patients
who are intolerant or insensitive to antiarrhythmic pharmacotherpies. A
variety of transcatheter ablation devices are in use today which employ
heating energy (e.g., radiofrequency, microwave, laser, and
high-frequency ultrasound) or freezing energy (e.g., rapid cooling using
liquefied refrigerants like nitrous oxide and argon) to destroy the
atrial tissue and block electrical conduction or source of the triggers
of atrial fibrillation. Currently, the technologies and devices for
thermal ablation are relatively mature and are in extensive use. By
contrast, cryoablation technologies, which may offer some key advantages
over thermal ablation in terms of better tissue preservation, are still
evolving and need further development.

The purpose of this SBIR contract solicitation is to foster novel
cryoablation technologies and devices in order to significantly improve
the efficacy and safety of cardiac ablation treatments over currently
available methods. Applications are invited from research teams to
develop innovative transcatheter cryoablation technologies and devices
to improve treatment of atrial fibrillation.

The Phase I research is expected to focus on demonstrations of
proof-of-concept of the new technologies and devices proposed (e.g.,
development and initial testing of the prototype) and how it can
significantly improve the safety and efficacy of treatment of atrial
fibrillation over currently available methods.

Phase II studies should extend the efforts of the Phase I studies and
focus on further refinement of the technologies and devices, their
testing in appropriate animal models, and fulfilling FDA regulatory
requirements in order to initiate human safety trials.

[]{#__RefHeading___Toc205616457 .anchor}048 Developing Novel
Anticoagulants and Synthetic Heparins

(Fast-Track proposals will be accepted.)

Anticoagulants are essential in treating stroke patients, deep vein
thrombosis, pulmonary embolism, cardiac arrhythmias, or during open
heart surgery, and kidney dialysis. Until very recently, pharmacologic
prophylaxis of thrombosis was based on three types of anticoagulants:
vitamin K antagonists (e.g., warfarin), unfractionated heparin (UFH),
and low-molecular-weight heparins (LMWH). The vitamin K antagonists, the
only oral anticoagulants currently approved for use, have a number of
limitations. There is a need for safer oral anticoagulants that do not
require routine coagulation monitoring. Despite advances with
low-molecular-weight heparin and unfractionated heparin, more potent
parenteral anticoagulants are still required. LMWHs, which are derived
from UFH using a variety of chemical and biosynthetic processes, have
different fine chemical structures that significantly impact their
activity and pharmacological profile. Recently oversulfated chondroitin
sulfate was identified as the contaminant in UFH that led to adverse
clinical events. Synthetic heparins that are pharmacologically
effective, safe and cheap could eliminate the concerns associated with
the animal derived products. Bleeding is the major complication
associated with all the anticoagulant drugs. Agents that target specific
steps in clot formation may be able to reduce this serious complication.
Given these considerations, development of new anticoagulants is likely
to take into account properties such as non-hemorrhagic side-effects,
drug-bioavailabilty, more favorable pharmocokinetics and a predictable
dose response that will not require hospitalization and coagulation
monitoring.

In keeping with our continuing quest for better anticoagulants, the goal
of this solicitation is to develop more effective, safer and cheaper
antithrombotic drugs. Phase I applications should focus on the
development of a well characterized compound, proof-of principle,
in-vitro testing and pharmacokinetic evaluations. Phase II will
translate the Phase I findings into large animal models, scale-up and
production. Programs that may be further advanced in development may
submit applications with appropriate Phase I milestones and Phase I and
II specific aims.

[]{#__RefHeading___Toc205616458 .anchor}049 Development of Gene Transfer
Approaches for Correction of Genetic Blood Diseases

(Fast-Track proposals will be accepted.)

Gene therapy has the potential to provide specific and effective
treatment for hereditary blood diseases such as the hemophilias and
sickle cell anemia. The development of safe delivery systems that are
targeted and efficient is critical to realizing effective therapy. There
has been major progress in the research of several viral vector
approaches, but additional work is needed to realize the full potential
of these systems. Toxicity, chromosomal integrations and immune response
are safety issues for viral vectors that need to be addressed as new
approaches are developed. Recent studies have increased the
understanding of the mechanisms involved in the development of undesired
side effects in gene therapy. Furthermore, animal models and methods
have been developed to evaluate the gene transfer approaches. Non-viral
gene delivery systems offer alternatives that may avoid some of the
safety issues of the viral vectors. However, these systems have
challenges of targeting select tissues and long term expression. All
systems must carefully consider all the safety issues, especially for
genetic blood diseases which require lifetime treatment. Each genetic
blood disease has its own unique requirements and challenges and careful
consideration should be given to achieve a safe and effective system
that addresses the needs of the specific disease.

Phase I applications should at a minimum evaluate the feasibility of the
gene transfer approach for delivery of the gene to correct a hereditary
blood disease. Phase II applications should at a minimum further develop
the gene transfer approach, evaluate safety and demonstrate efficacy in
an appropriate animal model of the specific blood disease.

[]{#__RefHeading___Toc205616459 .anchor}050 Wireless Communications
Systems for Magnetic Resonance Imaging (MRI) Guided Surgery

(Fast-Track proposals will be accepted.)

Magnetic resonance imaging has potential to revolutionize minimally
invasive surgery and interventional procedures, by affording
surgery-like visualization without conventional surgical incisions for
exposure. Unfortunately, magnetic resonance imaging creates acoustic
noise that makes it difficult or impossible for surgical or
interventional teams to communicate. The loud noise also makes it
difficult to communicate with and monitor awake patients undergoing
procedures inside the MRI bore. A few commercial systems are available
that suppress acoustic noise and permit "open microphone" communications
among staff and patients on two or more parallel audio channels.
However, these systems require tethered transmission lines that
dramatically impair staff mobility in a way that detracts from surgery
or procedure conduct. "Circulator" nurses and technologists are unable
to gather and assemble devices, implants, and drugs that may be stored
within or without the suite. Monitoring technologist and
anesthesiologists have insufficient mobility to move around the suite to
tend to instantaneous patient needs and administer medications.
Operators are unable to change position or move to different surgical
tables and fields.

Wireless communications systems are necessary to conduct advanced image
guided interventional and surgical procedures under real-time magnetic
resonance imaging. To date there are no suitable commercial solutions.

Wireless communication systems are technically feasible to support MRI
guided clinical interventional procedures. A development system should
be able to suppress at least 35-40 dB of acoustic noise to the operator
at the dominant frequencies generated during rapid magnetic resonance
imaging. The system should permit clear "open microphone" communications
between all staff and patients even during scanning. The system should
have at least two audio channels permitting all combinations of
monitoring and/or speaking to staff on either or both channels. The
system should be self-powered or battery powered to last at least 8
hours. The headset systems should be comfortable for prolonged wear, and
should have controls that can be mounted for operation by sterile
operators. The signal transmission should be robust to headset position
and orientation and should not require line-of-site alignment with a
single receiver. The system should afford headsets to least 6 operators
and one patient, as well as headset or hands-free communication with
technologist staff outside the scanner. The system should include
additional slave audio outputs. The system should include an
interruptible audio input for patient entertainment or distraction. The
system should operate at field strengths ranging between 1.0T and 3.0T.
The system should not generate radiofrequency noise that interferes with
MRI of hydrogen, carbon, fluorine, and phosphorus species used for MRI
in these fields. The system should be safe for operators and patients
inside and near the magnet bores. The system should not interfere with
common commercial Bluetooth and other radiofrequency patient physiologic
telemetry systems used during MRI.

The Phase I application should provide a working prototype for a
wireless communications system to support MRI guided clinical
interventional procedures.

The Phase II application will translate the Phase I findings into a
clinical grade device.

[]{#__RefHeading___Toc205616460 .anchor}National Institute on Alcohol
Abuse and Alcoholism (NIAAA)

The NIAAA supports research on the causes, prevention, control, and
treatment of the major health problems of alcohol abuse, alcoholism, and
alcohol-related problems. Through its extramural research programs, the
NIAAA funds a wide range of basic and applied research to develop new
and/or improved technologies and approaches for increasing the
effectiveness of diagnosis, treatment, and prevention. The NIAAA also is
concerned with strengthening research dissemination, scientific
communications, public education, and data collection activities in the
areas of its research programs.

This solicitation invites proposals in the following area:

[]{#__RefHeading___Toc205616461 .anchor}034 Simple, Low-Cost, Onsite
Biomarker Test Kits for Alcohol-Associated Disorders

(Fast-Track proposals will be accepted.)

Alcohol use and abuse have wide ranging effects on the public health.
Even moderate alcohol consumption can have deleterious effects on
multiple organ systems in the body. Several biomarkers have been in
limited clinical use for many years. The traditional biomarkers for
alcohol consumption include the enzymes gamma-glutamyl transferase
(GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT),
and carbohydrate-deficient transferrin (CDT). Other biomarkers include
mean corpuscular volume (MCV), 5-hydroxytryptophol (5-HTOL), a serotonin
metabolite, and ethyl glucuronide (EtG), a metabolite of alcohol.
Biomarkers of alcohol-induced tissue injury, such as alcoholic liver
disease (ALD), include alpha-smooth muscle actin (SMA), fibronectin,
collagen type I, serum hyaluronate, matrix metalloproteinase alpha and
chemokine ligand 2. Tumor necrosis factor increases with the degree of
heart dysfunction, while, biomarkers of fetal alcohol exposure and
pancreatitis include fatty acid ethyl esters (FAEE), ethyl oleate and
ethyl linoleate.

The use of many of these biomarkers in research and clinical practice
has been limited by the cost of the assays, the difficulty of the assay
technique, the accessibility of the biological source material, and the
need to process, store, and ship samples. Clinical trials of
therapeutics for alcohol-associated disorders could be significantly
advanced with low-cost onsite, field serviceable biomarker assays.
Sample collection and the assay must be relatively simple and acceptable
to practitioners and patients.

-   Phase I of the requested SBIR contract should be aimed at
    demonstrating the feasibility of the low-cost, onsite assay
    technology with potential alcohol-associated biomarkers. Emphasis
    should be placed on those biomarkers that show acceptable
    sensitivity and specificity for alcohol exposure or tissue damage
    over a reasonable time delay and utilize easily accessible tissues
    or employ non-invasive methods. Animal models and/or humans should
    be used for these studies. Fast Track (combined Phase I and
    Phase II) applications could be proposed. Two to three contracts are
    anticipated to be awarded for this topic.

[]{#__RefHeading___Toc205616462 .anchor}035 Biological Sample Repository
for Alcohol Research

(Fast-Track proposals will be accepted.)

The development of alcohol-related laboratory methodology and other
technology-driven translational research efforts, including alcohol
biomarker and alcohol biosensor development frequently require
well-characterized biological samples for method discovery and assay
validation. However, currently investigators must rely upon informal
relationships with colleagues to acquire, characterize, annotate, store
and ship such samples to them for use in their research. No standardized
sample set exists employing either alcohol-exposed human or animal
biological materials of interest to alcohol researchers. Such materials
of interest include blood products (e.g. whole blood, plasma, white
cells, and platelets), cerebrospinal fluid and urine from alcoholic and
non-alcoholic individuals of each sex obtained from genetically
representative ethnic groups wherein such individuals are or are not
exposed to known and standardized blood alcohol concentrations at the
time of collection. Tissue pathology samples (e.g. liver, brain, and
lung) from known alcohol and non-alcoholic individuals would also be
useful. In addition, a parallel sample set could be obtained for strains
of laboratory research animals commonly employed in basic alcohol
research (e.g. rat, mouse, hamster, rhesus monkey) with and without
standardized alcohol exposure. One to three contracts are anticipated to
be awarded for this topic.

The purpose of this SBIR Contract is to develop an Alcohol Research
Sample Repository that:

-   Acquires both human and animal model biological samples
    (with/without known alcohol exposure) in a standardized fashion,

-   Characterizes them in an information system,

-   Appropriately indexes and stores the samples to maintain their
    research utility,

-   Implements a distribution system to get samples to qualified
    investigators needing this resource to advance their alcohol
    research.

[]{#__RefHeading___Toc205616463 .anchor}036 Identification of miRNAs as
Biomarkers for Alcohol-Induced Disorders

(Fast-Track proposals will be accepted.)

Alcohol use and abuse have wide ranging effects on the public health.
Even moderate alcohol consumption can have deleterious effects on
multiple organ systems in the body. As with all disease, early detection
and early intervention improve prognosis and reduce complications. Thus,
there is a need for biomarkers that signal 1) alcohol consumption or
relapse in recovering alcoholics or 2) early alcohol-induced damage of
liver, pancreas, breast, immune function, heart and other tissues.
Therefore, NIAAA is committed to the development of highly predictive,
sensitive and reliable biomarkers for alcohol-induced disorders,
including alcohol-induced organ damage and alcohol dependence. For the
biomarkers to be of clinical significance, it is essential that the
tissues or samples used are easily obtainable. Sample collection and the
assay must be relatively simple and acceptable to practitioners and
patients.

MicroRNA (miRNA) analysis holds great promise as a measure of metabolic
changes that occur after alcohol consumption and for detection of tissue
injury. Changes in the miRNA panel resulting from alcohol exposure or
alcohol-induced disorders would be a valuable biomarker. Therefore, the
detection of changes in the full complement of miRNAs associated with
alcohol exposure or alcohol-induced disorders in biological specimens
can provide new avenues for alcohol biomarkers. Assay optimization and
validation should focus on easily obtainable biological tissues or
fluids, although validation of the method could use samples from blood,
brain, and liver. Phase I of the requested SBIR contract should be aimed
at the feasibility of the study and initial identification of miRNA
species that are altered by alcohol exposure or associated with
alcohol-related phenotypes in animal models or alcohol-induced disorders
in humans. If a sensitive, reproducible, high-capacity method is
demonstrated to be useful and cost-effective for small volume samples,
the purpose of a Phase II contract may be a service contract with NIAAA
to provide analysis of specimens from the greater alcohol community.
Such a service would allow extramural scientists to investigate specific
questions without redundancy of effort and would provide consistency
between laboratories.

Animal models and/or humans should be used for these studies. Fast Track
(combined Phase I and Phase II) applications could be proposed. One to
three contracts are anticipated to be awarded for this topic.

Areas to be addressed under this topic include, but are not limited to:

-   Identification of miRNAs, either single entities or combinations
    (biomarker signatures), for alcohol exposure, alcohol-induced organ
    damage (for liver, pancreas, lung, brain, etc) or alcohol dependence
    in blood or plasma and/or in other easily accessible tissues or by
    employing non-invasive methods.

[]{#__RefHeading___Toc205616464 .anchor}National Institute of allergy
and infectious diseases (NIAID)

The National Institute of Allergy and Infectious Diseases (NIAID)
conducts and supports basic and applied research to better understand,
treat, and ultimately prevent infectious, immunologic, and allergic
diseases. For more than 50 years, NIAID research has led to new
therapies, vaccines, diagnostic tests, and other technologies that have
improved the health of millions of people in the United States and
around the world.

The NIAID Small Business Programs (SBIR and STTR) judiciously fund
research and development of products or services that prevent, diagnose,
and treat infectious, immunologic, and allergic diseases. For
information on the NIAID Small Business Grants Program and links to
small business resources, see the NIAID Small Business Grants website at
<http://www.niaid.nih.gov/ncn/sbir/>.

This solicitation is for the NIAID SBIR Contracts Program. SBIR Phase I
and Phase II contract awards may not exceed the limits for total costs
(direct costs, facilities and administrative (F&A)/indirect costs, and
fee) listed under the topic area. Phase II proposals may only be
submitted upon the request of the NIAID Contracting Officer, if not
submitted concurrently with the initial Phase I proposal under the
Fast-Track procedure (described in Section 5).

[]{#__RefHeading___Toc205616465 .anchor}017 Clinical Sample Collection
and Processing Technologies for Infectious Disease Diagnostics

(Fast-Track proposals will be accepted.)

Budget (total costs): Phase I: \$250,000; Phase II: \$750,000

There is an urgent need for rapid, highly sensitive and specific
clinical diagnostics that are easy to use, cost-effective and can
diagnose individuals infected with pathogens or individuals that have
been exposed to toxins. The clinical sample collection and processing
steps represent barriers to the development of rapid medical diagnostics
for infectious diseases and toxins.

Improved clinical sample collection and processing technologies must be
developed for all classes of samples used to diagnose infectious
diseases and detect exposure to toxins, including nasopharyngeal fluids,
blood, plasma, serum, sputum, cerebrospinal fluid, urine, feces, etc.
The final purification product(s) may include nucleic acids, proteins,
lipids, metabolites, and/or other analytes of interest.

Project goal: The goal of this project is to develop rapid, modular,
clinical sample collection and processing technologies that can be
incorporated into integrated, closed sample infectious disease
diagnostic platforms. The final product should require minimal operator
effort and expertise, and should address one or more of the infectious
diseases listed on the NIAID Division of Microbiology "Small Business
High Priority Areas of Interest" website at
[[http://www.niaid.nih.gov/ncn/sbir/sbirareas.htm#dmid]{.underline}](http://www.niaid.nih.gov/ncn/sbir/sbirareas.htm#dmid).

Areas of research will include:

-   Development of improved methodologies and technologies for rapid
    clinical sample collection, processing, and if appropriate,
    concentration

-   Development, incorporation, and validation of process controls.

[]{#__RefHeading___Toc205616466 .anchor}National Institute on Drug Abuse
(NIDA)

NIDA's mission is to lead the nation in bringing the power of science to
bear on drug abuse and addiction, through support and conduct of
research across a broad range of disciplines and by ensuring rapid and
effective dissemination and use of research results to improve
prevention, treatment, and policy.

This solicitation invites proposals in the following areas:

[]{#__RefHeading___Toc205616467 .anchor}099 Innovative Technologies to
Support Economic Research in the Drug Abuse Treatment System

(Fast-Track proposals will not be accepted.)

This initiative will support research to design and develop data systems
for financial management and economic analysis of treatment programs and
larger systems in new healthcare settings and managed care networks.
Managerial decision-making requires the implementation of sophisticated
data systems to facilitate routine budgeting processes, allocation of
resources, performance measurement, and pricing decisions. The focus is
on the needs of managers within the organization and managers outside of
the organization. Data system development must be based on standard cost
behavior and profit analysis. Data systems must be designed with correct
cost concepts (accounting and economic) in order to permit cost and
pricing decisions to be developed for new treatment technologies and
management of ongoing systems. In research settings, such an initiative
is vital for the assessment of new technologies developed for transfer
to practice.

[]{#__RefHeading___Toc205616468 .anchor}100 Instrument Development

(Fast-Track proposals will not be accepted.)

Easy-to-use assessment instruments are needed to enhance epidemiology
research. Areas of interest include but are not limited to:

a\. *Community Assessment.* The development of community diagnostic
instruments for psychometrically sound assessment of community
characteristics is essential to improve our understanding of how
community factors affect drug abuse and ensuing behavioral and social
consequences. Standardized assessments of community characteristics are
needed to better understand the full impact of drug use and to develop
targeted interventions to specific community needs.

b\. *Assessment of Psychiatric Comorbidity in Community Settings.* Easy
to use, reliable, and valid instruments are needed to assess psychiatric
comorbidity in different populations of drug abusers, including
adolescents and those in community drug abuse treatment settings.

c\. *Assessment Instruments to Measure CNS Function Related to Drug
Abuse.* The development of age-appropriate assessment instruments to
measure behavioral and cognitive function over the course of development
will contribute to our understanding of vulnerability to drug abuse and
functional impairment due to drug use.

[]{#__RefHeading___Toc205616469 .anchor}101 Rapid Assessment Tools of
Sexual and Drug Use Risk Behaviors

(Fast-Track proposals will not be accepted.)

This SBIR concept seeks the development of rapid assessment tools for
sexual and drug use risk behaviors that provide feedback to client
populations about those risks and link that feedback to behavior change
messages. Clients can be provided with these messages directly or they
can be used as a basis for tailored, brief counseling by service
providers. Rapid assessment tools like these would have application in a
wide variety of health care and public health environments. They provide
a simple way of addressing sensitive behaviors and enabling the kind of
counseling that is otherwise very time-consuming for providers to
formulate and deliver. These tools also provide a way to bridge sexual
and drug use risks, which has often been difficult to accomplish in
practice. In settings such as STI clinics, providers have protocols and
benchmarks for addressing sexual behaviors, but do not have the same
means to deal with substance use, including non-injection drug use.
Conversely, substance use settings often have difficulty approaching
sexual behaviors and their risk reduction protocols often neglect or
provide limited coverage of sexual risks, even in the context of
substance use. There are AIDS research centers, AIDS service
organizations, community-based organizations and other high volume
settings that are seeking to build systems that can accept risk
assessments as well as modular behavior change tools in electronic
formats. These tools could be incorporated into routine services such as
primary care, STI screening, with prevention messages tailored to
different providers' needs (e.g., providers in an AIDS service
organization may have more familiarity with sexual and drug use risk
than end users in a general internal medicine clinic). In addition to
their value in integrating assessment and behavior change, the risk
assessment portions of these tools may provide process or outcome data
for the evaluation of interventions in a variety of settings,
particularly if they provide evidence of reliability and validity. These
tools also may provide a way of easily collecting routine client data in
agency settings that are required by CDC, HRSA, and other funders.

[]{#__RefHeading___Toc205616470 .anchor}102 Electronic Drug Abuse
Treatment Referral Systems for Physicians

(Fast-Track proposals will not be accepted.)

Research shows that primary care physicians often do not screen for drug
abuse disorders or HIV/AIDS. While this may be related to stigma
attached to illicit drug use and HIV/AIDS or to a lack of adequate
health insurance, it may also be due in large part to the lack of an
adequate referral system that primary care physicians can use for the
patients they identify as having a potential drug problem or are HIV
positive. The lack of a referral system places a greater burden on the
physician to secure treatment resources for the patient, and also places
the physician at greater risk if no appropriate treatment can be found.
The purpose of this initiative is to develop and test a practical and
usable electronic drug abuse treatment and HIV/AIDS referral system for
use by physicians in primary care settings, including doctor's offices,
emergency rooms, etc. The system should be targeted at local needs, for
example by taking into account local private insurance coverage and the
types of insurance accepted by local treatment providers. The referral
system should include an actively-maintained database of local
providers, and which should include information such as insurance
carrier, geographic "catchment" area of treatment providers, types of
substance disorders treated, types of co-occurring disorders (mental
disorders, etc.) treated, HIV status, gender, age, other pertinent
treatment factors needed by primary care physicians to make appropriate
referrals. The system should be designed to be reliable and efficient.
For example, it should allow the primary care physician to schedule an
appointment for the patient at the time of the visit or make other
needed arrangements to ensure a successful referral. The proposal should
address requirements both for primary care physicians and for drug abuse
treatment providers who enroll with the referral system. For example,
treatment providers should be able to "rapidly" assess referrals and
enroll those in need of treatment services. The applicant should
demonstrate a thorough understanding of the incentives and disincentives
that exist in primary care to screen, assess, and refer patients to
substance abuse treatment and HIV testing, as well as the incentives by
treatment providers to accept referrals for treatment services. The
applicant should design a Phase I study that demonstrates the
feasibility of creating an information and referral system that meets
the needs of the primary care physician who currently has no efficient
or reliable means of referring patients having a suspected substance use
disorder to treatment. Phase II will entail a demonstration of the
financial viability of the electronic referral system. The applicant
should be able to identify customers and should demonstrate the ability
to adapt the electronic referral system to the needs of specific
customers, such as physician groups, insurance payers, and treatment
providers.

[]{#__RefHeading___Toc205616471 .anchor}103 Virtual Reality Simulations
to Train Caregivers/Providers

(Fast-Track proposals will not be accepted.)

There is a growing movement and body of research on the power and
utility of virtual healing, virtual data collection, and virtual
training or service delivery. For instance, experiments have shown that
the experience of pain can be softened through virtual interventions
that redirect patients senses toward pleasurable memories and
sensations. In addition, many tools have been or are currently in
development to facilitate collection of data, and to promote use of
evidence-based prevention interventions. Virtual technology can also be
used as a tool to train service providers or caregivers in the
administration of best practices to participants in an intervention. As
an example, virtual technology could provide a "practice family" or a
set of example families to guide practitioners through conflict
resolution and mediation for use in family-based interventions. The
technology could also be used to assist service providers in addressing
the needs of vulnerable and difficult-to-reach populations. Web-based
and virtual reality platforms allow for multiple approaches to training
and service delivery, and could include game-based models of
trainer-participant/provider-client interactions. These platforms could
walk users through scenarios to promote skills-development, to test
response patterns in a wide variety of situations, and to gauge the
effectiveness of different techniques. The purpose of this SBIR contract
is to stimulate the development of virtual reality simulations to
enhance the quality of intervention training and/or service delivery.

[]{#__RefHeading___Toc205616472 .anchor}104 Improvement of Reliability
and Validity of Reporting of Sensitive Data

(Fast-Track proposals will not be accepted.)

The reliability and validity of self-report of drug use and related
behaviors (e.g., HIV risk behavior) is a matter of great concern. Use of
new technologies for real time data collection in ecological settings is
of great interest because these technologies enable collection of drug
consumption data in context. Studies to improve methodologies based on
variations of standard survey protocols or computer-assisted
self-interview (CASI) and personal interview (CAPI) are also encouraged.

[]{#__RefHeading___Toc205616473 .anchor}105 Development of Therapeutic
Agents for Substance Use Disorders

(Fast-Track proposals will be accepted.)

Budget (total costs): Phase I: \$150,000 (6 months); Phase II:
\$1,000,000 (1 year)

Project goals: The neurophysiological underpinnings of substance abuse
appear to involve numerous neurotransmitter systems including opioid,
dopamine, serotonin, GABA and glutamate across multiple brain regions.
Small businesses have used government grant programs to conduct basic
research and early preclinical testing; however, many of these projects
are still in an early drug development stage and are not yet candidates
for capital funding. Thus, the short-term goal of this SBIR contract is
to create a mechanism of 'bridge funding' whereby novel therapeutic
agents or immunotherapies that have demonstrated promising pre-clinical
findings can be further evaluated in clinical trials. It is anticipated
that these funds, long term, will help shepherd promising products from
'bench to bedside'.

Proposed work: The goal of this NIDA SBIR program is to assist small
businesses in developing a commercially-viable therapeutic agent that is
indicated for substance abuse (e.g., cocaine, opioids, cannabis and
methamphetamines) and nicotine dependence. Companies are asked to submit
proposals for the development of their own new chemical entities (NCEs)
or immunotherapies (e.g., vaccines, monoclonal antibodies). Novel NCEs
or immunotherapies should be in the late-stage preclinical development,
where the expected time to initial clinical testing is \<1 year.

Proposed work should prioritize initiating clinical trials as quickly as
is safely possible to expedite the identification of the most promising
treatment opportunities in an FDA-compliant manner. Studies can be in
the form of a pilot study, Phase I safety trial, or Phase II randomized,
double-blind, placebo-controlled clinical trial. Special emphasis will
be given to NCEs or immunotherapies designed to treat and/or prevent the
development of substance abuse and co-morbid psychological disorders.
Preliminary preclinical safety data should also be included. All
preliminary data submitted will remain confidential and the intellectual
property of the firm.

NIDA will provide assistance to the small business for the development
of its investigational new drug (IND)-directed developmental plan.
Regulatory guidance will be provided to help with filing of an
experimental IND with the US Food & Drug Administration (FDA).
Subsequently, the firm is encouraged to use these data to continue to
develop this therapeutic agent independently, in collaboration with
academia, or in partner with industry.

Phase I activities and expected deliverables:

-   Mutually agreed-upon developmental/statistical plan that describes
    in detail the experiment(s) necessary to file an (exploratory) IND,
    depending on the agent selected.

-   Demonstrated ability to deliver results for the initial set of
    experiments (project-specific, according to the
    development/statistical plan above).

-   Begin enrollment of clinical subjects.

Phase II activities and expected deliverables:

-   Completion of experiment(s) outlined in the development/statistical
    plan (can be re-evaluated, if needed).

-   If warranted, provide sufficient data to file an (exploratory) IND
    for the candidate therapeutic agent with indications for substance
    abuse and dependence.

-   As per the FDA's Exploratory IND Guidance, the firm should
    demonstrate the ability to produce a sufficient amount of
    clinical-grade materials suitable for an early clinical trial
    (<http://www.fda.gov/cder/guidance/7086fnl.htm>).

-   A comprehensive intellectual property (IP) and development plan,
    outlining how the company will commercialize the potential
    therapeutic agent.

Potential applicants should submit a letter of intent.

[]{#__RefHeading___Toc205616474 .anchor}106 Pharmaceutical Approaches
for Development of Pharmacotherapies for Drug Addiction

(Fast-Track proposals will be accepted.)

Budget (total costs): Phase I: \$150,000 (1 year); Phase II: \$1,000,000
(2 years)

NIDA is seeking SBIR contract proposals on innovative pharmaceutical
approaches to improve the effectiveness, lower toxicity, and/or minimize
the abuse potential of therapeutic agents for drug abuse/dependence. The
Specific areas of interest include, but are not limited to the
following:

1\) Approaches to improve bioavailability of compounds with poor oral
bioavailability. The pharmaceutical agents of interest include, but are
not limited to, delta-9-tetrahydrocannabinol (THC) and lobeline. THC has
been shown to alleviate marijuana withdrawal symptoms and thus has
potential for treating cannabinoid dependence. Lobeline is currently
under clinical evaluation as a potential pharmacotherapy for
methamphetamine abuse. The oral bioavailability of both THC and lobeline
is very low and frequent dosing is required. Formulations to improve
bioavailability and/or to reduce dosing frequency would be expected to
improve the therapeutic effectiveness.

> In Phase I, the contractor is expected to demonstrate the feasibility
> of the dosage form by formulating a prototype dosage form based on
> biopharmaceutical and pharmaceutical rationale. In Phase II, the
> contractor will carry out pharmacological, toxicological and
> pharmacokinetic evaluations. The contractor is expected to provide a
> GMP scale-up of a stable dosage form with acceptable in vitro and in
> vivo bioavailability in animal models and/or in humans.

2\) Development of controlled release dosage forms for addiction
treatment medications in order to maintain therapeutic drug levels for
extended periods of time to alleviate compliance problems associated
with addiction treatment or to significantly reduce the abuse potential
of prescription drugs/drug products.

> In Phase I, the contractor is expected to demonstrate the feasibility
> of the dosage form by formulating a prototype dosage form based on
> biopharmaceutical and pharmaceutical rationale. In Phase II, the
> contractor will carry out pharmacological, toxicological and
> pharmacokinetic evaluations. The contractor is expected to provide a
> GMP scale-up of a stable dosage form with acceptable in vitro and in
> vivo bioavailability in animal models and/or in humans.

3\) Approaches to improve the efficiency of large scale production of
currently available macromolecules (i.e. monoclonal antibodies and
vaccines) with potential for treating cocaine, methamphetamine or opiate
addiction.

> In Phase I, the contractor is expected to explore various technologies
> and approaches to improve the efficiency of large scale production of
> the macromolecules with potential for treating cocaine,
> methamphetamine or opiate addiction. The contractor shall produce
> pilot batches and demonstrate the feasibility of the scale-up through
> in vitro tests and/or preliminary in vivo evaluations of the batches.
> In Phase II, the contractor is expected to select the most promising
> technology/approach, establish the procedures for a GMP scale-up
> production, and manufacture the GMP batch of the macromolecule. The
> contractor shall also perform in vitro and in vivo characterizations
> including quality control and stability testing, and preliminary
> pharmacological, toxicological or immunological evaluations.

Potential applicants should submit a letter of intent.

[]{#__RefHeading___Toc205616475 .anchor}107 Design and Synthesis of
Treatment Agents for Drug Abuse

(Fast-Track proposals will be accepted.)

Budget (total costs): Phase I: \$100,000 (1 year); Phase II: \$750,000
(2 years)

The purpose of this contract is to design and synthesize novel compounds
intended specifically for the treatment of substance abuse including
cocaine, methamphetamine or cannabinoid abuse. The classes of
pharmacotherapeutic agents include, but are not limited to, compounds
interacting with corticotrophins, cannabinoid, biogenic amines, GABA,
and glutamate systems. The design and development of antibodies or
vaccines as immunopharmacotherapy for methamphetamine or opiate abuse
will also be of interest.

In Phase I, the Contractor will design and synthesize new entities as
potential treatment agents and carry out *in vitro* and/or *in vivo*
pharmacological screens. In Phase II, the Contractor will perform
pharmacological and toxicological evaluations and select lead compounds
as potential clinical candidates.

[]{#__RefHeading___Toc205616476 .anchor}108 Repository for Substance
Abuse Brain Imaging Data (SBIR/STTR)

(Fast-Track proposals will not be accepted.)

All classes of brain imaging studies, anatomical, functional and
neurochemical, are well suited for secondary analysis and meta-analysis.
A substantial barrier to conducting such secondary analysis is access to
primary data collected across multiple laboratories and multiple file
formats. However, there have been demonstration projects (e.g., fMRI
Data Center) that have successfully shown that brain imaging data can be
stored, retrieved and used for secondary analysis (c.f.,Van Horn JD,
Ishai A Mapping the human brain: new insights from FMRI data sharing
Neuroinformatics. 2007). However, existing repositories often are
limited to one imaging modality (e.g., anatomical or functional MRI)

This solicitation would seek proposals to establish a comprehensive
brain imaging repository that would be appropriate for substance abuse
researchers which could eventually be sustainable as a commercial
enterprise.

[]{#__RefHeading___Toc205616477 .anchor}109 Web Based
Cognitive/Neuropsychological Testing for Substance Abuse

(Fast-Track proposals will be accepted.)

This solicitation would emphasize the porting of one or more of either
existing or novel tasks that are relevant to substance abuse related
cognitive/neuropsychological dysfunctions to a web-based environment so
that testing may be conducted from any remote location with internet
access.

There is increasing evidence that cognitive and neuropsychological
dysfunctions are associated with substance abuse disorders. Such
dysfunctions can also include not only domains that are part of
classical cognitive/neuropsychological testing (e.g. memory, executive
function, and sensory/motor processes), but also domains that have
recently become amenable to objective testing, such as (but not limited
to) emotional and cue reactivity, inhibitory control, planning, risk and
decision-making, and even social perception and interactions. Cognitive
and neuropsychological dysfunctions appear to be not only a consequence
of drug use, but may also represent risk factors for initiation of drug
use as well as impediments to treatment and abstinence. Furthermore,
these cognitive/neuropsychological dysfunctions may be relatively subtle
or may not be accessible to awareness (i.e., is implicit) or overt
behavior. As a result, neither the patient nor a treatment provider may
be aware of these dysfunctions in the absence of specific testing.

Cognitive/Neuropsychological testing has traditionally been time
consuming to administer and score, but some tests can or have already
been adapted to computerized administration. Advances in computer
technology and the widespread availability of internet access opens the
possibility that subjects in research projects and patients in treatment
can be tested using interactive on-line versions of existing or novel
tasks. This solicitation proposes to take computerized administration of
these tasks to the next level so as to permit a person to take one or
more tests from any location with access to the internet. The
development of such on-line capabilities would greatly increase the
ability to collect test data from larger cohorts of subjects in a more
efficient manner than previously possible.

[]{#__RefHeading___Toc205616478 .anchor}110 Development of Science
Education Materials or Programs

(Fast-Track proposals will be accepted.)

For many years students in the United States have scored poorly on
standardized tests relative to their international peers. Furthermore,
student interest in science has been declining. At the same time, public
science literacy has remained low. Low science literacy among students
and other groups has many implications. In order for NIDA to fulfill its
mission, there is a need to ensure that adequate numbers of students are
entering science education tracks and eventually pursuing careers in
biomedical sciences. It is also important to the mission of NIDA that
other groups, such as the general public, health care workers, etc. are
scientifically literate. It is particularly important to NIDA that all
members of society understand the role of science, biology, and
technology as they relate to neuroscience and drug abuse and addiction
research. There is a lack of public understanding of behaviors that
increase the risk for drug abuse, the use of animals in drug abuse
related behavioral and biomedical research, and the necessity for basic
research to make progress toward improving health. Furthermore, there is
a substantial misunderstanding about the nature of addiction as a
biologically based brain disorder. To address all of these issues, it is
imperative that efforts be made to educate our nation's school children,
the general public, health care workers, members of the judicial system,
and other groups about the science of addiction.

Therefore to address these issues this contract solicitation seeks
innovative projects or programs that will substantially improve
scientific literacy among one or more of the following groups: 1)
students and teachers at the kindergarten through 12th grade levels; 2)
the general public; 3) health care practitioners; 4) members of the
judicial system; 5) other groups that have a need to be scientifically
literate. Programs or projects must seek to improve general scientific
literacy with a specific focus on drug abuse related research. For
example, a project could teach basic neuroscience first and then
subsequently teach how abused drugs act in the brain and body. Programs
and projects aimed at school children should convey the scientific
process in a way which makes learning science fun and interesting for
the students and which captures their enthusiasm for science. Student
programs and projects must also adhere to the National Science Education
Standards. Programs or projects aimed at other groups should be directed
to increasing their knowledge of scientific terms, concepts, reasoning,
and their ability to understand scientific public policy issues.
Regardless of the intended audience, all programs and projects must
include an evaluation component that can provide useful and accurate
information on the efficacy of the program or project.

Phase I should include studies to determine the best format for the
chosen audience (e.g. focus groups), studies that demonstrate
feasibility, and the development of a prototype.

Phase II should include continued formative evaluations to guide the
development of the program or project, development of the program or
project, and a summative evaluation to determine the project/program's
efficacy in improving science education/literacy.

[]{#__RefHeading___Toc205616479 .anchor}111 Screening, Characterization
and Validation Assays for Protein Capture Reagents

(Fast-Track proposals will not be accepted.)

NIDA seeks proposals to develop and validate methods to characterize
protein affinity reagents and to establish standard operating procedures
for those methods.

The utility of protein affinity reagents is greatly enhanced by
information regarding in situ or in vitro binding conditions, effects of
post-translational modifications of the protein target on reagent
binding, reagent selectivity and stability.

Phase I of this SBIR will be development and validation of methods for
such characterization. Part of Phase I will also be development of
standard operating procedures. It is important that methods developed
can be implemented for high throughput screening of affinity reagents.

Phase II will use methods and SOPs developed in Phase I to characterize
commercially available affinity reagents. The characterization data and
appropriate metadata will be made publicly available.

Contract submitted under this concept can be up to \$200,000 for phase 1
and \$1,500,000 for phase II. Contracts can also extend to up to 4 years
for the phase II award.

[]{#__RefHeading___Toc205616480 .anchor}112 Tool Development for New or
Improved Capture Reagents

(Fast-Track proposals will not be accepted.)

NIDA seeks proposals to begin to establish a library of protein capture
reagents for addiction-relevant proteins and their variants. Relevant
proteins would include membrane proteins such as receptors, transporters
and ion channels as well as signaling proteins, transcription factors
and other nuclear proteins.

Phase I (6 months) will be to develop new and improved in vitro
technologies to generate renewable protein capture reagents that have
the potential to specifically or selectively recognize, bind and
"capture" proteins and distinguish their natural variants \[splice
variants, post- translationally modified variants (e.g., glycosylation,
phosphorylation, acetylation, oxidation, etc.)\]. Initial feasibility
will be demonstrated by development of selective reagents for 10
addiction-relevant proteins including variants of those proteins.

Phase II (24 months) will cover development of selective reagents for
100-200 addiction- or neuroscience-relevant proteins including variants
of those proteins.

Contract submitted under this concept can be up to \$200,000 for phase 1
and \$1,500,000 for phase II. Contracts can also extend to up to 4 years
for the phase II award.

[]{#__RefHeading___Toc205616481 .anchor}National Institute of Mental
Health (NIMH)

The mission of the National Institute of Mental Health (NIMH) is to
transform the understanding and treatment of mental illnesses through
basic and clinical research, paving the way for prevention, recovery,
and cure. Mental disorders constitute an immense burden on the U.S.
population, with major depression now the leading cause of disability in
the U.S., and schizophrenia, bipolar disorder, and obsessive-compulsive
disorder ranked among the ten leading causes of disability. NIMH also
takes a leading role in understanding the impact of behavior on HIV
transmission and pathogenesis, and in developing effective behavioral
preventive interventions. The NIMH conducts a wide range of research,
research training, research capacity development, as well as public
information outreach and dissemination to fulfill its mission.

This solicitation invites proposals in the following areas:

[]{#__RefHeading___Toc205616482 .anchor}061 Home-Based Lithium Level
Testing for Bipolar Patients

(Fast-Track proposals will not be accepted.)

The purpose of this contract is to assess the feasibility of a
home-based lithium level test. Lithium is both an effective and commonly
used treatment for bipolar disorder (BD). Management of patients on
lithium, however, is complicated by a narrow therapeutic range (0.6 to
1.2 mmol/L) with inappropriate levels resulting in poor symptom control
or lithium toxicity. Improved lithium level monitoring could result in
better clinical management and increased treatment adherence.

Recently, a reliable office-based method for obtaining lithium levels
was developed and received FDA approval, indicating that lithium levels
can be obtained routinely and relatively inexpensively. As chronic
disease self-management models evolve, there is an increasing need to
provide patients with the tools to monitor and manage their care. A
home-based lithium level test would provide BD patients and their
families with the tools to monitor their lithium levels on a regular
basis and adjust treatment accordingly as directed by their health
professional.

Phase I should include development of a prototype home-based lithium
test, assess usability of the prototype with bipolar patients, and
compare the results of the prototype to standard lab-based lithium
levels. Since the degree of complexity of this project may require more
than six months to complete, the offeror should clearly identify the
amount of time and support needed to complete their proposed scope of
work. Up to one year of work would be allowed for a Phase I contract and
up to \$200,000 total costs. Phase II contracts would allow up to two
years and up to \$750,000 total costs.

[]{#__RefHeading___Toc205616483 .anchor}Centers for Disease Control and
Prevention (CDC)Number range CHAPTER

[]{#__RefHeading___Toc205616484 .anchor}National Center on Birth Defects
and Developmental Disabilities (NCBDDD)

[National Center on Birth Defects and Developmental Disabilities
(NCBDDD) (http://www.cdc.gov/ncbddd/)](http://www.cdc.gov/ncbddd/)
provides national leadership for preventing birth defects and
developmental disabilities and for improving the health and wellness of
people with disabilities. Our work includes research for helping
children to develop and reach their full potential and promoting health
and well-being among people of all ages with disabilities. Critical
evidence from this research advances knowledge of major risk and
protective factors and modifiable environmental exposures related to
birth defects, disabilities, and blood disorders. Research findings flow
to information consumers through a variety of channels including
peer-reviewed articles, reports, conference presentations and other
channels of communication such as web-based publication databases. The
knowledge gained from these studies provides an important basis for
informing others and for developing new prevention and intervention
strategies.

This solicitation invites proposals for the following topic area:

[]{#__RefHeading___Toc205616485 .anchor}008 Development of Website with
Modules for Study Participants and Fellow Researchers

Birth defects affect 1 in 33 babies and are a leading cause of infant
mortality in the United States. More than 5,500 infants die each year
because of birth defects. While we know how to prevent some birth
defects like spina bifida and fetal alcohol syndrome, the causes of
about two-thirds of birth defects are not known.

CDC is working with partners in Arkansas, California, Iowa,
Massachusetts, New Jersey, New York, North Carolina, Texas and Utah on
the Birth Defects Prevention Study (BDPS), the largest case control
study of children with birth defects in the United States. This ongoing
study enrolls mothers of children with birth defects, and mothers of
children without birth defects and asks them to participate in an
interview and to provide buccal swabs that will be used to study genetic
determinants.

Impact: Increasing the knowledge about risk factors for birth defects
will enable prospective parents to make choices to ensure a healthier
pregnancy. An interactive overview of the literature on risk factors for
birth defects for fellow researchers will improve the quality of birth
defects research worldwide.

Objective: There is a need to inform potential and past participants in
the BDPS as well as fellow researchers, the general public and policy
makers about the importance of the BDPS by showcasing its products, the
importance to participate from a parent's perspective and to be a
resource on risk factors for birth defects. We are seeking to identify a
vendor to develop an interactive website which will capture our audience
and provide them with the information they are looking for. It is
important that the website be 508 compliant and that it use creative
technologies to display the information. The system could possibly be
hosted on the CDC network and would then have to undergo a Federal
Information Security Management Act (FISMA) certification and
accreditation as well as adhere to CDC and Coordinating Center for
Health Promotion (CoCHP) standards for web development (i.e., secure
coding practices). We will need a module that will show our participants
what is involved in participating in the study, a module for scientists
and researchers that will let them search interactively through the
existing birth defects literature and a module for the general public on
what are birth defects and what is known about risk factors for major
birth defects. Once developed, different aspects of the website such as
the information research module can be adapted for other research or
commercial uses for information dissemination.

[]{#__RefHeading___Toc205616486 .anchor}009 Development of a Publication
Database and Information Retrieval System with Announcement Feature

Improving our ability to address a number of areas that contribute to
critical health outcomes is an important public health priority and
requires informing a variety of audiences with timely information. Some
examples demonstrating the significance of the research which supports
and addresses issues related to birth defects and developmental
disabilities, blood disorders, disabilities and human development are as
follows:

-   Birth defects affect 1 in 33 babies and are a leading cause of
    infant mortality in the United States. More than 5,500 infants die
    each year because of birth defects.

-   Bleeding and clotting disorders pose important problems for women
    because of the relationship of these disorders to reproductive
    issues.

-   In 2005, disability prevalence across all 50 states ranged from
    11.4% to 25.8%, with an average or median estimate of 20%. 

Objective: There is a need to identify a feasible, innovative technology
that improves upon how information in the existing database is archived,
up-dated and retrieved. The National Center on Birth Defects and
Developmental Disabilities proposes the following project for an SBIR
contract. We seek to develop an electronic tool to manage and inventory
our publications and presentations to support our research and public
health practice portfolio. This information should be available to
people within CDC as well as our external partners. We need an easily
maintained and up-datable, bibliographic database and informational
retrieval system capable of capturing the outputs generated by research
activities, grantees, collaboratives and conferences. It is important
that this system provide the public with an easy to access tool and
search mechanism to locate publication information to replace the
current system ([http://www2.cdc.gov/
ncbddd/pubs/](http://www2.cdc.gov/ ncbddd/pubs/)). This retrieval system
publication database will also be used internally for program evaluation
purposes.

Briefly, the system developed should: (a) be sufficiently robust as to
track publications and conference presentations into a searchable
bibliographic database and map these artifacts to the Center, Division,
HHS and CDC health protection goals and (b) make this information easily
accessible to a variety of information consumers (such as other
researchers, local, state and national organizations that deliver birth
defects prevention services and the general public). The system would be
hosted on the CDC network and must undergo a Federal Information
Security Management Act (FISMA) certification and accreditation as well
as adhere to CDC and Coordinating Center for Health Promotion (CoCHP)
standards for web development (i.e., secure coding practices).

For an excellent example of a searchable bibliographic database that
captures the agency specific publications, reports, symposium
proceedings and/book chapters that appear in the scientific literature,
please follow the links to the CDC National Institute for Occupational
Safety and Health (NIOSH) publication database (NIOSHTIC-2):

<http://www2a.cdc.gov/nioshtic-2/n2info.asp>

<http://infoserve.sandia.gov/electronic/nioshtic2.html>.

[]{#__RefHeading___Toc205616487 .anchor}010 Development of Standardized
Evaluation Software for Blood Disorder Public Health Surveillance
Systems

The Division of Blood Disorders (DBD) has established a public health
surveillance system called the Universal Data Collection (UDC) system in
the federally supported hemophilia treatment center (HTC) system
comprised of about 135 HTCs located primarily in educational
institutions throughout the United States and its territories.

The stakeholders have worked with a software development company to
create a specialized electronic medical record database for use in the
HTCs to monitor the care of their patients. DBD has worked with this
company to make it possible for the UDC surveillance data to be captured
by this software and transmitted to CDC. Most of the country's HTCs have
adopted this software which facilitates the collection of these data. In
addition, the stakeholders are working with the vendor to convert this
database to a web application.

Impact: It is important that the surveillance system be evaluated as
this transition is occurring to ensure that the resulting system is
useful, efficient, accurate, reliable and effective in the performance
of its purpose. The surveillance system is central to the Division's
ability to carry out our mission which is to reduce or prevent the
complications of bleeding and clotting disorders. The surveillance
system enables us to identify and measure the occurrence of
complications, identify risk factors and high risk groups, develop
interventions, and assess the effectiveness of the interventions in
decreasing the rate of the complications.

Objective: The objective of this announcement is to develop evaluation
software compatible for use with the specialized surveillance systems.
The software will be sold to treatment centers, other providers and
industry professionals as a means to validate individual and collective
health related events, gather credible information regarding performance
of the system and help DBD state and justify conclusions regarding the
validity of the data collected by this surveillance system.

[]{#__RefHeading___Toc205616488 .anchor}011 Animated Software depicting
Iron Out of Balance

Iron out of balance affects millions of Americans. It refers to a number
of disorders that occur when there is too little or too much iron in the
body. The cause of these disorders may be either inherited or acquired.

Hemachromatosis is an inherited disorder that leads to iron out of
balance. Persons with this disorder absorb too much iron from their
diet. It is estimated that one million U.S. Caucasians have the genetic
predisposition for hemochromatosis (HHC).

Iron out of balance may also be acquired as a result of repeated
transfusions. The management of blood disorders such as Thalassemia and
Sickle Cell Disease requires repeated transfusions which may result in
iron overload.

The body has no means of excreting iron, except in minute amounts;
therefore, over time, the excess iron accumulates in vital organs
resulting in disease such as cirrhosis, heart failure, arthritis,
diabetes, hormone imbalances or complete organ failure and death. Early
detection and treatment to remove iron excesses can save lives and
prevent disease.

Impact: Through early detection and treatment morbidity and mortality
associated with iron overload may be prevented. Research conducted by
the CDC and others indicates that primary care physicians may lack the
knowledge they need to be able to identify at risk patients. These
studies have also identified widespread misunderstanding among health
care professionals about the appropriate diagnostic tests and
treatments. Until the last decade, diagnosis of iron overloading
conditions most commonly relied on diagnosing the triad of cirrhosis,
diabetes mellitus, and skin bronzing, and was only confirmed through a
liver biopsy. These methods could only confirm disorders which had
progressed to their later stage, the impact of which resulted in high
excessive morbidity and mortality.

Objective: There is a need to enhance public health translation of
interventions developed and implemented to reduce complications of blood
disorders to medical personnel, patients and their family members and
communities. Improved translation activities will facilitate diagnosis,
management and screening for blood disorders. We are seeking to identify
a vendor to develop animated learning modules which enhance the
understanding of complicated blood disorders. Once developed the modules
would be validated and sold for profit to providers, patients, medical
schools, and industry professionals.

[]{#__RefHeading___Toc205616489 .anchor}012 Development and Evaluation
of Web-based Applications Using Emerging Technologies and New Media

NCBDDD's work includes identifying the causes of and preventing birth
defects and developmental disabilities, helping children to develop and
reach their full potential, and promoting health and well-being among
people of all ages with disabilities. One way in which NCBDDD
communicates our science related to birth defects, developmental
disabilities, disabilities, and blood disorders is through our Website.
Our goal for our Website is that our audiences are able to find
information easily, understand the information and use the information
appropriately. Our audiences include the public, partners, public health
and health professionals, educators, and policy-makers. To accomplish
our goal we have undertaken an initiative to improve the usefulness,
usability, and effectiveness of our existing website through a
user-centered, data-driven, research-based process.

Impact: Our website must be science-based, audience-focused,
standardized and streamlined, compliant with CDC and HHS standards. The
website will have an accessible reading level, and will be evaluated on
an ongoing basis. By creating a science-based, audience-focused website
that incorporates emerging technologies and new media we will increase
the impact of NCBDDD's science.

Objective: The objective of this announcement is to develop applications
using emerging technologies and new media that can be incorporated on
the NCBDDD Website. The applications should be interactive so that our
audiences may connect with our information effectively and efficiently.
Examples of possible applications are videos, eGames, or simulations.
These applications must be 508 compliant. The applications should be
based on principles and evidence-based research related to human
computer interaction, communication and education. Once developed and
evaluated, the technology or applications can be sold for profit.

[]{#__RefHeading___Toc205616490 .anchor}013 Application of Gaming
Technology to Communicate Health Messages and Promote Healthy Living
among Persons with Disabilities

About 50 million Americans, or one in five people, are living with at
least one disability, and most Americans will experience a disability
some time during the course of their lives. The Surgeon General's Call
to Action to Improve the Health and Wellness of Persons with
Disabilities encourages Americans to help increase the quality of life
for people with disabilities through better health care and
understanding. Being healthy means the same thing for all people-getting
and staying well to lead full, active lives. That means having the tools
and information to make healthy choices and knowing the risk factors for
illness. For people with disabilities, it also means that problems such
as pain, depression, and a greater risk for certain illnesses can be
treated or prevented.

Impact: People with disabilities, birth defects, developmental
disabilities, and blood disorders require health care, information, and
education to help them learn about and live healthy lifestyles.
Electronic games or eGames are an innovative tool to provide targeted
health messages about healthy living. These electronic applications have
been shown to improve health in a variety of target audiences and for a
number of health issues such as increasing physical activity, combating
dementia, or improving medical compliance in cancer patients.

Objective: The objective of this announcement is to develop an
application for cutting edge games and/or game technologies designed to
promote healthy living among persons (children, teens, and adults) with
disabilities, birth defects, developmental disabilities, and blood
disorders. For example, these could be applications/games designed to
improve self-care, to increase physical activity, or enhance other
health behaviors. These might be a series of interactive health games
that could be played through an electronic application such as the
Internet, a video game console, a mobile phone, or a portable media
player. Once developed, the technology or games could be sold for profit
to educators, health professionals, or the public.

[]{#__RefHeading___Toc205616491 .anchor}014 Use of Cutting-edge
Technology to Communicate with and Educate Health Care Professionals
about Birth Defects, Developmental Disabilities and Ways to Improve the
Health and Wellness of Persons with Disabilities

NCBDDD's work includes identifying the causes of and preventing birth
defects and developmental disabilities, helping children to develop and
reach their full potential, and promoting health and well-being among
people of all ages with disabilities. NCBDDD seeks to provide health
care professionals with current scientific information related to the
persons with birth defects, developmental disabilities, disabilities,
and blood disorders. To accomplish this NCBDD has developed practice
guidelines, continuing education courses, and a variety of materials.

Impact: It is important that NCBDDD reaches health care professionals,
including first responders, with timely, scientific information related
to those populations whom NCBDDD serves. For example, NCBDDD has
developed *Guidelines for Fetal Alcohol Syndrome Referral and Diagnosis*
and *Recommendations to Improve Preconception Health and Health Care*
designed to provide guidance to health care professionals. Additionally,
our information about vulnerable populations such as those who are
pregnant or have disabilities may be used to educate first responders
about how to best protect these persons during a disaster.

NCBDDD would like to translate our scientific information into
electronic and/or digital formats that would enhance the effectiveness
and efficiency in how we communicate our practice guidelines and
professional development materials with health care professionals.
Sharing this information with health care professionals who work
directly with the populations we serve will ultimately impact the heath
of those persons with birth defects, developmental disabilities,
disabilities and blood disorders.

Objective: The objective of this announcement is to develop an
application(s) using cutting edge technology to communicate with and
educate health care professionals about NCBDDD science and guidelines
related to birth defects, developmental disabilities, disabilities, and
blood disorders. The application should increase health care
professionals' knowledge, attitudes, and/or skills. The application(s)
could incorporate interactive game technologies, role-based electronic
simulations or interactive fiction. These could be communication and
educational activities designed for electronic applications such as the
Internet, a video game console, a mobile phone, or a portable media
player. Once developed, the technology or applications could be sold for
profit to health care professionals or health professions educators.

[]{#__RefHeading___Toc205616492 .anchor}National Center for Chronic
Disease Prevention and Health Promotion (NCCDPHP)

**The National Center for Chronic Disease Prevention and Health
Promotion** is leading efforts to promote health and well-being through
prevention and control of chronic diseases that all people might live
healthy lives free from the devastation of chronic diseases. Priorities
focus on well-being, health equity, research translation, policy
promotion and workforce development.

This solicitation invites proposals for the following topic areas:

The Division for Heart Disease and Stroke Prevention, National Center
for Chronic Disease Prevention and Health Promotion, in collaboration
with the National Centers (DHDSP/NCCDPHP/CDC) for Health Statistics
(NCHS/CDC) are working to collect, analyze, and disseminate data
relating to the screening, diagnosis, and management of hypertension and
to develop methods to improve the accuracy and reliability of electronic
blood pressure monitors.

[]{#__RefHeading___Toc205616493 .anchor}028 Inexpensive, Portable,
User-friendly Calibration of Aneroid and Electronic Blood Pressure
Devices

Proposals are invited for the development of an inexpensive, portable,
user-friendly method (i.e., instrument or device with corresponding
technique) to calibrate electronic blood pressure monitoring devices for
accurate and reliable readings of systolic and diastolic blood pressure,
pulse rate and pulse pressure. This method and device should include
documentation of its capacity, accuracy and reliability of the
calibration of the various equipment currently in use in the United
States (i.e., Omron, Hyundai, Lifesource). The methods should be
sufficiently portable to be able to be carried by any ambulatory adult
and require minimal amount of training for accurate and reproducible
calibration results of most all of the currently available commercial
brands of electronic blood pressure devices used in clinics, pharmacies,
hospitals, and homes. Evaluation of the method should address, at a
minimum: accuracy, reproducibility, ruggedness, costs of operation, user
friendliness, and portability.

Background: Since 2001 Mercury Reductive and Disposal, the use of the
mercury spyghmanometer blood pressure devices are being phased out due
to environmental concerns of mercury exposure (Sustainable Hospitals
Guidelines 2002). Professional aneroid blood pressure devices used in
hospitals and clinics that have lifetime calibration warranties and are
recommended to be maintained regularly for accuracy and reliability. The
seventh report of Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood (JNC7) recommends that all
non-mercury blood pressure devices are appropriately validated and
checked routinely for accuracy (in other words) calibrated (Chobanian et
al., 2003; Franklin et al. 2001). The use of electronic blood pressure
devices have become increasingly more popular in hospitals, clinics and
even in pharmacies for self monitoring or screening; new inexpensive and
portable methods of calibration are required. Additionally, when the
sixth report of Joint National Committee on Blood Pressure Education and
Control was released with recommendations for use of electronic home
blood pressure devices for hypertension control management, there is an
increased need for user-friendly, portable calibration devices. The
electronic home blood pressure devices are inexpensive and widely
available for the general population to buy at pharmacies, Walmart,
Target and other retail stores in the United States. Unfortunately, the
calibration of these electronic devices have not been developed.

Understanding the design and construction of the electronic blood
pressure device is integral to knowing the accuracy of the blood
pressure measurement taken for hypertension screening, diagnosis, and
management. Changes in the types of devices used during the past thirty
years can influence the outcome of the blood pressure measurement
readings that influence screening, diagnostic and management outcomes.
However, the accuracy and reproducibility of aneroid devices compared to
mercury device (considered the gold standard) are inherently
questionable due to the bellow/spring mechanism of the device as well as
the type of training required systolic and diastolic assessment inter
and intra-reader accuracy and reliability (personal communication
Yechaim Ostchega, 2008). Unfortunately, the calibration of these
electronic devices have not been developed. A recent study a NCHS was
conducted and found that the Omron could be Digimat calibrated and
proved to be more accurate and reliable than the aneroid device. Thus,
it is imperative that routine calibration of these electronic blood
pressure devices can be incorporated which required the development of
inexpensive, portable, user-friendly method (i.e., instrument or device
with corresponding technique).

The proposal should include 1) a plan to develop an inexpensive,
portable, user-friendly method (i.e., instrument or device with
corresponding technique) to calibrate aneroid blood pressure
spyghmanometer and electronic blood pressure monitoring devices for
accurate and reliable readings of systolic and diastolic blood pressure,
pulse rate and pulse pressure, 2) documentation of the capacity and
accuracy of the method, 3) verification of the reliability of the
calibration equipment for the various equipment, and 4) evidence that
the instrument or device with corresponding technique (method) is
applicable to all current varieties of commercial brands of aneroid and
electronic blood pressure devices used in clinics, pharmacies,
hospitals, and homes. Evaluation of the method should address, at a
minimum: accuracy, reproducibility, ruggedness, costs of operation, user
friendliness, and portability.

[]{#__RefHeading___Toc205616494 .anchor}029 Dynamic Health Promotion
Decision Making for Preconception Health and Healthcare

Develop a marketable software product to aide individuals to assess
their health risks and guide health care decisions.

Proposals are invited for development of a web-based dynamic education
and decision making software product that will assist individuals
decisions about risk reduction and health promotion interventions based
on the most current evidence tailored to their individual situation.
This education and decision making software must include a database of
the scientific literature that will support the dynamic decision making
based on the information provided by consumers. The tool developed under
this award must be focused on the content of preconception health and
healthcare and include both clinical lifestyle components. This software
has broad applications in other domains of health promotion for
consumers as well as for healthcare providers.

Background: In the last 100 years there has been substantial
improvements made in reducing both maternal and infant morbidity and
mortality. Unfortunately for the past 20 years we have seen a leveling
off and in some cases increasing rates of morbidity and mortality. The
reasons for the slowing of the improvement are not well understood. It
appears that we have maximized the improvements made through the
provision of prenatal care. Much of the morbidity and mortality observed
today is the result of health risks and chronic conditions that are
present long before pregnancy. There are efforts in the fields of public
health, clinical medicine, consumer education and policy and finance to
address this issue. One important component of these efforts is to
facilitate the education and support decision making of consumers on the
health risks associated with preconception health and healthcare.

Individual decision making around risk reduction and health promotion
information is highly complex. Individuals must consider multiple
behaviors and risks simultaneously and consider the best health
promoting behaviors that they can implement in their daily lives. For
these decisions to have impact on health and well being the information
provided needs to be based on scientific evidence, interpretable by the
individual and relevant to their specific situation. Currently there is
an endless amount of health related information available to
individuals, some of it science based some of it not and none of it is
organized in a manner that individuals can use in their daily lives.
Being able to provide individuals with decision making tools that can
provide evidence based information about their health conditions will
improve health literacy and support decisions about health behavior
change that is relevant to them.

The proposal plan should include:

1\. Collection and synthesis of the most current science on domains of
health and health behaviors related to preconception care including (but
not limited to) use of medications, management of chronic disease,
health promotion interventions to reduce risks, family planning methods,
environmental exposures and family history of genetic conditions.

2\. A dynamic database that can identify relevant information to
individuals based on responses to questions on general health and
condition specific questions.

3\. A software product that is consumer friendly and does not require
high computer and health literacy skills. This interactive software
should include general questions as well as specific questions about
risks identified in the initial screening/general health portion.

4\. An output mechanism that can provide the user information that is
understandable, relevant and useful in their day to day lives as well as
for guiding discussions with healthcare and social service providers.

CDC staff will be available for relevant discussions with the successful
vendor. The applicant will retain all rights for the commercial
marketing and application of this tool for other content areas and
audiences such as the medical community or the general public.

**The Prevention Research Centers Program**

The Prevention Research Centers (PRC) Program
([www.cdc.gov/prc](http://www.cdc.gov/prc)) enables CDC to fund
extramural research centers that add to knowledge and practice of
chronic disease prevention and control. The program aims to build
partnerships that draw on the perspectives and resources of diverse
communities and actively partner with them; build long-term
relationships for engaging communities as partners in research; work
with populations having the greatest burden of disease and disability,
especially people affected by adverse socioeconomic conditions;
implement and evaluate interventions that help improve health outcomes;
strive to develop communities\' long-term capacity; disseminate
successful results to comparable communities throughout the nation;
promote the quality and availability of public health services through
proven interventions; train and offer technical assistance to community
and public health practitioners; strengthen the public health
infrastructure by sharing information, offering training and technical
assistance, and testing interventions for implementation; and facilitate
communication among public health professionals and community members
through conferences, training, publications, and other means.

[]{#__RefHeading___Toc205616495 .anchor}030 Development and Evaluation
of a Quality and Affordable Electric-Assist Bicycle for Commuting

Studies have shown that integrating moderate cardiovascular exercise
into daily routines is highly beneficial to health. Cycling can help
with weight management; improve psychological well-being; maintain
strength and coordination; allow cyclist to absorb lower pollutant
levels from traffic fumes than from car driving; reduce carbon
emissions; reduce commuting expenses; reduce the stress of driving in
traffic; and create a sense of accomplishment.

Reports and studies show that people do not commute to work via a
bicycle for many reasons: 1) they are not physically fit; 2) roads are
not safe; 3) bicycle lanes are lacking; 4) it takes too much time to
commute; 5) distance between point A and B is too far; 6) terrain is
challenging (e.g., steep hills, potholes); 7) bicycle is uncomfortable;
8) do not own a reliable bicycle; 9) convenient and secure bicycle
parking is not available; 10) have to commute while at work; 11) the
nature of work does not allow for bicycle commuting; 12) no storage for
personal items; 13) have to shower to refresh; 14) have to have a change
of clothes; 15) vulnerable to weather conditions; and 16) possible
physical injuries resulting from falls or accidents.

The PRC Program is soliciting proposals from small businesses in
partnership with University of North Carolina at Chapel Hill Center for
Health Promotion and Disease Prevention (UNC PRC),
http://www.hpdp.unc.edu, to design and produce a quality and affordable
electric-assist bicycle for commuting. The PRC Program would like to
know if a combination of electricity and human power can increase
people's use of a bicycle for commuting to the work place. A qualified
small business with assistance from UNC PRC will be funded to design and
produce an electric-assist bicycle that creatively addresses the 16
barriers to bicycle commuting mentioned above. At a minimum, the
following criteria should be included in the design and production of
this bicycle: 1) Quality powerful hi-torque electric-motor; 2) Long-life
powerful re-chargeable battery; 3) Adjustable electric assist; 5)
Affordable; 6) High performance quality parts and accessories; 7)
Warranty comparable to that given by quality bicycle manufacturers; 8)
Attractive and light weight; 9) Base model includes needed accessories
(i.e., lock, mirror, storage rack, etc.)

In addition, UNC PRC together with the small business will pilot test
the new electric-assist bicycle. The pilot study should involve
appropriate stakeholders, quality community-based participatory research
methods, and a built-in social marketing component. The evaluation
should help determine whether an electric-assist bicycle can increase
bicycle commuting to, during, and from work, and measure intermediate
health outcomes or behaviors. Preparation of the application for this
solicitation must be done in collaboration with the small business and
UNC PRC.

[]{#__RefHeading___Toc205616496 .anchor}Immunization Safety Office

The Vaccination Technology (VAXTECH) Unit of the Immunization Safety
Office, CDC, promotes applied research and development to enhance the
effectiveness, efficiency, safety, and acceptability of immunization
through crosscutting initiatives, projects, and consultations. A major
focus is alternative delivery systems and related technologies for
safer, swifter, and simpler vaccination that avoid the dangers and
drawbacks of conventional needle and syringe. Such improvements in
vaccination support many of the Health Protection Goals of CDC and the
nation (<http://www.cdc.gov/osi/goals/goals.html>) by preventing disease
at various stages of life and work environments, and in response to
natural, inadvertent, and intentional threats to health.

VAXTECH invites phase I SBIR contract proposals in response to the
following solicitation:

[]{#__RefHeading___Toc205616497 .anchor}006 Novel or Enhanced Technology
for Vaccination Delivery and Immunization Programs

New or improved methods, systems, or accessories are encouraged in the
following areas, listed alphabetically:

**A) Cutaneous Vaccination.** For example, delivery systems, carrier
constructs, or adjuvants for depositing antigen into or onto the skin to
reach immunoactive tissues of the epidermis or dermis, such as patches,
minineedles, microneedles, microtines, or powders, using mechanical,
kinetic, electromagnetic, chemical, sonic, ballistic, or other means to
traverse the stratum corneum barrier.

**B) Jet Injection Vaccination.** For example, disposable-cartridge
injectors or accessories for pressurizing liquid vaccines to propel them
without needle into intramuscular (IM), subcutaneous (SC), and/or
intradermal (ID) target tissues.

**C) Logistics for Immunization Programs.** For example, antigen
carriers, formulation vehicles, or packaging systems for increased
thermostability to reduce the costs and constraints of the cold-chain,
for detecting freeze damage to avoid use of impotent product, for
simplified reconstitution of lyophilized vaccines, or for reduced
wastage from economical unit-dose primary containers.

**D) Oral Vaccination without Ingestion.** For example, constructs,
carriers, adjuvants, or other techniques to target antigen for delivery
to mucosal cells of the mouth or oropharynx (as distinct from ingestion
for uptake in the distal gastrointestinal tract), such as oral sprays,
sublingual tablets, or melting strips.

**E) Respiratory Tract Vaccination.** For example, 1) devices,
formulations, or constructs for delivery of wet liquid or dry powder
aerosols and nasal sprays to the upper or lower airways, 2) adjuvants or
other methods for improved uptake, efficiency, and immune response of
respiratory vaccines, or 3) *in vivo* animal, *in vitro* bench, or *in
silico* software models to facilitate study of this route.

Encouraged and prioritized for award are proposals with high potential
for dramatic improvements to overcome barriers and constraints for
immunization programs, and for early affordability in developing
countries. Credibility is enhanced by proposals which feature a specific
vaccine in combination with a novel technology as "proof of principle",
and include evidence of collaboration or support of the antigen
manufacturer.

The proposed research and development work will be evaluated by a
technical review panel applying the following criteria, which should be
addressed in substantial detail within the space limitations specified
elsewhere in this announcement: **1) Soundness and Technical Merit** (40
points) - *The scientific basis and preliminary track record of the
approach and the identification of clear measurable goals and milestones
to be achieved during Phase I.* **2) Personnel** (20 points) - *The
qualifications and experience of the proposed Principal Investigator,
supporting staff, and consultants.* **3) Technological Innovation** (10
points) - *The potential for advancing the state of the art of the
relevant field.* **4) Commercial Application** (10 points) - *The
potential for profitable viability in the marketplace.*
**5) Facilities** (10 points) - *The adequacy and suitability of the
available equipment and research environment for the proposed work.*
**6) Public Health Impact** (10 points) - *The potential for dramatic or
revolutionary impact on immunization programs and population
well-being.*

[]{#__RefHeading___Toc205616498 .anchor}National Center for Immunization
and Respiratory Diseases (NCIRD)

The Measles, Mumps, Rubella and Herpesvirus Laboratory Branch (MMRHLB),
Division of Viral Diseases, is responsible for providing laboratory
support for surveillance for measles, mumps, rubella and varicella
zoster in the United States. MMRHLB conducts a wide range of serologic
and molecular assays to detect infections and provide genetic
characterization of the agents responsible for these diseases. MMRHLB
also supports the Global Measles/Rubella Laboratory Network of the World
Heath Organization by serving as a Global Specialized Laboratory.

[]{#__RefHeading___Toc205616499 .anchor}001 Novel Methods for Detecting
Viruses in Clinical Samples

The MMRHLB has already developed a wide variety of standard PCR and real
time PCR techniques for detection of measles, mumps, rubella and herpes
viruses and is interested in new or improved methods to detect viral
proteins or nucleic acids in clinical samples. These novel techniques
should have high levels of sensitivity and specificity. Techniques which
require a minimum amount of specimen processing and handling, do not
require nucleic acid extraction or amplification and are amenable to
high throughput screening are especially desirable. Tests that could be
potentially deployed in resource limited areas would also be considered
a high priority.

The proposed research and development work will be evaluated by a
technical review panel applying the following criteria, which should be
addressed in substantial detail within the space limitations specified
elsewhere in this announcement: **1) Soundness and Technical Merit** (40
points) - *The scientific basis and preliminary track record of the
approach and the identification of clear measurable goals and milestones
to be achieved during Phase I.* **2) Personnel** (20 points) - *The
qualifications and experience of the proposed Principal Investigator,
supporting staff, and consultants.* **3) Technological Innovation** (10
points) - *The potential for advancing the state of the art of the
relevant field.* **4) Commercial Application** (10 points) - *The
potential for profitable viability in the marketplace.*
**5) Facilities** (10 points) - *The adequacy and suitability of the
available equipment and research environment for the proposed work.*
**6) Public Health Impact** (10 points) - *The potential for dramatic or
revolutionary impact on immunization programs and population
well-being.*

Those considering submission of proposals in response to this
solicitation are encouraged to contact the following
scientific/technical officer for questions and feedback on proposed
topics: Paul Rota, (prota@cdc.gov). Otherwise, general SBIR
administrative program questions should be posed to the appropriate
contact person, and formal letters of intent should be directed to the
relevant contracting officer, as instructed and both designated
elsewhere in this announcement.

# part II human subjects Research Guidance and Information Supplement

# 1. Introduction

A Protection of Human Subjects section of the Research Plan is required
for all proposals. The information provided in the section on Protection
of Human Subjects should be consistent with the information provided on
the face page of the application. []{.mark}

For all research involving human subjects, the Scientific Review Group
(SRG) will assess the adequacy of protections for research participants
against research risks, and the appropriate inclusion of women,
minorities, and children, based on the information provided in the
application.

To assist in preparing the section on Protection of Human Subjects, six
possible scenarios are provided in Section 2 below. All research
projects will fall into one of these six scenarios. Determine which
scenario the proposed research falls into, then go to the specific
instructions applicable to that scenario in [Section
3](#Human_Subjects_Research_Instruct) of the Supplement. Where
appropriate, Section 3 provides instructions on addressing the Inclusion
of Women and Minorities, the Targeted/Planned Enrollment Table, and the
Inclusion of Children. All definitions related to human subjects
research are linked to text found in Part I, Section 3,
[Definitions](#definitions). [Section
5](#Human_Subjects_Research_Instruct) of this Part includes descriptions
of and links to the DHHS Human Subjects Protections regulations and NIH
policies that apply to clinical research.

# 2. Scenarios

#### Scenario A. No Human Subjects Research {#scenario-a.-no-human-subjects-research .Subhead---No-TOC}

If no human subjects research is proposed in the proposal, check the box
marked "No" on the Proposal Cover Sheet (Appendix A) and indicate "No"
on the Proposal Summary and Data Record (Appendix G). If your proposed
research involves human specimens and/or data from subjects, you must
provide a justification for your claim that no human subjects are
involved in the Protection of Human Subjects section of the Research
Plan.

See the [instructions for Scenario
A](#scenario-a.-no-human-subjects-research-proposed).

#### Scenario B. Non-Exempt Human Subjects Research {#scenario-b.-non-exempt-human-subjects-research .Subhead---No-TOC}

If research involving human subjects is anticipated to take place under
the award, check the box marked "Yes" on the Proposal Cover Sheet
(Appendix A) and indicate "Yes" on the Proposal Summary and Data Record
(Appendix G). Enter your Human Subjects Assurance Number.

In the Protection of Human Subjects section of the Research Plan, you
must provide sufficient information for reviewers to determine that the
proposed research meets (1) the requirements of the DHHS regulations to
protect human subjects from research risks ([45 CFR Part
46](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)), and
(2) the requirements of NIH policies on inclusion of women, minorities,
and children. Research involving a clinical trial will fall under either
Scenario E or F below.

See the [instructions for Scenario
B](#scenario-b.-non-exempt-human-subjects-research-1).

#### Scenario C. Exempt Human Subjects Research {#scenario-c.-exempt-human-subjects-research .Subhead---No-TOC}

If **all** of the proposed research meets the criteria for one or more
of the exemptions from the requirements in the DHHS regulations
(46.101(b)), check the box marked "Yes" on the Proposal Cover Sheet
(Appendix A). Indicate "Yes" on the Proposal Summary and Data Record and
insert E-1, E-2, E-3, E-4, E-5, or E-6 as appropriate, in the field for
Exemption Number (Appendix G). Leave IRB Approval Date field blank since
a Human Subjects Assurance Number is not needed for exempt research.
Check "N/A" in field for "example of informed consent" and "Clinical
Protocol" as these are not required for exempt research.

In the section on Protection of Human Subjects in the Research Plan,
provide a justification for the exemption(s) containing sufficient
information about the involvement of the human subjects to allow a
determination by peer reviewers and NIH staff that claimed exemption(s)
is/are appropriate.

The PHS will make a final determination as to whether the proposed
activities are covered by the regulations or are in an exempt category,
based on the information provided in the Research Plan. When in doubt,
consult with the Office for Human Research Protections (OHRP),
Department of Health and Human Services by accessing their website
<http://www.hhs.gov/ohrp/> for guidance and further information.

The [exemptions](#Human_Subjects_exempt) appear in Part I, Section 3,
Definitions.

See the [instructions for Scenario
C](#Human_Subjects_Research_Instruct).

#### Scenario D. Delayed-Onset Human Subjects Research {#scenario-d.-delayed-onset-human-subjects-research .Subhead---No-TOC}

If human subjects research is anticipated within the period of the award
but plans for involvement of human subjects cannot be described in the
application as allowed by the DHHS regulations (45 CFR Part 46.118),
check "Yes" to "This proposed project involves human subjects" on the
Proposal Cover Sheet (Appendix A) and indicate "Yes" on the Proposal
Summary and Data Record (Appendix G). In the section on Protection of
Human Subjects in the Research Plan, you should either include an
explanation of anticipated protections for human subjects or an
explanation of why protections cannot be described.

Examples of delayed-onset of human subjects research include:

-   Human subjects research is dependent upon the completion of animal
    or other studies; or

-   Human subjects research protocols to be included will undergo an
    independent decision-making process (often defined by a FOA).

See [instructions for Scenario D](#Human_Subjects_Research_Instruct).

#### Scenario E. Human Subjects Research Involving a Clinical Trial {#scenario-e.-human-subjects-research-involving-a-clinical-trial .Subhead---No-TOC}

If research involving human subjects is anticipated to take place under
the award, and you intend to conduct a [clinical trial](#clinical_trial)
during the project period, check the boxes marked "Yes" on the Proposal
Cover Sheet (Appendix A) to "This proposed project involves human
subjects," and "Clinical Trial?" Indicate "Yes" on the Proposal Summary
and Data Record (Appendix G). In addition, complete the items regarding
the Institution's General Assurance, Institution's Review Board,
informed consent and clinical protocol.

In the section on Protection of Human Subjects in the Research Plan, you
must provide sufficient information for reviewers to determine that the
proposed research meets:

1\) the requirements of the DHHS regulations to protect human subjects
from research risks ([45 CFR Part
46](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm));

2\) NIH policy requirements for Data and Safety Monitoring for Clinical
Trials;

3\) the ClinicalTrials.gov requirements if applicable;

4\) the requirements of NIH policies on inclusion of women, minorities,
and children; and

5\) the requirements of NIH policy on reporting race and ethnicity data
for subjects in clinical research.

See [instructions for Scenario E](#Human_Subjects_Research_Instruct).

#### Scenario F. Human Subjects Research Involving an NIH-Defined Phase III Clinical Trial {#scenario-f.-human-subjects-research-involving-an-nih-defined-phase-iii-clinical-trial .Subhead---No-TOC}

If research involving human subjects is anticipated to take place under
the award, and you intend to conduct an [NIH-defined Phase III clinical
trial](#Human_Subjects_Defs_NIH_PhaseIII) during the project period,
check the boxes marked "Yes" to the following statement/questions on the
Proposal Cover Sheet (Appendix A):

-   This proposed project involves human subjects.

-   Clinical Trial?

-   Agency-Defined Phase III Clinical Trial?

Also indicate "Yes" on the Proposal Summary and Data Record (Appendix G)
to the following question: Does this proposal involve human subjects
research? In addition, complete the items regarding the Human Subjects
Assurance Number, Institution's Review Board, informed consent and
Clinical Protocol.

In the section on Protection of Human Subjects in the Research Plan, you
must provide sufficient information for reviewers to determine that the
proposed research meets:

1\) the requirements of the DHHS regulations to protect human subjects
from research risks ([45 CFR Part
46](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm));

2\) NIH policy requirements for Data and Safety Monitoring for Clinical
Trials;

3\) the ClinicalTrilas.gov requirements if applicable;

4\) the requirements of NIH policies on inclusion of women, minorities,
and children;

5\) additional Requirements for NIH-defined Phase III clinical trials;
and

6\) the requirements of NIH policy on reporting race and ethnicity data
for subjects in clinical research.

See [instructions for Scenario F](#Human_Subjects_Research_Instruct).

# 3. Instructions for Preparing the Section on Protection of Human Subjects

#### Scenario A. No Human Subjects Research Proposed {#scenario-a.-no-human-subjects-research-proposed .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research) No

[Exemption Claimed](#Human_Subjects_exempt) No

[Clinical Trial](#clinical_trial) N/A

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII) N/A

## Instructions and Required Information

In the proposal narrative, create a heading labeled "Protection of Human
Subjects" and include the following statement below the heading: "No
Human Subjects Research is proposed in this proposal."

If proposed studies using coded human data or biospecimens do not
involve human subjects as described in the OHRP Guidance on Research
Involving Coded Private Information or Biological Specimens
(<http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.htm>), provide
an explanation of why the proposed studies do not constitute research
involving human subjects.

The explanation could include: a description of the source of the
data/biospecimens; the role(s) of providers of the data/biospecimens in
the proposed research; and the manner by which the privacy of research
participants and confidentiality of data will be ensured.

Research that does not involve intervention or interaction with living
individuals, or identifiable private information, is not human subjects
research (see Part I, Section 3, [Definitions](#definitions)).

Research that only proposes the use of cadaver specimens is not human
subjects research because human subjects are defined as "living
individuals." The use of cadaver specimens is not regulated by 45 CFR
Part 46, but may be governed by other Federal, State or local laws.

#### Scenario B. Non-Exempt Human Subjects Research {#scenario-b.-non-exempt-human-subjects-research-1 .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research) Yes

[Exemption Claimed](#Human_Subjects_exempt) No

[Clinical Trial](#clinical_trial) No

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII) No

## Instructions and Required Information 

Although no specific page limitation applies to this section of the
proposal, be succinct.

In the proposal narrative, create a section entitled "Protection of
Human Subjects" and create a subheading for each of the following items.

Follow the instructions that are identified for each of the following
topics and provide the information that is requested:

Protections for Human Subjects - [Section 4.1 -
4.1.4](#protection-of-human-subjects)

Inclusion of Women and Minorities - [Section
4.2](#inclusion-of-women-and-minorities)

Targeted/Planned Enrollment Table - [Section
4.3](#Human_Subjects_Research_Instruct)

Inclusion of Children - [Section 4.4](#inclusion-of-children)

If the research involves collaborating sites, provide the information
identified above for each participating site.

#### Scenario C: Human Subjects Research Claiming Exemption 1, 2, 3, 4, 5, or 6 {#scenario-c-human-subjects-research-claiming-exemption-1-2-3-4-5-or-6 .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research) Yes

[Exemption Claimed](#Human_Subjects_exempt) 1, 2, 3, 4, 5, or 6

[Clinical Trial](#clinical_trial) Yes or No

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII) No

## Instructions and Required Information 

Although no specific page limitation applies to this section of the
proposal, be succinct. The [exemptions](#Human_Subjects_exempt) appear
in Part I, Section 3, [Definitions](#definitions).

Although the research may be exempt from the DHHS regulatory
requirements, it is still research involving human subjects and the
application must follow the instructions that are identified for each of
the following topics and provide the information that is requested.

In the proposal narrative, create a heading entitled "Protection of
Human Subjects" and include the following statement below the heading:
"This Human Subjects Research falls under Exemption(s) ... ."

Follow the instructions that are identified for each of the following
topics and provide the information that is requested:

Justification for Claimed Exemption(s):

> In this section, identify which exemption(s) (1, 2, 3, 4\*, 5, or 6)
> you are claiming. Justify why the research meets the criteria for the
> exemption(s) that you have claimed.\
> \
> If the research will include a clinical trial, even if exempt, include
> a Data and Safety Monitoring Plan -- [Section
> 4.1.5](#data-and-safety-monitoring-plan), and address the
> ClinicalTrials.gov requirements if applicable -- [Section
> 4.1.6](#clinicaltrials.gov-requirements).

Inclusion of Women and Minorities - [Section
4.2](#inclusion-of-women-and-minorities)

Targeted/Planned Enrollment Table - [Section
4.3](#Human_Subjects_Research_Instruct)

Inclusion of Children - [Section 4.4](#inclusion-of-children)\
\
\*NOTE: If all the proposed research meets the criteria for Exemption 4,
then the requirements for inclusion of women and minorities,
targeted/planned enrollment table, and inclusion of children, do not
need to be addressed.

#### Scenario D: Delayed-Onset Human Subjects Research {#scenario-d-delayed-onset-human-subjects-research .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research) Yes

[Exemption](#Human_Subjects_exempt) Yes or No

[Clinical Trial](#clinical_trial) Yes or No

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII) Yes or No

## Instructions and Required Information

In rare situations, proposals are submitted with the knowledge that
human subjects will be involved during the period of support, but plans
are so indefinite that it is not possible to describe the involvement of
human subjects in the proposal. The kinds of activities that lack
definite plans are often institutional awards where the selection of
specific projects is the institution\'s responsibility, research
training grants, and projects in which the involvement of human subjects
depends upon completion of instruments, animal studies, or purification
of compounds.

If the involvement of human subjects is indefinite, create a heading
entitled "Protection of Human Subjects" and provide a detailed
explanation why it is not possible to develop definite plans at this
time. The explanation should be specific and directly related to the
Specific Aims in the proposal. If the involvement of human subjects
depends upon information that is not presently available (e.g.,
completion of instruments, animal studies, purification of compounds),
be explicit about the information and the factors affecting the
availability of the information. Describe the information that will be
necessary in order to develop definite plans for the involvement of
human subjects, why that information is not currently available, and
when the information is expected to become available during the course
of the project.

If an award is made, prior to the involvement of human subjects the
grantee must submit to the NIH awarding office for prior approval either
(1) detailed information as required in the Research Plan, Protection of
Human Subjects (addressing risks to the subjects, adequacy of protection
against risks, potential benefits of the proposed research, importance
of the knowledge to be gained, and data and safety monitoring plan if
applicable) and certification of IRB approval, OR (2) if all of the
research meets the criteria for one or more exemptions, identification
of which exemption(s) is/are applicable to the research, and a
justification for the exemption with sufficient information about the
involvement of human subjects to allow a determination that the claimed
exemption is appropriate. If the research is not exempt, the request for
prior approval must also address the inclusion of women and minorities,
the inclusion of children, and provide completed targeted/planned
enrollment tables as required in the Research Plan.

Under no circumstance may human subjects be involved in non-exempt
research until approval is granted by the awarding entity, and
certification of IRB approval has been accepted by the agency.

In the proposal narrative, create a section entitled Protection of Human
Subjects and a subheading for each of the following items. Follow the
instructions that are identified for each of the following topics and
EITHER provide as much of the information that is requested as possible;
OR describe why it is not possible to provide the information due to
delayed-onset of human subjects research:

Protection of Human Subjects - [Section 4.1 -
4.1.4](#protection-of-human-subjects)

If the research will include a clinical trial, include a Data and Safety
Monitoring Plan - [Section 4.1.5](#data-and-safety-monitoring-plan), and
address the ClinicalTrials.gov requirements if applicable -- [Section
4.1.6](#clinicaltrials.gov-requirements).

Inclusion of Women and Minorities - [Section
4.2](#inclusion-of-women-and-minorities)

Targeted/Planned Enrollment Table - [Section
4.3](#Human_Subjects_Research_Instruct)

Inclusion of Children - [Section 4.4](#inclusion-of-children)

#### Scenario E: Clinical Trial {#scenario-e-clinical-trial .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research) Yes

[Exemption](#Human_Subjects_exempt) Yes or No

[Clinical Trial](#clinical_trial) Yes

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII) No

## Instructions and Required Information

In the proposal narrative, create a section entitled "Protection of
Human Subjects" and include the following statement below the heading:
"This Human Subjects Research meets the definition of a clinical trial."
(See definition of \"[clinical trial](#clinical_trial)\" in Part I.)
Create a subheading for each of the following items. Follow the
instructions that are identified for each of the following topics and
provide the information that is requested:

Protection of Human Subjects - [Section 4.1 -
4.1.6](#protection-of-human-subjects)

Inclusion of Women and Minorities - [Section
4.2](#inclusion-of-women-and-minorities)

Targeted/Planned Enrollment Table - [Section
4.3](#Human_Subjects_Research_Instruct)

Inclusion of Children - [Section 4.4](#inclusion-of-children)

If the research involves collaborating sites, provide the information
identified above for each participating site.

#### Scenario F: NIH Defined Phase III Clinical Trial {#scenario-f-nih-defined-phase-iii-clinical-trial .Subhead---No-TOC}

## Criteria

[Human Subjects Research](#human_subjects_research): Yes

[Exempt](#Human_Subjects_exempt): No

[Clinical Trial](#clinical_trial): Yes

[NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII): Yes

## Instructions and Required Information

In the proposal narrative, create a section entitled "Protection of
Human Subjects" and include the following statement below the heading:
"This Human Subjects Research involves an NIH-Defined Phase III Clinical
Trial." (See \"[NIH defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII)\" in
[Definitions](#definitions).)

Create a subheading for each of the following items. Follow the
instructions that are identified for each of the following topics and
provide the information that is requested:

Protection of Human Subjects - [Section 4.1 -
4.1.6](#protection-of-human-subjects)

Inclusion of Women and Minorities - [Section
4.2](#inclusion-of-women-and-minorities)

Additional Instructions and Requirements when NIH-Defined Phase III
Clinical Trials are Proposed - [Section
4.2.1](#Human_Subjects_Research_Instruct)

Targeted/Planned Enrollment Table - [Section
4.3](#Human_Subjects_Research_Instruct)

Inclusion of Children - [Section 4.4](#inclusion-of-children)

If the research involves collaborating sites, provide the information
identified above for each participating site.

# 4. Instructions Pertaining to Non-Exempt Human Subjects Research

In your proposal narrative, **create a section entitled "Human
Subjects."** Although no specific page limitation applies to this
section of the proposal, be succinct. Scientific Review Groups will
assess each proposal as being acceptable or unacceptable with regard to
the protection of human subjects. DHHS regulations and policies
governing human subjects research are described and referenced in
Section 5 below. **Use subheadings** to address the issues listed under
items 4.1-4.4 below. If your research includes a clinical trial, include
a subheading \"Data and Safety Monitoring Plan\" and follow the
instructions in 4.2 below. If your research includes an NIH-Defined
Phase III Clinical Trial, follow the additional instructions in 4.2.1
below.

## 4.1 Protection of Human Subjects

### 4.1.1 Risks to Human Subjects

a\. ***Human Subjects Involvement and Characteristics***

-   Describe the proposed involvement of human subjects in the work
    outlined in the Human Subjects Research section.

-   Describe the characteristics of the subject population, including
    their anticipated number, age range, and health status.

-   Identify the criteria for inclusion or exclusion of any
    subpopulation.

-   Explain the rationale for the involvement of special classes of
    subjects, such as fetuses, neonates, pregnant women, children,
    prisoners, institutionalized individuals, or others who may be
    considered vulnerable populations. Note that \'prisoners\' includes
    all subjects involuntarily incarcerated (for example, in detention
    centers) as well as subjects who become incarcerated after the study
    begins.

-   List any collaborating sites where human subjects research will be
    performed, and describe the role of those sites and collaborating
    investigators in performing the proposed research.

b\. ***Sources of Materials***

-   Describe the research material obtained from living individuals in
    the form of specimens, records, or data.

-   Describe any data that will be collected from human subjects for the
    project(s) described in the application.

-   Indicate who will have access to individually identifiable private
    information about human subjects.

-   Provide information about how the specimens, records, or data are
    collected and whether material or data will be collected
    specifically for the proposed research project.

c\. ***Potential Risks***

-   Describe the potential risks to subjects (physical, psychological,
    financial, legal, or other), and assess their likelihood and
    seriousness to the subjects.

-   Where appropriate, describe alternative treatments and procedures,
    including the risks and potential benefits of the alternative
    treatments and procedures, to participants in the proposed research.

### 4.1.2 Adequacy of Protection Against Risks

a\. ***Recruitment and Informed Consent***

-   Describe plans for the recruitment of subjects (where appropriate)
    and the process for obtaining informed consent. If the proposed
    studies will include children, describe the process for meeting
    requirements for parental permission and child assent.

-   Include a description of the circumstances under which consent will
    be sought and obtained, who will seek it, the nature of the
    information to be provided to prospective subjects, and the method
    of documenting consent. If a waiver of some or all of the elements
    of informed consent will be sought, provide justification for the
    waiver. Informed consent document(s) need not be submitted to the
    PHS agencies unless requested.

b\. ***Protections Against Risk***

-   Describe planned procedures for protecting against or minimizing
    potential risks, including risks to privacy of individuals or
    confidentiality of data, and assess their likely effectiveness.

-   Research involving vulnerable populations, as described in the DHHS
    regulations, Subparts B-D must include additional protections. Refer
    to DHHS regulations, and OHRP guidance:

-   Additional Protections for Pregnant Women, Human Fetuses and
    Neonates:
    <http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartb>

-   Additional Protections for Prisoners:
    <http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartc>

    OHRP Subpart C Guidance:
    <http://www.hhs.gov/ohrp/policy/index.html#prisoners>

-   Additional Protections for Children:
    <http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd>

    OHRP Subpart D Guidance: <http://www.hhs.gov/ohrp/children/>

-   Where appropriate, discuss plans for ensuring necessary medical or
    professional intervention in the event of adverse effects to the
    subjects. Studies that involve clinical trials (biomedical and
    behavioral intervention studies) must include a general description
    of the plan for data and safety monitoring of the research and
    adverse event reporting to the IRB, the NIH and others, as
    appropriate, to ensure the safety of subjects.

### 4.1.3 Potential Benefits of the Proposed Research to Human Subjects and Others

-   Discuss the potential benefits of the research to research
    participants and others.

-   Discuss why the risks to subjects are reasonable in relation to the
    anticipated benefits to research participants and others.

### 4.1.4 Importance of the Knowledge to be Gained 

-   Discuss the importance of the knowledge gained or to be gained as a
    result of the proposed research.

-   Discuss why the risks to subjects are reasonable in relation to the
    importance of the knowledge that reasonably may be expected to
    result.

NOTE: Test articles (investigational new drugs, devices, or biologics)
including test articles that will be used for purposes or administered
by routes that have not been approved for general use by the Food and
Drug Administration (FDA) must be named. State whether the 30-day
interval between submission of applicant certification to the FDA and
its response has elapsed or has been waived and/or whether use of the
test article has been withheld or restricted by the FDA, and/or the
status of requests for an Investigational New Drug (IND) or
Investigational Device Exemption (IDE) covering the proposed use of the
test article in the Research Plan.

### 4.1.5 Data and Safety Monitoring Plan

The NIH Data and Safety Monitoring Plan Policy is described and
referenced in [Section
5.3](#data-and-safety-monitoring-plans-for-clinical-trials).

-   If the research includes a clinical trial, create a heading entitled
    \"Data and Safety Monitoring Plan.\"

-   Provide a general description of a monitoring plan that you plan to
    establish as the overall framework for data and safety monitoring.
    Describe the entity that will be responsible for monitoring and the
    process by which Adverse Events (AEs) will be reported to the
    Institutional Review Board (IRB), the funding I/C, the NIH Office of
    Biotechnology Activities (OBA), and the Food and Drug Administration
    (FDA) in accordance with Investigational New Drug (IND) or
    Investigational Device Exemption (IDE) regulations. Be succinct.
    Contact the FDA (<http://www.fda.gov/>) and also see the following
    websites for more information related to IND and IDE requirements:\
    <http://www.access.gpo.gov/nara/cfr/waisidx_01/21cfr312_01.html>
    (IND)\
    <http://www.access.gpo.gov/nara/cfr/waisidx_01/21cfr812_01.html>
    (IDE)

-   The frequency of monitoring will depend on potential risks,
    complexity, and the nature of the trial; therefore, a number of
    options for monitoring trials are available. These can include, but
    are not limited to, monitoring by a:

> a\. PD/PI (required)
>
> b\. Institutional Review Board (IRB) (required)
>
> c\. Independent individual/safety officer
>
> d\. Designated medical monitor
>
> e\. Internal Committee or Board with explicit guidelines
>
> f\. Data and Safety Monitoring Board (DSMB). NIH specifically requires
> the establishment of Data and Safety Monitoring Boards (DSMBs) for
> multi-site clinical trials involving interventions that entail
> potential risk to the participants, and generally for Phase III
> clinical trials. Although Phase I and Phase II clinical trials may
> also use DSMBs, smaller clinical trials may not require this oversight
> format, and alternative monitoring plans may be appropriate.

-   A detailed Data and Safety Monitoring Plan must be submitted to the
    applicant\'s IRB and subsequently to the funding IC for approval
    prior to the accrual of human subjects
    (<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html>).
    For additional guidance on creating this Plan, see the above
    reference.

### 4.1.6 ClinicalTrials.gov Requirements

Public Law 110-85 mandates registration and results reporting of
\"applicable clinical trials\" in ClinicalTrials.gov. Under the statute
these trials generally include: (1) [Trials of Drugs and
Biologics]{.underline}: Controlled, clinical investigations, other than
Phase 1 investigations, of a product subject to FDA regulation; and (2)
[Trials of Devices]{.underline}: Controlled trials with health outcomes,
other than small feasibility studies, and pediatric postmarket
surveillance. Review the statutory definition of applicable clinical
trial to identify if registration is required to comply with the law
(See [PL
110-85](http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf),
Section 801(a), adding new 42 U.S.C. 282(j)(1)(A)
(<http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf>)).

NIH encourages registration of ALL trials whether required under the law
or not.

Registration is accomplished at the ClinicalTrials.gov Protocol
Registration System Information Website
(<http://prsinfo.clinicaltrials.gov/>). A unique identifier called an
NCT number will be generated during the registration process.

For new and renewal (competing) applications that include ongoing
clinical trials which require registration and results reporting,
provide the NCT number/s, Brief Title/s (as defined by
ClinicalTrials.gov, see <http://prsinfo.clinicaltrials.gov/>), and the
identity of the responsible party (or parties) in the human subjects
section of the Research Plan under a section heading entitled
ClinicalTrials.gov. The entity responsible for registering is the
"responsible party." The statute defines the responsible party as:

\(1\) the sponsor of the clinical trial (as defined in 21 C.F.R. 50.3)
(<http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/cfr_2003/aprqtr/pdf/21cfr50.3.pdf>),
or\
\
(2) the principal investigator of such clinical trial if so designated
by a sponsor, grantee, contractor, or awardee (provided that "the
principal investigator is responsible for conducting the trial, has
access to and control over the data from the clinical trial, has the
right to publish the results of the trial, and has the ability to meet
all of the requirements" for submitting information under the law)
(<http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf>).
*See* PL 110-85, Section 801(a), (adding new 42 U.S.C.
282(j)(1)(A)(ix)).

If a new applicable trial is proposed, under the heading
ClinicalTrials.gov include a statement that the application includes a
trial which requires registration in ClinicalTrials.gov. The signature
on the application of the Authorized Organizational Representative
assures compliance for the registration of any such trial.

## 4.2 Inclusion of Women and Minorities

Create a section heading entitled \"Inclusion of Women and Minorities\"
and place it immediately following the "Protection of Human Subjects\"
section. Although no specific page limitation applies to this section of
the proposal, be succinct. The NIH Policy on the Inclusion of Women and
Minorities in Clinical Research is described and referenced in [Section
5.6](#nih-policy-on-the-inclusion-of-women-and-minorities-in-clinical-research).

Scientific Review Groups will assess each proposal as being acceptable
or unacceptable with regard to the protection of human subjects.

In this section of the Research Plan, address, at a minimum, the
following four points:

1\. The targeted/planned distribution of subjects by sex/gender and
racial/ethnic groups for each proposed study or protocol using the
format in the Targeted/Planned Enrollment Table. (Instructions for
completing this table are provided below in 4.3.) If using existing
specimens and/or data without access to information on the distribution
of women and minorities, so state and explain the impact on the goals of
the research as part of the rationale that inclusion is inappropriate
(item 3 below). Alternatively, describe the women and minority
composition of the population base from whom the specimens and/or data
will be obtained. Include the Targeted/Planned Enrollment Table in this
section.

2\. A description of the subject selection criteria and rationale for
selection of sex/gender and racial/ethnic group members in terms of the
scientific objectives and proposed study design. The description may
include, but is not limited to, information on the population
characteristics of the disease or condition under study.

3\. A compelling rationale for proposed exclusion of any sex/gender or
racial/ethnic group (see examples below).

4\. A description of proposed outreach programs for recruiting
sex/gender and racial/ethnic group members as subjects.

Examples of acceptable justifications for exclusion of:

A. ***One gender:***

1\. One gender is excluded from the study because:

-   inclusion of these individuals would be inappropriate with respect
    to their health;

-   the research question addressed is relevant to only one gender;

-   evidence from prior research strongly demonstrates no difference
    between genders; or

-   sufficient data already exist with regard to the outcome of
    comparable studies in the excluded gender, and duplication is not
    needed in this study.

2\. One gender is excluded or severely limited because the purpose of
the research constrains the applicant\'s selection of study subjects by
gender (e.g., uniquely valuable stored specimens or existing datasets
are single gender; very small numbers of subjects are involved; or
overriding factors dictate selection of subjects, such as matching of
transplant recipients, or availability of rare surgical specimens).

3\. Gender representation of specimens or existing datasets cannot be
accurately determined (e.g., pooled blood samples, stored specimens, or
data-sets with incomplete gender documentation are used), and this does
not compromise the scientific objectives of the research.

B. ***Minority groups or subgroups:***

1\. Some or all minority groups or subgroups are excluded from the study
because:

-   inclusion of these individuals would be inappropriate with respect
    to their health;

-   the research question addressed is relevant to only one racial or
    ethnic group;

-   evidence from prior research strongly demonstrates no differences
    between racial or ethnic groups on the outcome variables;

-   a single minority group study is proposed to fill a research gap; or

-   sufficient data already exists with regard to the outcome of
    comparable studies in the excluded racial or ethnic groups and
    duplication is not needed in this study.

2\. Some minority groups or subgroups are excluded or poorly represented
because the geographical location of the study has only limited numbers
of these minority groups who would be eligible for the study, and the
investigator has satisfactorily addressed this issue in terms of:

-   the size of the study;

-   the relevant characteristics of the disease, disorder or condition;
    or

-   the feasibility of making a collaboration or consortium or other
    arrangements to include representation.

3\. Some minority groups or subgroups are excluded or poorly represented
because the purpose of the research constrains the applicant\'s
selection of study subjects by race or ethnicity (e.g., uniquely
valuable cohorts, stored specimens or existing datasets are of limited
minority representation, very small numbers of subjects are involved, or
overriding factors dictate selection of subjects, such as matching of
transplant recipients or availability of rare surgical specimens).

4\. Racial or ethnic origin of specimens or existing datasets cannot be
accurately determined (e.g., pooled blood samples, stored specimens or
data sets with incomplete racial or ethnic documentation are used) and
this does not compromise the scientific objectives of the research.

### 4.2.1 Additional Instructions and Requirements When NIH-Defined Phase III Clinical Trials Are Proposed

If the proposed research includes an [NIH-Defined Phase III Clinical
Trial](#Human_Subjects_Defs_NIH_PhaseIII), the section on Inclusion of
Women and Minorities also must address whether clinically important
sex/gender and/or race/ethnicity differences are expected from the
intervention effect. The discussion may include supporting evidence
and/or data derived from animal studies, clinical observations,
metabolic studies, genetic studies, pharmacology studies, and
observational, natural history, epidemiology and other relevant studies.
The discussion of expected sex/gender and/or race/ethnicity differences
in intervention effect must include selection and discussion of one of
the following analysis plans:

-   Plans to conduct valid analyses to detect significant differences in
    intervention effect among sex/gender and/or racial/ethnic subgroups
    when prior studies strongly support these significant differences
    among subgroups, *or*

-   Plans to include and analyze sex/gender and/or racial/ethnic
    subgroups when prior studies strongly support no significant
    differences in intervention effect between subgroups.
    (Representation of sex/gender and racial/ethnic groups is not
    required as subject selection criteria, but inclusion is
    encouraged.), *or*

-   Plans to conduct valid analyses of the intervention effect in
    sex/gender and/or racial/ethnic subgroups (without requiring high
    statistical power for each subgroup) when the prior studies neither
    support nor negate significant differences in intervention effect
    between subgroups.

## 4.3 Instructions for Completing the Targeted/Planned Enrollment Tables for Reporting Race and Ethnicity Data for Subjects in Clinical Research

The NIH Policy on Reporting Race and Ethnicity Data for Subjects in
Clinical Research is described and referenced in [Section
5.8](#nih-policy-on-reporting-race-and-ethnicity-data-subjects-in-clinical-research).

A. New Proposals

All new clinical research studies should collect and report information
on participants with respect to two categories of ethnicity and five
categories of race. The Inclusion Enrollment Report
(<http://grants.nih.gov/grants/funding/424/SF424R-R_enrollmentreport.doc>)
for reporting summary data on participants to NIH includes two
categories of ethnicity and five categories of race and is based on the
Office of Management and Budget (OMB) reporting standards for data on
race and ethnicity. Investigators should review the instructions and
Frequently Asked Questions about using the Enrollment Table format at
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html>.

When reporting these data in the aggregate, investigators should report:
(a) the number of research participants in each ethnic category; (b) the
number of research participants who selected only one category for each
of the five racial categories; (c) the total number of research
participants who selected multiple racial categories reported as the
"number selecting more than one race," and (d) the number of research
participants in each racial category who are Hispanic or Latino.
Investigators may provide the detailed distributions, including all
possible combinations, of multiple responses to the racial designations
as additional information. However, more detailed data should be
compiled in a way that they can be reported using the required
categories.

**Instructions for Completing Targeted/Planned Enrollment Table**

(<http://grants.nih.gov/grants/funding/424/SF424R-R_enrollment.doc>)

Provide the study title.

The "Total Planned Enrollment" means the number of subjects that are
expected to be enrolled in the study, consistent with the definition in
ClinicalTrials.gov.

The "Total Planned Enrollment" will be reported in two ways in the
table: by "Ethnic Category" and by "Racial Categories."

"Ethnic Category": Provide the numeric distribution of the Total Planned
Enrollment according to ethnicity and sex/gender in the top part of the
table.

"Racial Categories": Provide the numeric distribution of the Total
Planned Enrollment, this time by racial categories and sex/gender, in
the bottom part of the table. Note that Hispanic is an ethnic, not a
racial, category.

If there is more than one study/protocol, provide a separate table for
each.

List any proposed racial/ethnic subpopulations below the table.

**Submitting Applications or Proposals Using Existing Data in Clinical
Research with No Plans for Collecting New/Additional Data:**

Investigators are instructed to provide plans for the total number of
subjects proposed for the study and to provide the distribution by
ethnic/racial categories and sex/gender using the Targeted/Planned
Enrollment Table. Under these circumstances, investigators are not
required to re-contact subjects solely to comply with the newly revised
categories.

**If Data Collection is Ongoing, Such that New Human Subjects Will be
Enrolled and/or Additional Data Will be Collected from Human Subjects:**

Investigators should report ethnicity/race and sex/gender sample
composition using the Inclusion Enrollment Report.

**If Data Collection is Complete, Such that No New/Additional Subject
Contact is Planned**:

Investigators should use the Inclusion Enrollment Report.

**Research Conducted at Foreign Sites:**

If proposed studies involve a foreign site, investigators are encouraged
to design culturally sensitive and appropriate data collection
instruments that allow research participants to self-identify their
racial and ethnic affiliation. However, these items should be designed
in a way that they can be aggregated into the OMB-required categories.
Also, the investigator can report on any racial/ethnic subpopulations by
listing this information in an attachment to the required table. This
may be particularly useful when distinctive subpopulations are relevant
to the scientific hypotheses being studied.

When completing the tables that describe research in foreign sites,
investigators should asterisk and footnote the table indicating that
data includes research participants in foreign sites. If the aggregated
data only includes participants in foreign research sites, the
investigator should provide information in one table with an asterisk
and footnote. However, if the study includes both domestic and foreign
sites, the investigator should complete two separate tables -- one for
domestic and another for foreign participants.

B. Progress Reports

The Inclusion Enrollment Report
(<http://grants.nih.gov/grants/funding/424/SF424R-R_enrollmentreport.doc>)
must be used for reporting accrual data to the NIH. In annual progress
reports, investigators conducting clinical research are required to
provide the cumulative total enrollment of subjects to-date, showing the
distribution by ethnic/racial categories and sex/gender on the Inclusion
Enrollment Report, and update the Targeted/Planned Enrollment Table as
needed.

## 4.4 Inclusion of Children

The NIH Policy on Inclusion of Children is referenced and described in
[Section 5.7](#nih-policy-on-inclusion-of-children). Instructions for
this item under the "Human Subjects" heading of the Research Plan are as
follows:

-   Create a section entitled "Inclusion of Children" and place it
    immediately following the Targeted/Planned Enrollment Table.

-   For the purpose of implementing these guidelines, a *child* is
    defined as an individual under the age of 21 years (for additional
    information see
    <http://grants.nih.gov/grants/funding/children/children.htm> and
    <http://grants.nih.gov/grants/guide/notice-files/not98-024.html>).

-   Provide either a description of the plans to include children, or,
    if children will be excluded from the proposed research,
    application, or proposal, present an acceptable justification for
    the exclusion (see below).

-   If children are included, the description of the plan should include
    a rationale for selecting a specific age range of children. The plan
    also must include a description of the expertise of the
    investigative team for dealing with children at the ages included,
    of the appropriateness of the available facilities to accommodate
    the children, and the inclusion of a sufficient number of children
    to contribute to a meaningful analysis relative to the purpose of
    the study.

-   Scientific Review Groups will assess each proposal as being
    acceptable or unacceptable with regard to the age-appropriate
    inclusion or exclusion of children in the research project.

-   When children are involved in research, the Additional Protections
    for Children Involved as Subjects in Research ([45 CFR Part 46
    Subpart D (http://www.hhs.gov/ohrp/humansubjects/guidance/
    45cfr46.htm#subpartd)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd))
    apply and must be addressed under the Protections Against Risk
    subheading (4.1.2.b).

**Justifications for Exclusion of Children**

For the purposes of this policy, all individuals under 21 are considered
children; however, exclusion of any specific age group, such as
individuals under 18, should be justified in this section. It is
expected that children will be included in all clinical research unless
one or more of the following exclusionary circumstances can be fully
justified:

1\. The research topic to be studied is not relevant to children.

2\. There are laws or regulations barring the inclusion of children in
the research.

3\. The knowledge being sought in the research is already available for
children or will be obtained from another ongoing study, and an
additional study will be needlessly redundant. Documentation of other
studies justifying the exclusions should be provided. NIH program staff
can be contacted for guidance on this issue if the information is not
readily available.

4\. A separate, age-specific study in children is warranted and
preferable. Examples include:

a\. The condition is relatively rare in children, as compared to adults
(in that extraordinary effort would be needed to include children,
although in rare diseases or disorders where the applicant has made a
particular effort to assemble an adult population, the same effort would
be expected to assemble a similar child population with the rare
condition); or

b\. The number of children is limited because the majority are already
accessed by a nationwide pediatric disease research network; or

c\. Issues of study design preclude direct applicability of hypotheses
and/or interventions to both adults and children (including different
cognitive, developmental, or disease stages or different age-related
metabolic processes). While this situation may represent a justification
for excluding children in some instances, consideration should be given
to taking these differences into account in the study design and
expanding the hypotheses tested, or the interventions planned, to allow
inclusion of children rather than excluding them.

5\. Insufficient data are available in adults to judge potential risk in
children (in which case one of the research objectives could be to
obtain sufficient adult data to make this judgment). Although children
usually should not be the initial group to be involved in research
studies, in some instances, the nature and seriousness of the illness
may warrant their participation earlier based on careful risk and
benefit analysis.

6\. Study designs are aimed at collecting additional data on
pre-enrolled adult study subjects (e.g., longitudinal follow-up studies
that did not include data on children).

7\. Other special cases can be justified by the investigator and found
acceptable to the review group and the Institute Director.

# 5. Human Subjects Research Policy

Human Subjects Research Policy includes DHHS regulations for the
protection of human subjects and the following NIH policies related to
human subjects research.

## 5.1 Protection of Human Subjects

The Department of Health and Human Services (DHHS) regulations for the
protection of human subjects provide a systematic means, based on
established, internationally recognized ethical principles, to safeguard
the rights and welfare of individuals who participate as subjects in
research activities supported or conducted by the DHHS. The regulations
stipulate that the awardee organization, whether domestic or foreign,
bears responsibility for safeguarding the rights and welfare of human
subjects in DHHS-supported research activities. The regulations require
that offeror organizations proposing to involve human subjects in
nonexempt research hold a Federal-wide Assurance (FWA) with the Office
for Human Research Protections (OHRP), and establish appropriate
policies and procedures for the protection of human subjects. These
regulations, [45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm),
Protection of Human Subjects, are available from OHRP, Department of
Health and Human Services, The Tower Building, 1101 Wootton Parkway,
Suite 200, Rockville, MD; telephone: 1-866-447-4777 (toll-free) or (240)
453-6900; email: <ohrp@osophs.dhhs.gov>.

Nonexempt research involving human subjects may only be conducted under
a DHHS award if the organization is operating in accord with an approved
FWA and provides verification that an Institutional Review Board (IRB)
that is registered under the specific FWA has reviewed and approved the
proposed activity in accordance with the DHHS regulations. No award to
an individual will be made unless that individual is affiliated with an
assured organization that accepts responsibility for compliance with the
DHHS regulations. Foreign offeror organizations must also comply with
the provisions of the regulations unless a determination of equivalent
protections is made in accord with 45 CFR 46.101(h).

Under DHHS regulations to protect human subjects, certain research areas
are [exempt](#Human_Subjects_exempt). However, if an offeror makes
inappropriate designations of the noninvolvement of human subjects or of
exempt categories of research, this may result in delays in the review
of an application or the return of the application without review. The
PHS will make a final determination as to whether the proposed
activities are covered by the regulations or are in an exempt category,
based on the information provided in the Research Plan. With the
exception of research projects that meet the criteria for Exemption 4,
studies that are exempt from the human subjects regulatory requirements
must still address the inclusion of women, minorities and children in
the study design.

Regulations of the Food and Drug Administration (21 CFR 50, 21 CFR 56)
generally apply to biomedical research involving an unapproved drug,
device or biologic and may apply to certain studies of approved
products. Additional information on FDA regulations is available at
<http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm>.
If work falls under FDA\'s regulatory requirements, the grantee must
follow both DHHS and FDA human subject protection regulations.

The *National Institutes of Health Guidelines for Research Involving
Recombinant DNA Molecules (NIH Guidelines)* apply to all projects
(NIH-funded and non NIH-funded) involving recombinant DNA molecules that
are conducted at or sponsored by an institution that receives NIH
support for recombinant DNA research. As defined by the *NIH
Guidelines*, recombinant DNA molecules are either: (1) molecules that
are constructed outside living cells by joining natural or synthetic DNA
segments to DNA molecules that can replicate in a living cell; or (2)
DNA molecules that result from the replication of those described in
(1). The *NIH Guidelines* set forth principles and standards for safe
and ethical conduct of recombinant DNA research and apply to both basic
and clinical research studies. The *NIH Guidelines* should be carefully
reviewed and implemented to ensure that proper biosafety and containment
practices are employed for all projects involving recombinant DNA
research, including review by an Institutional Biosafety Committee that
meets the requirements of the *NIH Guidelines*. Further, the *NIH
Guidelines* include special review and reporting requirements for the
conduct of human gene transfer studies (under Appendix M). Failure to
comply with the *NIH Guidelines* may result in suspension, limitation,
or termination of NIH funds for recombinant DNA research at the
organization or a requirement for NIH prior approval of any or all
recombinant DNA projects at the organization. A copy of *the NIH
Guidelines* is posted at the following URL:
<http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html> and may be
obtained from the NIH Office of Biotechnology Activities, 6705 Rockledge
Drive, Suite 750, Bethesda, MD 20892, 301-496-9838.

Federal requirements to protect human subjects apply to most research on
human specimens (such as cells, blood, and urine), residual diagnostic
specimens, and medical information. Research involving the collection or
study of existing data, documents, records, pathological specimens,
diagnostic specimens, or tissues that are individually identifiable is
considered "research involving human subjects." The NIH Office of
Extramural Research Human Subjects website contains additional
information and Frequently Asked Questions to help investigators
understand how these federal requirements apply to their research. See
<http://grants.nih.gov/grants/policy/hs/index.htm>.

The DHHS regulations require the NIH to evaluate all proposals involving
human subjects
(<http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.120>).
This independent evaluation is conducted at the NIH through the peer
review system and NIH staff review, and, as required, will take into
consideration 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. On the basis of this evaluation, the NIH may approve or
disapprove the proposal, or enter into negotiations to develop an
approvable one.

## 5.2 Vulnerable Populations

Investigators who conduct research involving pregnant women, human
fetuses and neonates, prisoners, or children, must follow the provisions
of the regulations in Subparts B, C, and D of [45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm),
respectively. The subparts describe the additional protections required
for conducting research involving these populations. Relevant
information may be obtained at the OHRP website
(<http://www.hhs.gov/ohrp/policy/index.html>).

REMINDER: DHHS regulations at [45 CFR Part 46, Subpart C
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#
subpartc)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartc)
describe requirements for additional protections for research involving
prisoners as subjects *or* individuals who become prisoners after the
research has started. Refer to:
[[http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm]{.underline}](http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm)
for complete instructions.

[Exemptions 1-6](#Human_Subjects_Exemption_Cat) do **not** apply to
research involving prisoners or subjects who become prisoners (see
[Subpart C
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartc)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartc)).
Although Exemptions 1 and 3-6 apply to research involving children (see
[Subpart D (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#
subpartd)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd)),
[Exemption 2](#Human_Subjects_Exemption2) can only be used for research
involving educational testing or observations of public behavior when
the investigator(s) do not participate in the activities being observed.

## 5.3 Data and Safety Monitoring Plans for Clinical Trials 

For each proposed clinical trial, NIH requires a data and safety
monitoring plan that describes oversight and monitoring to ensure the
safety of participants and the validity and integrity of the data. The
level of monitoring should be commensurate with the risks and the size
and complexity of the clinical trial. Prior to the accrual of human
subjects, a detailed data and safety monitoring plan must be submitted
to the offeror's IRB and to the funding entity for approval. Adverse
Events must be reported to the IRB, the NIH funding Institute or Center,
and other appropriate offices or agencies. This policy requirement is in
addition to any monitoring requirements imposed by [45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
NIH policy specifically requires the establishment of a Data and Safety
Monitoring Board (DSMB) for multi-site clinical trials involving
interventions that entail potential risk to the participants, and
generally for Phase III clinical trials.

## 5.4 IRB Approval

NIH does not require certification of IRB approval of the proposed
research prior to NIH peer review of a proposal. See
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-031.html>.

Following NIH peer review, the offeror organization will be notified of
the need for review and approval of the proposed research by an IRB that
is registered with OHRP. See <http://www.hhs.gov/ohrp/> to register an
IRB. Certification of IRB approval must be sent to the Grants Management
Office identified in the notice requesting documentation. Certification
of IRB review and approval must include: the PHS SBIR proposal number,
title of the project, name of the program director /principal
investigator, date of IRB approval, and appropriate signatures. Grantees
may also use the optional form "Protection of Human Subjects - Assurance
Identification/IRB Certification/Declaration of Exemption (Common Rule)"
(OMB Form No. 0990-0263
<http://www.hhs.gov/ohrp/humansubjects/assurance/OF310.rtf>) to meet
this requirement.

The OHRP has determined that an institution is automatically considered
to be engaged in human subjects research when it receives an NIH award
to support nonexempt human subjects research. See
<http://www.hhs.gov/ohrp/humansubjects/assurance/engage.htm>. All
institutions engaged in human subjects research must obtain a Federal
Wide Assurance (FWA) from OHRP. Instructions for applying for a Federal
Wide Assurance (FWA) are available from the OHRP website at
<http://www.hhs.gov/ohrp/assurances/assurances_index.html>.

Any modifications to the Research Plan in the proposal, required by
either NIH or by the IRB, must be submitted with follow-up certification
of IRB approval to the NIH before the competing award is made. It is the
responsibility of the PD/PI and the offeror organization to submit the
follow-up documentation.

If more than a year will have elapsed between the initial IRB review
date and the anticipated award date, the awarding unit staff shall
require re-review by the IRB prior to award.

## 5.5 Required Education in the Protection of Human Research Participants

NIH requires education on the protection of human research participants
for all individuals identified in PHS applications as Senior/key
Personnel who will be involved in the design or conduct of human
subjects research, before funds are awarded for applications or contract
proposals involving human subjects. For information relating to this
requirement, see the following notices
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html> and
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-061.html>,
and Frequently Asked Questions at:
<http://grants.nih.gov/grants/policy/hs_educ_faq.htm>. Prior to award,
offerors will be required to provide a description of education
completed in the protection of human subjects for all Senior/key
Personnel involved in the design or conduct of human subjects research.
Although NIH does not endorse specific programs, there are curricula
available that can provide guidance or that can be modified to provide
training in this area. See
<http://cme.cancer.gov/clinicaltrials/learning/humanparticipant-protections.asp>
for computer-based training developed for NIH that can be downloaded at
no charge. For information on facilitating education and developing
curricula, see <http://www.nih.gov/sigs/bioethics>.

## 5.6 NIH Policy on the Inclusion of Women and Minorities in Clinical Research

NIH policy requires that women and members of minority groups and their
subpopulations must be included in all NIH-supported biomedical and
behavioral research projects involving [clinical
research](#clinical_research) unless a clear and compelling rationale
and justification establishes to the satisfaction of the relevant IC
Director that inclusion is inappropriate with respect to the health of
the subjects or the purpose of the research. Exclusion under other
circumstances may be made by the Director, NIH, upon the recommendation
of an IC Director based on a compelling rationale and justification.
Cost is not an acceptable reason for exclusion except when the study
would duplicate data from other sources. Women of childbearing potential
should not be routinely excluded from participation in clinical
research. All NIH-supported biomedical and behavioral research involving
human subjects is defined as clinical research. This policy applies to
research subjects of all ages.

The inclusion of women and members of minority groups and their
subpopulations must be addressed in developing a research design
appropriate to the scientific objectives of the study. The Research Plan
should describe the composition of the proposed study population in
terms of sex/gender and racial/ethnic group, and provide a rationale for
selection of such subjects. Such a plan should contain a description of
the proposed outreach programs for recruiting women and minorities as
participants. See
<http://grants.nih.gov/grants/funding/women_min/women_min.htm>.

## 5.7 NIH Policy on Inclusion of Children 

Research involving children (see definition of "[child](#child)") must
comply with the NIH Policy and Guidelines on the Inclusion of Children
in Clinical Research. Investigators should obtain full copies of the
Policy and Guidelines from NIH staff, or from
<http://grants.nih.gov/grants/funding/children/children.htm>.

NIH policy requires that children (i.e., individuals under the age of
21) must be included in all clinical research, conducted or supported by
the NIH unless there are clear and compelling reasons not to include
them. Therefore, proposals for clinical research must include a
description of plans for including children. If children will be
excluded from the research, the proposal must present an acceptable
justification for the exclusion.

The involvement of children as subjects in research must be in
compliance with all applicable subparts of [45 CFR Part 46
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)](http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm)
as well as with other pertinent Federal laws and regulations.

IRBs have special review requirements to protect the well-being of
children who participate in research. These requirements relate to risk,
benefit, parental/guardian consent, and assent by children, and to
research involving children who are wards of the state or of another
institution. The local IRB approves research that satisfies the
conditions set forth in the regulations.

## 5.8 NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical Research

The Office of Management and Budget (OMB)
(<http://www.whitehouse.gov/omb/fedreg/ombdir15.html>) defines minimum
standards for maintaining, collecting and presenting data on race and
ethnicity for all Federal reporting agencies (including NIH). The
standards were revised in 1997 and include two ethnic categories
(Hispanic or Latino and Not Hispanic or Latino) and five racial
categories (American Indian or Alaska Native, Asian, Black or African
American, Native Hawaiian or Other Pacific Islander, and White). Reports
of data on race and ethnicity shall use these categories. The categories
in this classification are social-political constructs and should not be
interpreted as being anthropological in nature. NIH is required to use
these definitions to allow comparisons to other federal databases,
especially the census and national health databases. The following
definitions apply to the minimum standards for the ethnic and racial
categories.

#### Ethnic Categories: {#ethnic-categories .Subhead---No-TOC}

**Hispanic or Latino:** A person of Cuban, Mexican, Puerto Rican, South
or Central American, or other Spanish culture or origin, regardless of
race. The term, "Spanish origin," can be used in addition to "Hispanic
or Latino."

**Not Hispanic or Latino**

#### Racial Categories:  {#racial-categories .Subhead---No-TOC}

**American Indian or Alaska Native:** A person having origins in any of
the original peoples of North, Central, or South America, and who
maintains tribal affiliation or community attachment.

**Asian:** A person having origins in any of the original peoples of the
Far East, Southeast Asia, or the Indian subcontinent including, for
example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the
Philippine Islands, Thailand, and Vietnam. (Note: Individuals from the
Philippine Islands have been recorded as Pacific Islanders in previous
data collection strategies.)

**Black or African American:** A person having origins in any of the
black racial groups of Africa. Terms such as "Haitian" or "Negro" can be
used in addition to "Black or African American."

**Native Hawaiian or Other Pacific Islander:** A person having origins
in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific
Islands.

**White:** A person having origins in any of the original peoples of
Europe, the Middle East, or North Africa.

**Ethnic/Racial Subpopulations:** In addition to OMB ethnic and racial
categories, NIH uses the following definition for ethnic/racial
subpopulations:

Subpopulations: Each ethnic/racial group contains subpopulations that
are delimited by geographic origins, national origins, and/or cultural
differences. It is recognized that there are different ways of defining
and reporting racial and ethnic subpopulation data. The subpopulation to
which an individual is assigned depends on self-reporting of specific
origins and/or cultural heritage. Attention to subpopulations also
applies to individuals who self identify with more than one race. These
ethnic/racial combinations may have biomedical, behavioral, and/or
social-cultural implications related to the scientific question under
study.

#### Guidance on Collecting Race and Ethnicity Data from Human Subjects {#guidance-on-collecting-race-and-ethnicity-data-from-human-subjects .Subhead---No-TOC}

When an investigator is planning to collect data on ethnicity and race,
the categories identified above should be used. The collection of
greater detail is encouraged, for example on ethnic/racial
subpopulations. However, any collection that uses more detail must be
designed in a way that data can be aggregated into these minimally
required categories. Use self-report or self-identification to collect
this information by asking two separate questions -- one on ethnicity
and one on race. Collect ethnicity information first followed by the
question on race and provide subjects with the option to select more
than one racial category. An example of a format for collecting
information from study subjects in the US that meets the OMB
requirements can be found in the Ethnic Origin and Race section of the
Personal Data Form Page
<http://grants.nih.gov/grants/funding/phs398/phs398.html> in the PHS
398.

See NIH Policy on [Inclusion of Women and
Minorities](#nih-policy-on-the-inclusion-of-women-and-minorities-in-clinical-research)
and <http://grants.nih.gov/grants/funding/women_min/women_min.htm>.

## 5.9 Research on Transplantation of Human Fetal Tissue

In signing the proposal Cover Page, the Authorized Organizational
Representative/Corporate Official of the offeror organization certifies
that if research on the transplantation of human fetal tissue is
conducted, the offeror organization will make available, for audit by
the Secretary, DHHS, the physician statements and informed consents
required by section 498A (b)(2) and (c) of the Public Health Service
Act, 42 U.S.C. 289g (b)(2) and (c), or ensure DHHS access to those
records, if maintained by an entity other than the offeror organization.

## 5.10 Research Using Human Embryonic Stem Cells

In signing the proposal Cover Page, the Authorized Organizational
Representative/Corporate Official of the offeror organization certifies
that if research using human embryonic stem cells is proposed, the
offeror organization will be in compliance with the "Notice of Extended
Receipt Date and Supplemental Information Guidance for Applications
Requesting Funding that Proposes Research with Human Embryonic Stem
Cells"
(<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-006.html>).
See <http://stemcells.nih.gov/index.asp> for additional information on
stem cells, and <http://stemcells.nih.gov/policy/guidelines.asp> for
Federal policy statements and guidelines on federally funded stem cell
research.

## 5.11 ClinicalTrials.gov Requirements

In signing the proposal Cover Page, the Authorized Organizational
Representative/Corporate Official of the offeror organization certifies
that if the research is an applicable clinical trial under Public Law
110-85, the offeror organization will be in compliance with the
registration and reporting requirements of Public Law 110-85, if
applicable
([http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=
f:publ085.110.pdf](http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf)).
The law, enacted 09/27/2007, amends the Public Health Service Act to
expand the scope of clinical trials that must be registered in
ClinicalTrials.gov. It also increases the number of registration fields
that must be submitted, requires certain results information to be
included, and sets penalties for noncompliance.

The trials that must be registered are called "applicable clinical
trials." Under the statute these trials generally include: (1) Trials of
Drugs and Biologics: Controlled, clinical investigations, other than
Phase 1 investigations, of a product subject to FDA regulation; and (2)
Trials of Devices: Controlled trials with health outcomes, other than
small feasibility studies, and pediatric postmarket surveillance. NIH
encourages registration of ALL trials whether required under the law or
not.

For additional information see NIH Guide Notices at
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html> and
<http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-023.html>.

[]{#Human_Subjects_Research_Instruct .anchor}