COLLABORATIVE CENTERS FOR PARKINSON"S DISEASE ENVIRONMENTAL RESEARCH

Release Date:  December 6, 2001

RFA:  RFA-ES-02-003 (See Notice NOT-ES-07-002 
Notice of New Round of Competition with Broadened Scope)
(see NOT-ES-04-007)

National Institute of Environmental Health Sciences
 (http://www.niehs.nih.gov)

Letter of Intent Receipt Date:  February 14, 2002
Application Receipt Date:       March 14, 2002

PURPOSE OF PROGRAM

A variety of lines of evidence suggest that both environmental and genetic 
factors contribute to sporadic Parkinson"s Disease (PD), the most common form 
of the disease.  Identification of the full complement of relevant 
environmental and genetic components, and an understanding of their 
interactive roles in the neurodegenerative process, is lacking.  Such 
information is critical for designing effective prevention and intervention 
strategies.  To accelerate the pace of progress in this important area and the 
translation of findings into the public health arena, the NIEHS is creating a 
Collaborative Centers for Parkinson"s Disease Environmental Research (CCPDER) 
Consortium Program to foster multidisciplinary research approaches to 
elucidate gene-environment interactions in PD.  This program seeks to provide 
the science-based foundation for efforts to prevent and/or ameliorate the 
devastating effects of this disease.  

The NIEHS CCPDER Consortium Program will consist of a highly interactive 
national network that will be formed from up to three individual CCPDERs.  The 
network will function to share data and resources and engage in the planning 
and conduct of collaborative studies to understand the joint contribution of 
genes and environment in the etiology of PD.  In addition to its role in the 
larger network, each CCPDER will engage in a self-contained program of 
research activities that focus on gene-environment interactions in PD.  Each 
CCPDER will consist of a multidisciplinary team with expertise in several of 
the following areas: (1) basic cellular and molecular neurobiology, (2) human 
genetics, (3) epidemiology, (4) clinical research, and (5) community outreach 
and education.  Each CCPDER will support several integrative research projects 
and core services/facilities as may be needed for the proposed research. An 
integrative research project is one that proposes new work to amplify, extend 
or bridge an existing external peer reviewed and funded grant or grants in PD 
and that will incorporate multidisciplinary research approaches. Taken 
together, the integrative projects contained within a CCPDER will address an 
overarching gene-environment hypothesis or set of hypotheses in PD. 

To facilitate joint activities among CCPDERs, one CCPDER will be selected to 
serve as a Coordinating Center (CCPDER-CC).  The CCPDER-CC will develop a 
formal mechanism for ongoing information exchange with PD patient advocates 
that includes opportunities for advocates to provide input concerning research 
directions and priorities. Collaborative activities among CCPDERs will be 
overseen by a CCPDER Consortium Program Steering Committee involving 
representation from each CCPDER and from the NIEHS.  The individual CCPDERs 
will be funded through an NIH Cooperative Agreement U54 mechanism, the goal of 
which is to maximize the collaborative utilization of the unique resources in 
infrastructure and expertise that will be created. 

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 Request for Applications, 
Collaborative Centers for Parkinson"s Disease Environmental Research, is 
related to the priority area of environmental health.  Potential applicants 
may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic non-profit and for-profit 
organizations, private and public, such as universities, colleges, private 
companies, hospitals, laboratories, units of state or local governments, and 
eligible agencies of the Federal government.  The applicant institution must 
be domestic. Foreign institutions are not eligible for U54 grants.  
Racial/ethnic minority individuals, women, and persons with disabilities are 
encouraged to apply as Principal Investigators. Applicants will be allowed to 
propose multi-institutional arrangements within the context of a single CCPDER 
application.  At the time of submission, at least two of the integrative 
research projects for a CCPDER must be from investigators at the applicant 
organization.  

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Cooperative 
Agreement (U54 Specialized Cooperative Center program award mechanism).  The 
total project period requested for applications responding to this RFA is five 
years.  A U54 mechanism provides support for both research project components 
and core facilities.  A cooperative agreement is an  "assistance" mechanism 
(rather than an "acquisition" mechanism) in which substantial NIH scientific 
or programmatic involvement with the awardee is anticipated during the 
performance of the activity.  Under the cooperative agreement, the NIEHS role 
is to support and/or stimulate the recipient"s activity by working jointly 
with the award recipient as a partner, but it is not to assume direction, 
prime responsibility, or a dominant role in the activity.  Details of the 
responsibilities, relationships and governance of the studies to be funded 
under a cooperative agreement are discussed later in this document under the 
section "Terms and Conditions of Award".  The anticipated award date is August 
2002. This RFA is a one-time solicitation.  The NIEHS has not yet determined 
whether this or a related RFA will be issued in the future to continue the 
program described in this RFA.

FUNDS AVAILABLE

The NIEHS has budgeted total costs of up to $4 million (overall program) for 
each of the five years for awards made in response to this RFA.  The NIEHS 
expects to make up to 3 awards as a result of this RFA.  Two of the three 
CCPDER awards may receive up to $860,000 (Direct Cost) in each of the five 
years.  One CCPDER will be selected (see AWARD CRITERIA) to serve as a 
Coordinating Center (CCPDER-CC), an additional $122,000 (Direct Cost) may be 
requested for activities associated with this function.  Thus, the CCPDER-CC 
may receive up to $982,000 ($860,000 plus $122,000 Direct Costs) in each of 
five years.  Because the nature and scope of the research posed in 
applications may vary, it is anticipated that the size of the awards may vary.  
The number of awards and the level of awarded support depend on the receipt of 
a sufficient number of applications of high scientific merit.  Although this 
RFA program is provided for in the financial plans of the NIEHS, awards 
pursuant to this RFA are contingent upon the availability of funds for this 
purpose.  Unless otherwise noted, all NIH grant policies apply.  

RESEARCH OBJECTIVES 

Background

Spurred by recent landmark scientific findings, there is now an emerging 
appreciation that Parkinson"s disease, like most human diseases, reflects the 
interaction of genetic susceptibility with environmental exposure(s).  What is 
lacking, however, is a clear mechanistic understanding of the nature of such 
interactions in disease causation. Such information is essential for 
developing rational approaches to disease prevention and intervention.  

It is envisioned that the CCPDER Consortium Program will provide a formal 
mechanism to strengthen the integrative collaboration among scientists engaged 
in fundamental laboratory research in PD and geneticists, clinicians and 
epidemiologists.  Historically, such integration has provided some of the most 
significant advances in the field of Parkinson"s disease.  As one example, the 
initial clinical observations of MPTP-exposed subjects in the 1980"s led to 
the best available animal model of PD, opened fruitful lines of investigation 
into other potential environmental exposures and provided a mechanistic 
framework for studying nigral cell death mechanisms.  Likewise, the recent 
identification of alpha synuclein mutations in rare familial PD stimulated 
intense mechanistic investigations of the functional roles of this protein 
family and its interaction with potential environmental risk factors.  The aim 
of the Consortium would be to increase the speed with which newly promising 
lines of investigation such as these can be identified and pursued at multiple 
levels of analysis and for which greater resources can be targeted.  

The three main research objectives of the CCPDER Consortium Program are to: 

o Identify genetic and environmental factor interactions that contribute to   
PD.  

o Provide a mechanistic understanding of how gene-environment interactions 
trigger the pathophysiological processes that ultimately produce PD.

o Develop the knowledge base to enable translation of research findings into 
rational prevention and intervention strategies for PD.

Research Opportunities:

An NIEHS sponsored scientific workshop was held in Colorado Springs prior to 
the International Neurotoxicology Society"s 2001 conference.  Both the 
workshop and the conference focused on gene-environment interactions in PD.  
After consideration of the research findings and knowledge gaps identified at 
these meetings, a number of fruitful research questions that are well suited 
to the multidisciplinary approach envisioned in the CCPDER Consortium program 
have been formulated.  These specific research opportunities are: 

o Mutations and polymorphisms in relevant PD genes:
Defining the genetic susceptibilities of this disease are critical for 
understanding the molecular pathways leading to PD and how environmental 
exposures can trigger key events in these pathways.  Studies of familial PD 
have revealed a number of causative disease genes and/or loci with apparent 
Mendelian inheritance patterns, including alpha-synuclein and parkin.  Other 
studies have sought to identify PD susceptibility genes using linkage studies 
in families, DNA sequencing of candidate genes, and allelic association 
studies.   In most cases, the candidate genes tested have been those with 
clear relevance to potential mechanisms of PD pathogenesis, including genes 
involved in detoxification of exogenous agents.  A number of positive genetic 
associations with PD have been reported (e.g., CYP2D6 and MAOB) although many 
findings have been inconsistent.  A major difficulty in identifying 
susceptibility genes that confer increased risk but do not cause the disease 
is the need for large sample sizes, with appropriate controls and standardized 
diagnostic criteria.  Clearly, improvements in study design are needed to 
tease out genetic factors that may impart small but significant risk of PD. 
Studies to elucidate how PD susceptibility genes may interact with 
environmental agents to trigger the neurodegenerative processes observed in PD 
are of particular interest.

o Environmental risk factors:
Epidemiological studies have associated occupational exposures to heavy metals 
and agricultural chemicals with the risk of developing PD.  Though the picture 
is not complete, there is ample preliminary evidence to consider this a 
fruitful avenue of research. A related and critically important need is for 
improvements and standardization in exposure assessment methodologies.  The 
long preclinical course of PD, and the consequent need for retrospective 
assessments, makes this an especially challenging task.  The relationships 
between these exposures and genetically determined individual differences are 
of special interest.  Multidisciplinary efforts to elucidate the biochemical 
mechanisms underlying epidemiological findings in PD are warranted.  Recent 
studies examining the interaction of pesticides with alpha synuclein 
demonstrate the utility of such an approach.

o Oxidative stress:
There is a vast literature on the role of reactive oxygen in neuronal 
degeneration.  The knowledge that many environmental toxicants are known and 
putative oxidative stressors provides a mechanistic link to PD, but a cohesive 
description of the primary events as well as a reason for the special 
selectivity of the nigral neurons in PD has thus far defied resolution.  A 
number of factors that merit further study are (1) dopamine metabolism to 
isoquinones and thioethers, (2) iron metabolism, and (3) mitochondrial complex 
I dysfunction.  The relation between oxidative stress and lipid peroxidation, 
DNA adducts, the generation of nitric oxide and the formation of 
peroxynitrites, are other areas of possible relevance to PD research.  The 
joint effects of environmental agents and PD susceptibility genes on cellular 
oxidative stress, and their impact on apoptosis pathways are of special 
interest.

o Neuroprotection:
Studies to understand mechanisms of neuroprotection could have immediate 
relevance to the clinical setting and are especially suited to a 
multidisciplinary approach.  Evidence exists from epidemiological studies that 
smokers and coffee drinkers have a lower risk of developing PD.  Despite the 
myriad of chemicals in cigarette smoke, the most productive avenue of study 
appears to be on the role of nicotine.  Similarly, the potential for the 
protective effect of caffeine in coffee has engendered the greatest interest.  

o Protein aggregation and metabolism:
Protein overexpression and aggregation appear to be part of the cascade of 
events associated with PD.  There is a clear need for a better understanding 
of which events are critical to developing PD and which are a consequence of 
PD development, but not implicated in its development.  An understanding of 
Lewy body formation is essential. In addition to elucidating the process by 
which Lewy bodies form, it has yet to be resolved as to whether their 
formation plays a part in a toxic or protective process. A related need is to 
define pathways of alpha synuclein aggregation, its protein partners and its 
role in nigral cell death.  Likewise, the role of ubiquitin and protein 
degradation/ proteosomal pathways in the neurodegenerative process merits 
further investigation.

o Development of new animal models:
Without new and better disease models, translation of research findings to the 
clinical setting is stymied. Models that can be used to elucidate the 
interaction of genetic susceptibility with environmental exposures are of 
special interest.  A number of promising animal models of PD have been 
developed recently, including ones based on exposure to pesticides and 
agrichemicals (e.g., rotenone, paraquat and maneb) as well as transgenic 
models of alpha synuclein expression in mice and Drosophila.  Further studies 
to exploit these models, and to develop new models, are needed.  

o Other Research Opportunities:
The roles of the inflammatory process and endotoxin exposure also have been 
implicated in the degenerative process and deserve further study.  The 
development of both biomarkers of exposure and disease are needed. All 
research areas would benefit from reliable biomarkers for accurate diagnosis.  

The above research opportunities are not intended as an exhaustive list, but 
as examples of research questions that lend themselves to the 
multidisciplinary approach envisioned by the CCPDER Consortium program.  
Applicants are urged to consider any additional research opportunities that 
are consistent with the stated goals of the CCPDER Consortium program. 

ORGANIZATION OF CCPDERs

Each CCPDER will have a team of appropriate investigators, a set of 
integrative research projects and a collection of support cores. There must be 
substantive and documented departmental and institutional infrastructure, 
support for and commitment to the proposed CCPDER.  Each CCPDER applicant must 
also document their willingness to cooperate in a coordinated manner within 
the CCPDER network.  Investigators with the qualifications to be members of a 
CCPDER research team, and to contribute to such a unique enterprise, may be 
located in different geographic locations.  Therefore, collaborations among 
different domestic institutions are encouraged, if scientifically appropriate. 
The terminology used throughout this document relative to CCPDERs is as 
follows:

COLLABORATIVE CENTER FOR PARKINSON"S DISEASE ENVIRONMENTAL RESEARCH (CCPDER): 
The organized awardee infrastructure supporting a coordinated U54 program of 
NIEHS mission relevant research being conducted by an organized group of 
scientists.  CCPDER consist of three components: integrative research 
projects, an administrative core and resource, service or facilities cores. 

CCPDER COORDINATING CENTER (CCPDER-CC):  A CCPDER with the additional 
responsibility of providing administrative coordination of Consortium meetings 
and workshops and information dissemination to affected scientific and lay 
communities. 

CCPDER CONSORTIUM PROGRAM:  An interacting consortium group comprised of up to 
three U54 CCPDERs awarded as a result of this RFA.

INTEGRATIVE RESEARCH PROJECT:  A research project that proposes new work to 
amplify, extend or bridge an existing external peer reviewed and funded grant 
or grants in PD and that will incorporate multidisciplinary research 
approaches. 

PRINCIPAL INVESTIGATOR.  Each CCPDER will have a Director (the CCPDER 
Principal Investigator) who will make scientific and administrative decisions 
relating to the CCPDER, will oversee identification and selection of key 
personnel, and will be responsible for allocation and monitoring of CCPDER 
funds.  The CCPDER Director must also direct one of the integrative research 
projects that comprise the CCPDER.  The CCPDER Director must have significant 
and documented expertise in PD and a strong commitment to studying gene-
environment interactions in PD.  The CCPDER Director must have existing 
external peer-reviewed funding in PD that will continue for at least two years 
following the receipt of the CCPDER award (August 2002).  This funding should 
be from regular research grants supported by NIEHS, other NIH institutes and 
centers, and other governmental and private agencies in the area of PD.

PROJECT LEADERS.  Each integrative research project (defined below) will be 
directed by a competent and experienced scientist with expertise in PD or a 
closely related area of neurodegeneration.  The scientist responsible for a 
specific project within the overall CCPDER may be identified as that project"s 
Project Leader, Co-Principal Investigator or Director.  Project Leader is the 
preferred term.  Collectively, the Project Leaders must comprise a 
multidisciplinary team with expertise in cellular and molecular neurobiology 
in addition to at least two of the following four areas of PD research: (1) 
human genetics, (2) epidemiology, (3) clinical research, and (4) community 
outreach and education.   Each project leader must have existing external 
peer-reviewed funding in PD or a closely related neurodegenerative disease.  
This funding must continue for at least two years following the receipt of the 
CCPDER award (August 2002) and must provide the primary scientific foundation 
for the proposed integrative research project.  This peer-reviewed funding 
should be from individual investigator research grants or equivalent 
subprojects of program grants supported by NIEHS, other NIH institutes and 
centers, and other governmental and private agencies in the area of PD or a 
conceptually related area of neurodegeneration.  

INTEGRATIVE RESEARCH PROJECTS.  Each CCPDER will propose at least three 
integrative research projects in the general area of gene-environment 
interaction in PD.  These projects must be guided by a unifying hypothesis or 
interrelated set of hypotheses. Although existing external peer-reviewed grant 
funding must provide the scientific foundation for each integrative research 
project, the studies proposed in each integrative research project in the 
CCPDER application must represent a clear and significant extension or 
amplification of a single existing external peer reviewed grant.  
Alternatively, an integrative research project may propose studies that 
bridge, or tie together, two or more existing external peer reviewed grants.  
The integrative research project cannot represent a duplication of the 
currently funded research contained within the parent grant(s).  Each 
integrative research project proposed must incorporate a multidisciplinary 
approach.  

SCIENTIFIC FUNDING BASE. The collective scientific funding base for each 
CCPDER, defined as the set of external peer reviewed grants that provide the 
foundation for the integrative research projects, must total at least $500,000 
in annual direct costs.  This funding base must extend for at least two years 
following the receipt of the CCPDER award (August 2002). Each integrative 
research project can be based on more than one existing grant, as in the case 
where an integrative research project has the goal of bridging the efforts of 
two or more existing grants.  In such cases, at least one of the grants must 
meet the two year funding duration requirement cited above and will serve as 
the qualifying grant for that integrative research project, the grant or 
grants that bridge to the qualifying grant must extend for at least one year 
following CCPDER award receipt (August 2002).  Each existing grant may provide 
the primary basis for only one integrative research project.  That is, it is 
not permissible to propose two or more integrative research projects that 
represent different extensions or different bridging efforts of the same 
existing grant or set of grants. 

CORES.  A Core is a shared central laboratory or clinical research facility, 
service, or resource.  All Cores must serve a minimum of two integrative 
research projects.  As a minimum, each CCPDER will propose an Administrative 
Core and a Research Development Core.  The administrative Core will provide a 
structure to coordinate and integrate CCPDER components and activities, plan 
and review utilization of funds and provide support and advice to the CCPDER 
Principal Investigator in his/her oversight of the activities of the CCPDER. 
The Research Development Core will provide a structure for developing and 
supporting pilot projects, including those to be conducted collaboratively 
with other CCPDERs.  An applicant may propose additional technical/facility 
Cores as required to conduct the proposed integrative research projects.  A 
CCPDER may propose new Core(s) or may describe a mechanism to access (e.g., 
fee for service or shared costing) existing Cores. Applicants may propose use 
of Core services located outside of the applicant institution through a 
subcontractual arrangement.  Each Core is directed by a faculty investigator 
(the Core Director) with substantial expertise related to the core.  Two 
important and related considerations are (1) the degree to which currently 
funded investigators within or outside the CCPDER will use and will benefit 
from core resources and (2) the degree to which the resources will promote new 
and/or expanded PD research efforts within the overall activities of the 
CCPDER Consortium Program.

An Executive Committee (composed of Core directors and Project leaders) must 
be established in each CCPDER to assist the CCPDER Director in making 
scientific and administrative decisions. The executive committee should be 
encouraged to seek outside advice and consultation, both from within the 
institution and from other institutions, in its monitoring and development of 
the scientific content and direction of the program.  

An External Advisory Committee to each CCPDER, consisting of scientists from 
outside of the institution or consortium, must also be proposed.  The External 
Advisory Committee members should neither be contacted nor recruited until the 
NIH review process is complete. This committee will be used to evaluate the 
programs of the CCPDER, research progress, the effectiveness of communications 
within the CCPDER, and any other activities for which outside expertise is 
required or desirable.  The committee should meet annually and prepare a 
report including recommendations to assist the CCPDER.  It is expected that 
this committee include significant representation from PD advocacy groups.  
The NIEHS Extramural Science Administrator and the NIEHS Extramural Program 
Administrator (see definitions under SPECIAL REQUIREMENTS FOR COOPERATIVE 
AGREEMENT section) for the CCPDER Consortium Program should be invited to 
attend each meeting as observers.  A copy of the advisory committee report 
should be sent to the NIEHS Extramural Science Administrator and to the NIEHS 
Extramural Program Administrator.

An applicant responding to this RFA who wishes to be considered to be a 
Coordinating Center (CCPDER-CC) should indicate this interest and must include 
additional Core components.  That is, the CCPDER-CC must include an 
Information Dissemination/Outreach Core to provide a formal mechanism for 
making available information about Consortium activities to the affected 
scientific and lay communities.  Applicants who do not wish to be considered 
for a CCPDER-CC should not include this Core.  The Information 
Dissemination/Outreach Core will be responsible for creating and maintaining a 
listserver and website for the CCPDER Consortium Program suited for use by 
both the scientific and lay communities interested in PD.  The website should 
include timely information about the CCPDER Consortium Program, activities and 
accomplishments.  The prospects for translation of CCPDER research findings 
into clinical practice should be highlighted.  In addition, the CCPDER-CC will 
have an expanded Administrative Core to provide for effective coordination of 
one annual CCPDER Consortium Program general scientific meeting to report and 
evaluate progress of the integrative research projects and one annual 
scientific workshop on an emerging topic in PD.  The scientific topic for the 
annual workshop will be determined by the CCPDER Consortium Program Steering 
Committee.  The CCPDER Consortium Program annual scientific meeting should 
include a forum for information exchange with PD advocacy groups, including 
opportunities for advocates to provide input concerning CCPDER Consortium 
activities.  In addition to the $860,000 (Direct costs) that may be requested 
to support a CCPDER, an applicant may request an additional $122,000 Direct 
costs annually to support the additional responsibilities associated with a 
CCPDER-CC.  Thus, an applicant for the CPDER-CC may request $982,000 ($860,000 
plus $122,000) in Direct Costs, annually. 

I.  Terms and Conditions of Award

The following terms and conditions will be incorporated into the U54 award 
statement, and will be provided to the appropriate Institutional Official, at 
the time of award.  Failure to abide by any of the TERMS AND CONDITIONS OF 
AWARD pertaining to awardee responsibilities as stipulated, may result in 
reduction of funding, withholding of support, or suspension or termination of 
award.

These special TERMS AND CONDITIONS OF AWARD are in addition to, and not in 
lieu of, otherwise applicable OMB administrative guidelines, HHS grant 
administration regulations at 45 CFR Parts 74 and 92 [Part 92 is applicable 
when State and local Governments are eligible to apply], and other HHS, NIH, 
and NIH grant administration policies.

A.  The administrative and funding instrument used for this program will be 
the Cooperative Agreement (U54 Specialized Center).  The cooperative agreement 
is an "assistance" mechanism (rather than an "acquisition" mechanism), in 
which substantial NIH scientific and/or programmatic involvement with the 
awardee is anticipated during the performance of the activity. Under the 
Cooperative Agreement, the NIH purpose is to support and/or stimulate the 
recipient"s activity by involvement in and otherwise working jointly with the 
award recipient in a partner role, but it is not to assume direction, prime 
responsibility, or a dominant role in the activity.  Consistent with this 
concept, the dominant role and prime responsibility for the activity supported 
by a cooperative agreement resides with the awardee for the project as a 
whole, although specific tasks and activities in carrying out the study will 
be shared among the awardee(s) and the NIEHS.

B.  Awardee Rights and Responsibilities:

1.  The Principal Investigator is the scientist who is designated by the 
awardee institution who will direct the U54 CCPDER.  The Principal 
Investigator will have primary authority and responsibility to define 
objectives and approaches, and to plan and oversee the proposed research.  The 
Principal Investigator will assume responsibility and accountability to the 
applicant institution and to the NIEHS for the performance and proper conduct 
of the research in accordance with the TERMS AND CONDITIONS OF AWARD.

The Principal Investigator of each U54 CCPDER will:
o Manage the coordination of the specific integrative research projects
o Oversee the management of the administrative and facilities cores
o Provide yearly summaries of progress during the annual CCPDER Consortium 
Program Steering Committee meetings.

The Principal Investigator of the U54 CCPDER-Coordinating Center (CC) will:
o Manage the coordination of the Information Dissemination Outreach Core 
specific to this Center, including coordination with the NIEHS for the 
standards and practices associated with the CCPDER Website as described in the 
RFA.
o Direct the planning and management of annual CCPDER Consortium Program 
general scientific meetings and workshops.
o Provide yearly summaries of progress of the Information Dissemination 
Outreach Core during the annual CCPDER Consortium Program Steering Committee 
meetings.

2.  The Principal Investigator or designated representative will serve as a 
voting member of the CCPDER Program Steering Committee and will attend 
meetings as scheduled.

3.  Awardees will retain custody of, and have primary rights to data developed 
under awards, subject to Government rights of access consistent with HHS, PHS, 
and NIH policies.  Under the terms of OMB circular A-110, data generated by 
grantees is now subject to the Freedom of Information Act.  Data and 
procedures for its use developed under the U54 may be considered unique 
research resources.  The policy of the PHS is to make available to the public 
results and accomplishments of activities that it funds.  All awardees must 
adhere to PHS policy for distribution of unique research resources produced 
with PHS funding, which was published at: 
http://www.nih.gov/od/ott/RTguide_final.htm.  Publication or oral presentation of 
work done under this agreement will require appropriate acknowledgement of 
NIEHS support: see Acknowledgement of Federal Funding (Section 507) in the 
Notice of Legislative Mandates Contained in the FY2000 Omnibus Appropriations 
at:  http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-010.html.  
Dissemination of information, data or substances supplied by NIEHS will 
require clearance by NIEHS to assure conformity with any existing 
confidentiality agreements with the primary suppliers of such information, 
data or substances to the NIEHS.

4.  Possessory rights of physical materials acquired during the course of 
research rests with the applicant.  Prior to award, the applicant must 
formulate a policy for final disposition of such physical materials and 
ownership rights in the event that such physical materials are transferred to 
other parties who use them to make discoveries.

C.  NIEHS Extramural Staff Responsibilities
 
1. NIEHS EXTRAMURAL SCIENCE ADMINISTRATOR (ESA): The NIEHS extramural program 
staff scientist who will have substantial scientific involvement during the 
conduct of this CCPDER Consortium Program activities, through technical 
assistance, advice, and coordination above and beyond normal program 
stewardship for grants.  The NIEHS extramural science administrator will 
assist in avoiding unwarranted duplication of effort across CCPDERs, help 
coordinate collaborative research efforts that involve multiple CCPDERs, serve 
on the organizing committee for the annual CCPDER Consortium Program 
scientific meetings and workshops, facilitate interactions between the awardee 
and the national PD advocacy community, provide recommendations concerning the 
format and content of the CCPDER Consortium Program website and other outreach 
materials produced by the CCPDERs, and assist in the integration of the CCPDER 
Consortium Program with existing NIEHS scientific resources and programs.  The 
NIEHS Science Administrator will be selected by the NIEHS, will be distinct 
from the NIEHS Extramural Program Administrator and will be a voting member of 
the CCPDER Consortium Program Steering Committee. In all cases the role of the 
ESA will be to provide scientific program coordination of CCPDER research 
activities to assist and facilitate, but not to direct, these research 
activities.

Upon recommendation of the ESA, NIEHS may provide a U54 CCPDER Consortium 
Program member access to physical and/or intellectual resources from NIEHS to 
support appropriate CCPDER program activities when such resources are required 
to meet the Terms and Conditions for Award for a CCPDER.

The NIEHS ESA will serve as the CCPDER program liaison to the NIEHS and, in 
this capacity, the NIEHS ESA represents and makes presentations on behalf of 
the CCPDER program to the NIEHS for the purpose of administratively evaluating 
the overall effectiveness and achievements of the combined consortium 
laboratories contributing to the overall national CCPDER Consortium Program of 
the NIEHS.  

2.  EXTRAMURAL PROGRAM ADMINISTRATOR (EPA):  The NIEHS will select one 
extramural program administrator to administer the cooperative agreement 
awards for the CCPDER program.  The EPA, who is separate and distinct from the 
ESA, will provide the NIEHS stewardship of the cooperative agreement awards 
during the performance of the awarded research activities.  The EPA will 
monitor the adequacy of each individual CCPDER award progress annually and 
provide the usual grant stewardship and administrative assistance for each 
individual cooperative agreement.

The NIEHS retains the option for the EPA to recommend to the NIEHS Director 
the withholding or reduction of support or suspension or termination of 
funding for any project within a CCPDER of the Consortium that substantially 
fails to achieve its milestone goals. The NIEHS also retains the option for 
withholding or reduction of support or suspension or termination of funding 
for any CCPDER U54 Specialized Center cooperative agreement that materially 
fails to comply with the Terms and Conditions of the award

D. Collaborative Responsibilities

The CCPDER Consortium Program Steering Committee is the governing oversight 
committee of the CCPDER Consortium Program.  The Steering Committee consists 
of the NIEHS Extramural Science Administrator and two individuals from each 
CCPDER: the principal investigator and one integrative Project Leader 
designated by each Principal Investigator.  Each Steering Committee membership 
identified in this definition has one vote in the deliberations and actions of 
the Steering Committee. A chairperson, not from the NIEHS, will be selected by 
majority vote of the Steering Committee members.  

The Steering Committee will meet at least once annually at either the NIEHS in 
Research Triangle Park, NC or at a time and place agreed upon by the Steering 
Committee. The purpose of this (these) meeting(s) is(are) to set performance 
priorities, evaluate performance milestones, and plan for the future 
coordinated experimental studies of the CCPDER Consortium Program. The 
Steering Committee will be responsible for establishing priorities for 
collaborative inter-CCPDER activities that will be supported by the Research 
Development Cores of the individual CCPDERs.  The Steering Committee will 
evaluate and select pilot projects, consistent with the established research 
priorities and scope, and will oversee and monitor the progress of these 
studies. The Steering Committee meetings will be coordinated with the annual 
general scientific meeting of the CCPDER Consortium Program.  The Steering 
Committee may add non-voting scientific advisors to provide expert opinions on 
specific subject areas as deemed necessary by its deliberations. Other NIEHS 
program staff, as approved by the Steering Committee, may attend the Steering 
Committee meeting.  The Steering Committee may, as deemed necessary, establish 
tasked subcommittees.  NIEHS program staff may serve on these subcommittees. 
The Steering Committee will serve as the main governing board of the CCPDER 
Consortium Program.  An arbitration process will be established, as detailed 
further below, to resolve any disagreement that may arise between NIEHS 
program scientists and the non-government membership of the Steering 
Committee. 

Members of the Steering Committee will:
o Accept and participate in the cooperative nature of the group.
o Attend Steering Committee meetings to review results, evaluate data, check 
progress toward milestones, and conduct planning and prioritizing activities 
of the CCPDER Consortium.

A planning meeting of the CCPDER Steering Committee will be convened by the 
NIEHS extramural program staff shortly after the U54 awards have been made.  
At this meeting, a Chair will be selected and the group may:
o Draft a charter/operations manual that details policies and procedures and 
agree on the terms of this charter/operations manual.
o Determine a plan for scheduling the time and place of future meetings.
o Review criteria and performance measures for coordination activities.
Subsequent meetings will conduct the Steering Committee functions described 
earlier in this section.

E. Arbitration Panel
An arbitration panel is an advisory panel formed to review scientific or 
programmatic disagreement (within the scope of the award) that may arise 
between the awardee and NIEHS.  The arbitration panel will be composed of 
three members: (i) a designee of the Steering Committee chosen without NIEHS 
staff voting, (ii) one NIEHS designee, and (iii) a third designee with 
relevant expertise who is chosen by the other two.  In the case of a 
disagreement between a single CCPDER and the NIEHS, the first member of the 
arbitration panel may be chosen by the individual CCPDER awardee.  The 
Arbitration Panel will help resolve both scientific and programmatic issues 
that develop during the course of work and that could restrict progress. For 
U54 Center grant awardees, this special arbitration procedure in no way 
affects the awardee"s right to appeal an adverse action that is otherwise 
appealable in accordance with NIH regulations 42 CFR Part 50, Subpart D and 
HHS regulation at 45 CFR Part 16.

DATA AND SAFETY MONITORING

It is the policy of NIH that provision be made for the oversight and 
monitoring of all intervention studies to ensure the safety of participants 
and the validity and integrity of the data.  The NIH policy was published in 
the NIH Guide to Grants and Contracts, June 10, 1998 and is available at: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.  NIMH guidance 
on data safety and monitoring is available at: 
http://www.nimh.nih.gov/research/safetymonitoring.cfm.  For the CCPDER 
Consortium Program, an independent panel of experts, constituting a Data 
Safety and Monitoring Board, will be appointed by NIH to monitor safety, 
quality of data collection, and integrity of the study.  

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

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

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH 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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address:  http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of the policy from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
policy that was published in the NIH Guide for Grants and Contracts, June 5, 
2000 (Revised August 25, 2000), available at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH GRANTS POLICY STATEMENT

The NIH Grants Policy Statement (NIHGPS) has been revised and reissued.  The 
provisions of the revised NIHGPS are effective for all funded NIH grants and 
cooperative agreements with budget periods beginning on or after March 1, 
2001.  The revised NIHGPS is available at: 
http://grants.nih.gov/grants/policy/nihgps_2001.

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 a 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.  Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site.
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-004.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.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted. 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 institute 
staff to estimate the potential review workload and plan the review.

The letter of intent should be sent by February 14, 2002 to:

Ethel Jackson, DDS
Chief, Scientific Review Branch
Division of Extramural Research and Training
111 Alexander Drive
P.O. Box 12233
Research Triangle Park, NC  27709
Phone:  (919) 541-7846
Fax:  (919) 541-2503
email:  jackson4@niehs.nih.gov

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html must be 
used in applying for these grants. This version of the PHS 398 is available in 
an interactive, searchable format.  For further assistance contact GrantsInfo, 
Telephone 301/435-0714, Email:  GrantsInfo@nih.gov.

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

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, SUITE 1040 - MSC 7710
BETHESDA, MD  20892-7710
or BETHESDA, MD  20817 (for express/courier service)

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

Ethel Jackson, DDS
Chief, Scientific Review Branch
Division of Extramural Research and Training
111 Alexander Drive
P.O. Box 12233
Research Triangle Park, NC  27709
Phone:  (919) 541-7846
Fax:  (919) 541-2503
email:  jackson4@niehs.nih.gov

Applications must be received by March 14, 2002.  If an application is 
received after that date, it will be returned to the applicant without review. 
The Center for Scientific Review (CSR) will not accept any application 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.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

SPECIAL INSTRUCTIONS FOR ALL APPLICANTS

Applicants must consider and address the following in the preparation of 
applications called for in this RFA:

1.	 Special budget considerations
Each CCPDER applicant must include a budget for travel funds for selected key 
personnel (named below) to attend two annual meetings.  One of the meetings 
will be the CCPDER Consortium Program scientific meeting.  This scientific 
meeting will be used to present and evaluate the status of CCPDER Consortium 
Program research projects.  The annual CCPDER Consortium Program Steering 
Committee meeting will be coordinated with this meeting.  The second meeting 
will be a CCPDER Consortium Program workshop that explores an emerging area of 
science relevant to gene-environment interactions in PD.  Travel funds 
requested for these two annual meetings should be sufficient to allow travel 
of the CCPDER Principal investigator, each of the integrative research project 
leaders and Facility Core Directors, and when appropriate, other key 
scientific personnel engaged in the conduct of the integrative research 
projects.  

An amount of $75,000 must be included in the Research Development Core for 
each CCPDER for the funding of inter-CCPDER studies as determined by the 
priorities and guidelines established by the CCPDER Steering Committee.

An applicant who requests consideration for the CCPDER-CC may request up to an 
additional $122,000 direct costs to support the additional administrative 
aspects associated with the this coordination role and with the activities of 
the required Information Dissemination Core.  Thus, the costs requested for a 
CCPDER-CC may be up to $982,000 ($860,000 for CCPDER activities and $122,000 
for additional activities as a CCPDER-CC).

2.	Special research considerations
The integrative research projects proposed in the CCPDER application must be 
in the general area of gene-environment interaction in PD and these projects 
must be guided by a clearly articulated unifying hypothesis or interrelated 
set of hypotheses.  Thus, the integrative research projects must represent a 
cohesive and meaningful program of research, with clear interrelationships 
among project leaders and project goals. Each integrative project must employ 
a multidisciplinary approach.  An existing peer reviewed externally funded 
grant or grants, with at least two years of funding remaining at the time of 
the CCPDER award (August 2002) must be used to provide the scientific 
foundation for each integrative research project.  The work in the proposed 
integrative research projects must clearly and significantly amplify, extend 
or bridge the existing research grants and must not represent a mere 
duplication of the currently funded grant or grants.  Thus, the applicant must 
indicate clearly how the integrative research project builds onto or bridges 
to the parent grant or grants yet proposes new work. 

c.  Special information considerations
Applicants must include their specific plans for responding to the "Terms and 
Conditions of Award" section.  Applicants should state their willingness to 
collaborate and share data freely with the other CCPDER program awardees, to 
participate in planning and to serve on the CCPDER Consortium Program Steering 
Committee and be bound by its decisions for setting the standards and 
guidelines for the consortium program operations, and to be able and willing 
to share data and communicate with each other and the NIEHS in an internet 
environment.  Applicants should also describe how they would comply with the 
involvement of an NIEHS Extramural Science Administrator.

APPLICATION FORMAT

Applications are to be submitted on Form PHS 398 (rev 5/2001). All 
instructions and guidelines accompanying the PHS 398 are to be followed, with 
the exception of the sections modified by the specific instructions described 
below. 

In lieu of the preprinted Table of Contents outline on Form Page 3 of PHS 398, 
a Table of Contents should be prepared listing all of the major sections 
described below and paginated to enable reviewers to find specific information 
readily.

The Table of Contents should contain the information described below.  It 
should be divided into the following sections:  Section I - General 
Information, Section II - Research Plan, and Section III - Appendix. The 
following guidelines will provide directions and descriptions for preparing 
each section. Major areas to be listed and paginated in the Table of Contents 
are underlined.

SECTION I - GENERAL INFORMATION

A. FACE PAGE 

Complete all items on the application"s face page. This is Form Page 1 of the 
application, number succeeding pages consecutively.

On line 2, enter the appropriate Request for Applications (RFA) number and 
title, for those applicants applying under the CCPDER-CC, list after the RFA 
title CCPDER-CC and mark the YES box.

B. DESCRIPTION AND PERSONNEL 

On Form Page 2, describe briefly the research program, indicate the emphasis 
of the component research projects, and identify the purposes of the proposed 
cores.

List key scientific and technical personnel participating in the CCPDER. Use 
continuation pages as necessary, numbering consecutively.

C. TABLE OF CONTENTS 

Prepare the Table of Contents as noted above. The major areas to be listed are 
enumerated in these instructions.

D. BUDGET ESTIMATES 

Prepare a series of composite Budget Tables for the CCPDER as requested below.  
A separate detailed budget is required for each research project and 
for each core unit.

1. Composite Budget

a. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 
398 to present the total direct cost budget for all requested support for the 
first year. For each category, such as "PERSONNEL," "EQUIPMENT," etc., list 
the amount requested for each research project and for each core unit.
 
If consortium arrangements have been made involving other institutions or 
organizations, include total costs (direct and F&A) associated with such third 
party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category. Costs for 
purchased services should be itemized under "OTHER EXPENSES."

b. Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS 
398 to prepare a budget, by category, that provides direct cost totals for 
each year of requested support.

2.Individual Project and Core Budgets

a. First year (use Form Page 4 of PHS 398 for each)

b. Total project period (use Form Page 5 of PHS 398 for each)

Consortium Budgets (if applicable) should be presented as described in Item 1 
(Composite Budget), including a budget for the entire proposed project period. 
Total Direct and F & A costs of sub-awardees are to be shown under 
"CONSORTIUM/CONTRACTUAL COSTS" on individual research project or core budgets 
and a detailed consortium budget is to be inserted following the appropriate 
research project or core budgets.

Budget Justifications: Describe the specific functions of key scientific and 
technical personnel, consultants, collaborators, and support staff. For all 
years, explain and justify any unusual items such as major equipment or 
alterations and renovations. For future years of support requested, justify 
any significant increases in any category over the first 12-month budget 
period.  Identify such significant increases with asterisks against the 
appropriate amounts. 

E. BIOGRAPHICAL SKETCH 

Biographical sketches are required for all key scientific personnel 
participating in the research projects and core units as listed on PHS 398 
Format at Page 2. 

Beginning with the CCPDER Director, and following in alphabetical order, 
submit biographical sketches as described in the "Instructions for PHS-398 
Format at Page 6. 

F. RESOURCES 

Overall CCPDER (two page limit). Briefly describe the features of the 
institutional environment that are or would be relevant to the effective 
implementation of the proposed program. As appropriate, describe available 
resources, such as clinical and laboratory facilities, participating and 
affiliated units, patient populations, geographical distribution of space and 
personnel, and consultative resources. Use continuation pages as needed.

SECTION II – INTEGRATIVE RESEARCH PLAN

Include a detailed Table of Contents with pagination (numeric only) at the 
beginning of Section II. Identify each research project or core unit by title, 
and assign each research project a number (I, II, III) and each core unit a 
capital letter (A,B,C) that reflects the order in which the integrative 
research projects and core units are presented in the application research 
plan. For each integrative research project and core unit, provide the name of 
the Principal Investigator or Core Director, and biographical sketches for 
personnel not identified previously.

A. INTRODUCTORY OVERVIEW (20-page limit)

Provide an overview of the entire proposed CCPDER highlighting its central 
theme and goals with respect to gene-environment interactions in PD.  Describe 
how the overall CCPDER can achieve its major objectives.  Explain the proposed 
contribution of each of the projects in achieving the objectives of the 
CCPDER.  Furthermore, the administrative arrangements and support necessary to 
effect the research should be carefully described in the application.  Shared 
resources should be described.  In addition, provide detailed information on 
collaborations, recruitment, facilities and resources. 

1. Purpose and Objectives of the CCPDER. Discuss the philosophy and objectives 
of the CCPDER and general plans for the proposed grant period. Discuss the 
composite research program, highlighting its central theme. List by title and 
investigator the integrative research projects and core units, showing the 
interrelationship between the integrative research projects and the core units 
and their relationship to the central theme.  Describe relevant history 
leading up to the CCPDER application.

Applicants should note that the Principal Investigator and leaders of 
integrative research project must comprise a multidisciplinary team with 
expertise in cellular and molecular neurobiology in addition to at least two 
of the following four areas of PD research: (1) human genetics, (2) 
epidemiology, (3) clinical research, and (4) community outreach and education.

2. Documentation of currently funded research base (not to exceed two pages).    
Provide a consolidated list of the collective scientific funding base for each 
CCPDER.  The funding base is defined as the set of external peer reviewed 
grants that provide the foundation for the integrative research projects.  The 
funding base list should be organized by the integrative research projects 
proposed in the application.  For each integrative project, the title, funding 
source, annual direct costs, duration of award, and brief description must be 
provided for each parent grant.  

Applicants should note that this funding base must total at least $500,000 in 
annual direct costs and that the funding base must extend for at least two 
years following the receipt of the CCPDER award (August 2002). Each 
integrative research project can be based on more than one existing grant, as 
in the case where an integrative research project has the goal of bridging the 
efforts of two or more existing grants.  Each existing grant may provide the 
primary basis for only one integrative research project, however.  That is, it 
is not permissible to propose two or more integrative research projects that 
represent different extensions of the same existing grant or set of grants. 
The funding base should be from external peer reviewed research grants 
supported by the NIEHS, other NIH institutes and centers, and other 
governmental and private agencies in the area of PD or a closely related area 
of neurodegeneration. 

2.  Administration, Organization, and Operation of the CCPDER.  Include 
information on the support and commitment of the parent institution for the 
CCPDER, the authority of the CCPDER Director, the use of the executive and 
external advisory committees, and the method of determining core access and 
space assignment.  Describe organizational framework and provide an 
organizational chart. Applicants should note that External Advisory Committee 
members should not be recruited until the NIH review of applications is 
complete.  Representation of PD patient advocates is required for the External 
Advisory Committee.

3.  Assurances and Collaborative Agreements. Any arrangements for 
collaborative and cooperative endeavors or subcontracting should be 
highlighted. Letters of Intent to Collaborate and Letters of Agreement from 
consultants should be referenced here and included at the end of the 
appropriate research project or core unit. 

The applicant must include a statement of acceptance of NIEHS staff 
participation as described in "NIEHS Extramural Staff Responsibilities." In 
addition, a statement by the Principal Investigator must be included, 
accepting participation on the CCPDER Program Consortium Steering Committee 
and implementing, if applicable, the goals, procedures and policies agreed 
upon by this Steering Committee.

B.  INTEGRATIVE RESEARCH PROJECT DESCRIPTION 

Identify each project by a Roman numeral (I, II, III…) and a title.

Integrative research projects should be organized in the standard PHS 398 
format of an R01 proposal with sections for an abstract, specific aims, 
background and significance, preliminary results, experimental design and 
methods and literature cited.  Each integrative research project must 
represent a significant amplification, extension, integration or bridging of 
an existing peer-reviewed and externally funded research grant or grants.  In 
addition to a description of the specific aims of the integrative research 
project, the application should include a description of the original aims of 
the parent grant(s).  Preliminary data collected under the auspices of the 
parent grant(s) may be included if directly relevant to the aims of the 
integrative research project.  The primary focus, however, should be how the 
proposed new integrative research project extends or builds onto or bridges 
the parent grant(s) by incorporating or strengthening multidisciplinary 
approaches to the stated problem.  To avoid potential for duplication of 
effort, the applicant must clearly articulate how the new work proposed 
differs from that approved in the existing grant or grants that provide the 
scientific foundation for the integrative research project.  Each integrative 
research project should indicate the interrelationships with other proposed 
integrative research projects.  Applicant should describe a plan for achieving 
the stated goals of the Integrated Research Project if the parent grant 
funding is discontinued.

C. CORE DESCRIPTIONS

Identify each proposed core unit by a letter (A, B, C...) and a title 
(GENE EXPRESSION, NEUROIMAGING, ANIMAL MODELS...). 

The Technical Core(s) (limited to five pages) should be organized in the 
standard PHS 398 format.  Applicants should include a description of key 
professional and support staff functions, space and physical resources and 
current and projected services to other core units and integrated research 
projects, and to the CCPDER as a whole. Applicants may propose new Cores or 
may describe a plan for accessing existing Core facilities through fee for 
service or cost sharing arrangements.  Applicants may propose use of Core 
services located outside of the applicant institution through a subcontractual 
arrangement.  

D. ADMINISTRATIVE CORE UNIT DESCRIPTION (three page limit)

The Administrative Core should be organized in the standard PHS 398 format 
(limited to five pages).  Within this section, applicants should include a 
description of the formation of an External Advisory Committee, its role and 
operational processes associated with the committee.  Although a general 
description of the number and characteristics of committee members should be 
provided, External Advisory Committee members should not be recruited until 
the NIH review of applications is complete.  Representation of PD patient 
advocates is required for the External Advisory Committee.  Applicants who 
desire consideration for the CCPER-CC role should include in the 
Administrative Core section a clear description of a management and 
organization plan for the required annual scientific CCPDER Consortium program 
meeting and workshop.  A plan for establishing a formal relationship with 
national PD patient advocacy groups, that includes substantive participation 
in the annual science CCPDER Consortium Program meetings, should be included.

E.  INFORMATION DISSEMINATION/OUTREACH CORE DESCRIPTION (ten page limit)

An Information Dissemination/Outreach Core is a required element for CCPDER 
applicants who wish to be considered to be the CCPPDER-CC.  Applicants who do 
not wish to be considered for a CCPDER-CC should omit this section.  The 
Information Dissemination/Outreach Core should be organized in the standard 
PHS 398 format.  The applicant should describe a plan for creating and 
maintaining a listserver and website that provides general information about 
the overall CCPDER Consortium structure and function, specific integrative 
research projects and other CCPDER Consortium program activities. The web 
pages, related databases and interactive web application pages, if any, will 
be housed on NIEHS web and database servers. The pages will be designed and 
implemented with technologies supported by NIEHS, including the Oracle 
database engine and Cold Fusion web application development environment. These 
tools will be employed on this project as necessary to meet the functional 
goals of the site. The applicant will develop and maintain these products in 
conformance with NIEHS web and database development standards and will 
interact with NIEHS information technology staff as required to ensure that 
these standards are being met.  The website content must be designed for use 
by both the scientific and lay communities.  A plan for gathering and updating 
information from individual CCPDERs should be included. The website should 
include a searchable database for accessing CCPDER-generated documents and 
materials, including reports and any educational/outreach materials produced 
by individual CCPDERs.  The applicant must describe an ongoing process for 
soliciting input from PD patient advocate representatives concerning website 
design and content.  The website must include a clear description of the 
relevance of the CCPDER Consortium program to the public health arena (i.e., 
prevention and intervention strategies in PD).

F.  RESEARCH DEVELOPMENT CORE UNIT DESCRIPTION (Six page limit)

The applicant must describe a process for soliciting and evaluating the 
scientific merit of pilot projects, and for evaluating progress of these 
awards.  A minimum amount of $75,000 direct costs annually should be budgeted 
for three one-year awards of up to $25,000.  These awards will be to fund 
studies involving investigators at multiple CCPDERs.  The solicitation and 
review of future applications will be overseen by the CCPDER Consortium 
Program Steering Committee. The applicant should include an initial pilot 
project description (five page limit) that demonstrates an initial pilot 
project expressing novel ideas and concepts for a pilot project effort. 
Preliminary data extensive technical justifications are not required. The 
focus of the pilot project should be on the novel concept and its feasibility.

E.  CHECKLIST - As required in Form PHS 398

SECTION III - APPENDIX

Include materials as appropriate (see PHS 398).

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the program staff in the Division of Extramural Research and 
Training (DERT), NIEHS.  Incomplete and/or non-responsive applications will be 
returned to the applicant without further consideration.

The specific points of consideration for completeness and responsiveness to 
the RFA are: (1) the general completeness of the application and the 
organizational adequacy for review (this includes both scientific and 
budgetary considerations). The specific points of programmatic responsiveness 
to this RFA include: (1) the appropriateness of the science proposed in regard 
to the mission of the NIEHS and the documentation as requested in this RFA. 

Applications that are complete and responsive to this RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by DERT, NIEHS, in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will receive a written 
critique and 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, assigned a priority score and receive a second 
level review by the National Advisory Environmental Health Sciences Council.

REVIEW CRITERIA FOR THE EVALUATION OF THE OVERALL PROGRAM APPLICATION

The overall program application is evaluated by considering the integrative 
research projects, supporting cores, and the administrative structure, and how 
these multi disciplinary components function together to achieve the goals of 
the CCPDER program.  For the application to receive an overall priority score, 
it must consist of at least three approved integrative research projects, each 
of which has multiple specific aims and are found to have significant and 
substantial merit. The applicant should not be penalized if the parent 
grant(s) for an Integrative Research Project has only the minimum (2 years) 
duration.  Scientific relevance of the project should guide the overall merit 
of the project. 

Specific scientific consideration factors to be evaluated in the consideration 
of the program are as follows:
o  Scientific merit of the program as a whole, as well as that of the 
individual parts.
o  Significance of the overall program goals.  This includes the significance 
and importance of the research program to furthering knowledge of gene 
environment interactions in PD.
o  Cohesiveness and multidisciplinary scope of the program and the 
coordination and interrelationships of all individual research projects and 
cores to the common theme of the CCPDER consortium program.
o  Leadership and scientific ability of the principal investigator and his or 
her commitment and ability to develop a well-defined central research focus 
and to devote adequate time and effort to work within the parameters of the 
CCPDER program research consortia.
o  Past accomplishments of the research team (Principal Investigator, Project 
and Core Leaders)in the proposed areas of research.

REVIEW CRITERIA FOR INTEGRATIVE RESEARCH PROJECTS

The review of the individual Integrative Research Projects is similar to the 
review of individual project grant applications (RO1).  Accordingly, these 
projects must have substantial scientific merit.  The review criteria 
(Significance, Approach, Innovation and Environment) are intended to encourage 
reviewers to focus on the global impacts of each project and the program 
overall, rather than concentrating on the experimental details and their 
critiques.  The review criteria are as follows:

o  Significance: Does this study address an important problem?  If the aims of 
the application are achieved, how will scientific knowledge be advanced?  What 
will be the effect of these studies on the concepts or methods that drive this 
field?

o   Approach: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?  What is the strength of the multidisciplinary approach 
for achieving the stated aims?  What is the adequacy of the proposed plan for 
the Integrative Research Project if the parent grant funding is discontinued?

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

o  Investigator: Is the investigator appropriately trained and well suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers?

o Environment: Does the scientific 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?  Is there evidence of institutional support?

o  When human subjects are involved, the adequacy of plans to include women 
and minorities in the study design and the potential of that design to address 
scientific question(s) proposed must be addressed.

REVIEW CRITERIA FOR INDIVIDUAL TECHNICAL FACILITY CORES

o  Utility of the core to the CCPDER, each core should provide essential 
facilities or service for two or more projects judged to have substantial 
merit (e.g., the number of projects that will benefit from centralized 
administrative and research services, the economy of effort that will be 
realized through use of shared services, etc.)
o  Quality of the facilities or services provided by this core (including 
procedures, techniques, and quality control) and criteria for prioritization 
of usage.
o  Qualifications, experience and commitment of the personnel involved in the 
core.
o  Appropriateness of the budget.

REVIEW CRITERIA FOR RESEARCH DEVELOPMENT CORE

o  Adequacy of process described for soliciting and evaluating pilot projects, 
and for documenting and evaluating progress of pilot projects.
o  Appropriateness of the budget.
o  Conceptual Innovation, relevance to CCPDER goals and technical feasibility 
of the proposed pilot project.

REVIEW CRITERIA - ADMINISTRATIVE CORE

For all applications, in addition to evaluating the scientific components, the 
review will also assess:
o  Environment and resources in which the research will be conducted, 
including availability of space, equipment, or other resources as required, 
and the potential for interaction with scientists from other departments ,
o  Institutional commitment to the requirements of the program, including 
fiscal responsibility and management capability of the institution to assist 
the principal investigator and his or her staff in following DHHS, PHS, and 
NIH policy,
o  Administrative planning and leadership capability to provide for internal 
quality control of ongoing research, the research needs of the consortia, 
allocation of funds, enhancement of internal communication and cooperation 
among the investigators involved in the program, communication with the 
consortia, and replacement if the principal investigator if required on an 
interim or permanent basis,
o  Appropriateness of the budget in relation to the proposed program,
o  Human subject"s protection, animal welfare, and biohazard issues.

REVIEW CRITERIA FOR INFORMATION DISSEMINATION CORE (applies only to CCPDER-CC 
applicants)

o  Experience and commitment of the personnel involved in the core.  Technical 
qualifications of the personnel to provide the desired product using specified 
tools and methods.  (As described in the RFA under Information 
Disssemation/Outreach Core description) 
o  Quality and innovation of overall plan for website design and 
implementation.
o  Appropriateness of planned content and website elements to achieve the 
goals of information dissemination to both scientific and lay communities.
o  Adequacy of plans for evaluating, updating and maintaining the website.
o  Cost-effectiveness of the plans for the Information Dissemination/Outreach 
Core.
o  Adequacy of plans for soliciting input from PD patient advocates.
o  Appropriateness of the budget.

SCHEDULE

Letter of Intent Receipt Date:  February 14, 2002
Application Receipt Date:       March 14, 2002
Peer Review Date:               April 2002
Council Date:                   August 2002
Earliest Anticipated Award:     August 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review),
o Programmatic priorities, and
o Availability of Funds
An award will not be able to be offered for applications that do not have the 
following approved application components as a result of the peer review 
outcome:
o A minimum of three approved integrative research projects, and
o An approved administrative Core.
It should also be noted that Technical Cores that do not serve at least two 
approved research projects will not be able to be funded as independent Cores.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.  Direct inquiries regarding programmatic 
issues to:

Cindy P. Lawler, Ph.D.
Scientific Program Administrator
Organs and Systems Toxicology Branch
Office of Program Development
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
Box 12233, MD EC-23
Research Triangle Park, NC  27709
Telephone:  (919) 316-4671
Fax:  (919) 541-5064
E-mail:  lawler@niehs.nih.gov

Annette Kirshner, Ph.D.
Scientific Program Administrator
Organs and Systems Toxicology Branch
Office of Program Development
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
Box 12233, MD EC-23
Research Triangle Park, NC  27709
Telephone:  (919) 541-0488
Fax:  (919) 541-5064
E-mail:  kirshner@niehs.nih.gov

Direct inquiries regarding fiscal matters to:

Lerlita D. Garcia
Grants Management Specialist
Grants Management Branch
Office of Program Operations
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
Box 12233, MD EC-22
Research Triangle Park, NC  27709
Telephone:  (919) 316-4638
Fax:  (919) 541-2860
E-mail:  garcia1@niehs.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.113.  Awards are made under authorization of the public Health Service Act, 
Title IV, Part A (Public Law 78-410, as amended by Public law 99-158, 42 USC 
241 and 285) and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Part 74 and 92.  This program is not subject 
to the intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.

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

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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