MEASUREMENT TOOLS FOR ALTERED AUTONOMIC FUNCTION IN SPINAL CORD INJURY AND 
DIABETES: SBIR/STTR

RELEASE DATE:  July 1, 2004

RFA NUMBER:   RFA-HD-04-018 

EXPIRATION DATE:  October 22, 2004

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)  

COMPONENTS OF PARTICIPATING ORGANIZATION: 
National Institute of Child Health and Human Development (NICHD) 
 (http://www.nichd.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.865, 93.847

LETTER OF INTENT RECEIPT DATE: September 21, 2004
APPLICATION RECEIPT DATE: October 21, 2004  

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Project Period and Amount of Award
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

NOTICE:  This Request for Application (RFA) must be read in conjunction with 
the current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, CENTERS 
FOR DISEASE CONTROL AND PREVENTION, and FOOD AND DRUG ADMINISTRATION FOR SMALL 
BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER 
(STTR) GRANT APPLICATIONS.  The solicitation (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf [PDF] or 
http://grants.nih.gov/grants/funding/sbirsttr1/index.doc [MS Word]) contains 
information about the SBIR and STTR programs, regulations governing the 
programs, and instructional information for submission. All of the 
instructions within the SBIR/STTR Omnibus Solicitation apply with the 
following exceptions: 

o Special receipt date  
o Initial review convened by the NICHD Division of Scientific Review    

PURPOSE OF THIS RFA

The National Institute of Child Health and Human Development (NICHD) and the 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
invite small business grant applications to conduct research on measurement 
tools or devices for altered autonomic functions in persons with spinal cord 
injury (SCI) or diabetes mellitus. Critical disruptions or imbalances of 
autonomic function can result from SCI and diabetes and lead to serious, long-
term conditions that negatively impact on survival, quality of life and 
neuronal repair after SCI. Although there has been an ongoing need for 
improved measurement tools or devices for changes in autonomic function, 
productive research in this area has been both difficult and nominal. 
Scientists and/or engineers are encouraged to address this underserved area 
with innovative research and technology for the development of user-friendly 
and reasonably priced tools and devices that are specifically designed for the 
clinic, laboratory and/or residence and will enable detection and/or 
assessment of changes in autonomic functions. These measurement tools could 
also be used for clinical trials and for the detection or assessment of other 
medical conditions. Approaches may include animal or human subject models and 
may focus on one or more specific autonomic functions. Applicants are strongly 
encouraged to include appropriate bioengineering and clinical collaborations 
to achieve clinically relevant tools or devices. Personnel with appropriate 
expertise should be involved in all phases of the proposed effort, including 
development of initial concepts and approaches, design of the tool or device, 
and fabrication and construction or validation of useful clinical measurement 
tools or devices for individuals with autonomic neuropathy.

RESEARCH OBJECTIVES

Background 

The autonomic nervous system (ANS) innervates every organ and regulates a vast 
array of functions, such as blood flow and pressure, body temperature, stress 
responses, and control for reflex responses via sensory messages from the skin 
and internal organs to the brain. Dysfunction of ANS can, therefore, manifest 
in the cardiovascular system as orthostatic hypotension, hypertension, and 
silent myocardial ischemia, in the gastrointestinal system as nausea, 
vomiting, constipation, and diarrhea, and in the genitourinary system as 
bladder and erectile dysfunction. Both spinal cord injury and diabetes can 
lead to autonomic dysfunction from different etiologies, but with overlapping 
signs and symptoms. 

The incidence of spinal cord injuries (SCI) is approximately 10,000 cases per 
year in the United States, with an increasing prevalence as persons with SCI 
survive longer and reach older ages. The spinal cord is an important regulator 
of the ANS and its injury can lead to an imbalance between the "fight or 
flight" activities of the sympathetic system and the "rest and digest" 
activities of the parasympathetic systems. SCI can result in secondary 
complications that include potentially life-threatening conditions such as 
autonomic dysreflexia with increased blood pressure, sweating, and other 
elevated autonomic reflexes. The responsiveness and timeliness of acute and 
chronic medical management of secondary complications can greatly affect 
patient outcome and the severity of the disabilities over time. Improved and 
more appropriate tools and devices that are designed for use in the clinic or 
residence could enable this medical management. An example of a beneficial 
tool would be a device designed for the clinic to accurately measure blood 
flow within the spinal cord for the purpose of assessing the environmental 
milieu over time and the changes in conditions that may affect dynamic 
processes such as neuronal repair and degeneration.

Over 18 million Americans have diabetes and are at risk of developing 
complications from hyperglycemia and associated conditions. A common 
complication of diabetes is autonomic neuropathy which can produce symptoms of 
delayed gastric emptying, diarrhea, constipation, urine retention, and 
erectile dysfunction. For cardiac manifestations, diabetic autonomic 
neuropathy can be relatively asymptomatic, yet its presence can increase the 
five-year mortality rate by five fold for individuals with diabetes. However, 
despite its negative effect on survival and quality of life, diabetic 
autonomic neuropathy is poorly understood, under diagnosed and inadequately 
treated. One cause for this situation is the deficiency of objective measures 
of autonomic function. Standardization of most tests for genitourinary or 
gastrointestinal function or sweating, sympathetic skin responses or pupillary 
reflexes is lacking. Tests for cardiovascular autonomic neuropathy have been 
developed, but only for parasympathetic responses. Clinical studies to better 
understand this condition and clinical trials to test therapeutics need 
reliable, objective outcome measures. 

Although new or improved measurement tools are needed for autonomic 
dysfunction, the amount of productive research in this area is very small as 
reflected by the sparse literature and scarcity of NIH-funded projects. This 
initiative addresses the need for tools and technologies for clinicians (e.g., 
neurologists, endocrinologists, physiatrists, etc.) and researchers to collect 
meaningful measurements of autonomic functions in the clinical setting. 

Scope 

SBIR or STTR grant applications responsive to this initiative may include, but 
are not limited to, research projects with innovative designs or approaches 
for the development of measurement assessment tools or devices. Potential 
products should be capable of reliable and accurate detection, measurement, 
and/or data correlations of autonomic function(s) that are important for the 
care management and treatment of persons with SCI or diabetes. An important 
objective is for the proposed device to be affordable, user friendly, and 
designed for use in an unsupervised environment such as the home or extended 
care facility, a clinic, a medical office, or in a research laboratory. The 
proposed measurement tool may be developed to interface with an existing piece 
of equipment but should be specifically designed to address the needs of 
persons with SCI or diabetes. 

The scope of possible project areas may be broad due to the complexity of SCI 
or diabetes medical issues, but the proposed objectives must be feasible 
within the framework of the SBIR/STTR mechanism. It is acknowledged that to 
meet the objectives for some types of projects, studies may need to address 
complex physiological and technical issues. The design and development of a 
prototype device may require further research on the functional properties to 
be detected or measured, as well as extensive assessment and evaluation of the 
device. The long-range objectives may include approaches using animal models 
and/or human subjects. Proposed products may be directed toward the clinic, 
the home residence, or to the research laboratory with goals that will 
ultimately lead to useful clinical devices. 

Applications with multidisciplinary research projects should demonstrate the 
potential for integrative collaboration/consultation among a team of 
investigators such as bioengineer(s) and clinician(s) with an understanding of 
the complex and dynamic interactions of the autonomic nervous system in 
persons with SCI or diabetes. An informed justification of why and how the 
proposed tool or device could be beneficial for assessing the autonomic 
dysfunction or changes in persons with acute and/or chronic SCI or diabetes is 
expected. Essential to Phase I feasibility applications are adequate 
descriptions and rationale for the identified problem and objectives of the 
proposal, and clearly defined Phase I milestones and prospective Phase II 
goals. Responsive applications will include thorough and detailed descriptions 
and justifications for the chosen approaches, assessment criteria, evaluation 
procedures, and outcome measures for the tool or device. Consideration of 
alternative options for high-risk approaches is recommended. When animal or 
human subjects research is proposed, the application must thoroughly and 
completely address all of the pertinent issues described in the PHS 398 
application instructions. An adequately focused project will have an expected 
scope and completion time that will be compatible with the NIH SBIR/STTR 
program. 

The following are examples of possible measurement tools and focus areas for 
consideration. This list is not meant to be a comprehensive or restrictive 
list of appropriate responses to this RFA, but merely examples of research and 
development needs: 

o Systems that include wearable devices that are specifically designed to 
monitor autonomic functions of individuals in unsupervised environments, such 
as the home and extended care facilities in order to identify clinically 
significant events. 

o Smart, wearable or implantable devices that remotely monitor important 
changes or dysfunction of the autonomic systems and/or provide data for an 
early prediction of pathophysiological changes or clinical outcomes.

o Novel devices (e.g., imaging tools) or innovative modifications to existing 
technology that can detect and measure incremental blood flow changes in 
regions of the spinal cord and/or to correlate blood flow data with other 
physiological changes due to chronic or sporadic autonomic dysfunction.

o Innovative tools that monitor and assess changes in autonomic functions, 
such as postural blood pressure or galvanic skin response, and correlate these 
changes with other physiological parameters during different states of stress, 
activity, spasticity, etc.

o Innovative devices that measure and assess pain during variable states of 
activity, spasticity, or autonomic dysfunction and provide data that can be 
correlated with changes in other autonomic responses.

o Innovative technologies for detecting and monitoring incremental changes in 
sensory function such as progressive gain or loss of sensation, or development 
of musculoskeletal, visceral or neuropathic pain symptoms.

o Novel designs for measurement tools or devices that identify changes in a 
person's condition and indicate ongoing pathophysiological processes as he/she 
develops or ages over time.

o Quantitative tests of autonomic dysfunction that can readily be used in an 
outpatient setting. These tests should give reliable results that are not only 
useful for determining progression in individual patients, but also for 
assessing dysfunction based on standardized results. Development of these 
tests or reliable surrogates for autonomic dysfunction is critical as outcome 
measures for drug trials to gain FDA approval of treatments for this 
condition.

o Tests for detection and/or assessment of early signs of autonomic 
dysfunction. These tests are particularly needed for bladder dysfunction, 
which occurs in 37-50 percent of diabetic individuals, and gastrointestinal 
dysfunction, which has a large range of manifestations. Yet, for both of these 
complications, only complex, specialized tests that measure gross functional 
changes are available.

o A measurement tool for rapid pre-operative screening for cardiovascular 
autonomic neuropathy to identify patients at risk for cardiovascular lability 
and hypothermia. 

Note:  Although an ideal measurement tool for the clinic might have a 
universal design, it may be more feasible or appropriate to target the device 
with regard to specific conditions that may affect autonomic function, such as 
the level or severity of the SCI and the age range of the subjects.

MECHANISM OF SUPPORT

This RFA uses the SBIR and STTR mechanisms, which are set-aside programs. As 
an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project. Future unsolicited, competing continuation 
applications based on this project will compete with all SBIR/STTR 
applications and will be reviewed according to the customary peer review 
procedures.  The anticipated award date is July 1, 2005. Applications that are 
not funded in the competition described in this RFA may be resubmitted as NEW 
SBIR/STTR applications using the standard receipt dates for NEW applications 
described in the current SBIR/STTR Omnibus Solicitation.
   
This RFA uses just-in-time concepts. It also uses the modular budgeting as 
well as the non-modular budgeting formats. Specifically, if you are submitting 
an application budget of $100,000 total costs (direct, F&A and fee) or less, 
use the modular budget format. For applications requesting more than $100,000, 
use the non-modular budget format. Instructions for both are described in the 
current SBIR/STTR Omnibus Solicitation.  This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm. 

Except as otherwise stated in this RFA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, December 2003, 
available at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm. 

Applications may be submitted for support as Phase I STTR (R41) or Phase I 
SBIR (R43) grants. This RFA does NOT include the SBIR/STTR Fast-Track option 
as described in the SBIR/STTR Omnibus Solicitation and does not support Phase 
II SBIR or STTR mechanism. Upon successful completion of Phase I research 
funded by this RFA, the Phase II application must be a logical extension of 
the Phase I research and will be submitted using the standard receipt dates 
for new and competing continuation applications described in the current 
SBIR/STTR Omnibus Solicitation 
(http://grants.nih.gov/grants/funding/sbir.htm#sol).  

PROJECT PERIOD AND AMOUNT OF AWARD

The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines of 
funding support and project duration periods for SBIR and STTR Phase I awards. 
For this RFA, Phase I budgets up to $150,000 total costs per year and time 
periods up to one year for Phase I may be requested. Total costs include 
direct costs, F & A, and fee/profit.

FUNDS AVAILABLE

The NICHD intends to commit approximately $600,000 and the NIDDK intends to 
commit approximately $400,000 in FY 2005 to support five to eight new Phase I 
applications under the SBIR/STTR set-aside funding mechanism.  Because the 
nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award will 
also vary.  Although the financial plans of the ICs provide support for this 
program, awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of meritorious applications. 

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only small business concerns are eligible to submit SBIR/STTR applications.  A 
small business concern is one that, on the date of award for both Phase I and 
Phase II agreements, meets ALL of the criteria as described in the current 
SBIR/STTR Omnibus Solicitation.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to develop 
an application for support.  Individuals from underrepresented racial and 
ethnic groups as well as individuals with disabilities are always encouraged 
to apply for NIH programs.  On an SBIR application, the principal investigator 
must have his/her primary employment (more than 50 percent) with the small 
business at the time of award and for the duration of the project. The PI on 
an STTR application may be employed with the small business concern or the 
participating non-profit research institution as long as s/he has a formal 
appointment with or commitment to the applicant small business concern, which 
is characterized by an official relationship between the small business 
concern and that individual. 

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:  

o Direct your questions about scientific/research issues to:  

Nancy Shinowara, Ph.D.
Spinal Cord & Musculoskeletal Disorders & Assistive Devices Program          
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, 2A03, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6838
FAX: (301) 402-0832
Email:  shinowan@mail.nih.gov 

Teresa L. Z. Jones, M.D. 
Program Director for Diabetes Complications
Division of Diabetes, Endocrinology and Metabolism 
National Institute of Diabetes and Digestive and Kidney Diseases 
6707 Democracy Boulevard, Room 651, MSC 5460
Bethesda, MD 20892-5460
Telephone:  (301) 435-2996
FAX:  (301) 480-3503
Email:  jonest@extra.niddk.nih.gov

o Direct your questions about peer review issues to:  

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 496-1485
FAX: (301) 402-4104
Email:  stretchr@mail.nih.gov 

o Direct your questions about financial or grants management matters to:  

John ‘Chris’ Robey
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6996
FAX: (301) 451-5510
Email:  robeyj@mail.nih.gov 

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes 
the following information:  

o Descriptive title of the proposed research 
o Name, address, and telephone number of the Principal Investigator 
o Names of other key personnel 
o Participating institutions 
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.

The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to:  

Nancy Shinowara, Ph.D.
Spinal Cord & Musculoskeletal Disorders & Assistive Devices Program          
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, 2A03, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6838
FAX: (301) 402-0832
Email:  shinowan@mail.nih.gov 

SUBMITTING AN APPLICATION

The PHS 398 research grant application must be used for all SBIR/STTR Phase I, 
Phase II and Fast-Track applications (new and revised.)  Effective October 1, 
2003, applications must have a Dun and Bradstreet (D&B) Data Universal 
Numbering System (DUNS) number as the Universal Identifier when applying for 
Federal grants or cooperative agreements. The DUNS number can be obtained by 
calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 
of the face page of the PHS 398 form. The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 
398. Helpful information for advice and preparation of the application can be 
obtained at: http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf. The 
NIH will return applications that are not submitted on the 5/2001 version of 
the PHS 398.  For further assistance contact GrantsInfo, Telephone: (301) 435-
0714, Email: GrantsInfo@nih.gov. 

USING THE RFA LABEL:  The RFA label available in the PHS 398 application form 
must be affixed to the bottom of the face page of the application.  Type the 
RFA number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.  The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.doc or 
http://grants.nih.gov/grants/funding/phs398/labels.pdf. 

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of 
the application, including the Checklist, and three signed photocopies, in one 
package to: 

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

To expedite the review process, at the time of submission, send two additional 
copies of the application to:  

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510, MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852 (for express/courier service)

RECEIPT OF APPLICATIONS:  Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an application 
is received after that date, it will be returned to the applicant without 
review.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within eight weeks.

The Center for Scientific Research (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. However, when a previously unfunded application, originally 
submitted as an investigator-initiated application, is to be submitted in 
response to an RFA, it is to be prepared as a NEW application.  That is, the 
application for the RFA must not include an Introduction describing the 
changes and improvements made, and the text must not be marked to indicate the 
changes from the previous unfunded version of the application.  

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NICHD.  Incomplete and/or nonresponsive applications 
will be returned to the applicant without further consideration.  
Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NICHD in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will: 

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the NICHD or NIDDK National Advisory 
Council.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals within the context of the 
SBIR/STTR Program.  The scientific review group will address and consider each 
of the following criteria in assigning the application’s overall score:

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

(1) Significance:  Does the proposed project have commercial potential to lead 
to a marketable product or process? Does this study address an important 
problem? What may be the anticipated commercial and societal benefits of the 
proposed activity? If the aims of the application are achieved, how will 
scientific knowledge be advanced? Does the proposal lead to enabling 
technologies (e.g., instrumentation, software) for further discoveries? Will 
the technology have a competitive advantage over existing/alternate 
technologies that can meet the market needs? 

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Is the proposed plan a sound approach for establishing technical and 
commercial feasibility? Does the applicant acknowledge potential problem areas 
and consider alternative strategies? Are the milestones and evaluation 
procedures appropriate?

(3) Innovation:  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies? Are the aims original and 
innovative? 

(4) Investigators:  Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR? Is the work proposed appropriate to the 
experience level of the Principal Investigator and other researchers, 
including consultants and subcontractors (if any)? Are the relationships of 
the key personnel to the small business and to other institutions appropriate 
for the work proposed? 

(5) Environment:  Is there sufficient access to resources (e.g., equipment, 
facilities)? Does the scientific and technological environment in which the 
work will be done contribute to the probability of success? Do the proposed 
experiments take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements? 

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

o If the application includes a multidisciplinary team of investigators, does 
it demonstrate the potential for integrative collaboration/consultation among 
these investigators and an understanding of the complex and dynamic 
interactions of the autonomic nervous system in persons with SCI and/or 
diabetes? 

o Is there appropriate and informed justification of why and how the proposed 
tool or device could be beneficial for assessing the autonomic dysfunction or 
changes for persons with acute and/or chronic SCI or diabetes? 

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of human 
subjects and protections from research risk relating to their participation in 
the proposed research will be assessed. (See additional information and 
criteria included in the section on Federal Citations, below.)

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH:  The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See additional information and Inclusion Criteria in the sections 
on Federal Citations, below.)
Human Subjects: 

1. Protection of Human Subjects from Research Risks - for all studies 
involving human subjects. See instructions and "Guidance for Preparing the 
Human Subjects Research Section.” If an exemption is claimed, is it 
appropriate for the work proposed? If no exemption is claimed, are the 
applicant's responses to the six required points appropriate? Are human 
subjects placed at risk by the proposed study? If so, are the risks reasonable 
in relation to the anticipated benefits to the subjects and others? Are the 
risks reasonable in relation to the importance of the knowledge that 
reasonably may be expected to be gained? Are the plans proposed for the 
protection of human subjects adequate? 

2. Inclusion of Women Plan - for clinical research only.  Does the applicant 
propose a plan for the inclusion of both genders that will provide their 
appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

3. Inclusion of Minorities Plan - for clinical research only.  Does the 
applicant propose a plan for the inclusion of minorities that will provide 
their appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

4. Inclusion of Children Plan- for all studies involving human subjects.  Does 
the applicant describe an acceptable plan in which the representation of 
children of all ages (under the age of 21) is scientifically appropriate and 
recruitment/retention is addressed realistically? If not, does the applicant 
provide an appropriate justification for their exclusion? 

5. Data and Safety Monitoring Plan – for clinical trials only.  Does the 
applicant describe a Data and Safety Monitoring Plan that defines the general 
structure of the monitoring entity and mechanisms for reporting Adverse Events 
to the NIH and the IRB?

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the required five items described under Vertebrate 
Animals (section f of the Research Plan instructions) will be assessed. 

BIOHAZARDS:  Is the use of materials or procedures that are potentially 
hazardous to research personnel and/or the environment proposed? Is the 
proposed protection adequate? 

ADDITIONAL REVIEW CONSIDERATIONS:  The following items may be also be 
considered by reviewers but will not be included in the determination of 
scientific merit.

BUDGET:  The reasonableness of the proposed budget may be considered.
For all applications, is the percent effort listed for the PI appropriate for 
the work proposed? On applications requesting up to $100,000 total costs, is 
the overall budget realistic and justified in terms of the aims and methods 
proposed? On applications requesting over $100,000 in total costs, is each 
budget category realistic and justified in terms of the aims and methods? 

PERIOD OF SUPPORT:  The appropriateness of the requested period of support in 
relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: September 21, 2004
Application Receipt Date: October 21, 2004
Peer Review Date:  March 2005
Council Review:  June 2005
Earliest Anticipated Start Date:  July 01, 2005

AWARD CRITERIA

Criteria that will be used to make award decisions include: 

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities

REQUIRED FEDERAL CITATIONS

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities involving 
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of 
Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA 
Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained 
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that:  a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them.  

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application.  
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information," 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). 

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH processes 
involving the review, funding, and progress monitoring of grants, cooperative 
agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.  Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas.  This 
RFA is related to one or more of the priority areas.  Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.  

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.


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