PHARMACOGENETICS RESEARCH NETWORK AND KNOWLEDGE BASE

Release Date:  April 7, 2000

RFA:  GM-00-003

National Institute of General Medical Sciences (http://www.nigms.nih.gov/)
National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov/)
National Human Genome Research Institute (http://www.nhgri.nih.gov/)
National Institute of Environmental Health Sciences 
(http://www.niehs.nih.gov/)
National Library of Medicine (http://www.nlm.nih.gov/)
National Institute of Mental Health (http://www.nimh.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (http://www.niaaa.nih.gov/)

Letter of Intent Receipt Date:  June 9, 2000
Application Receipt Date:       August 9, 2000

PURPOSE

This announcement presents the opportunity to compete to join the recently 
established Pharmacogenetics Research Network and Knowledge Base.  The 
original initiative (RFA GM-99-004, see 
http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-99-004.html) 
was designed to stimulate the creation of a network 
of multidisciplinary, collaborative research groups of investigators that 
support the development of a public Pharmacogenetics Knowledge Base.  The 
intention of this RFA is to expand the scope of the network by adding more 
groups interested in studying how genetic variation contributes to 
interindividual differences in drug responses by collecting comprehensive, 
integrative information about specific proteins and genes.  The focus of 
research for a group will again not be specified, although variations in the 
effects of drugs as mediated by target receptors (or pharmacodynamics) are of 
particular interest.  No further applications will be sought for a group that 
provides a comprehensive production databank or repository.  However, 
applications will be accepted that offer a component or tool that complements 
the existing Pharmacogenetics Knowledge Base.  All groups will be expected to 
work cooperatively towards the goal of making the Pharmacogenetics Knowledge 
Base an information resource of maximum utility to the entire research 
community, that can stimulate future hypothesis-driven research. 
This is one of a pair of initiatives designed to address the collection of 
fundamental knowledge required to predict interindividual differences in drug 
responses.  This RFA is suitable for research conducted by multiple 
collaborative arrangements.  A companion program announcement (PA) entitled 
 Mechanisms Underlying Individual Variations in Drug Responses  (PA-99-016, 
see http://grants.nih.gov/grants/guide/pa-files/PA-99-016.html) describes 
opportunities for support via traditional individual investigator-initiated 
research projects.

HEALTHY PEOPLE 2010

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

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) cooperative 
agreement (U01) award mechanism, an "assistance" mechanism, which is 
distinguished from a regular research grant in that substantial programmatic 
involvement by NIH staff with the awardees is anticipated.  The cooperative 
agreement is used when participation by NIH staff is warranted to support and 
stimulate the recipients  activities by involvement in and otherwise working 
jointly with the award recipients in a partnership role; NIH staff will not 
assume direction, prime responsibility, or a dominant role in the activity.  
Details of the responsibilities, relationships, and governance of studies 
funded under cooperative agreements are discussed later in this document under 
the section Terms and Conditions of Award.  Each component of the 
Pharmacogenetics Research Network and Knowledge Base will be awarded as a 
separate U01.

All applications will be assigned to NIGMS initially for administrative 
reasons.  After discussion with the other participating Institutes, 
applications may be reassigned where they are programmatically most 
appropriate.  Because the scope of research proposed in response to this RFA 
may encompass the interests of several Institutes, applications may receive 
dual assignments based upon established PHS referral guidelines.  The 
anticipated earliest award date is April 1, 2001. 

FUNDS AVAILABLE 

NIH intends to commit approximately $5 to $10 million in FY 2001 to fund 
applications in response to this RFA.  It is anticipated that there will be 
two to four additional groups funded, although the actual funding plan will 
depend upon the scientific opportunities presented and the results of the peer 
review process.  An applicant may request a project period of up to four years 
and a budget for direct costs of up to $2 million per year, with 3% 
inflationary increases allowed in the future years.  Because the nature and 
scope of the proposed research will vary, it is anticipated that the sizes of 
the awards will also vary.  Although the financial plans of the Institutes 
provide support for this program, the awards pursuant to this RFA are 
contingent upon the availability of funds and receipt of a sufficient number 
of applications of outstanding scientific and technical merit.  New and 
renewal applications in this area may be supported in future years, depending 
upon the success and the needs of the Pharmacogenetics Research Network and 
Knowledge Base.  

RESEARCH OBJECTIVES

Background:

Genetic variants can be identified in individuals, families, and populations 
for proteins and genes involved in determining drug responses.  Much more 
biological and clinical research is needed beyond accumulating sequences and 
identifying polymorphisms (variants that occur with a frequency of 1% or 
greater) to correctly interpret the functional consequences of genetic 
variation.  In order to understand which sequence variations are functional 
and how they actually contribute to individual differences in drug responses, 
the genetic variation (genotype) must be related to biochemical changes in 
proteins, to cell and organ functions, to systemic effects, and to the range 
of possible clinical expressions (phenotype).  Once comprehensive biological 
information for a particular protein or gene and its corresponding variants 
has been assembled, it can be catalogued in a manner that is accessible and 
interpretable to a wide range of scientists.  The Pharmacogenetics Knowledge 
Base will link genes and their sequence variants to their encoded proteins, 
their functional changes, and consequent drug response phenotypes (and 
sometimes disease phenotypes). 

Scope and Objectives:

The Pharmacogenetics Research Network and Knowledge Base will have the 
capacity to collect genetic sequence information, detect polymorphic variants, 
identify the functional consequences of genetic variation, and rigorously 
correlate this information with clinical drug responses.  This announcement 
seeks to expand the scope of the network. 

Investigators trained in different areas working as collaborative teams are 
needed to achieve insights into the contribution of genetic variation to 
determining individual drug responses.  Rigorous studies, both basic and 
clinical, are needed to correlate phenotype with genotype.  Researchers 
working at levels ranging from the most molecular to the most clinical, in the 
fields of pharmacology, physiology, genetics, genomics, medicine, medicinal 
chemistry, epidemiology, statistics, bioinformatics, and computational biology 
must demonstrate that they can work together, so that functional variation in 
proteins and genes that may play essential roles in determining drug responses 
can be studied, interpreted, and related to clinical research situations in a 
rapid and efficient manner. 

In this RFA, NIH does not plan to specify in advance which additional 
proteins, genes, or diseases are to be studied in the Pharmacogenetics 
Research Network and Knowledge Base; investigators will propose where they 
want to concentrate their activities.  Both variation in drug 
biotransformation and elimination pathways (pharmacokinetics) and variation in 
the direct effects of drugs on cells and tissues (pharmacodynamics) are of 
interest overall.  However, variation in the effects of drugs as mediated by 
their target proteins in cells and tissues are now of particular interest to 
add to the network.  The receptors and enzymes that are involved in the 
etiology of many major common diseases, for example asthma, cancer, 
cardiovascular diseases, neuropsychiatric disorders, diabetes, and 
inflammation are potential drug targets. The underlying theme should be a 
search for pharmacogenetically important sequence variation.  In some 
instances, a search based upon a candidate gene approach may be appropriate; 
in other situations, a gene discovery program may be a better strategy.  
Preference will be given to groups that add to the breadth of the entire 
Pharmacogenetics Research Network’s efforts. 

The Pharmacogenetics Research Network and Knowledge Base should ultimately 
encompass a variety of pharmacologically important proteins and genes.  This 
will be accomplished by funding a balanced series of Research Groups and 
Knowledge Base Groups that are studying a range of different proteins or genes 
and systematically organizing this information.  For a description of the 
existing funded groups and subject areas that comprise the Pharmacogenetics 
Research Network and Knowledge Base, see 
http://www.nigms.nih.gov/funding/pharmacogenetics.html after April 1, 2000 
(this date is approximate, depending upon when the awards are actually made).   

Research Group Description and Tasks
A Research Group is a group of multidisciplinary, collaborating scientists (at 
one or several sites) employing state-of-the-art, comprehensive approaches to 
examining functional variation in the proteins or genes of interest involved 
in drug responses.  Each should be formed by self-assembly of a highly 
integrated group of investigators into a cross-disciplinary team, and each 
will have a unique blend and breadth of complementary research expertise.  A 
Research Group will conceive, develop, and conduct research focused on 
proteins or genes or a disease of interest to that group, where genetic 
variation is suspected to play a role in determining interindividual 
differences in drug responses. 

In some cases, there may be selected individuals, families, populations, or 
patients already phenotyped for a drug response or for disease progression, 
that can be used to relate a characteristic drug response to a genetic 
variant.  Clinical or epidemiological studies for linkage or association may 
be used to identify genes of interest, and functional studies can be designed 
to examine proteins that may contribute to drug response variations.  
Corresponding sequences from appropriate reference animals may also be 
examined, or mutant, transgenic, or knock-out organism studies may be 
included, as long as the goal is to identify human genetic drug response 
targets or variants.  

The biochemical significance of genetic sequence variation in coding and non-
coding regions should be examined.  There may be a functional role for genetic 
variation in altered transcription, structure, splicing, or stability of mRNA, 
as well as changes in the structure, function, regulation, modification, or 
degradation of the encoded protein(s).  Further human studies may be necessary 
to learn allele frequencies, characterize patterns of inheritance, or 
establish prevalence of a genotype (or haplotype) in selected populations, in 
order to make future predictions of drug responses.  Additionally, the 
population significance can be addressed with statistical associations made 
between genotype and phenotype.  In many circumstances, there may be modifying 
factors (e.g., environment, diet, age, gender) in addition to genetic 
variation, and these contributions should be examined where possible.  

A resource to search for possible variants is the NHGRI Human DNA Polymorphism 
Discovery Resource (see 
http://www.nhgri.nih.gov/Grant_info/Funding/discover_polymorphisms.html), 
which is a diversity-rich, anonymous sample set stored at the NIGMS Human 
Genetic Cell Repository at the Coriell Institute for Medical Research (see 
http://locus.umdnj.edu/nigms/).  Investigators are specifically encouraged to 
use this resource to add to the current body of SNP information, and to 
deposit the information in the SNP database (dbSNP).

It is expected that members of a Research Group will typically have research 
experience with the proteins or genes of interest.  Members of the group 
should represent many of the areas of expertise required to address the 
research problem in a comprehensive manner through collaborations either on- 
or off-site.  Equipment, staffing, or resources may be needed, such as 
acquisition of current technologies for SNP detection, or establishment of a 
transgenic animal colony to study disease progression and variable responses 
to drug therapy.  New technologies may be needed to detect genotype or measure 
phenotype.  New data analysis or mathematical tools may be required at a 
Research Group site, and these can be developed in order to aid in 
interpreting results, such as discerning causality versus association of 
genetic variation.  These situations are only examples; there are many 
possibilities.  

Applicants should request the funds necessary to assemble a Research Group 
with a cross-disciplinary, comprehensive approach to detecting and studying 
pharmacogenetic variation in their selected class of proteins or genes or area 
of focus.  Research Groups should be well-integrated and will be expected to 
represent their research areas.  A mechanism should be proposed to collect 
views from other members of the specific research communities studying the 
proteins or genes of interest.  These views will be presented and discussed at 
the Steering Committee meetings (see below).

Knowledge Base Group Description and Tasks
A Knowledge Base Group is a group of bioinformatics scientists contributing to 
the aim of designing and developing a public Pharmacogenetics Knowledge Base, 
which will become available to all researchers for study and analysis.  This 
repository will contain and correlate the information necessary to make 
pharmacological, and possibly disease-related, interpretations based upon 
genetic variation.  A central Pharmacogenetics Knowledge Base is currently 
under development.  Therefore, no further applications will be sought for a 
comprehensive production databank or repository.  However, a potential 
applicant may propose a component or tool that is complementary to and 
consistent with the existing Pharmacogenetics Knowledge Base.

The Pharmacogenetics Knowledge Base (see a description of the funded Knowledge 
Base at http://www.nigms.nih.gov/funding/pharmacogenetics.html) will link 
genomic, molecular, cellular, and clinical data for systems where variation 
information is required to optimally predict therapeutic drug responses.  A 
secure, stable, interactive central structure is being created that will link 
to other biological and clinical data resources.  The primary Knowledge Base 
Group will cover the design, implementation, and maintenance of the 
repository.  Modelling and analysis of the data, as well as the development of 
support strategies to fulfill both the submitters  and the users  requirements 
are planned.

Ultimately, the Pharmacogenetics Knowledge Base should serve as a foundation 
for future hypothesis-driven experiments, and will be a useful resource to 
discover previously unsuspected correlations, perhaps with genes not yet known 
to contribute to individual variations in drug responses.  The 
Pharmacogenetics Knowledge Base architecture should evolve to integrate all 
types of information regarding sequence, function, structure, and 
distribution, and reflect concepts where possible such as temporal or 
sequential responses.  It must allow for the possibility of multiple functions 
per gene, and for genes that interact with non-genetic factors such as the 
environment, leading to complex predictors of a drug response.  

While one Pharmacogenetics Knowledge Base is the final goal, it may be 
necessary to develop it in stages, thus applications for significant 
components that complement the central Pharmacogenetics Knowledge Base will be 
considered.  A new Knowledge Base Group may propose to develop computational 
tools to view and evaluate the data in different ways, and to query the data 
to identify new relationships, for example, the regulation of blocks of genes, 
or pleiotropic responses.  The goal will be to explore complex, interconnected 
data, with as yet unknown patterns and relationships, and to integrate the 
data in order to enhance understanding of its biological significance. 

All aspects of the component design should be considered and discussed, and 
the approaches proposed should be clearly explained and justified.  In the 
final form, these functions must be presented in a user-friendly manner.  
Examples should be given where possible.  A willingness and practical ability 
to work with the central Pharmacogenetics Knowledge Base Group are required.  
Resources should be requested commensurate with these and other goals as they 
are identified.

Steering Committee Description and Tasks
A Steering Committee will be the main governing body for the Pharmacogenetics 
Research Network and Knowledge Base.  The Steering Committee will include 
representation from each of the new Research Groups and Knowledge Base Groups 
(along with the existing awarded groups), up to two additional NIH 
Scientist/Administrators (beyond the six identified in the original RFA) of 
the appropriate scientific expertise (e.g., pharmacology, genetics, 
epidemiology), as well as selected scientists other than the awardees when 
additional expertise is required to provide committee breadth and balance.  
NIH representation on the Steering Committee will never make up a majority of 
the total number. 

The Steering Committee will discuss the overall progress made within the 
Pharmacogenetics Research Network and Knowledge Base at its meetings.  The 
committee will make recommendations regarding how data should be obtained and 
expressed, in order to encourage data collection that is as uniform and yet as 
complete as possible and maximally valuable to all investigators.  The 
committee will discuss and advise development of the Pharmacogenetics 
Knowledge Base, and it will seek to develop common guidelines and procedures 
for depositing the information.  The committee will work to set standards for 
data format and nomenclature.  The Steering Committee will also identify and 
discuss any issues that arise in connection with the scientific aspects of the 
Pharmacogenetics Research Network and Knowledge Base.  It can create 
information-gathering subcommittees to follow up on particular issues or needs 
at any time.

The Steering Committee will also listen to the views of the scientific 
research communities which the Research Groups represent in their respective 
fields, and consider how the Pharmacogenetics Research Network and Knowledge 
Base can have an impact on the larger community.  In exchange for gaining the 
equipment, staffing, resources, and infrastructure, the Research Groups must 
be willing to consider addressing these future, related scientific needs when 
the time comes, as discussed through the Steering Committee.  One Research 
Group might consent to assume a particular task, subject to mutual agreement, 
and funding being provided by NIH for a project.  In this manner, the 
Pharmacogenetics Research Network can serve as a resource for scientists 
conducting investigations outside of the Research Groups.

The Steering Committee will in general advise NIH on scientific opportunities, 
emerging needs, or impediments.  There should be continued dialogue and a 
bidirectional exchange of ideas and information between the biological and the 
informatics dimensions of the overall Pharmacogenetics Research Network and 
Knowledge Base.  To facilitate this bidirectional exchange, each Research 
Group will be asked to identify a key data liaison individual with the 
appropriate experience to interact with the central Pharmacogenetics Knowledge 
Base. 

Applicants should request funds incorporating to a plan to send the Principal 
Investigator or his/her designate to attend the Steering Committee meetings in 
Bethesda, MD at least twice per year.  Funds should also be requested to 
permit the data liaison individual to meet with a representative of the 
Pharmacogenetics Knowledge Base at least twice per year in Bethesda, MD (these 
meetings may be held at alternate sites).    

SPECIAL REQUIREMENTS FOR COOPERATIVE AGREEMENTS 

I.  Definitions

AWARDEE:  The institution to which a cooperative agreement is awarded

COOPERATIVE AGREEMENT (U01):  An assistance mechanism in which there is 
anticipated substantial programmatic involvement by NIH staff with the 
recipient organizations during performance of the planned activities
PRINCIPAL INVESTIGATOR:  The person who assembles the project (for either a 
Research Group or Knowledge Base Group) and is responsible for submitting the 
application in response to this RFA and for performance of the project

PHARMACOGENETICS RESEARCH NETWORK AND KNOWLEDGE BASE:  A series of Research 
Groups and Knowledge Base Group(s), each funded by a separate cooperative 
agreement, working together to study pharmacogenetic variation
 
RESEARCH GROUP:  A group of multidisciplinary, collaborating biological 
scientists (at one or several sites) employing a state-of-the-art, 
comprehensive approach to examining functional variation in the proteins or 
genes of interest involved in drug responses

KNOWLEDGE BASE GROUP:  A group of bioinformatics scientists or computational 
biologists responsible for contributing to the design, development, 
implementation, or maintenance of the central Pharmacogenetics Knowledge Base

PHARMACOGENETICS KNOWLEDGE BASE:  A comprehensive central public repository, 
with computational tools, for the storage, integration, and use of 
pharmacogenetic/pharmacogenomic information

NIH SCIENTIST/ADMINISTRATORS:  Representative NIH extramural staff (up to 
eight) who serve on the Steering Committee, who have substantial coordinating 
scientific roles on the Steering Committee and can guide its recommendations 
based upon their knowledge of other, related NIH-supported research and 
resource activities

NIGMS PROGRAM DIRECTOR:  NIGMS extramural staff person who provides 
stewardship for the awards, and evaluates and implements the advice of the 
Steering Committee for allocating NIH support; the NIGMS Program Director also 
coordinates administrative management of the Pharmacogenetics Research Network 
and Knowledge Base

STEERING COMMITTEE:  A committee that is the main governing body of the 
Pharmacogenetics Research Network and Knowledge Base.  Membership will include 
representation from each of the Research Groups and Knowledge Base Groups, NIH 
Scientist/Administrators of the appropriate scientific expertises, as well as 
selected scientists other than the awardees where additional expertise is 
required, when necessary for committee breadth and balance.  NIH 
representation on the Steering Committee will never make up a majority of the 
total. 

ARBITRATION PANEL:  A panel formed as needed to review scientific or 
programmatic disagreements (within the scope of the award) that may arise 
between the Pharmacogenetics Research Network and Knowledge Base and the NIH.  
It will be composed of three members:  a designee of the Steering Committee 
chosen without NIH staff voting, one NIH designee, and a third designee with 
expertise in the relevant area who is chosen by the other two; in the case of 
an individual disagreement, the first member may be chosen by the individual 
awardee.  

II.  Terms and Conditions of Award

The following Terms and Conditions will be incorporated into the award 
statement and will be provided to the Principal Investigator as well as to the 
appropriate institutional official, at the time of award.  The following 
special terms 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, PHS, and NIH grant administration policies:

The administrative and funding instrument used for this program will be the 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism), in which substantial NIH programmatic involvement 
with the awardees is anticipated during performance of the activities.  Under 
the cooperative agreement, the NIH purpose is to support and stimulate the 
recipients  activities by involvement in and otherwise working jointly with 
the award recipients in a partnership role; it is not to assume direction, 
prime responsibility, or a dominant role in the activities.  Consistent with 
this concept, the dominant role and prime responsibility resides with the 
awardees for the project as a whole, although specific tasks and activities 
may be shared among the awardees and the NIH through the Steering Committee.  

1. Principal Investigator Rights and Responsibilities

The Principal Investigator will coordinate project activities scientifically 
and administratively at the Institution.  The Principal Investigator will have 
the primary responsibility for defining the details for projects within the 
guidelines of this RFA, and for performing the scientific activities.  A 
Principal Investigator will agree to accept close coordination, cooperation, 
and participation of NIH staff in those aspects of management of the project 
as described under "NIH Scientist/Administrator Responsibilities".  Awardees 
agree to accept and implement the guidelines of the Steering Committee 
regarding data release into the Pharmacogenetics Knowledge Base.  Awardees 
will retain custody of and have primary rights to the data developed under 
these awards, subject to Government rights of access consistent with current 
HHS, PHS, and NIH policies.  

The Principal Investigator of a Research Group or Knowledge Base Group will:

o    Determine and coordinate the experimental approaches and procedures
o    Set project milestones for the Research Group or Knowledge Base Group 
o    Accept and implement common guidelines approved by the Steering Committee
o    Submit data to the Pharmacogenetics Knowledge Base, according to policies 
agreed upon and established by the Steering Committee 
o    Solicit representative views of other researchers for the proteins or 
genes of interest
o    Attend Steering Committee meetings, and participate in the cooperative 
nature of the group

2. NIH Scientist/Administrators Responsibilities

The NIH Scientist/Administrators are representative NIH extramural staff (up 
to eight) who will serve on the Steering Committee based upon their areas of 
scientific expertise (e.g., pharmacology, genetics, epidemiology) and actively 
guide development of the Pharmacogenetics Research Network and Knowledge Base 
by providing overall advice and coordination.  They should facilitate a 
partnership relationship between NIH and the Research Groups and Knowledge 
Base Groups, and ensure that the directions taken remain consistent with NIH’s 
missions and goals.  They will make recommendations and provide specific 
guidance to aid in both accomplishing the existing goals and addressing 
emerging research opportunities.  These tasks are in addition to the normal 
stewardship role of providing scientific oversight, as well as monitoring 
adherence to policies and procedures specific to the funding Institute.  The 
role of NIH staff will be to facilitate and contribute, but not to direct 
activities.  It is anticipated that decisions will be reached by consensus 
with the Principal Investigators through the Steering Committee. 

The NIH Scientist/Administrators will:

o    Actively share his/her relevant expertise and overall knowledge
o    Help to coordinate activities among the awardees, commensurate with their 
expertise
o    Be information resources about ongoing NIH-supported research and 
resource collections 
o    Attend Steering Committee meetings, and participate in the cooperative 
nature of the group
o    Promote the Pharmacogenetics Knowledge Base to the scientific community 
at large
o    Assist in implementing recommendations for allocating NIH support among 
the awardees
o    Monitor adherence to policies and procedures of the funding Institute

3. Collaborative Responsibilities

A Steering Committee will serve as the governing board of the Pharmacogenetics 
Research Network.  Membership will include representation from each of the 
Research Groups and Knowledge Base Groups, up to eight NIH 
Scientist/Administrators of the appropriate scientific expertises (e.g., 
pharmacology, genetics, epidemiology), as well as selected scientists other 
than the awardees when additional expertise is required as necessary for 
committee breadth and balance.  The rest of the Steering Committee will 
appoint these members by majority vote.  NIH representation on the Steering 
Committee will not make up a majority of the total number.  Each member will 
have one vote.  The NIGMS Program Director is not a member of the Steering 
Committee, but will facilitate creation of the group and will attend all 
meetings.  Awardee members of the Steering Committee will be required to 
accept and implement common guidelines and procedures approved by the Steering 
Committee.

The NIGMS Program Director will schedule the meetings of the Steering 
Committee and actively assist the Chair in developing the meeting agendas.  
The Chair will run the Steering Committee meetings.  Two meetings will be held 
each year, usually in Bethesda, MD.  Around the time of the meetings, the data 
liaisons of the Research Groups and representatives of the Pharmacogenetics 
Knowledge Base will also meet, possibly in Bethesda, MD, or possibly at the 
central Pharmacogenetics Knowledge Base site.  Subcommittees may be 
established by the Steering Committee as necessary.  Additional members may be 
added by action of the Steering Committee, through discussion with the NIGMS 
Program Director.  The NIGMS Program Director will ensure coordination of the 
Steering Committee’s activities and implementation of the group’s 
recommendations. 

The Steering Committee will:

o    Serve as the main governing board
o    Discuss progress within the Pharmacogenetics Research Network and 
Knowledge Base 
o    Set standards and work to standardize data format and nomenclature
o    Develop common guidelines and procedures
o    Consider the representative views of other researchers
o    Participate in the process of developing a cohesive group
o    Advise NIH on scientific opportunities, emerging needs, or impediments
o    Ensure the timely release of data to the Pharmacogenetics Knowledge Base

4. Administrative Coordination Activities

The NIGMS Program Director will assume responsibility for normal stewardship 
of the awards, and for coordination of the Pharmacogenetics Research Network 
and Knowledge Base.  Logistical arrangements will be made for the Steering 
Committee meetings and other administrative duties related to the committee 
functions, such as conference calls, report mailings, publications tracking, 
etc.  These activities may be accomplished by a variety of arrangements, such 
as by adding funds to the Research Groups or Knowledge Base Groups to support 
an administrative contractor.  Data and intellectual property will not be 
handled centrally prior to its public release; the awardees are responsible 
for providing data tracking.  If clinical studies are proposed, NIH may 
establish a Data and Safety Monitoring Board(s).  

5. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within 
the scope of the award) between award recipients and the NIH may be brought to 
arbitration.  An Arbitration Panel composed of three members will be convened.  
It will be composed of three members:  a designee of the Steering Committee 
chosen without NIH staff voting, one NIH designee, and a third designee with 
expertise in the relevant area who is chosen by the other two; in the case of 
an individual disagreement, the first member may be chosen by the individual 
awardee.  This special arbitration procedure in no way affects the awardee's 
right to appeal an adverse action that is otherwise appealable in accordance 
with PHS regulations 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR 
Part 16.

6. Milestones and Evaluations

Applicants should define yearly milestones in their applications (as well as 
in their progress reports), and the selected awardees will have the 
opportunity to modify these milestones at the time of their awards.  The 
awardees  milestones will be provided to the Steering Committee.  It is 
expected that the milestones should be adjusted annually at the award 
anniversary dates, both to incorporate a group’s scientific accomplishments 
and progress in the field in general, as well as to reflect the 
recommendations of the Steering Committee.  In accordance with the procedure 
described above, the NIH Scientist/Administrators may recommend augmenting any 
project, as discussed through the Steering Committee, or reducing or 
withholding funds for any project that substantially fails to meet its 
milestones or to remain state-of-the-art. 

The Director, NIGMS, retains the right to call a meeting of advisors, most 
likely members of the National Advisory General Medical Sciences Council or 
their designee(s), at any time to provide advice on the scientific progress of 
the Pharmacogenetics Research Network and Knowledge Base.  It is anticipated 
that such a group of advisors may want to attend a meeting of the Steering 
Committee as part of its fact-finding mission.  Any information or reports 
will be shared with the other Institutes/Centers of the NIH participating in 
this initiative and the Director, NIH.
 
ISSUES IN RESEARCH INVOLVING HUMAN SUBJECTS 

The nature of the research proposed in response to this initiative will likely 
include applications to conduct studies on the genetic basis of variation in 
drug responses among different racial, ethnic, and sociocultural populations, 
or in individuals and families affected by particular diseases.  Sensitivity 
to issues involving the protection of human subjects will be required in 
approaching this research.  Every effort should be made to consider the 
potential impact of the proposed research on the particular group proposed for 
study.  Careful consideration should be given to the potential risks of 
stigmatization and discrimination as well as the benefits of the knowledge to 
be gained.  Thorough, current, and clear informed consent of the appropriate 
scope must be obtained from all participants.  Subjects must be informed about 
the potential for information generated from their samples being deposited 
into the Pharmacogenetics Knowledge Base.  

The value of the information gained through studies of human genetics will be 
diminished if that information is misinterpreted or misused to stigmatize or 
discriminate against defined populations.  Thought must be given to these 
issues in human subjects research prior to responding to this RFA with a 
application.  Clear plans for recruitment, informed consent, and the 
protection of privacy and confidentiality of human subjects should be 
addressed in the application and will be considered during the review process.  
Potential applicants are referred to the NIH Office of Protection from 
Research Risks (OPRR, http://grants.nih.gov/grants/oprr/oprr_t.htm) for 
discussion of the NIH application requirements, and also to the OPRR 
Institutional Review Board Guidebook Chapter 5 - Human Genetics Research 
(http://www.hhs.gov/ohrp/irb/irb_chapter5.htm) and other applicable 
sections, as well as to the Ethical, Legal, and Social Issues Program (ELSI) 
of NHGRI (http://www.nhgri.nih.gov/ELSI/) for discussion of human subjects 
protections related to human genetic research.  

Applicants are particularly directed to review the advice received from the 
NIGMS Populations Advisory Group found at 
http://www.nigms.nih.gov/funding/pharmacogenetics.html.  NIH Program Staff 
(listed below) may also be contacted and can provide guidance on current NIH 
policies and practices in this area.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that women and members of minority groups and their 
subpopulations must be included in all NIH supported biomedical and behavioral 
research projects involving human subjects, unless a clear and compelling 
rationale and justification is provided 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 research involving human subjects should read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which was published in the Federal Register of March 28, 1994 (FR 
59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 
11, March 18, 1994, and is available at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html. 

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

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

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 for 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.

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 
and facsimile numbers of the Principal Investigator, the identities of other 
key personnel and participating institutions, and the number and title of this 
RFA.  Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information it 
contains allows I/C staff to estimate the potential review workload and plan 
the review.  

The letter of intent is to be sent by June 9, 2000 to:

Rochelle M. Long, Ph.D.
Pharmacology, Physiology, and Biological Chemistry Division
NIGMS, NIH
Building 45, Room 2AS.49G, MSC 6200
45 Center Dr. (for express/courier service)
Bethesda, MD  20892-6200
Telephone:  (301) 594-1826
Fax:  (301) 480-2802
E-mail:  [email protected]

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, E-mail:  
[email protected], URL: http://grants.nih.gov/grants/forms.htm.

The RFA label available in the PHS 398 (rev. 4/98) 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 sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

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

Rochelle M. Long, Ph.D.
Pharmacology, Physiology, and Biological Chemistry Division
NIGMS, NIH
Building 45, Room 2AS.49, MSC 6200
45 Center Dr. (for express/courier service)
Bethesda, MD  20892-6200
Telephone:  (301) 594-1826
Fax:  (301) 480-2802
E-mail:  [email protected]

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

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 application requirements:

An integrated application should be prepared for either a Research Group or a 
Knowledge Base Group.  The aim is to present a comprehensive and cross-
disciplinary team approach to the problem being studied.  Some components may 
exist as cores or resources that are integral to the entire group.  The 
components are expected to be much more interdependent than typically found in 
other large grant applications (such as program project grant applications).  

Each entire application should have a face page, abstract, consolidated 
budget, key personnel listing, biographical sketches, other support, existing 
resources and facilities, letters of collaboration, etc.  The page limit for 
the research plan (including specific aims, background and significance, 
preliminary studies, and research design and methods) is increased to 60 pages 
total.  See also the specific instructions for a Research Group or Knowledge 
Base Group application below.

For a Research Group, an overview section should be prepared that includes an 
overall description which defines the scope and objectives, and provides the 
rationale for selection of the area of scientific concentration.  Usually, for 
a Research Group, this would be the choice of proteins or genes, or perhaps a 
disease/model of interest, where genetic variation contributes to differences 
in drug responses.  The application should have sections that are highly 
integrated, in order to provide a multidisciplinary approach to studying the 
proteins or genes of interest.  All parts of the application must be described 
in sufficient detail to be completely understood, with the appropriate goals 
and timetable.  

These additional criteria should now be specifically addressed in all new or 
revised Research Group applications -

1. Explain the impact of understanding the pharmacogenetics of the proteins, genes, 
or disease(s) being studied, and how adding this area to the Network will advance 
the field overall.

2. Defend the effectiveness of the strategy chosen to approach the problem, and why 
it was chosen over the alternative approaches (e.g. a candidate gene vs. a gene 
discovery approach).

3. Justify how the subject area of the application complements the existing 
network of funded cooperative agreements (see the funded investigators and 
subject areas posted at 
http://www.nigms.nih.gov/funding/pharmacogenetics.html).

For a Knowledge Base Group, an overview section should be prepared that 
includes an overall description which defines the scope and objectives, and 
presents a strategy for creating a central, public Pharmacogenetics Knowledge 
Base.  All parts of the application must be described in sufficient detail to 
be completely understood, with the appropriate goals and timetable. 
 
These additional criteria should now be specifically addressed in all new or 
revised Knowledge Base Group applications  

1. Defend how the component or computational tool complements the existing 
Pharmacogenetics Knowledge Base structure, and offers an additional 
dimension or feature not previously available, yet supports a single 
information repository.

2. Justify how the subject area of the application fits in with the existing 
network of funded cooperative agreements (see the funded investigators and 
subject areas posted at 
http://www.nigms.nih.gov/funding/pharmacogenetics.html).

Additionally, the following areas should be addressed, where appropriate, in 
the respective applications: 

For a Research Group, describe the timing for release of data into the 
Pharmacogenetics Knowledge Base (this may be modified by recommendation of the 
Steering Committee), or other databases

For a Research Group, describe plans for handling intellectual property 
resulting from the studies, or for commercialization of any discoveries (and 
implications for participating subjects)

For a Research Group, describe plans for human subjects, including 
definition(s) of the population(s), plans for recruitment, informed consent 
forms (describing anticipated risks and benefits, plans for subject 
confidentiality, deposition of information into a database, follow-up with 
participants), plans for stored or shared samples (and the prior informed 
consents permitting this), or use of any established sample sets 

For a Research Group, describe the phenotyping criteria (use NIH standards 
where standardized criteria exist, e.g., information on clinical diagnostic 
tests used for studies of the genetics of brain disorders such as 
schizophrenia, bipolar disorder, and late-onset Alzheimer’s disease can be 
found at http://zork.wustl.edu/nimh/NIMH_initiative/
NIMH_initiative_link.html)

For a Research Group, a data liaison person with the appropriate experience 
should be identified, who will interact with the Pharmacogenetics Knowledge 
Base 

For a Knowledge Base Group, describe the timing and method desired for receipt 
of information into the Pharmacogenetics Knowledge Base, as appropriate for 
the scope of the application (this may be modified by recommendation of the 
Steering Committee)

For a Research Group or Knowledge Base Group, identify any unique resources, 
services, or facilities at the institution (even if support is not sought 
here, e.g., a General Clinical Research Center, GCRC)

For a Research Group or Knowledge Base Group, describe in detail any other 
support that significantly impacts this application (even if funding is not 
sought here, e.g., where knowledge of the ongoing research projects is 
essential to the evaluation of this application)

For a Research Group or Knowledge Base Group, describe plans for sharing any 
materials with other researchers (e.g., samples, reagents, software)

For a Research Group or Knowledge Base Group, specify the yearly milestones 
(these will be provided to the Steering Committee, if the application is 
awarded)

For a Research Group or Knowledge Base Group, describe the mechanism for 
administration of the research activities within the Group (e.g., regular 
meetings, staffing, data exchange, external evaluations, etc.)

For a Research Group or Knowledge Base Group, state the mechanism for 
collecting other researchers  views

For a Research Group or Knowledge Base Group, funds should be requested for 
the Principal Investigator or his/her designate to attend two Steering 
Committee meetings annually in Bethesda, MD

For a Research Group or Knowledge Base Group, funds should be requested for 
the data liaison person to meet with a representative of the Pharmacogenetics 
Knowledge Base two times annually in Bethesda, MD (these meetings may be moved 
to the central Pharmacogenetics Knowledge Base site, if practical)

For a Research Group or Knowledge Base Group, funds should be requested to 
cover any data tracking and monitoring procedures, or data transfer activities 
associated with coordination of the Pharmacogenetics Research Network and 
Knowledge Base (e.g., reporting to a Data and Safety Monitoring Board for 
clinical studies, costs of depositing data into the Pharmacogenetic Knowledge 
Base, etc.)

For a Research Group or Knowledge Base Group, the intellectual property 
policies of the applicant institution should be presented 

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the Center for 
Scientific Review (CSR) and for responsiveness by NIGMS.  Incomplete and/or 
non-responsive applications will be returned to the applicant without further 
consideration.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
CSR, 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 appropriate National Advisory Council or Board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments reviewers will be asked to 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.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that 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, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

1. 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?

2. 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?

3. Innovation:  Does the program employ novel concepts, approaches or method?  
Are the aims original and innovative?  Do the projects challenge existing 
paradigms or develop new methodologies or technologies?

4. Investigator:  Are the investigators 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 (if any)?

5. 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?

Applicants will be evaluated in the review process for their response to the 
Research Objectives, described above, and for their ability to create an 
infrastructure through complementary, synergistic connections.  In addition, 
the scientific and technical criteria listed in the special application 
requirements above will be considered and judged for appropriateness.  The 
initial review group will also examine any special needs for the protection of 
human subjects and the safety of the research environment. 

In accordance with NIH policy, all applications will be reviewed with respect 
to the following:

o    The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated.

o    The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o    The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

o    The adequacy of the proposed plan to share data.

o    The additional scientific and technical merit criteria specific to the 
objectives of the RFA as described above, under Special Application 
Requirements.

Schedule

Letter of Intent Receipt Date:    June 9, 2000
Application Receipt Date:         August 9, 2000
Peer Review Date:                 Fall 2000 
Advisory Council Date:            January 2001
Earliest Anticipated Award Date:  April 1, 2001

AWARD CRITERIA

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

o    scientific merit (as determined by peer review)
o    availability of funds
o    program priorities
o    programmatic balance

The NIH retains the flexibility to select and assemble components of the 
Pharmacogenetics Research Network and Knowledge Base that optimally blend the 
research areas, experience, creativity, and the applicants  collective 
knowledge and combined expertises in the background sciences.

INQUIRIES
 
Inquiries concerning this RFA are encouraged.  NIH staff welcome the 
opportunity to clarify any issues or questions from potential applicants.

Frequently asked questions will be posted at 
http://www.nigms.nih.gov/funding/pharmacogenetics.html and updated as 
necessary.

Direct inquiries regarding programmatic issues to:

Rochelle M. Long, Ph.D.
Pharmacology, Physiology, and Biological Chemistry Division
NIGMS, NIH
Building 45, Room 2AS.49G, MSC 6200
(45 Center Drive for express/courier service)
Bethesda, MD  20892-6200
Telephone:  (301) 594-1826
Fax:  (301) 480-2802
E-mail:  [email protected]

Susan Banks-Schlegel, Ph.D.
Division of Lung Diseases
NHLBI, NIH
6701 Rockledge Drive, Room10018
Bethesda, Maryland 20892-7952
Telephone:  (301) 435-0202
Fax:  (301) 480-3557
E-mail:  [email protected]

Lisa D. Brooks, Ph.D.  
Division of Extramural Research
NHGRI, NIH. 
Building 31,  Room B2B07
Bethesda, MD 20892-2033
Telephone:  (301) 435-5544
Fax:  (301) 480-2770
E-mail:  [email protected]

Jose Velazquez, Ph.D.
Division of Extramural Research and Training
NIEHS, NIH 
P.O. Box 12233
Research Triangle Park, NC  27709
Telephone:  (919) 542-4998
Fax:  (919) 541-4937
E-mail:  [email protected]

Hemin Chin, Ph.D.
Division of Basic and Clinical Neuroscience Research
NIMH, NIH
Parklawn Building, Room 10C-26
Rockville, MD  20857
Telephone:  (301) 443-1706
Fax:  (301) 443-9890
E-mail:  [email protected]

Thomas Kresina, Ph.D.
Division of Basic Research
Willco Building, Suite 402
NIAAA, NIH
Bethesda, MD  20892-7003
Telephone:  (301) 443-6537
Fax:  (301) 594-0673
E-mail:  [email protected]

Peter Clepper
Division of Extramural Programs
One Rockledge Center, Room 301, MSC 6075
NLM, NIH
Bethesda, MD  20892-6075
Telephone:  (301) 594-4882
Fax:  (301) 402-2952
E-mail:  [email protected]

Direct inquiries regarding review issues to:

Jeanne N. Ketley, Ph.D.
Cardiovascular Sciences Integrated Review Group
CSR, NIH
Two Rockledge Center, Room 4130, MSC 7814
Bethesda, MD 20892-7814
(6701 Rockledge Drive and zip code 20817 for express/courier service)
Telephone:  (301) 435-1789
Fax:  (301) 480-2644
E-mail:  [email protected]

Direct inquiries regarding fiscal matters to:

Antoinette Holland
Grants Administration Branch
NIGMS, NIH
Building 45, Room 2AN.50B, MSC 6200
(45 Center Drive for express/courier service)
Bethesda, MD  20892-6200
Telephone:  (301) 594-5132
Fax:  (301) 480-3423
E-mail:  [email protected]

Jane R. Davis
Grants Operations Branch
NHLBI, NIH
Two Rockledge Center, Room 7174
Bethesda, MD  20892-7926
Telephone:  (301) 435-0166
Fax:  (301) 480-3310
E-mail:  [email protected] 

Jean Cahill
Grants Management Office
NHGRI, NIH
Building 38A, Room 613
Bethesda, MD  20892-6050
Telephone:  (301) 402-0733
Fax:  (301) 402-1951
E-mail:  [email protected]

Dorothy Duke
Division of Extramural Research and Training
NIEHS, NIH
P.O. Box 12233, MD EC-22
Research Triangle Park, NC  27709
Telephone:  (919) 541-2749
Fax:  (919) 541-2860
E-mail:  [email protected]

Diana S. Trunnell
Grants Management Branch
NIMH, NIH
Parklawn Building, Room 7C-08
Rockville, MD  20857
Telephone:  (301) 443-2805
Fax:  (301) 443-6885
E-mail:  [email protected]

Linda Hilley
Grants Management Branch
NIAAA, NIH
Willco Building, Suite 504
Bethesda, MD  20892-7003
Telephone:  (301) 443-4704
Fax:  (301) 443-3891 
E-mail:  [email protected]

Dwight Mowery
Division of Extramural Programs
One Rockledge Center, Room 301, MSC 6075
NLM, NIH
Bethesda, MD  20892-6075
Telephone:  (301) 594-4221
Fax:  (301) 402-2952
E-mail:  [email protected] 

Although the National Cancer Institute (NCI) is not a formal participant in 
this RFA, NCI maintains an interest in genes and proteins involved in the 
activity or metabolism of agents used in the prevention and treatment of 
cancer, or in the cause and progression of cancer.  For more information at 
NCI contact: Mary K. Wolpert, Ph.D., (301) 496-8783, 
[email protected].

Although the National Institute on Drug Abuse (NIDA) is not a formal 
participant in this RFA, NIDA is interested in the genetics of drug abuse 
vulnerability, and has a cell and data repository (The NIDA Center for Genetic 
Studies) that receives clinical and genetic data related to addiction.  For 
more information at NIDA contact:  Jonathan Pollock, Ph.D., (301) 443-6300, 
[email protected].

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.113, 93.172, 93.242, 93.273, 93.837, 93.879, 93.859, 93.862 (NIEHS, NHGRI, 
NIMH, NIAAA, NHLBI, NLM, NIGMS [2]).  Awards are made under authorization of 
the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended 
(42 USC 241 and 284) and administered under NIH Grants Policy Statement 
(10/1/98) and Federal Regulations 42 CFR 52 and 45 CFR Part 74.  This program 
is not subject to the intergovernmental review requirements of Executive Order 
12372 or Health Systems Agency review.

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

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