NEUROLOGICAL INDICES OF LONG TERM SOLVENT EXPOSURE IN WORKERS 

RELEASE DATE:  September 8, 2003

RFA Number:  RFA-OH-04-001

Department of Health and Human Services

PARTICIPATING INSTITUTES AND CENTERS (ICs): 

National Institute for Occupational Safety and Health, (NIOSH),
Centers for Disease Control and Prevention (CDC)
 (http://www.cdc.gov/niosh/homepage.html)

NOTE:  THE POLICIES, GUIDELINES, TERMS, AND CONDITIONS STATED IN THIS 
ANNOUNCEMENT MAY DIFFER FROM THOSE USED BY THE NIH.

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  CFDA 93.262

LETTER OF INTENT RECEIPT DATE:  November 3, 2003

APPLICATION RECEIPT DATE:  December 17, 2003

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the RFA
o Research Objectives
o Mechanism(s)of Support
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

PURPOSE OF THIS RFA

National Institute for Occupational Safety and Health (NIOSH), Centers for 
Disease Control and Prevention (CDC), announces the availability of fiscal 
year (FY) 2004 funds for grant applications for research on long-term 
occupational exposures to organic solvents and chronic neurologic effects of 
such exposures.  Projects are sought that use quantifiable techniques to 
assess long-term exposures to organic solvents, and use objective diagnostic 
tools to assess the chronic neurologic effects of long-term occupational 
solvent exposure.  Findings from these projects are intended to 
quantitatively document long-term occupational exposure to organic solvents, 
objectively characterize related chronic neurologic outcomes, and analyze 
dose-response relationships between exposures and outcomes.  Studies on non-
occupational exposures to organic solvents are not responsive to this RFA.

RESEARCH OBJECTIVES

Background

Organic solvents are widely used in manufacturing, transportation, and other 
industrial sectors.  These compounds are used in the manufacture of paints, 
dyes, agricultural products, and many other products.  Because organic 
solvents are ingredients of many products such as paints and cleaning agents, 
they are also found in non-manufacturing workplaces and non-work settings.  
Thus, workers can be exposed to a variety of organic solvents at various 
exposure levels throughout their lifetime.  Some workers may have repeated 
exposures to very high organic solvent levels many times during the course of 
their working life. Over the past few decades significant advances have 
occurred in the field of retrospective exposure assessment and in the 
diagnostic tools for assessing neurological impairment. Certain industrial 
sectors such as railroading, painting, manufacturing, and machining have 
significant numbers of workers potentially exposed to organic solvents.  Thus 
workers in these industrial sectors would be appropriate subjects for studies 
of chronic neurological effects related to long-term exposures to organic 
solvents.

Although there is substantial literature on the neurological effects of 
short-term exposures to organic solvents and chronic effects of non-working 
exposures, the neurological effects of long-term exposures in the workplace 
are not well understood.  The neurological symptoms and objective findings of 
workers with long-term exposures to organic solvents are not specific to 
occupational exposures.  They can often be attributed to other causes, such 
as medical conditions and other nonworking-related factors.  Some case 
reports of neurologically impaired workers have used nonspecific symptoms (a 
measurement of effect) as surrogates for exposure, and individuals with 
nonworking-related causes of impairment have not been routinely excluded.  
Some studies have compared neurologically impaired workers who had a history 
of long-term or heavy solvent exposure with healthy unexposed workers.  
Nonworking-related causes in the differential diagnosis of the neurological 
conditions were not routinely ruled out, as would be warranted in medical 
practice.  Such studies are biased to show that exposed persons are 
neurologically impaired and unexposed persons are not neurologically 
impaired.  They do not prove that organic solvent exposure caused the 
neurological condition.  Cross-sectional studies have not clearly established 
an association between long-term solvent exposure and chronic neurological 
impairment, and have not shown evidence of dose-response relationships.  
Often, these types of studies have been limited by inadequate 
characterization of the exposure history.  When studies have used 
neuroimaging techniques such as computed tomography (CT), magnetic resonance 
imaging (MRI), single photon emission computed tomography (SPECT); they have 
compared neurologically impaired exposed workers with healthy unexposed 
workers.  Despite this bias toward finding abnormalities among the exposed 
workers, differences between impaired and healthy workers, when found, were 
not significant, thus leading to questions about the sensitivity of the 
diagnostic tool for detecting abnormalities and about current hypotheses 
about the pathologic processes that cause the impairment.  Questions were 
also raised about the specificity of diagnostic tools in differentiating 
among multiple possible causes of an abnormality.

The limitations of previous studies are now better understood, and include 
selection bias, inadequately quantified exposure assessments, use of 
nonspecific neurological outcome variables, inclusion of individuals with 
neurological outcomes from nonworking-related causes, and lack of sensitivity 
and specificity of neurodiagnostic tools.  With the clarification of research 
needs to address the limitations of earlier studies, the advances in 
techniques to assess exposures and health outcomes, and the existence of 
worker populations with long-term exposures to organic solvents, the time may 
be ripe for studies to quantify long term solvent exposures and neurological 
and other health outcomes.  The results of well designed studies should 
provide more meaningful results about dose-response relationships between 
occupational exposures to organic solvents and chronic neurological 
conditions.  They should also lead to better understanding about the causes 
and characteristics of neurological effects associated with long-term organic 
solvent exposure.

Goals

The goals of this initiative are to quantify organic solvent exposures in 
workers in a selected industry, to objectively and quantitatively assess 
chronic neurological conditions, and to characterize dose-response 
relationships between organic solvent exposures and chronic neurological 
conditions.  Railroad workers and construction painters are of particular 
interest as these groups have documented long-term organic solvent exposures.  
Since identification of the neurological effects of toxic agents is complex 
and often times subjective in nature, the approach for this RFA is to 
encourage (1) the characterization of actual or estimated cumulative exposure 
to organic solvents, other neurotoxicants such as pesticides, and other 
workplace exposures, and (2) the use of a battery of objective measurements 
of neurological function, such as cognitive testing and neuroimaging tools.  
To establish a dose-response relationship, workers with various levels of 
solvent exposure, including no exposure, should be included in the study.  
The study population could include current workers (for whom industrial 
hygiene measurements of current workplace levels should be obtained) as well 
as former workers.  Nonwork-related factors known to have neurological 
effects should be controlled for or used as exclusion criteria.

See Useful References After AUTHORITY AND REGULATIONS (Below). 

MECHANISM OF SUPPORT

This RFA will use the research project grant (R01) award mechanism(s).  As an 
applicant you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project will 
compete with all investigator-initiated applications and will be reviewed 
according to the customary peer review procedures.  The anticipated award 
date is February 1, 2004.  Applications that are not funded in the 
competition described in this RFA may be resubmitted as NEW investigator-
initiated applications using the standard receipt dates for NEW applications 
described in the instructions to the PHS 398 application.

This PA uses just-in-time concepts.  It also uses the modular budgeting as 
well as the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.  

FUNDS AVAILABLE

NIOSH intends to commit approximately $1,000,000 in fiscal year (FY) 2004 to 
fund two to three new and/or competitive continuation grants in response to 
this RFA. An applicant may request a project period of up to three years and 
a budget for direct costs of up to $400,000 per year.  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 NIOSH provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications. 

ELIGIBLE INSTITUTIONS

You may submit (an) application (s) if your institution has any of the 
following characteristics:

o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories.
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic and foreign
o Faith-based organizations
o Federally recognized Indian Tribes, Tribal Governments, Colleges, and/or 
Organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Individuals with the skills, knowledge, and resources necessary to carry out 
the proposed research are invited to work with their institutions 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 NIOSH programs.

Note: Title 2 United States Code section 1611 states that an organization 
described in section 501(c)(4) of the Internal Revenue Code that engages in 
lobbying activities is not eligible to receive Federal funds constituting an 
award, grant, or loan.

SPECIAL REQUIREMENTS

Applicants should fully describe the plan to recruit study sites across an 
industry (to characterize exposures in that industry) and to enroll workers 
willing to participate in the study.  Letters of cooperation from employers 
and unions would provide some measure of the anticipated success of the plan.

The following should be addressed in a clear and organized manner (see also 
peer review criteria section):

o Timeline: a detailed timeline for the proposed study must be included in 
the application.

o In a separate section labeled, Participant Notification of Study Results, 
the applicant should describe plans for notifying participants about their 
individual results and the overall results of the study. 

Applicants should highlight unique expertise and/or unusual opportunities as 
related to the purpose of this RFA.  Examples include, but are not limited 
to: 

o Expertise in specialized areas with potential applications to the 
issues/questions considered in this RFA, conducting epidemiologic field 
studies of working populations, experience in exposure assessment;

o Access to a range of work sites varied enough to characterize the industry 
being studied, and to workers at those sites who are willing to participate 
in studies of solvent exposures;

o Expertise in assessing solvent and other exposures in individual job 
settings, as well as documentation of all exposures;

o Expertise in neurologic assessment techniques, such as the use of 
neuroimaging tools and the interpretation of neuroimaging results;

o Expertise in the clinical assessment of neurologic conditions and their 
differential diagnoses.

o Expertise in negotiating with work site management and unions in field 
settings.

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.  This RFA and other CDC Announcements can be found on the CDC 
HomePage at http://www.cdc.gov, under the Funding Section (see Grants and 
Cooperative Agreements, scroll down to Occupational Safety and Health).  This 
RFA can also be found on the NIOSH HomePage 
http://www.cdc.gov/niosh/homepage.html, under Extramural Programs, Current 
Funding Opportunities.

Direct your questions about scientific/research issues to:

Michael Galvin, Ph.D.
Scientific Program Administrator
Office of Extramural Programs
Centers for Disease Control and Prevention
National Institute for Occupational Safety and Health
1600 Clifton Road, N.E.
Building 24, Room 1536, MS E-74
Atlanta, GA  30333
Telephone:  (404) 498-2524
FAX:  (404) 498-2571
Email: mtg3@cdc.gov

Direct your questions about peer review issues to:

Pervis C. Major, Ph.D.
Scientific Review Administrator
Office of Extramural Programs
National Institute for Occupational Safety and Health
Centers for Disease Control and Prevention (CDC)
1095 Willowdale Rd
Morgantown, WV 26505
Telephone 304-285-5979
Fax 304-285-6147
Email: pmajor@cdc.gov 

Direct inquiries about financial or grants management matters to:

Ms. Cynthia Mitchell, Contract Specialist
Acquisition and Assistance Field Branch
Centers for Disease Control and Prevention 
626 Cochrans Mill Road
Pittsburgh, Pennsylvania 15236-0070
Announcement Number OH-04-001
Telephone:  (412) 386-6434
Email: CMitchell@cdc.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 an application, the information that it contains is 
used 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 and should be sent to: 

Pervis C. Major, Ph.D.
Scientific Review Administrator
Office of Extramural Programs
National Institute for Occupational Safety and Health
Centers for Disease Control and Prevention (CDC)
1095 Willowdale Rd
Morgantown, WV 26505
Telephone 304-285-5979
Fax 304-285-6147
Email: pmajor@cdc.gov 

SUBMITTING AN APPLICATION   

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  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.  It can be obtained by calling (866) 705-5711 or on the web at 
http://www.dunandbradstreet.com.  There is no charge for the number. The PHS 
398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html 
in an interactive format. For further assistance contact GrantsInfo, Telephone 
301/435-0714, Email: GrantsInfo@nih.gov.  

SUPPLEMENTARY INSTRUCTIONS:

If the proposed project involves organizations or persons other than those 
affiliated with the applicant organization, letters of support and/or 
cooperation must be included. 

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/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 (CSR)
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application and all 
copies of appendix material must also be sent to:

Pervis C. Major, Ph.D.
Scientific Review Administrator
Office of Extramural Programs
National Institute for Occupational Safety and Health
Centers for Disease Control and Prevention (CDC)
1095 Willowdale Rd
Morgantown, WV 26505
Telephone 304-285-5979
Fax 304-285-6147
Email: pmajor@cdc.gov 

APPLICATION PROCESSING: Applications must be received by the application 
receipt date listed in the heading of the RFA.  If an application is received 
after that date, it will be returned to the applicant without review.  

The Center for Scientific Review (CSR) and NIOSH 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.  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 CSR and 
responsiveness by NIOSH.  Incomplete applications will be returned to the 
applicant without further consideration. And, if the application is not 
responsive to the RFA, NIOSH staff may contact the applicant to determine 
whether to return the application to the applicant or submit it for review in 
competition with unsolicited applications at the next appropriate NIH review 
cycle.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by a scientific review group convened by 
NIOSH 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 applicants deemed to have the highest 
scientific or technical 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 of review by the NIOSH Secondary Review Committee.

REVIEW CRITERIA

The criteria that NIOSH will use to review applications for scientific merit 
and for meeting program objectives are provided below.  In the written 
comments, reviewers will be asked to discuss the following aspects of the 
application in order to judge the likelihood that the proposed research will 
have a substantial impact on the pursuit of these goals:

o Significance
o Approach
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  The application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example it may propose to carry out 
important work that by its nature is not innovative but essential to move a 
field forward.

SIGNIFICANCE: Does this study address an important problem related to the 
research areas outlined in this announcement?  If the aims of the application 
are achieved, how will scientific knowledge be advanced?  What will be the 
effect of this study on the concepts or methods that drive this field?  Is 
the study population appropriate?  Will the proposed research contribute to 
the overall aims of addressing questions of causation and of better defining 
the dose-response relationships between varying levels of occupational 
exposures to organic solvents and neurologic outcomes?

APPROACH: Are the conceptual framework, design (including composition of 
study population), methods, and analyses adequately developed, well-
integrated, and appropriate to the aims of the project?  Does the applicant 
acknowledge potential problem areas, such as the limitations of earlier 
studies, and consider alternative approaches?   Does the study have a well 
defined and described cohort within a specific industry? Does the recruitment 
plan address the need to enroll workers with a range of exposures to organic 
solvents (high, medium and low) with sufficient exposure contrast to assess 
response to exposure?  Does the study have an appropriate control population?  
Is the plan for assembling work sites and participants suitable for this 
study?  Does the project employ standardized, comparable approaches for 
exposure assessment? Does the study have an appropriate design for 
determining a history of long-term exposure to organic solvents?  Does the 
study have an appropriate design for reliably quantifying exposures to 
organic solvents?  Does the study use valid, appropriately sensitive and 
specific, and reliable objective neurodiagnostic tools and techniques?  Are 
the approaches for assessing working memory appropriate and state of the art?  
Does the study use appropriate validated cognitive testing methods?  Does the 
study adequately address the limitations of neuroimaging and other diagnostic 
tools?  Does the study have an appropriate analysis plan for assessing the 
relationship between solvent exposure and neurologic changes?  Does the study 
appropriately control for nonworking-related factors related to neurologic 
impairment?  Does the study exclude individuals from the analysis if their 
neurologic conditions can be explained by nonworking related causes?  Is the 
time line for the study appropriate and well described?

INNOVATION: Does the project employ novel concepts, approaches, or methods?  
Are the aims original and innovative?  Does the project challenge existing 
paradigms or develop new methodologies or technologies?

INVESTIGATOR: Are the Principal Investigator and his/her team appropriately 
trained and with adequate experience to conduct both exposure and health 
assessments in order to evaluate exposure response?  Does the team have a 
multidisciplinary background to design and conduct a prospective 
epidemiologic field study? Within the team is there expertise in neurologic 
assessment techniques, such as the use of neuroimaging tools and the 
interpretation of neuroimaging results, and clinical expertise in neurologic 
diagnoses? Is the work proposed appropriate to the experience level of the 
principal investigator and his/her collaborators?

ENVIRONMENT: Does the scientific environment in which the work will be 
performed contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific environment 
or employ useful collaborative arrangements?  Is there documentation of 
cooperation from stakeholders in the project, where applicable?  Is there 
evidence of institutional support and availability of resources necessary to 
perform the project?

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

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

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 will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score.     

BUDGET: The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.  

o  Availability of special opportunities for furthering research programs 
through the use of unusual talent resources, populations, or environmental 
conditions in other countries which are not readily available in the United 
States or which provide augmentation of existing U.S. resources.  

Programmatic Review Criteria

o  Magnitude of the problem in terms of numbers of workers affected.
o  Severity of the disease or injury in the worker population.
o  Priority will be given for studies on railroad workers and construction
painters

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  November 3, 2003
Application Receipt Date:  December 17, 2003
Earliest Anticipated Start Date:  February 1, 2004

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit
o Availability of funds
o Programmatic priorities
o Population studied (railroad workers and construction painters are a 
priority)
REQUIRED FEDERAL CITATIONS

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

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy, 
effectiveness and comparative trials (phase III). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.    (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or 
more in direct costs in any single year are expected to include a plan for 
data sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing  Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

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 are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

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

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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

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

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). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with 
the exception of small health plans which have an extra year to comply).  

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.

LOBBYING RESTRICTIONS: Applicants should be aware of restrictions on the use 
of Health and Human Services (DHHS) funds for lobbying of Federal or State 
legislative bodies.  Under the provisions of 31 U.S.C. Section 1352, 
recipients (and their subtier contractors) are prohibited from using 
appropriated Federal funds (other than profits from a Federal contract) for 
lobbying congress or any Federal agency in connection with the award of a 
particular contract, grant, cooperative agreement, or loan.  This includes 
grants/cooperative agreements that, in whole or in part, involve conferences 
for which Federal funds cannot be used directly or indirectly to encourage 
participants to lobby or to instruct participants on how to lobby.

In addition, no part of the Centers for Disease Control and Prevention (CDC) 
appropriated funds 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 or local 
legislature, except in presentation to the Congress or any State or local 
legislature itself.  No part of the appropriated funds 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 or local 
legislature.

Any activity designed to influence action in regard to a particular piece of 
pending legislation would be considered "lobbying."  That is lobbying for or 
against pending legislation, as well as indirect or "grass roots: lobbying 
efforts by award recipients that are directed at inducing members of the 
public to contact their elected representatives at the Federal or State 
levels to urge support of, or opposition to, pending legislative proposals is 
prohibited.  As a matter of policy, CDC extends the prohibitions to lobbying 
with respect to local legislation and local legislative bodies.

The provisions are not intended to prohibit all interaction with the 
legislative branch, or to prohibit educational efforts pertaining to public 
health.  Clearly there are circumstances when it is advisable and permissible 
to provide information to the legislative branch in order to foster 
implementation of prevention strategies to promote public health.  However, 
it would not be permissible to influence, directly or indirectly, a specific 
piece of pending legislation.

It remains permissible to use CDC funds to engage in activity to enhance 
prevention; collect and analyze data; publish and disseminate results of 
research and surveillance data; implement prevention strategies; conduct 
community outreach services; provide leadership and training; and foster safe 
and healthful environments.

Recipients of CDC grants and cooperative agreements need to be careful to 
prevent CDC funds from being used to influence or promote pending 
legislation.  With respect to conferences, public events, publication, and 
"grassroots" activities that relate to specific legislation, recipients of 
CDC funds should give attention to isolating and separating the appropriate 
use of CDC funds from non-CDC funds.  CDC also cautions recipients of CDC 
funds to be careful not to give the appearance that CDC funds are being used 
to carry out activities in a manner that is prohibited under Federal law.

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 PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/.

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)(cite appropriate authorizations) and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92 (cite relevant regulations). 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 (also cite other relevant 
policies)

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.

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.

USEFUL REFERENCES

Albers JW, Berent S [2000].  Controversies in neurotoxicology: Current 
status.  Neurol Clin 18:741-764.

Albers JW, Wald JJ, Garabrant DH, Trask CL, Berent S [2000].  Neurologic 
evaluation of workers previously diagnosed with solvent-induced toxic 
encephalopathy.  J Occup Environ Med 42:410-423.

Frey KA [2000].  Neuroimaging in neurotoxicology.  Neurol Clin 18:615-629.

Frumkin H, Ducatman A, & Kirkland K [1997].  Solvent exposure in the railroad 
industry (letter to the editor).  J Occup Environ Med 39:926-930.

Ridgway P, Nixon TE, Leach JP (2003).  Occupational exposure to organic 
solvents and long-term nervous system damage detectable by brain imaging, 
neurophysiology or histopathology.  Food Chem Toxicol 2003; 41 (2) : 153-87.


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