and Human Services (HHS)
EXPIRED
POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS NETWORK
Release Date: May 29, 2001
RFA: RFA-DK-01-029 (Reissued as RFA-DK-07-504 and RFA-DK-07-008)
National Institute of Diabetes and Digestive and Kidney Diseases
Letter of Intent Receipt Date: October 16, 2001
Application Receipt Date: November 16, 2001
PURPOSE
The Division of Kidney, Urologic and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) invites cooperative agreement applications to establish a
network to design and implement clinical trials to slow the progressive
loss of renal function in polycystic kidney disease (PKD). The
Network, consisting of a Data Coordinating Center (DCC) and
Participating Clinical Centers (PCCs), will develop and execute both
pilot and feasibility trials and a large randomized controlled clinical
trial on blockade of the renin-angiotensin axis in patients with PKD.
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,
Polycystic Kidney Disease Treatment Network , 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, for-profit and non-profit
institutions, public and private organizations, such as universities,
colleges, hospitals, units of State and local government, and eligible
agencies of the Federal government. Foreign institutions are not
eligible to apply. Racial/ethnic minorities, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
An institution or organization may apply for both a Participating
Clinical Center and a Data Coordinating Center. However, separate
applications are required for each of these study components. The same
person may not serve as the Principal Investigator of a PCC and the
DCC, and other key staff cannot be shared by these study units.
MECHANISM OF SUPPORT
The administrative and funding instrument to be used for these awards
will be the cooperative agreement (U01). The cooperative agreement is
an assistance mechanism in which substantial NIDDK scientific and
programmatic involvement is anticipated during the performance of the
activity. Under the cooperative agreement, the NIDDK’s purpose is to
support and encourage the recipient’s activities by working jointly
with the awardees in a partnership role, but not to assume direction,
prime responsibility, or dominance. Details of the responsibilities,
relationships, and governance of a study funded under a cooperative
agreement are described under the section entitled Terms and
Conditions of Award. The total project period for applications
submitted in response to this RFA is seven years. The anticipated
award date is June 1, 2002. At this time, the NIDDK has not determined
whether or how this solicitation will be continued beyond the present
RFA.
FUNDS AVAILABLE
The NIDDK plans to make four awards for Participating Clinical Centers
and one award for a Data Coordinating Center. Approximately $1,500,000
total cost (direct plus facilities and administrative costs) is
expected to be available during year one of the study. In all
subsequent years $3,000,000 will be available under this RFA. It is
anticipated that the award for each Participating Clinical Center will
be about $250,000 total cost in year one and $500,000 total cost in all
subsequent years. The award for the Data Coordinating Center will be
about $500,000 total cost in year one and approximately $1,000,000
total cost in all subsequent years of the program.
The number of awards to be made is dependent on the receipt of a
sufficient number of applications of high scientific merit and
availability of funds. Although this program is provided for in the
financial plans of the NIDDK, awards pursuant to this RFA are
contingent upon the availability of funds and the receipt of a
sufficient number of applications of outstanding scientific and
technical merit.
RESEARCH OBJECTIVES
Background
Polycystic kidney disease (PKD) is a serious, burdensome and costly
disease. The cystic diseases are the fourth leading cause of chronic
renal failure in the nation. Important advances in understanding the
molecular basis of autosomal dominant PKD (ADPKD1 and ADPKD2) have
generated intense interest, and have provided investigators with new
research opportunities. Increased understanding of the underlying
molecular processes that result in cyst formation and cyst growth is
yielding improved animal models of disease. A number of agents are
established to slow cyst growth in animal models, and these
experimental strategies should yield potential new therapeutic
approaches to the disease in man.
Appropriate clinical interventions to ameliorate the course of PKD need
to be developed and tested. Several previous studies have established
that in PKD patients with renal insufficiency, glomerular filtration
rate (GFR) declines rather rapidly. Nevertheless, through much of the
course, GFR is relatively stable, and detectable decreases in GFR occur
relatively late in the natural history of the disease. Current
approaches to treatment of patients with PKD have not succeeded in
slowing the progressive decline in GFR that frequently results in end-
stage renal failure. Treatment of hypertension has not been
definitively shown to retard loss of renal function in patients with
PKD, and it is unclear whether target blood pressures should be lower
in these patients than in the general population.
A sizable body of data supports the effectiveness of converting enzyme
inhibitors (CEI) in slowing the progression of other renal diseases,
particularly those associated with proteinuria. These agents remain the
most effective strategy to prevent or delay chronic renal failure, but
the effectiveness of this class of agent in PKD is not clear. There is,
however, biological evidence compatible with the hypothesis that
interruption of the renin-angiotensin-aldosterone axis might have a
protective effect in PKD. Some studies in animal models support this
hypothesis. In polycystic kidneys from human patients, there is
evidence for high tissue renin, and there is clinical evidence for
activation of the renin-angiotensin axis in hypertensive patients with
PKD.
The results of randomized interventional clinical trials of CEI in PKD
have been contradictory, although the total number of patients studied
has been relatively small. Many nephrologists elect to use CEIs for
blood pressure management, particularly in patients with PKD who also
have some degree of proteinuria. In addition to converting enzyme
inhibitors, other strategies to block this pathway include angiotensin
receptor blockers and aldosterone antagonists, agents which potentially
could be administered either alone or together with CEI.
The NIDDK has recently funded the Consortium for Radiologic Imaging
Studies of Polycystic Kidney Disease (CRISP) (RFA-DK-99-003) to
determine whether changes in anatomic characteristics of the kidneys of
patients with PKD will be useful in providing surrogate measures for
disease progression. Although data from these studies are not
presently available, preliminary findings from this group over the next
several years might inform the designs of clinical trials in patients
with PKD in the near future.
B. Research Goals and Scope
The goal of this research initiative is to identify strategies to slow
the progressive loss of renal function in polycystic kidney disease
(PKD). To achieve this goal, this initiative will establish the
infrastructure to examine the effect of clinically practical
interventions, such as single and combination drug regimens, on the
outcomes of patients with PKD. This RFA solicits applications from
investigator teams proposing to serve as either a Participating
Clinical Center (PCC) or a Data Coordinating Center (DCC) in this
research network.
It is anticipated that the studies to be conducted by this consortium
in this RFA will take place in four PCCs over a period of seven years.
It is envisioned that each PCC will act as a referral center, with the
capacity to enroll a total of approximately 500 patients with PKD. The
data collection activities of the PCCs will be supported by a single
DCC.
The objectives of this RFA are to select a DCC and PCCs to:
Recruit, evaluate, and follow sizable numbers of patients with PKD who
will be appropriate for and willing to participate in interventional
trials.
Participate in pilot and feasibility studies and a full-scale
interventional trial.
Design the study protocols and write the manual of operations.
Develop operational plans for the trial(s), including strategies for
recruitment, screening, enrollment and adherence to study protocols.
Develop a specimen bank and information data system from study samples
and patient information.
C. Study Design
The design of the final research protocols for implementation by the
PKD Clinical Trials Network will be developed during the Planning Phase
by the Steering and Planning Committee, and will be subject to review
by a Data and Safety Monitoring Board. The intent of this RFA is that
the trial network should implement both a large multicenter trial
examining the effect of renin-angiotensin blockade on progression of
PKD and one or more pilot and feasibility studies examining innovative
strategies for slowing the progression of PKD. The entire
collaborative clinical trial network will function in several phases.
Applicants for PCCs should present two research protocols in their
applications: 1) A proposal for a large trial to examine the hypothesis
that interruption of the renin-angiotensin-aldosterone axis offers
clinical benefit to patients with polycystic kidney disease, and 2) A
proposal for a pilot and feasibility study examining the effect of an
innovative strategy for PKD treatment.
For the large trial, applicants should propose a specific trial design,
intervention, eligibility and exclusion criteria, and outcome measures.
It is the intent of this RFA that this trial should ultimately provide
pragmatic advice to clinicians caring for PKD patients, and that the
trial should use an outcome measure that directly assesses clinical
benefit. For example the study could assess whether the intervention
delays the time to dialysis, doubling of serum creatinine or death.
Since the PCC’s will be acting as referral centers and executing the
trial in patients referred over a broad geographical area, simplicity
of trial design will be important.
Topics suitable for pilot and feasibility studies include, but are not
limited to the following:
The safety of new agents for treatment of PKD,
The impact of blockade of the intensive blockade of the renin
angiotensin axis on potassium homeostasis in patients with PKD and
renal insufficiency,
The impact of innovative interventions on surrogate markers for cyst
growth or cyst growth assessed by imaging methods,
The impact of innovative interventions on possible mechanisms of
cystogenesis, such as loss of heterozygosity,
The safety or effectiveness of potential interventions in special
populations of patients with PKD.
For each of the proposed clinical protocols, the PCC applicants should
discuss the characteristics and number of potential participants that
would be available from their own geographic region. Provision of
recruitment data regarding previous studies in patients with PKD is
encouraged. Provision should be made for meeting the appropriate
representation of genders, minorities and children, as required for
successful accomplishment of study goals.
STUDY COMPONENTS
1. Participating Clinical Centers (PCCs)
A PCC will be actively involved in the recruitment, evaluation,
treatment, and follow-up of PKD patients as appropriate study subjects.
It should consist of an interdisciplinary team of clinical
investigators and appropriate personnel, such as a research coordinator
and clerical staff. An application for a PCC should provide evidence
that the investigators are capable of recruiting a sufficient number of
participants for the proposed trials. Applicants for PCCs should
describe the target population from which they expect to recruit PKD
patients as study participants, and plans for recruitment of women,
minorities, and children. PCCs will be required to submit study data
to the DCC expeditiously. The PCC must work in concert with the DCC to
implement procedures for uniform data collection, handling and
transmittal of data, as well as data audits and other data quality
control procedures as established by the study protocol(s). The
Principal Investigator and co-investigators in each PCC should be
skilled in collaborative clinical investigation. There should be
evidence of strong institutional support for the PCC, including
adequate space in which to conduct clinical activities and obtain
research protocol data, and sufficient office space for staff. An
organizational structure for the PCC should be set forth in the
application delineating lines of authority and responsibility for
dealing with problems in all general areas as well as a statement
regarding willingness to follow commonly agreed upon protocols.
The applicant should include a succinct discussion of previous relevant
research efforts, including experience such as evaluating renal
functional or radiologic parameters over time. The applicant should
also discuss in detail the recruitment strategies to be employed to
obtain the expected number of study participants, and approaches to
attain high levels of adherence to interventions. In most cases,
recruitment of large numbers of PKD patients will require agreements
between the PCC and other health care providers.
2. Data Coordinating Center (DCC)
The DCC will have primary responsibility for collecting, editing,
storing, and analyzing data generated by the PCCs, and for establishing
and implementing data auditing and quality control procedures for each
aspect of the studies. The DCC will participate in trial design by
providing needed biostatistical expertise. For example, the DCC will
provide realistic estimates of the power and sample size of the
clinical trials proposed during Phases I and II (see below).
The DCC should establish a core facility for clinical specimen handling
and analyses, and establish the informatics systems for data
collection. The DCC will be responsible for the analysis of the
clinical data generated by the PCCs. The DCC will coordinate banking
of biologic samples at a repository to be established by the NIDDK.
Sub-contracting of various aspects of the DCC to other institutions
with special expertise may be included in the application.
The DCC should be prepared to assume a key role in overseeing
implementation of and adherence to the study protocol(s), and assuring
quality control of the data collected. The DCC will be expected to
provide appropriate biostatistical, data management, and administrative
expertise. The DCC will be expected to provide the NIDDK with a well
documented data set after the termination of the studies supported by
this RFA. The DCC also will be expected to generate appropriately
detailed reports to the Steering and Planning Committee (see below) and
to the Data Safety and Monitoring Committee (see below) at regular
intervals, and will be responsible for the logistics and planning of
the meeting of these committees and their subcommittees.
Applicants for the DCC should provide a detailed description of prior
experience in multicenter clinical studies.
Study Phases
The program will be carried out in three phases over a seven-year
period.
Phase I (Months 1-6): Protocol Development.
Work to be performed during this phase includes the development of the
interventional protocols, including procedures and forms for data
collection, by the Steering and Planning Committee. A manual of
operations including well-defined procedures for the studies and for
the training and certification of clinical personnel in study
procedures will be written. Parameters to be assessed in Central
Laboratories will be outlined. The Data Coordinating Center will begin
computer programming to establish the database for the study. The
collaborative protocols for the trial(s) will be developed by the
Steering Committee (composed of the awardees and the NIDDK Project
Scientists). Prior to implementation of any trial(s), the protocol(s)
and Manual of Operations will be reviewed, and must be approved by the
Data Safety and Monitoring Committee (see below). Any pilot and
feasibility study, and the long-term study will move into operational
phase (Phase II) only with the concurrence of the Data Safety and
Monitoring Committee and the NIDDK. During this phase, outlay of funds
will be primarily for appropriate levels of salary support for
investigators to develop the trial protocol(s) and Manual of
Operations, and for travel to the Steering and Planning Committee
meetings.
Phase II (Months 7-78): Recruitment of Study Participants/Initiation
of Pilot and Feasibility Studies and Therapeutic Interventional
Trial(s)/Follow-up Assessments/Development of Further Interventions.
At the beginning of this period, training of study staff will begin, to
ensure uniform protocols and provide certification for study
procedures. Over this period potentially eligible participants will be
identified, invited to the PCCs for baseline assessment, and those
found eligible will be asked to enter the appropriate trial(s). During
this phase the full component of personnel will be included in the
budget. Concurrent with recruitment, follow-up of all study
participants will be conducted in a standardized fashion over regular
intervals. Further interventions will be developed as necessary during
this phase, as an ongoing process, as determined by the results of
pilot and feasibility studies. The Data Safety and Monitoring
Committee will review the progress of recruitment yearly, review
interim outcomes and recommend to the NIDDK whether the trial(s) should
continue, and will review subsequent trials proposed by the Steering
and Planning Committee during this Phase. The major activity during
the first half of this phase will be the recruitment, assessment,
enrollment and retention of patients in the trial(s). Preparation of
manuscripts describing recruitment of the subjects, baseline
demographic and clinical characteristics of the participants, and the
cross-sectional relationships between level of renal function and other
parameters, including clinical, demographic, radiographic, and
laboratory measurements will begin to be developed in the first half of
this phase. The major activity during the latter part of this phase
will be manuscript preparation and follow-up clinic visits. Follow-up
and data collection on study participants will continue throughout this
phase, as determined by the study protocol(s). Manuscripts will be
prepared and submitted for publication on the interim findings from the
study, and the results of completed pilot and feasibility studies or
interventional trials. The last follow-up visit of study participants
will be scheduled during the final two months of this phase.
Phase III (Months 79-84): Final Data Analysis and Close-out of the
PCCs and the DCC.
During the final six months of the program, the activities include
final data analyses and preparation of manuscripts on the findings from
the trials. The Participating Clinical Centers, the Data Coordinating
Center, and all central facilities will be closed-out in the last two
months of this phase of the study.
Study Organization
Participating Clinical Centers
The Participating Clinical Center investigators will have direct
responsibility for developing the study protocol(s) and uniform data
collection forms, identifying potentially eligible study participants,
assessing their eligibility to participate in the clinical trials,
conducting baseline and follow-up visits, obtaining blood, urine, and
other biological samples, performing renal functional and other
measurements, collecting data, and transmitting it in a timely fashion
to the Data Coordinating Center. They, along with staff from the Data
Coordinating Center and the various central laboratories, will also be
responsible for making presentations at scientific meetings, and for
writing and publishing manuscripts on the findings of their studies.
Data Coordinating Center
The Data Coordinating Center will be responsible for assisting the PCC
investigators, through the Steering and Planning Committee, in
developing the trial protocol(s) during Phases I and II. The Data
Coordinating Center will create data collection forms based on input
from the Steering and Planning Committee. The Data Coordinating Center
will be responsible for establishing a database to accommodate data
sent by the Participating Clinical Centers, developing a web-based data
communication system, assessing data quality and completeness
throughout the study, and providing general assistance to the
Participating Clinical Centers to maintain long-term participation of
the study subjects and their adherence to the study protocols.
Adherence of the participants will be monitored and reported by the DCC
at regular intervals during the trial(s) to the PCCs and to the Data
Safety and Monitoring Committee. The Data Coordinating Center will
also perform analyses as suggested by the Participating Clinical
Centers, as well as propose original analyses to the collaborative
group for their consideration. The Data Coordinating Center will
prepare periodic reports on the progress of the study, including data
quality control, and interim and final results to the Steering and
Planning Committee, the NIDDK and the Data Safety and Monitoring
Committee. The DCC will be responsible for coordinating transfer of
biologic samples to a repository to be established by the NIDDK. The
Data Coordinating Center will be responsible for arranging meetings and
conference calls of the Steering and Planning Committee, meetings of
the Data Safety and Monitoring Committee, and will perform other
administrative functions necessary to coordinate the efficient
operation of the PKD Clinical Trials Network. The Data Coordinating
Center will establish, via subcontracts, Central Laboratories and other
necessary adjuncts to the study, as necessitated by the study
protocol(s). The DCC will be expected to provide the NIDDK with data
in a uniform, usable platform throughout the course of the studies and
after the termination of the studies supported by this RFA.
Steering and Planning Committee
The primary governing body of the study will be the Steering and
Planning Committee, comprised of each of the Principal Investigators of
the Participating Clinical Centers and the Principal Investigator of
the Data Coordinating Center, the Chairperson of the Steering and
Planning Committee, and the NIDDK Project Scientists (described in
detail under Terms and Conditions). The Steering and Planning
Committee will develop policies for the study pertaining to access to
patient data and specimens, ancillary studies, performance standards,
and publications and presentations. They will meet initially to
develop the study protocol(s) and subsequently to discuss the progress
of the study and to consider problems arising during its conduct. The
Steering and Planning Committee may establish subcommittees on such
topics as recruitment, quality control, and publications and ancillary
studies. Small working groups may be established to prepare
manuscripts and presentations.
Data Safety and Monitoring Committee
An independent group of experts in areas such as nephrology,
epidemiology, radiology, ethics, and biostatistics who are not
otherwise involved in the study, as well as lay persons, will be
recruited by the NIDDK to evaluate the proposed protocol(s) and review
periodically the progress of the study (described in detail under Terms
and Conditions).
Project Scientists
The NIDDK will identify two Project Scientists for the study. The
Project Scientists will assist the Steering and Planning Committee and
the Data Safety and Monitoring Committee in carrying out the study
(described in detail under Terms and Conditions).
SPECIAL REQUIREMENTS
Terms and Conditions of Award
The following terms and conditions will be incorporated into the award
statement and provided to each Principal Investigator as well as to the
institutional officials at the time of the award. These terms are in
addition to, not in lieu of, otherwise applicable Office of Management
and Budget (OMB) administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Part 74 and 92, and other HHS and NIH Grants
Administration policy statements.
The administrative and funding instrument used for this program is the
cooperative agreement (U01), an assistance mechanism (rather than an
acquisition mechanism), in which substantial NIH scientific and/or
programmatic involvement with awardees is anticipated during the
performance of the activity. Under the cooperative agreement, the
NIH’s 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, primary
responsibility, or a dominant role in the activity. Consistent with
the cooperative agreement concept, the dominant role and prime
responsibility for the planned activity reside with the awardees for
the project as a whole, although specific tasks and activities in
carrying out the activity will be shared among the awardees and NIDDK
Project Scientists.
Responsibilities of the Participating Clinical Centers: The
Participating Clinical Centers will have primary responsibility for
developing the study protocol(s), recruiting a sufficient number of
study participants, maintaining high rates of follow-up and data
collection, ensuring adherence to the study protocol(s) on the part of
the investigative team and the subjects, obtaining data of high
quality, transmitting it accurately and expeditiously to the DCC, and
interpreting, presenting, and publishing findings from the study. A PCC
will work collaboratively with the other PCCs and the DCC, and will
follow study protocols.
Responsibilities of the Data Coordinating Center: The Data
Coordinating Center will assist in protocol development and preparation
of scientific publications. The Data Coordinating Center has the major
responsibility of creating a database and data collection systems for
the Clinical Centers, providing ongoing evaluation of data quality and
performance monitoring of the PCCs, and performing statistical analyses
of the data. The DCC will be expected to provide the NIDDK with data
in a uniform, usable platform throughout the course of the studies and
after the termination of the studies supported by this RFA. The DCC
will coordinate transfer of biologic samples to a repository to be
established by the NIDDK. In addition, the Data Coordinating Center
will supply logistical support for the meetings of the Steering
Committee and the Data Safety and Monitoring Committee.
(1) Awardees Rights and Responsibilities
Awardees will have substantial and lead responsibilities in all tasks
and activities. These include protocol development, enrollment of
study participants, data collection, data quality control, management
of the trial(s), final data analyses and interpretation, and
preparation of publications. The awardees agree to work cooperatively
with the other PCCs and agree to follow the common protocol(s)
developed by the Steering and Planning Committee. The awardees agree
also to transmit the study data in a timely manner according to study
protocol(s) to the Data Coordinating Center for combination and
analysis. Awardees will retain custody of and have primary rights to
their data developed under these awards for the duration of the awards,
subject to Government (e.g., NIDDK, NIH, or PHS) rights or access
consistent with current HHS and NIH policies.
(2) NIDDK Staff Responsibilities
The NIDDK will name two Project Scientists from within the Division of
Kidney, Urologic and Hematologic Diseases whose function will be to
assist the Steering and Planning Committee in carrying out the study.
The Project Scientists will have experience in nephrology and the
development and conduct of multi-center clinical trials. The Project
Scientists will have substantial scientific-programmatic involvement in
assisting protocol development, quality control, interim data analysis,
final data analysis and interpretation, preparation of publications,
and will provide assistance in coordination and performance monitoring.
The NIDDK Project Scientists will have voting membership on the
Steering and Planning Committee (constituting a single vote). One of
the NIDDK Project Scientists will also serve as Executive Secretary of
the Data Safety and Monitoring Committee. The NIDDK reserves the right
to terminate or curtail the study (or an individual award) in the event
of difficulties in recruiting participants to the study, maintaining
high rates of follow-up and data collection/completion of participants
tests, in timely data reporting, achieving high levels of data quality,
maintaining adherence to the study protocol(s), working cooperatively
or other major breaches of the protocol(s), or human subject or ethical
issues that may dictate a premature termination.
(3) Collaborative Responsibilities
The Steering and Planning Committee, composed of each of the Principal
Investigators of the PCCs, the Principal Investigator of the DCC, the
NIDDK Project Scientists, and the Chairperson of the Steering and
Planning Committee, will be the main governing board of the study. The
Committee will have the primary responsibility for developing the study
protocol(s), facilitating the conduct of participant follow-up and
testing, monitoring completeness of data collection adherence to
protocol(s), and timely transmission to the Data Coordinating Center,
and reporting the study results. It will also be responsible for
establishing study policies in such areas as access to patient data and
specimens, ancillary studies, publications and presentations, and
performance standards.
Each member of the Steering and Planning Committee will have one vote
(NIDDK will have one vote), and all major scientific decisions will be
determined by a majority vote of the Steering and Planning Committee.
A Chairperson will be chosen by the NIDDK from among the Steering and
Planning Committee members (but not one of the NIDDK Project
Scientists) or alternatively, from among experts in such fields as
nephrology, or clinical trials design, who are not participating
directly in the study.
An independent Data Safety and Monitoring Committee (DSMC), selected by
the Director, NIDDK, will review periodically the progress of the study
to ensure patient safety during the conduct of the trial(s). This
group will include experts in the relevant medical, epidemiological,
radiological, statistical, and ethics fields, as well as lay
representatives, who are not otherwise involved in the study. The DSMC
will review the study protocol(s) as developed during Phases I and II,
and will evaluate results, monitor data quality, participant safety,
and provide operational and policy advice to the Steering and Planning
Committee and to the NIDDK regarding the status of the study. One of
the NIDDK Project Scientists will serve as Executive Secretary of the
Data Safety and Monitoring Committee. The members of the DSMC will
review the PKD Clinical Trials Network’s progress and will report to
the NIDDK at least once each year, or more often if necessary.
(4) Arbitration
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award) between recipients and the NIDDK may be
brought to arbitration. An arbitration panel will be composed of three
members, one selected by the Steering and Planning Committee (with the
NIDDK member not voting) or by the individual awardee in the event of
an individual disagreement, a second member selected by NIDDK, and the
third member selected by the two prior selected members. This special
arbitration procedure in no way affects the awardee’s right to appeal
an adverse action that is otherwise appealable in accordance with the
PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation 45 CFR
Part 16.
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
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 1003-43).
Eleven investigators proposing research involving human subjects should
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities
as Subjects in Clinical Research," published in the NIH Guide for
Grants and Contracts on August 2, 2000
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a
complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:
The revisions relate to NIH defined Phase III clinical trials and
require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual,
and to conduct and report 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 the 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. 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 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 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.
LETTER OF INTENT
Prospective applicants are asked to submit, by October 16, 2001, a
letter of intent that includes a descriptive title of the proposed
research, name, address, and telephone number of the Principal
Investigator, identities of other key personnel and participating
institutions, and 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 it contains allows the NIDDK
staff to estimate the potential review workload and avoid conflict of
interest in the review. The letter of intent is to be sent to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
6707 Democracy Boulevard, Room 752
Room 752, MSC 5452
Bethesda, Maryland 20892-5452 (for courier service use 20817)
Telephone: (301) 594-8885
Fax: (301) 480-3505
Email: fc15y@nih.gov
APPLICATION PROCEDURES
Applications must be submitted on the standard research grant
application form PHS 398 (rev. 4/98). See "Budget Preparation by Year
section below for additional instructions. Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, Maryland 20892-7910, telephone (301) 710-0267, E-mail:
GrantsInfo@nih.gov.
The RFA label available in the form PHS 398 must be affixed to the
bottom of the face page. 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. For purposes of identification
and processing, item 2 of the face page of the application must be
marked YES and the RFA number and the words Polycystic Kidney
Disease Clinical Trials Network must be typed in.
The RFA label and line 2 of the application should both indicate the
RFA number. The RFA label must be affixed to the bottom of the face
page. 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.
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 and
appendices must be sent to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
6707 Democracy Boulevard, Room 752
Room 752 MSC 5452
Bethesda, Maryland 20892-5452
(For express/courier service, use 20817)
Applications must be received by November 16, 2001. If an application
is received after this 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 a substantial revision of an application
already reviewed, but such an application must follow the guidance in
the PHS 398 applications instructions for the preparation of revised
applications, including an introduction addressing the previous
critique.
The page limitations for applications responding to this RFA will be
those outlined in the current PHS 398 application kit (25 pages for the
Research Plan, sections A-D). Within the 25 page limit, a guideline
for pilot and feasibility studies is two pages, and four pages for the
full scale interventional trial.
Information to be Included in Application
Details of Participation in Proposed Study Protocol(s):
Applicants for both the DCC and the PCC should present two research
protocols in their applications: 1) A proposal for a large trial to
examine the hypothesis that interruption of the renin-angiotensin-
aldosterone axis offers clinical benefit to patients with polycystic
kidney disease, 2) A proposal for a pilot and feasibility study
examining the effect of an innovative strategy for PKD treatment. The
laboratory and medical tests, questionnaires, and other data collection
and the frequency of assessment during follow-up must be specified.
Applicants for the PCC should provide detailed information regarding
the size of the potential pool of PKD patients who will be willing to
come to the PCC to participate in screening visits to assess study
eligibility, and a reasonable projection of the proportion of patients
screened and found eligible that would be willing to commit to
participation in pilot and feasibility trials and a long-term trial as
described in this RFA. A detailed description of the PKD patients
targeted for intervention as well as a comprehensive plan to recruit
patients must be provided. Realistic rates of study drop-outs and
outmigration should be proposed. Efforts to maintain follow-up of
study participants must also be described. Applicants must consider
the sample size proposed in this RFA in light of their previous
research and clinical activities.
In addition to trial protocols, applications for the DCC should include
plans for data collection, and overall quality control of the study.
The applicant should indicate willingness to take the lead in
determining effect sizes and proposing power analyses for studies
considered by the consortium. An administrative plan to coordinate the
activities of the Central Laboratories, including quality control and
data transmission to the Data Coordinating Center must be included in
the application. The experience of the DCC in developing and
maintaining web-based data collection systems for large-scale, multi-
center studies, including clinical trials should be documented. Plans
for transferring biologic samples to a repository to be established by
the NIDDK should be outlined. A description of anticipated problems in
carrying out this study and their proposed solutions must be included
in the application.
Institutional Support: There should be evidence of strong
institutional support for the study, including adequate space in which
to conduct participant evaluations and follow-up (PCCs) and data
analysis/management (DCC) activities. A PCC application should
delineate facilities available for assessment of renal functional and
radiologic parameters in a large group of study participants. An
organizational structure for the study should be set forth in the
application, delineating lines of authority and responsibility for
dealing with anticipated problems in all general areas as well as
stated willingness to follow the commonly agreed-upon protocol(s).
Previous Experience: The applicant should include a succinct
discussion of previous relevant research efforts in multi-center
clinical trials, and any relevant experience/success in working
collaboratively with investigators outside their own research
institution. Experience in the recruitment and retention of
participants for long-term studies should be described. Expertise in
renal functional assessments and radiologic evaluation of patients with
renal disease should be included. Previous participation in studies of
racial and ethnic minority populations should be included.
Suggested Personnel Requirements: The application must describe the
expertise of key scientific, technical and administrative personnel and
include a mechanism for replacing key professional or technical
personnel should the need arise. For the Participating Clinical
Centers, expertise in nephrology and clinical trials is required.
Personnel may be full-time or part-time and may serve in more than one
capacity, as appropriate. A suggested Participating Clinical Center
study team might include, besides a Principal Investigator, a co-
investigator (M.D. or Ph.D.), a radiologist, study coordinators, GFR
technician, appointment scheduler/administrative assistant and data
entry clerk. Personnel required for the Data Coordinating Center must
include expertise in biostatistics, epidemiology, data management,
computer programming and database development. Experience in the use
of web-based data collection systems in a multi-center study setting is
also necessary. Inclusion of consultants as necessary is possible.
Budget Preparation by Year
Applicants for the Participating Clinical Centers and the Data
Coordinating Center must include an adequately justified year-by-year
budget, reflecting the major changes in proposed activities as the
study progress through its various phases. Budgets should reflect the
number of patients proposed for the pilot and feasibility studies and
the long-term interventional trial.
Note: The PHS Form 398 will be used for each proposed year (12 months
each) in accordance with the project objectives proposed specified
above in the "Information to be Included in Application" section. The
PHS Form accommodates up to 5 years in composite budget information,
however as prescribed in the "Application Procedures" section the
applicant shall include the 6th and 7th year composite budget
information as required congruent with the individual year 6 and 7
budgetary information.
The applicants shall not submit budget information in modular format
and cost projections should adequately correspond to the scope of
research proposed.
Phase I (First 6 months of Year 1). The budget will be for development
of the protocol(s) by the Participating Clinical Centers in
collaboration with the Data Coordinating Center. The Data Coordinating
Center will establish the database necessary to accommodate the data
transmitted by the PCCs. A web-based technology for data transmission
will be established in Phase I that will be efficient, and will protect
study participant privacy. The Data Coordinating Center will identify
and establish subcontracts with Central Laboratories and other support
centers as necessitated by the study protocol(s). It is expected that
the Data Coordinating Center will purchase all the necessary hardware
and software for data transmission from the PCCs for their use in the
study. The proposed study protocol(s) will also be reviewed by the
Data Safety and Monitoring Committee and must be approved prior to
implementation. The travel budget for Phase I should be estimated
based on travel for two key investigators to attend two-day, monthly
meetings of the Steering and Planning Committee in the Washington, D.
C. area. The first meeting will be held June 4 and 5, 2002.
Phase II (Months 7-78). The budget for the Participating Clinical
Centers should reflect the level of effort necessary to recruit the
entire study groups, implement the interventions, and perform baseline
and follow-up studies. Follow-up data will be collected by the PCCs. A
guideline is to devote approximately 25% of resources in Phase II to
pilot and feasibility studies and 75% to the long-term interventional
trial. Trials may be developed during this phase based on findings of
earlier pilot and feasibility studies. The major activities in this
phase are enrollment, follow-up and assessment of study participants.
Initially, data analysis of the recruitment experience and baseline
characteristics of the study participants will be undertaken. The
first manuscripts will focus on cross-sectional findings. Subsequently,
manuscripts will deal with interim findings and results of the pilot
and feasibility studies. Data analysis will be conducted and papers
addressing the secondary goals of the studies will also be prepared.
Costs should be included for any specialized studies of renal function
(such as GFR measurement) and for other necessary parameters consistent
with pilot and feasibility studies or large interventional trials. In-
clinic visit follow-up of the study participants will be terminated
during the last several months of Phase II.
The Data Coordinating Center will receive and store the data
transmitted by the Participating Clinical Centers, assess its
completeness, provide feedback to the PCCs regarding data quality, and
prepare progress reports for the Steering and Planning Committee and
the Data Safety and Monitoring Committee on the progress of the
trial(s). The budget should include costs associated with necessary
Central Laboratories and with transfer and maintenance of biologic
samples in a repository to be established by the NIDDK.
This phase of the program will require meeting approximately every four
months in the Washington, D.C., area. The travel budget for Phase II
should be estimated based on travel for the Principal Investigator and
the Study Coordinator as well as any other key personnel for both the
Participating Clinical Centers and the Data Coordinating Center.
Travel for key staff at the Participating Clinical Centers and the Data
Coordinating Center should be budgeted each year for centralized
training and recertification of PCC staff.
Central training will occur annually and key staff should be budgeted
to travel to the Washington, D. C. area.
For a PCC, the budget should request support for the minimum number of
full and/or part-time staff to successfully carry out the proposed
studies. PCC personnel could include a Principal Investigator, co-
investigator(s), study coordinators, GFR technician, appointment
scheduler/administrative assistant, and data entry clerk. The PCC
should budget for renal functional and radiologic assessments, as well
as other clinical laboratory measurements to be obtained over the
course of the trials.
For applications for the Data Coordinating Center, the budget should
include the time and effort of key personnel for database management,
programming, data analysis, and administrative functions to support the
collaborative group. The budget should also include subcontracts for
Central Laboratory and facilities and costs associated with maintenance
of biologic samples in a repository to be established by the NIDDK.
Travel by Data Coordinating Center staff to Washington, D.C., and
coordination for a meeting with the Data Safety and Monitoring
Committee should be planned and budgeted for annually by the DCC.
Phase III (Months 79-84). Final Data Analysis and Close-out of the
Participating Clinical Centers, the Data Coordinating Center, and
Central Laboratories.
The major activities during this Phase include final data analysis of
the trial(s). Manuscripts describing these findings will be prepared
and submitted to peer-reviewed scientific journals for publication.
The Participating Clinical Centers, the Data Coordinating Center and
the Central Laboratories will be closed-out during the last two months
of this phase of the program. Two meetings of the Steering and
Planning Committee and one meeting of the Data Safety and Monitoring
Committee will be held in Phase III.
The following is a list of yearly major activities to assist in the
preparation of budgets for each of the five years of the program.
Year 1 (Months 1-6): Develop the study protocol and data collection
forms for the collaborative studies by means of meetings every month.
The database will be established by the Data Coordinating Center. A
web-based data transmission system will also be developed by the Data
Coordinating Center. Central Laboratories will be identified and
established by the Data Coordinating Center. Recruitment plans will be
developed by the PCCs. Computer hardware and software will be purchased
by the Data Coordinating Center for use by the PCCs.
Year 1 (Months 6-12): The Participating Clinical Centers begin
recruitment and screening of study participants, and beginning
implementing interventions. Participant follow-up assessment begins.
New trials are proposed. Database development is continued by the Data
Coordinating Center. The Central Laboratories will begin functioning.
Year 2-6 (Months 13-78): Recruitment of study participants continues.
Participant follow-up assessment by the PCCs continues. Reports on
recruitment rates, data quality, and baseline characteristics of study
participants will be prepared by the Data Coordinating Center. Plans
for data analysis on the recruitment experience and baseline findings
are established by the Data Coordinating Center. Reports on data
quality, and follow-up studies will be generated by the Data
Coordinating Center during Years 3-6. Manuscripts describing the
recruitment experience, baseline clinical and demographic
characteristics of the participants, and initial results of pilot and
feasibility trials will be prepared based on analyses from the Data
Coordinating Center. Manuscripts describing other findings from the
study will be prepared based on data analyses from the Data
Coordinating Center. New trials will be proposed and implemented in the
earlier parts of this Phase based on the findings of initial studies.
The PCCs and the Data Coordinating Center, and whenever appropriate the
Central Laboratories, will participate in special studies.
Year 7 (First 6 months): Participant follow-up assessment by PCCs
continues. Data analysis and manuscripts will be prepared addressing
findings of the various trials. Plans will be established for study
close-out.
Year 7 (Last 6 months): Final follow-up clinic visits are conducted.
Plans will be established for final data analyses by the Data
Coordinating Center and Clinical Centers. Final data analyses will be
performed and major reports and manuscripts prepared. The Data
Coordinating Center, the PCCs and the Central Laboratories will be
closed-out.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the CSR
and for responsiveness by the NIDDK. 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 the NIDDK in accordance with the review
criteria stated below. As part of the initial merit review, a process
will be used by the initial review group in which 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 of review by the National Diabetes
and Digestive and Kidney Disease Advisory Council.
Review Criteria
Applicants are encouraged to submit and describe their own ideas about
how best to meet the goals of the cooperative study as outlined in this
RFA, and are expected to address issues identified under INFORMATION TO
BE INCLUDED IN APPLICATIONS. In the written comments, reviewers will
be asked to discuss the following aspects of the application. This will
apply to all elements, including the proposed long-term interventional
trial and the pilot and feasibility studies, 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.
Review Criteria for Participating Clinical Centers
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?
Approach: Does the applicant propose sound approaches to achieve the
aims of the RFA? Is the potential pool of study participants available
to the investigator outlined clearly? Have realistic estimates been
made regarding the number of participants who will prove to be eligible
for the studies? Among persons found eligible during screening, have
realistic participation rates been applied to meet the sample size
goals stated in the RFA? Has the racial, ethnic, and gender
composition of the proposed study participants been adequately
described, and plans described for appropriate analyses? Has
information on the distribution of renal function of the population
targeted for recruitment been discussed? What plans have been
presented to ensure the high rates of follow-up and high rates of
adherence mandated by the study protocol? What steps are planned for
data quality control? The applicant must provide plans to ensure the
complete, reliable, and timely transmission of study data to the Data
Coordinating Center. Knowledge of the possible problems associated
with the conduct of multi-center trials and any potential issues of
importance in this study should be described.
Investigators: Is the Principal 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? Are the Principal Investigator and her/his co-
investigators experienced in collaborating with other investigators in
a multi-center study? Are the investigators willing to participate in
establishing and conducting a common protocol? Does the Principal
Investigator and the proposed study team possess experience in
recruiting participants to pilot and feasibility studies and to long-
term interventional studies? Does the Principal Investigator and the
proposed study team possess experience in clinical trial design to
ensure meaningful participation in Phases I and II of the PKD Clinical
Trials Network? Is there sufficient diversity in the proposed study
team to allow the PKD Clinical Trials Network to propose a variety of
clinically meaningful trials in Phases I and II?
Necessary Expertise: Documented experience in nephrology, and
specifically in the field of polycystic kidney disease, and clinical
trial methodology is required. Experience in renal functional and
radiologic assessments is highly desirable.
Staff Qualifications: Documented specific competence and relevant
experience of professional, technical, and administrative staff
pertinent to the operation of a Participating Clinical Center are
required.
Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Documented adequacy of
the proposed facility and space is necessary. Is there evidence of
institutional support and commitment for the proposed program?
Access to Large Number of Eligible Patients and Ability to Recruit
Large Numbers of Patients in Clinical Trials: Evidence of the ability
to access large numbers of appropriate patients from which potential
study participants will be recruited is necessary. Documentation must
be provided on the ability to contact patients identified in order to
invite them to more detailed, clinical assessments of their eligibility
to participate in the trial(s). Provisions must be made to ensure
subject confidentiality and ethical standards.
Recruitment of Women and Minority Participants: Has the applicant
described in detail the distribution of minority participants to be
recruited? Is the racial and ethnic composition of the proposed
recruited population similar to the U.S. PKD patient population?
Review Criteria for a Data Coordinating Center:
Significance: Does the study address an important problem? If the
aims of the applications 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?
Approach: Does the applicant acknowledge potential problem areas and
consider alternative tactics in the implementation and performance of
the trials necessary to achieve the goals of this RFA? What is the
approach to handle missing follow-up data and patient non-adherence?
Experience in developing protocols, developing web-based technology for
data collection, establishing and maintaining large databases for data
from the Participating Clinical Centers, plans for analysis of the
combined data, and efforts to ensure high quality data collection, and
ensuring study participant adherence and confidentiality will be
evaluated.
Investigators: Is the Principal 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? Are the Principal Investigator and her/his co-
investigators experienced in collaborating with other investigators in
a multi-center study? Documented experience in epidemiology, clinical
trial methodology and biostatistics is required. Does the applicant
have expertise in longitudinal data analysis, including renal
functional and radiologic measurements? The level of expertise of
consultants in nephrology will be considered. Experience in database
development, data management, and statistical analysis is required.
The ability of the investigators from the Data Coordinating Center to
take the lead in developing a cooperative relationship among the
Participating Clinical Centers and the Central Laboratories, and to
exercise appropriate leadership in matters of study design, data
acquisition, data management, data quality, data analysis, repository
function, and administration and coordination of Steering and Planning
Committee meetings will be considered.
Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Documented adequacy of
the proposed facility and space is necessary. Is there evidence of
institutional support and commitment for the proposed program?
In addition to the above criteria, in accordance with NIH policy, all
applications will be reviewed with respect to the following.
The reasonableness of the proposed budget for each year of the program.
The adequacy of the proposed protection for humans and the environment,
to the extent they may be adversely affected by the studies described
in this RFA. The scientific review group will also examine the safety
of the research environment.
Schedule
Letter of Intent Receipt Date: October 16, 2001
Application Receipt Date: November 16, 2001
Special Review Committee: April 2002
NDDK Advisory Council: May, 2002
Anticipated Award Date: June, 2002
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Ability to assess eligibility of, enroll, and maintain patients in
clinical trials of interventions appropriate for PKD.
o Scientific merit as determined by peer review
o Availability of funds
o Cost
o The size and gender, racial and ethnic composition of the proposed
patient study populations.
o Geographic distribution of the Participating Clinical Centers
INQUIRIES
Written and telephone inquiries concerning this RFA are strongly
encouraged. The opportunity to clarify any issues or questions form
potential applicants is welcome.
For information relating to the NIDDK, programmatic inquiries may be
made to:
John Kusek, PhD, or
Paul L. Kimmel, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Room 617 MSC 5458
6707 Democracy Boulevard
Bethesda, Maryland 20892-5458 (for express or courier service use
20817)
Telephone: (301) 594-7717
FAX: (301) 480-3510
Email: Dr. Kusek jk61x@nih.gov
Dr. Kimmel pk77g@nih.gov
Fiscal and administrative inquiries may be directed to:
Ms. Teresa Farris
Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Room 728 MSC 5456
6707 Democracy Boulevard
Bethesda, Maryland 20892-5456 (for express/courier service use 20817)
Telephone: (301) 594-7682
FAX: (301) 480-3504
Email: tf102y@nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
Nos. 93.849 and 93.864. 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 Public Health Service grants policies 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 Public Health Service strongly encourages all grant and contract
recipients to provide a smoke-free work place 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 Public Health Service mission to protect and advance the physical
and mental health of the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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