PROSPECTIVE COHORT STUDY OF CHRONIC RENAL INSUFFICIENCY
Release Date: September 21, 2000
RFA: DK-01-005 (Reissued as RFA-DK-07-502)
National Institute of Diabetes and Digestive and Kidney Diseases
Applicant Information Forum Date: December 11, 2000
Letter of Intent Receipt Date: February 28, 2001
Application Receipt Date: March 28, 2001
PURPOSE
The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) has a longstanding interest in supporting epidemiological
studies of end-stage renal disease (ESRD) patients. A substantial
number of these studies, many emanating from the United States Renal
Data System (URSRDS), has led to significant improvements in the
treatment and quality of life of ESRD patients. In contrast, our
understanding of the epidemiology of chronic renal disease prior to
ESRD, during a period of reduced renal function or chronic renal
insufficiency, is far less advanced. The NIDDK invites cooperative
agreement applications for investigators to establish Clinical Centers
to conduct a seven-year prospective cohort study of patients with
chronic renal insufficiency. This Request for Applications (RFA) also
seeks a Data Coordinating Center to assist the Clinical Centers in
carrying out this cohort study. The primary goals of the cohort study
in persons with chronic renal insufficiency with mild to moderately
reduced levels of renal function are two-fold, to determine the risk
factors for accelerated decline in renal function, and to determine the
incidence and identify risk factors for cardiovascular disease.
Because of the relative and increasing importance of diabetes as a
cause of ESRD, approximately one-half of the study participants in the
cohort study will be diabetic.
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,
Prospective Cohort Study of Chronic Renal Insufficiency , 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 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 Clinical Center and the Data
Coordinating Center.
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 September 30, 2001. 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 six awards for Clinical Centers and one award
for a Data Coordinating Center. Approximately $4,000,000 total cost
(direct plus facilities and administrative costs) is expected to be
available during year one of the study. In all subsequent years
$6,000,000 will be available under this RFA. It is anticipated that
the award for each Clinical Center will be about $500,000 total cost in
year one and $650,000 total cost in all subsequent years. The award
for the Data Coordinating Center will be about $1,000,000 total cost in
year one and approximately $2,100,000 total cost in all subsequent
years of the program. If the budget for either a Clinical Center or
Data Coordinating Center exceeds the amount specified above the
applicant must contact the Clinical Trials Program Director (contact
information in the section, INQUIRIES), DKUHD, NIDDK, prior to
submitting the grant application.
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
End-stage renal disease is an important medical and public health
problem in the United States that disproportionately affects racial and
minority populations. According to the USRDS, at the end of 1997 over
300,000 patients were receiving treatment for ESRD and nearly 80,000
new patients started ESRD treatment during the same year. The number
of ESRD patients is steadily increasing. The absolute number of ESRD
patients has more than doubled and the incidence rate has doubled from
1988 to 1997. Two important factors associated with this dramatic rise
are the increasing prevalence of diabetes and the continuing high rates
of uncontrolled high blood pressure observed in this country. Despite
the prominence of diabetes and hypertension in increasing the risk of
developing chronic renal disease the factors responsible for
accelerating decline in renal function once chronic renal disease has
been established are considerably less well defined. While there has
been substantial interest during the past two decades to better
understand the risk factors for progression of chronic renal disease
(i.e., accelerated decline in renal function), there have been only a
small number of epidemiological studies examining this issue. Of the
studies conducted, all of them have had important shortcomings. Their
major limitations include retrospective study design, small sample
size, short-term follow-up, use of select populations such as clinical
trial participants, lack of ethnic and racial diversity of the study
populations, exclusion or low rates of participation of women, use of
crude measures of renal function, limited assessment of potential risk
factors, and inclusion of only select causes of renal disease, among
others. Therefore, it is not surprising that the demographic,
clinical, and laboratory factors examined in these studies explain only
a small percentage of the variability in renal function decline between
patients. This suggests that there remains a significant number of
important but as of yet unidentified patient, genetic, environmental,
and health care utilization related risk factors for rapid loss of
renal function in persons with established chronic renal disease.
The survival of ESRD patients is significantly poorer when compared to
patients with other major illnesses such as prostate and colon cancer.
In 1996 the adjusted (for age, race, sex, and primary cause of ESRD)
death rate for all incident ESRD patients was 19.8 per 100 patient
years at risk for patients in the first year of ESRD therapy. The
death rate for ESRD patients with renal disease due to diabetes is even
higher. Strikingly, cardiovascular disease mortality rates among all
ESRD patients are approximately 10 to 20 times those in the general
population with cardiac arrest of unknown cause, acute myocardial
infarction, and all other cardiac causes accounting for nearly one-half
of the deaths in hemodialysis patients greater than 20 years of age.
In contrast to the many studies of cardiovascular disease in ESRD
patients, most notably in those undergoing hemodialysis, there is a
noticeable lack of epidemiological studies documenting the occurrence
of and risk factors for cardiovascular disease in persons with chronic
renal insufficiency in the U.S. However, several small retrospective
and prospective studies conducted in Europe suggest that the incidence
rate of cardiovascular disease is at least three times more frequent
among patients with chronic renal insufficiency resulting primarily
from non-diabetic renal disease compared to the general population. In
contrast, a recent report from the Framingham Heart Study found that
among women, mild chronic renal insufficiency was not associated with
an increased risk for cardiovascular events or all-cause mortality in
men and in women, whereas in men there was an increase in all-cause
mortality but not cardiovascular events. The impact of chronic renal
disease on morbidity and mortality in diabetic patients is especially
striking. For example, in insulin-dependent diabetic patients with
overt nephropathy, the excess mortality may be up to one hundred times
that of an otherwise matched normal population. Much of this mortality
burden is due to an excess of cardiovascular deaths, which is over
several hundred times higher in young insulin-dependent diabetic
patients on renal replacement therapy compared with a normal
population. Likewise, the impact of cardiovascular disease among non-
insulin dependent diabetics with nephropathy is substantial. The
reasons for the increased risk for cardiovascular disease among
diabetic and non-diabetic patients with nephropathy are unclear.
Although traditional risk factors such as hypertension, hyperlipidemia,
hyperglycemia, tobacco use, and physical inactivity are considered
important risk factors for cardiovascular disease in patients with
chronic renal insufficiency, the relative importance of each of these
risk factors compared to nontraditional risk factors (i.e., chronic
inflammation, infection, oxidative stress, elevated homocysteine
levels, fibrinogen, etc.), is not known. Thus, further studies are
needed to determine the risk factors for cardiovascular disease and the
relative magnitude of their effects in persons with chronic renal
insufficiency and to evaluate the contribution of uremia to the
pathophysiology of cardiovascular disease. These studies, however,
must include ethnically and racially diverse populations with chronic
renal diseases representing the major causes of ESRD in the United
States.
Research Goals and Scope of the Activity
The purpose of this RFA is to solicit applications from investigators
proposing to serve as a Clinical Center or a Data Coordinating Center
to develop and conduct a multi-institution, prospective cohort study of
patients with chronic renal insufficiency. Investigators will
collaborate to develop a protocol with primary emphasis on assessing
risk factors for both the accelerated loss of renal function and the
occurrence of cardiovascular disease. Patients with chronic renal
disease and decreased renal function are most likely to be identified
in a time-efficient and cost-effective manner from established sources
of medical care such as outpatient clinics and health maintenance
organizations where information on serum creatinine is readily
available. This RFA does not intend to support large-scale screening
programs utilizing tests of renal function (i.e. serum creatinine) to
recruit cohort study participants. However, there may be certain
circumstances where specialized screening may be performed by the
Clinical Centers to recruit minority or other participants at high risk
for accelerated decline in renal function into the cohort study that
otherwise would not be identified via traditional sources of medical
care. Potentially eligible participants with a serum creatinine value
suggesting that they would meet the glomerular filtration rate (GFR)
eligibility range (see below) will be further assessed during a period
of baseline screening. Upon entry into the cohort study, participants
will be regularly followed and assessed by Clinical Center staff for a
period, on average, of approximately 5 years. Baseline and follow-up
measurements will be standardized across the Clinical Centers. Central
Laboratories and Central Reading Centers will be utilized to maintain
strict quality control of selected tests and procedures. A Central
Repository will be established by the NIDDK to genetic and other
material.
The two primary goals of this solicitation are as follows:
To determine risk factors for rapid progression of chronic renal
disease.
To determine the incidence of and risk factors for cardiovascular
disease.
The following are examples of the types of secondary goals that should
be planned for the cohort study.
To describe the relationship between baseline and follow-up levels of
microalbuminuria (urinary albumin excretion > 30 mg/24 hours),
proteinuria (urinary albumin excretion > 1g/24 hours) and subsequent
loss of renal function, treatment for ESRD, cardiovascular disease
morbidity, and cardiovascular disease mortality in different gender and
ethnic groups.
To examine factors associated with worsening of cardiovascular disease.
To plan and conduct gender and racial/ethnic subgroup analyses as
warranted by the evidence.
To describe patterns of nutrition and the development of malnutrition.
To assess the rates and causes of hospitalization, and the prevalence
and incidence of other important co-morbid events and diseases.
To document overall and cause-specific mortality rates.
To describe patterns and levels of use of health services resources.
To measure quality of life and psychological factors that may be
associated with decline in renal function and the development of
cardiovascular disease.
To identify practice patterns of physicians with respect to chronic
renal insufficiency patients.
To obtain biological specimens (to be maintained in a central
repository) for concurrent and future evaluation of genetic and
biochemical risk factors for accelerated decline in renal function and
development/progression of cardiovascular disease and other diseases.
To collect and evaluate information on family members of the cohort
study participants that may be useful in studies of genetic factors
associated with increased susceptibility to chronic renal disease and
cardiovascular disease.
To determine the incidence of cardiovascular disease, other co-morbid
medical conditions, hospitalization, and mortality in patients after
treatment for ESRD has been initiated.
To describe the patterns of access to chronic renal insufficiency and
ESRD therapy.
To conduct subgroup analyses by cause of renal disease, gender, and
ethnicity for renal disease progression and cardiovascular disease.
The purpose of this RFA is to establish a cohort of patients with
chronic renal insufficiency whose distribution of clinically and
pathologically diagnosed causes of renal disease represents, as much as
feasible, the major causes of ESRD found in the U.S. The goal of this
RFA is to recruit a cohort of study participants whose racial, ethnic,
and gender composition reflects the United States end-stage renal
disease patient population. It is envisioned that diabetic patients
will comprise approximately 50% of the cohort. The total sample size
for the cohort study is projected to be approximately 3,000. It is
anticipated that this number of participants will permit subgroup
analyses of the major outcomes (renal function decline, ESRD, incidence
of cardiovascular disease) of the study among diabetic compared to non-
diabetic patients and by other primary causes of renal disease.
Currently there are no widely accepted and standardized definitions for
mild and moderate chronic renal insufficiency. For the purposes of
this RFA and to provide guidelines for targeting populations for
further screening for entry into the cohort study, the lower value for
serum creatinine in women and men with mild chronic renal insufficiency
is suggested as 1.4 mg/dl and 1.7 mg/dl, respectively. It is
envisioned that the range of renal function as assessed by the
glomerular filtration rate (GFR) will be approximately 30 70
ml/min/1.73m2. It is anticipated that GFR will be measured twice during
baseline and once annually during follow-up. Although levels of serum
creatinine to be considered for initial screening and a study
eligibility GFR range are suggested in this RFA, investigators may wish
to propose their own criteria for these renal function parameters.
However, it is important to note that any recommendations for study
entry based on GFR must be accompanied by evidence from the published
literature that a sufficient number of cohort study participants will
not only have renal function decline at an accelerated rate but also
experience the necessary number of cardiovascular disease events during
the period of time specified in this RFA to achieve the goals of the
study.
Because cardiovascular disease imposes such a significant burden on
ESRD patients, a major emphasis of the cohort study will be observing
the treated natural history of cardiovascular disease. Evidence of
cardiovascular disease will be carefully assessed during baseline and
during follow-up. A major effort will be placed on identifying risk
factors for incident cases of cardiovascular disease and worsening of
established disease. To that end the following tests and procedures to
assess cardiovascular disease status may be considered in the design of
the cohort study protocol: electrocardiogram, echocardiography,
ultrasound measurement of the carotid arteries, and electron-beam
computed tomography of the heart. Other measurements of cardiovascular
disease may also be proposed for implementation in the entire cohort
study population or defined subgroups. However, these recommendations
must be supported by published literature and their utility and
practicality in a multi-center study as described in this RFA must be
considered.
Because little is known about the natural history of cardiovascular
disease in patients undergoing renal replacement therapy, the cohort
study will continue to follow participants after they reach end-stage
renal disease.
The information obtained from this prospective cohort study of chronic
renal insufficiency will serve to identify the point at which promising
interventions could be evaluated in clinical trials. In addition,
professional and public education programs to prevent ESRD and to
reduce the burden of cardiovascular disease in patients with chronic
renal insufficiency and ESRD in the U.S. will benefit from these
findings.
Study Phases
The timetable for the cohort study may be subdivided into four 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 study protocol,
including forms for data collection, for the cohort study by the
Steering and Planning Committee. Central Laboratories, and Reading
Centers. A Central Repository for genetic and other material will be
established and supported directly by the NIDDK. The Data Coordinating
Center will begin computer programming to establish the database for
the study. Prior to implementation of the cohort study, the protocol
will be reviewed and must be approved by external advisors.
Phase II (Months 7-24): Recruitment of Cohort Study
Participants/Initiate Follow-up and Clinic Visit Assessment. Over this
period of 18 months potentially eligible participants will be
identified, invited to the Clinical Centers for baseline assessment,
and those found eligible will be asked to enter into the cohort study.
Concurrent with recruitment, follow-up of all study participants will
be conducted in a standardized fashion over regular intervals. The
external advisors will review the progress of recruitment at its mid-
point (about Month 16 in Phase II) and recommend to the NIDDK whether
the cohort study should continue. Preparation of manuscripts
describing recruitment of the cohort, baseline demographic and clinical
characteristics of the participants, and the cross-sectional
relationships between level of renal function and cardiovascular
disease status using clinical, demographic, and laboratory measurements
will begin to be developed in the latter months (Months 18 to 24) of
this phase.
Phase III (Months 25-78): Follow-up of Cohort Study Participants and
Participants Post-ESRD Treatment. The major activity during this
period will be follow-up clinic visits. Questionnaires will be
administered to assess various demographic, nutritional and quality of
life factors, renal function will be measured, cardiovascular studies
will be performed, and will be laboratory tests performed in all cohort
study participants. Follow-up and data collection on cohort study
participants who reach ESRD will be performed after initiation of renal
replacement therapy (renal transplantation, hemodialysis, peritoneal
dialysis) with modification of data collection, measurements, and
follow-up visit schedule, as necessary and described in the study
protocol. Follow-up assessment of patients who have reached ESRD
includes determining the incidence of cardiovascular disease, other co-
morbid medical conditions, frequency and cause of hospitalization,
overall and cause-specific mortality, selected laboratory measurements
and procedures to evaluate cardiovascular disease. Manuscripts will be
prepared and submitted for publication on the cross-sectional and
initial longitudinal findings from the study. The last follow-up visit
of cohort study participants will be scheduled during the final four
months of this phase. Data collection for persons who previously
reached ESRD will also be terminated at that time.
Phase IV (Months 79-84): Final Data Analysis and Close-out of the
Clinical Centers and the Data Coordinating Center. During the final
six months of the program, the activities include final data analysis
and preparation of manuscripts on the findings from the cohort study,
including the morbidity and mortality experience in persons treated for
ESRD. The Clinical Centers, the Data Coordinating Center, and all
central facilities (excluding the Central Repository) will be closed-
out in the last two months of this phase of the study. It is
anticipated that the National Institutes of Health will maintain the
Central Repository for genetic and other material beyond the seven
years of this program.
Study Outline
STUDY COMPONENTS
Clinical Centers
The Clinical Center investigators will have direct responsibility for
developing the study protocol and uniform data collection forms,
identifying potentially eligible study participants, assessing their
eligibility to participate in the cohort study, conducting baseline and
follow-up visits, obtaining blood, urine, and other biological samples,
performing renal function 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 and reading centers, will also be
responsible for making presentations at scientific meetings and writing
and publishing manuscripts on the findings of their studies.
Data Coordinating Center
The Data Coordinating Center will be responsible for assisting the
Clinical Center investigators through the Steering and Planning
Committee in developing the cohort study protocol. 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 Clinical Centers, developing a web-based data transmission
system, assessing data quality and completeness throughout the study,
and provide general assistance to the Clinical Centers to maintain
long-term participation of the cohort study subjects. The Data
Coordinating Center will also perform analyses as suggested by the
Clinical Centers, Central Laboratories and Central Reading 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 group of external advisors. The Data Coordinating
Center will be responsible for arranging meetings and conference calls
of the Steering and Planning Committee, meetings of the external
advisors, and will perform other administrative functions necessary to
coordinate the efficient operation of the collaborative study group.
The Data Coordinating Center will establish, via subcontracts, Central
Laboratories and Reading Centers, as deemed necessary by the study
protocol. They will also provide administrative coordination for the
Central Repository to be established and directly supported by the
NIDDK to store genetic material and other biological specimens obtained
from cohort study participants.
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 Clinical Centers and the Principal Investigator of the Data
Coordinating Center, the Chairperson of the Steering and Planning
Committee, and the NIDDK Project Scientist (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 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,
measurement of renal function, risk factor assessment for renal disease
and cardiovascular disease, cardiovascular studies, quality control,
and publications and ancillary studies. Small working groups may be
established to prepare manuscripts and presentations.
External Advisors
An independent group of experts in areas such as nephrology,
cardiology, preventive medicine, epidemiology, nutrition, ethics,
health economics, and biostatistics who are not otherwise involved in
the study will be recruited by the NIDDK to evaluate the proposed
protocol 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
external advisors 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.
Responsibilities of the Clinical Centers: The participating Clinical
Centers will have primary responsibility for developing the study
protocol, recruiting a sufficient number of study participants,
maintaining high rates of follow-up and data collection, obtaining data
of high quality, and interpreting, presenting, and publishing findings
from the study.
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, ongoing evaluation of data quality and
performance monitoring of the Clinical Centers, and statistical
analyses of the data.
(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, final data
analysis and interpretation, and preparation of publications. The
awardees agree to work cooperatively with the other Clinical Centers
and agree to follow the common protocol developed by the Steering and
Planning Committee. The awardees agree also to transmit the agreed
upon study data in a timely manner according to study protocol 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 studies. The Project
Scientists will have substantial scientific-programmatic involvement in
protocol development, quality control, interim data analysis, final
data analysis and interpretation, preparation of publications, and
coordination and performance monitoring. The NIDDK Project Scientists
will have voting membership on the Steering and Planning Committee and
will have one vote. One of the NIDDK Project Scientists will also
serve as Executive Secretary of the external advisors. 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
cohort study, maintaining high rates of follow-up and data
collection/completion of participants tests, in timely data reporting,
achieving high levels of data quality, working cooperatively or other
major breaches of the protocol, or human subject ethical issues that
may dictate a premature termination. The NIDDK Project Scientists will
establish the Central Repository for genetic and other material.
(3) Collaborative Responsibilities
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
purpose is to support and/or stimulate the recipient’s activity by
involvement in and otherwise working jointly with the award recipient
in a partner role, but it is not to assume direction, prime
responsibility, or a dominant role in the activity. Consistent with
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 Scientist.
The Steering and Planning Committee, composed of each of the Principal
Investigators of the Clinical Centers, the Principal Investigator of
the Data Coordinating Center, the NIDDK Project Scientists, and the
Chairman of the Steering and Planning Committee, will be the main
governing board of the study. This committee will have the primary
responsibility for developing the study protocol, facilitating the
conduct of participant follow-up and testing, monitoring completeness
of data collection 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
the NIDDK Project Scientist) or alternatively, from among experts in
the field of nephrology, cardiology, preventive medicine, nutrition, or
epidemiology who are not participating directly in the study. An
independent group of external advisors, selected by the Director,
NIDDK, will review periodically the progress of the study. This group
will include experts in the relevant medical, epidemiological,
statistical, and ethics fields who are not otherwise involved in the
study. The external advisors will review the study protocol and
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 group. The
members of the group will review progress and 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 are provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43).
All investigators proposing 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 are 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.
Investigators should consider the available evidence and discuss the
NIH Phase III Clinical Trial requirements for planning analyses of
gender or subgroup differences in their applications and protocols, and
conducting and reporting on these analyses in reports to NIH and in
manuscripts for publication.
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/not98-025.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.
INFORMATION FOR PROSPECTIVE APPLICANTS
Open Forum
A one-day open information forum will be held for prospective
applicants on December 11, 2000, from 1 p.m. to 4 p.m. (EST) in
Building 1, Room 151, on the campus of the National Institutes of
Health. At this forum NIDDK program staff will address any questions
that prospective applicants might have regarding the
clinical/scientific concepts of the RFA. Attendance is not required
and is not a pre-condition for submission of an application.
Applicants planning to attend this meeting should submit their
questions in writing (electronic mail is acceptable) to John W. Kusek,
Ph.D. at the address listed under INQUIRIES at least two weeks in
advance of the forum.
Information on the Web
For those who cannot attend the December 11 forum, a website will
contain a summary of that meeting. It will also contain questions of
general interest asked by prospective applicants and their answers.
Prospective applicants are encouraged to check this website frequently
while preparing an application. The website can be reached through the
following URL: http://www.niddk.nih.gov/fund/crfo/rfas.htm.
LETTER OF INTENT
Prospective applicants are asked to submit, by February 28, 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 plan 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 653, MSC 5452
Bethesda, Maryland 20892-5452 (for courier service use 20817)
Telephone: (301) 594-8885
Fax: (301) 480-3505
Email: hagana@extra.niddk.nih.gov
APPLICATION PROCEDURES
Applications must be submitted on the standard research grant
application form PHS 398 (rev. 4/98). 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 Prospective Cohort Study
of Chronic Renal Insufficiency 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
must be sent to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
6707 Democracy Boulevard
Room 653 MSC 5452
Bethesda, Maryland 20892-5452 (For express/courier service, use 20817)
Applications must be received by March 28, 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.
Information to be Included in Applications
Details of the Proposed Study Protocol: Applicants for a Clinical
Center should describe a research plan involving multi-center
participation to address the objectives of the study and to reach the
study goals. Applicants should outline the rationale and background of
the proposed prospective cohort study and follow-up data collection of
participants after they have reached ESRD. Major entry and exclusion
criteria, including measures of renal function, should be described and
justified. The type of laboratory and medical tests, questionnaires,
and other data collection should be specified and the frequency of
assessment during follow-up must be specified. Particular emphasis
should be given to measurement of renal function and tests to determine
prevalence of cardiovascular disease at baseline and its incidence
and/or progression during follow-up. An application for a Clinical
Center must provide credible evidence of the size of the potential pool
of participants based on an objective measure of renal function, an
estimate of the proportion of persons with mild to moderate chronic
renal insufficiency who will be willing to come to the Clinical Center
to participate in a screening visit to assess cohort study eligibility,
and a reasonable projection of the proportion who were screened and
found eligible that would be willing to commit to participation in a
long-term follow-up study as described in this RFA. A detailed
description of the gender and racial/ethnic composition of the
population of chronic renal insufficiency patients targeted for
recruitment as well as a comprehensive plan to recruit a cohort of
patients reflecting the make-up of the U.S. end-stage renal disease
patient population must be provided. Realistic rates of study drop-
outs and out migration from the study should be proposed. Efforts to
maintain follow-up of cohort study participants must also be described.
Applicants must consider the sample size proposed in this RFA and
include a discussion of event rates (ESRD, incident cardiovascular
disease), the expected rate of decline in renal function (GFR)
anticipated in the cohort, and the statistical power of the study for
subgroup analyses (diabetics vs. non-diabetics, within major causes of
renal disease, gender, and racial/ethnic subgroup). Recommendations
for serum creatinine values for screening and GFR eligibility range for
the cohort study differing from those included in the RFA must be
justified with published information. Applications for the Data
Coordinating Center should also include a proposed design for a
prospective cohort study of chronic renal insufficiency patients as
described in this RFA, a plan for the study of cohort study
participants post-initiation of renal replacement therapy, plans for
data collection, and overall quality control of the study. Information
on proposed plans for study-wide data analysis should be included,
including the analysis of the cohort study phase and the post-ESRD
treatment follow-up phase. Applicants must also consider the sample
size proposed in this RFA and include a discussion of event rates
(ESRD, incident cardiovascular disease), the expected rate of decline
in renal function (GFR) anticipated in the cohort, and the statistical
power of the study for subgroup analyses (diabetics vs. non-diabetics,
within major causes of renal disease). An administrative plan to
coordinate the activities of the Central Laboratories and Central
Reading Centers, including quality control and data transmission to the
Data Coordinating Center must be included in the application. The
identification and access of genetic material and other biological
specimens stored in the Central Repository must also be delineated. A
description of anticipated problems in carrying out this study and
their proposed solutions should 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 follow-up (Clinical Centers) and data
analysis/management (for the Data Coordinating Center) activities. 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.
Previous Experience: The applicant should include a succinct
discussion of previous relevant research efforts in epidemiological
population studies, 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. 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 Clinical Centers, expertise
in nephrology, cardiology, and epidemiology is required. Personnel may
be full-time or part-time and may serve in more than one capacity, as
appropriate. A suggested Clinical Center study team may include besides
a Principal Investigator, a co-investigator (M.D. or Ph.D.), study
coordinators, GFR technician, appointment scheduler/administrative
assistant and data entry clerk. Expertise required for the Data
Coordinating Center must also 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. Consultants
in nephrology, cardiology, nutrition, quality of life, and health
resource utilization assessment are also advisable.
Budget Preparation by Year
Applicants for the 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. Note that budgets are not to be prepared in
modules. Also note that the Central Repository established for the
cohort study will be supported directly by the NIDDK and not via a
subcontract to the Data Coordinating Center.
Phase I (First 6 months of Year 1). The budget will be for development
of the protocol by the 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 Clinical
Centers. A web-based technology for data transmission will be
established in Phase I that will protect study participant privacy.
The Data Coordinating Center will identify and establish subcontracts
with Central Laboratories and Central Reading Centers as specified by
the study protocol. It is expected that the Data Coordinating Center
will purchase the hardware and software necessary for data transmission
from the Clinical Centers. The proposed study protocol will also be
reviewed by the external advisors and must be approved prior to its
implementation. The travel budget for Phase I should be estimated
based on travel for two key investigators to attend two-day, every two
months meetings of the Steering and Planning Committee in the
Washington, D. C. area.
Phase II (Months 7-24). The budget for the Clinical Centers should
reflect the level of effort necessary to recruit the entire study
cohort and perform baseline and follow-up studies. Follow-up data will
also be collected by the Clinical Centers. Costs should be included
for specialized studies of renal function (GFR measurement) and
cardiovascular studies (echocardiography, carotid ultrasound, electron
beam computed tomography). The Data Coordinating Center will receive
and store the data transmitted by the Clinical Centers, assess its
completeness, provide feedback to the Clinical Centers regarding data
quality, and prepare progress reports for the Steering and Planning
Committee and the group of external advisors on the progress of the
cohort study. The budget should include costs associated with a
Central Biochemistry Laboratory, a Central GFR Laboratory, and central
facilities for reading the echocardiography, carotid ultrasound, and
electron beam computed tomogaphy). Costs associated with a Central
Repository for genetic and biochemical material will be borne directly
by the NIDDK. However, the Data Coordinating Center should budget
staff to coordinate the activities of the Central Repository as it
pertains to quality control. 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 Clinical Centers and the Data
Coordinating Center. Budgets for the Data Coordinating Center should
include travel for any consultants. Travel for key staff at the
Clinical Centers and the Data Coordinating Center should be budgeted
each year for central training.
Phase III (Months 25-78). The major activities in this phase are
follow-up and assessment of cohort study participants. Initially, data
analysis of the recruitment experience and baseline characteristics of
the cohort study participants will be undertaken. The first
manuscripts will focus on cross-sectional findings. Subsequently, the
manuscripts will deal with longitudinal changes in renal function and
occurrence of cardiovascular disease in the cohort and other outcomes
of interest. Data analysis will be conducted and papers addressing the
secondary goals of the cohort study will also be prepared. Renal
function measurements and studies of cardiovascular disease will
continue during follow-up. A Central Biochemistry Laboratory, Central
GFR Laboratory, and Central Reading Facilities for echocardiography,
ultrasound, and electron beam computed tomography continue to operate
to handle follow-up data. The Central Repository will receive,
process, and store specimens from cohort study participants. In-clinic
visit follow-up of the cohort study participants, including those
followed post-ESRD treatment, will be terminated during the last
several months of Phase III.
Three meetings of the investigators should be budgeted for each year of
this phase of the study. Central training will occur annually and key
staff should be budgeted to travel to the Washington, D. C. area.
For a Clinical Center, the budget should request support for the
minimum number of full and/or part-time staff to successfully carry out
the proposed cohort study. A Clinical Center personnel list could
include a principal investigator, co-investigator, study coordinators,
GFR technician, appointment scheduler/administrative assistant, and
data entry clerk.
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 a
Central GFR Laboratory, Central Biochemistry Laboratory,
Echocardiography Reading Center, Ultrasound Reading Center, and
Electron Beam Computed Tomography Reading Center. As noted previously,
funding for the Central Repository will be directly from the NIDDK.
Travel by Data Coordinating Center staff to Washington, D.C. for a
meeting with the group of external advisors should be planned and
budgeted for annually.
Phase IV (Months 79-84). Final Data Analysis and Close-out of the
Clinical Centers, the Data Coordinating Center, Central Biochemistry
Laboratory, the Central GFR Laboratory and Central Reading Facilities
for Echocardiography, Ultrasound, and Electron Beam Computed
Tomograpghy. The major activities include final data analysis of the
cohort study. Final data analysis will also be conducted on the post-
ESRD treatment experience of the cohort study participants.
Manuscripts describing these findings will be prepared and submitted to
peer-reviewed scientific journals for publication. The Clinical
Centers, the Data Coordinating Center, the Central Laboratories, and
Central Reading Centers 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 group of external advisors
will be held in Phase IV.
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 two
months. 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, and Reading
Centers will be identified and established by the Data Coordinating
Center. Recruitment plans are further developed by the Clinical
Centers. Computer hardware and software will be purchased by the Data
Coordinating Center for use by the Clinical Centers. The Central
Repository will be identified by the NIDDK.
Year 1 (Months 7-12): The Clinical Centers begin recruitment and
screening of cohort study participants. Participant follow-up
assessment begins. Database development is continued by the Data
Coordinating Center. The Central Biochemistry Laboratory, the Central
GFR Laboratory, the Central Repository, and Central Facilities for
Echocardiography, Ultrasound, and Electron Beam Computed Tomography
will begin functioning. The Central Repository will become operational.
Year 2 (12 months): Recruitment of cohort study participants continues
and is completed at the end of year two. Participant follow-up
assessment by the Clinical Centers continues. Reports on recruitment
rates, data quality, and baseline characteristics of study participants
prepared by the Data Coordinating Center. Plans for data analysis on
the recruitment experience and baseline findings are established by the
Data Coordinating Center.
Year 3 (12 months): Participant follow-up assessment by the Clinical
Centers continues. Reports on data quality, and follow-up studies
generated by the Data Coordinating Center. Manuscripts describing the
recruitment experience, baseline clinical and demographic
characteristics of the participants, and unique aspects of this cohort
study are prepared based on analyses from the Data Coordinating Center.
Year 4 (12 months): Participant follow-up by the Clinical Centers
continues. Manuscripts describing short-term changes in renal
function, changes in cardiovascular disease risk factors, and other
findings from the study are prepared based on data analysis from the
Data Coordinating Center. The Clinical Centers and the Data
Coordinating Center, and whenever appropriate the Central Reading
Centers and Central Laboratories, will participate in special
epidemiological studies such as nested case-control studies of risk
factors for renal disease progression and occurrence of cardiovascular
disease.
Year 5 (12 months): Participant follow-up assessment by the Clinical
Centers continues. Data analysis and manuscripts prepared addressing
secondary goals of the cohort study.
Year 6 (12 months): Participant follow-up assessment by the Clinical
Centers continues. Continued data analysis by the Data Coordinating
Center and preparation of manuscripts by the Clinical Centers and
investigators from the Central Reading Centers on primary and secondary
goals of the study. Plans will be established for study close-out.
Year 7 (First 6 months): Final follow-up clinic visit is conducted.
Data collection for patients receiving treatment for ESRD is concluded.
Plans will be established for final data analysis by the Data
Coordinating Center and Clinical Centers.
Year 7 (Last 6 months): Final data analysis will be performed and
major reports and manuscripts prepared. The Data Coordinating Center,
the Clinical Centers, the Central Laboratories, and the Central Reading
Center, 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, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of the applications under review, will be
discussed, assigned a priority score, and receive a second level review
by the National Diabetes and Digestive and Kidney Diseases 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 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 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 a sound study design and methods
to achieve the aims of the RFA? Is the potential pool of cohort 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 cohort study based on level of renal
function? 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 cohort been adequately described, and plans described for
appropriate analyses? Has information on the distribution of renal
disease of the population targeted for recruitment been discussed?
What plans have been presented to ensure high rates of follow-up and
high rates of participation in answering questionnaires and undergoing
tests mandated by the study protocol? What risk factors (i.e.,
demographic, clinical, and laboratory measurements) are proposed to be
included in the study protocol to explain decline in renal function and
development of cardiovascular disease? What measurements will be used
to assess cardiovascular disease status at baseline and during follow-
up? Have the sample size and power calculations and proposed subgroup
analyses been adequately addressed? 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 epidemiological studies 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 long-term follow-up studies?
Necessary Expertise: Documented experience in nephrology, cardiology,
and epidemiology is required. Demonstrated knowledge of clinical
aspects of chronic renal disease and cardiovascular disease is
required.
Staff Qualifications: Documented specific competence and relevant
experience of professional, technical, and administrative staff
pertinent to the operation of a 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 Patient Databases: Evidence of the ability to access
large patient databases containing information on level of renal
function and/or diagnoses of chronic renal disease from which potential
cohort study participants will be recruited is necessary.
Documentation must be provided on the ability to contact patients
identified in these databases in order to invite them to a more
detailed, in-clinic assessment of their eligibility to participate in
the cohort study. The necessary administrative arrangements to access
these databases and to contact individual patients must also be
included in the application.
Recruitment of 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. end-stage renal disease 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: A design for a cohort study should be included in the
application for a Data Coordinating Center. Is a sound design proposed
for the cohort study and are the planned follow-up studies and
examinations reasonable to achieve the goals of the RFA. Are the
conceptual framework, design, and methods adequately developed, well
integrated, and appropriate to the aims of the project? Does the
applicant acknowledge potential problem areas and consider alternative
tactics? Experience in developing protocols, developing web-based
technology for data collection, establishing and maintaining large
databases for data from the Clinical Centers, plans for analysis of the
combined data, and efforts to ensure high quality data collection, and
ensuring study participant confidentiality will be evaluated. Have the
sample size estimates and power calculations been described in detail?
Have adequate statistical plans been included for subgroup analyses?
What is the approach to handle missing follow-up data?
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 and
biostatistics is required. Does the applicant have expertise in
longitudinal data analysis, including renal function measurements?
Demonstrated knowledge of clinical aspects of chronic renal disease and
cardiovascular disease from either a co-investigator or consultant will
be judged. The level of expertise of consultants in nephrology,
cardiology, quality of life and health resource utilization 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, the
Central Laboratories, and the Central Reading Centers and exercise
appropriate leadership in matters of study design, data acquisition,
data management, data quality, data analysis, and administration and
coordination of Steering and Planning Committee 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
Applicant Information Forum Date: December 11, 2000
Letter of Intent Receipt Date: February 28, 2001
Application Receipt Date: March 28, 2001
Special Review Committee: June/July 2001
NDDK Advisory Council: September, 2001
Anticipated Award Date: September, 2001
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit as determined by peer review
o Availability of funds
o Cost
o The distribution of the causes of renal disease, racial and ethnic
composition of the population targeted for recruitment
o Geographic distribution of the 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 W. Kusek, Ph.D.
or Paul L. Kimmel, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Room 617 (J. Kusek, Ph.D.) or Room 607 (P.L. Kimmel, M.D.) 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: kusekj@ep.niddk.nih.gov
kimmelp@ep.niddk.nih.gov
Fiscal and administrative inquiries may be directed to:
Teresa A. Farris
Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Room 630 MSC 5456
6707 Democracy Boulevard
Bethesda, Maryland 20892-5456 (for express/courier service use 20817)
Telephone: (301) 594-7682
FAX: (301) 480-3504
Email: farrist@ep.niddk.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
|
|
|
|
Department of Health and Human Services (HHS)
|
|
|
|
NIH... Turning Discovery Into Health®
|