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) 435-0714, 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.



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