FREQUENT HEMODIALYSIS CLINICAL TRIALS
RELEASE DATE: December 4, 2002
RFA: DK-03-005 (Reissued as RFA-DK-07-503)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov)
LETTER OF INTENT RECEIPT DATE: February 14, 2003
APPLICATION RECEIPT DATE: March 14, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations:
PURPOSE OF THIS RFA
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 for a Data and
Analysis Coordinating Center (DACC) and two Coordinating Clinical
Centers (CCCs) to design, develop and implement clinical treatment
trials of frequent hemodialysis for patients with end stage renal
disease (ESRD). The DACC and CCCs will propose trial designs for the
studies. It is anticipated that two trials will be initiated, one
comparing short daily hemodialysis with conventional dialysis and one
comparing long nocturnal dialysis with conventional dialysis. The goal
of the RFA is to test the feasibility of randomizing a representative
sample of dialysis patients into either (a) conventional three times
per week dialysis, or (b) one of the two forms of frequent dialysis
named above and to obtain preliminary data on the impact of these
modalities on patient well-being. It is expected that patients will be
followed for a minimum of six months and that intermediate outcomes
will be tracked such as anemia, nutritional status, blood pressure,
left ventricular hypertrophy, exercise tolerance, medication use,
hospitalizations, etc. Based on the results of these trials, NIDDK
will determine the advisability of continuing with a large scale trial
of daily dialysis, powered to measure the impact of more frequent
dialysis on hard endpoints, such as mortality and/or cardiovascular
outcomes.
The structure of the trials will be determined in part by the
proposals. However, it is expected that the DACC will be responsible
for coordinating the project design, monitoring data collection, and
statistical analyses. Each CCC will be responsible for enrolling
patients into the trials, monitoring the dialysis interventions, and
data collection. It is not necessary that a CCC be able to enroll the
entire patient cohort at a single site. A CCC may work out cooperative
arrangements with a network of dialysis providers to reach enrollment
goals. It is expected that CCCs will be given a fixed payment for the
infrastructure for the trial and variable payments based on attaining
enrollment goals.
RESEARCH OBJECTIVES
A. Background
End stage renal disease afflicts approximately 380,000 Americans. Most
are receiving hemodialysis three times per week. This frequency of
hemodialysis, while conventional and capable of sustaining life, has no
solid scientific basis. Although this schedule is compatible with
prolonged survival for some patients, the annual mortality rates are
quite high for the entire population of ESRD patients.
More frequent hemodialysis has been employed by some centers in small
numbers of selected patients. The modalities have included home and in-
center hemodialysis delivered four to seven times per week with
standard blood and dialysate flow rates. Some centers have employed a
day time therapy of shorter duration per dialysis session than with the
thrice weekly schedule. Alternatively, in the nocturnal version, lower
than standard flow rates have been used but for longer periods of time
than the usual, often 8 hours per night. The results of these
approaches to increased frequency have been reportedly good. Reductions
in blood pressure, serum phosphate levels and erythropoietin
requirements have been noted. Improved patient well being has also been
reported. However, these observations derive from small groups of
selected patients in a few centers.
Large numbers of subjects (N = 1,000 or more) are generally required to
assess the effect of any change in ESRD therapy on mortality and
cardiovascular events, e.g. stroke, myocardial infarction and heart
failure, all of which often complicate ESRD. Based on previous studies
of small numbers of daily dialysis patients, and the uncertain ability
to randomize patients into daily versus conventional frequency, the
trials conducted under this RFA will focus on intermediate outcomes.
These outcomes include blood pressure, LVH, nutritional status, anemia
quality of life, and vascular access.
B. Research Goals and Scope
The goal of this research initiative is to establish two clinical
centers to conduct a trial of more frequent hemodialysis. It is the
intent of this solicitation to invite applications from investigators
who wish to apply their expertise to the testing of more frequent
hemodialysis. This RFA solicits applications from investigators
proposing to serve as a Coordinating Clinical Center or a Data and
Analysis Coordinating Center to develop and conduct such a trial.
It is anticipated that the studies to be conducted by this consortium
in this RFA will take place in two CCCs over a period of four years.
It is envisioned that each CCC will need to enroll a total of between
150 and 200 patients on dialysis. As stated above, the CCCs may chose
to work out cooperative arrangements with a network of dialysis
providers in order to reach enrollment goals. The data collection
activities of the CCCs will be supported by a single DACC.
C. Study Design
Applicants for both the CCC and the DACC should respond with research
protocols involving clinical trials to address the objectives of the
study and to reach the study goals described in this RFA, and include
detailed plans regarding their participation in clinical trials.
Applicants should outline the rationale and background of the proposed
study, study design and protocols, eligibility and exclusion criteria,
and type of patients to be included in the protocols, and baseline and
outcome measures to be assessed, in their applications. For each of
the clinical protocols, the CCC 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 ESRD is required.
Study Phases
The program will be carried out in three phases over a four-year
period.
Phase I (Months 1-12): 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 (see Cooperative
Agreement Terms and Conditions of Award). 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 and Analysis Coordinating Center will begin computer
programming to establish the database for the study. The collaborative
protocols for the trials will be developed by the Steering Committee.
Prior to implementation of the trials, the protocols and manual of
operations will be reviewed, and must be approved by the External
Advisory Committee (see Cooperative Agreement Terms and Conditions of
Award). The study will move into operational phase (Phase II) only
with the concurrence of the External Advisory 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 13-36): Recruitment of Study Participants/Initiation
of Interventional Trials
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 CCCs for baseline assessment, and those
found eligible will be asked to enter the appropriate trial. 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. The External Advisory Committee will review the progress of
recruitment at 6 month intervals, review interim outcomes and recommend
to the NIDDK whether the trial(s) should continue. The major activity
during the first half of this phase will be the recruitment,
assessment, enrollment and retention of patients in the trials.
Manuscripts describing recruitment of the subjects, and baseline
demographic and clinical characteristics of the participants will be
prepared. Follow-up and data collection on study participants will
continue throughout this phase, as determined by the study protocols.
Manuscripts will be prepared and submitted for publication on the
interim findings from the study. The last follow-up visit of study
participants will be scheduled during the final two months of this
phase.
Phase III (Months 37-48): Final Data Analysis and Close-out of the
CCCs and the DACC.
During the final twelve months of the program, the activities include
final data analyses and preparation of manuscripts on the findings from
the trials. The Coordinating Clinical Centers, the Data and Analysis
Coordinating Center, and all central facilities will be closed-out in
the last two months of this phase of the study.
Study Organization
The Study organization will include Coordinating Clinical Centers, a
Data and Analysis Coordinating Center, a Steering and Planning
Committee, and an External Advisory Committee (see descriptions under
Cooperative Agreement Terms and Conditions of Award).
MECHANISM OF SUPPORT
This RFA will use the NIH U01 award mechanism(s). As an applicant you
will be solely responsible for planning, directing, and executing the
proposed project. This RFA uses just-in-time concepts.
The NIH (U01) is a cooperative agreement award mechanism in which the
Principal Investigator retains the primary responsibility and dominant
role for planning, directing, and executing the proposed project, with
NIH staff being substantially involved as a partner with the Principal
Investigator, as described under the section "Cooperative Agreement
Terms and Conditions of Award"
The total project period for applications submitted in response to this
RFA is four years. The anticipated award date is September 1, 2003.
FUNDS AVAILABLE
The NIDDK plans to make two awards for Coordinating Clinical Centers
and one award for a Data and Analysis Coordinating Center.
Approximately $1,000,000 total cost (direct plus facilities and
administrative costs) is expected to be available during the first year
of the study and $3,000,000 for each of the remaining three years of
the study. It is anticipated that the award for each Coordinating
Clinical Center will be about $250,000 total cost in year one,
$1,250,000 total cost in the second and third years, and $1,000,000
total cost in the fourth year. The award for the Data and Analysis
Coordinating Center will be about $500,000 total cost in years one,
two, and three of the program, and $1,000,000 in the fourth year. As
noted in the Purpose section above, payments to the CCCs will be
dependent, in part, on obtaining enrollment goals.
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.
To defray the costs of more frequent dialysis, the Centers for Medicare
and Medicaid Services (CMS) has authorized one additional composite
rate payment per week for the duration of the trials to cover the
reasonable costs of the provision of the additional dialysis sessions.
CMS will also permit additional home dialysis training payments at the
composite payment rate plus $20 per training session. Payment would be
made for each training session incurred for up to 5 weeks. These
payments will not be paid through this U01 mechanism but will be paid
through the normal Medicare payment billing system. More information
about dialysis payment levels can be obtained from the persons listed
in the Inquiries section at the end of this document.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with their
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
Cooperative Agreement 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
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 the
NIDDK Project Scientist.
(1) Awardees' Rights and Responsibilities
Awardees will have primary responsibility for the project as a whole,
including protocol development, enrollment of study participants, data
collection, data quality control, management of the trials, final data
analyses and interpretation, and preparation of publications. 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.
Coordinating Clinical Centers
The Coordinating 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 measures of dialysis delivery and
other measurements, collecting data (both clinical and cost related),
and transmitting it in a timely fashion to the Data and Analysis
Coordinating Center. They, along with staff from the Data and Analysis
Coordinating Center, will also be responsible for making presentations
at scientific meetings and writing and publishing manuscripts on the
findings of their studies. A CCC will work collaboratively with the
other CCC and the DACC, and will follow study protocols.
Data and Analysis Coordinating Center
The Data and Analysis Coordinating Center will be responsible for
assisting the CCC investigators, through the Steering and Planning
Committee, in developing the trial protocol(s) during Phases I and II.
The Data and Analysis Coordinating Center will create data collection
forms based on input from the Steering and Planning Committee. The Data
and Analysis Coordinating Center will be responsible for establishing a
database to accommodate data sent by the Coordinating Clinical Centers,
developing a web-based data communication system, assessing data
quality and completeness throughout the study, and providing general
assistance to the Coordinating Clinical Centers to maintain long-term
participation of the study subjects and their adherence to the study
protocols. The Data and Analysis Coordinating Center will also create
a web site for study information available to the public.
The Data and Analysis Coordinating Center will also perform analyses as
suggested by the Coordinating Clinical Centers, as well as propose
original analyses to the collaborative group for their consideration.
The Data and Analysis 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 External Advisory Committee.
The DACC will be responsible for coordinating transfer of biologic
samples and, to a repository to be established by the NIDDK. The Data
and Analysis Coordinating Center will be responsible for arranging
meetings and conference calls of the Steering and Planning Committee
and will perform other administrative functions necessary to coordinate
the efficient operation of the Frequent Hemodialysis Clinical Trial
Network. The Data and Analysis Coordinating Center will establish, via
subcontracts, Central Laboratories and other necessary adjuncts to the
study, as necessitated by the study protocol(s). The DACC will be
expected to provide the NIDDK and CMS with data (both clinical and cost
related) in a uniform, usable platform throughout the course of the
studies and after the termination of the studies supported by this RFA.
(2) NIDDK Staff Responsibilities
The NIDDK will name a Program Director and a Project Scientist to the
project from within the Division of Kidney, Urologic and Hematologic
Diseases. The Program Director will be responsible for the overall
management of the project and will oversee all operational aspects of
the project. The Program Director will assist the Steering and
Planning Committee in carrying out the study and will serve as
Executive Secretary of the External Advisory Committee. The Project
Scientist 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 Scientist will have a voting membership on the
Steering and Planning 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. The study will
progress from one phase to the next only with NIDDK approval.
(3) Centers for Medicare and Medicaid Services (CMS) Staff
Responsibilities
The CMS will name one project liaison representative to participate in
these trials and assist the NIDDK in carrying out the study. The
liaison representative will have experience in Medicare ESRD program
and payment policy. The liaison representative will serve as a voting
member of the steering and planning committee and will attend meetings
of the EAC. The project liaison representative will have substantial
involvement in the development of cost data collection design,
collection and analysis. The DACC and CCCs will cooperate with the
Centers for Medicare and Medicaid Services (CMS) in the design and
collection of cost data relevant to the provision of daily dialysis.
This will include the costs of training patients as well as the weekly
maintenance costs of providing daily dialysis.
(4) Collaborative Responsibilities
The Steering and Planning Committee, composed of each of the Principal
Investigators of the CCCs, the Principal Investigator of the DACC, the
NIDDK Project Scientist, the Chairperson of the Steering and Planning
Committee, and the CMS liaison representative will be the main
governing board of the study. NIDDK may supplement the Steering and
Planning Committee with experts in the fields of nephrology, clinical
trials, and statistics as deemed necessary. This 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 and Analysis 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,
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 or CMS representatives).
An independent External Advisory Committee (EAC), 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 EAC
will review the study protocol(s) as developed during Phases I and II,
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 representatives will serve as Executive Secretary of the
External Advisory Committee. The members of the EAC will review the
trials' progress and report to the NIDDK at least once each year, or
more often if necessary.
(5) 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.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research, peer review, and financial or grants
management issues:
o Direct your questions about scientific/research issues to:
Paul Eggers, Ph.D,
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 617 MSC 5458
Bethesda, Maryland 20892-5458
(for express or courier service use 20817)
Telephone: (301) 594-7717
FAX: (301) 480-3510
Email: pe39h@nih.gov
Thomas Hostetter, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 647 MSC 5458
Bethesda, Maryland 20892-5458
(for express or courier service use 20817)
Telephone: (301) 594-8864
FAX: (301) 480-3510
Email: th192u@nih.gov
o Direct your questions about peer review issues to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752 MSC 5452
Bethesda, MD 20892
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: fc15y@nih.gov
o Direct your questions about financial or grants management matters
to:
Ms. Helen Ling
Senior Grants Management Specialist
Grants Management Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 732
MSC 5456
Bethesda, MD 20892-5456
(For Express Mail Use Zip Code 20817)
Telephone: (301) 594-8857
Fax: (301) 480-3504
Email: hl12d@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does
not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning
of this document. The letter of intent should be sent to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752 MSC 5452
Bethesda, MD 20892
(Courier use ZIP 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: fc15y@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). The PHS 398 is
available at https://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form must be affixed to the bottom of the face page
of the application. Type the RFA number on the label. Failure to use
this label could result in delayed processing of the application such
that it may not reach the review committee in time for review. In
addition, the RFA title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked. The RFA
label is also available at:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: 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
any appendices must be sent to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752 MSC 5452
Bethesda, MD 20892
(Courier use ZIP 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: fc15y@nih.gov
APPLICATION PROCESSING: Applications must be received by the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude
the submission of substantial revisions of applications already
reviewed, but such applications must include an Introduction addressing
the previous critique.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIDDK.
Incomplete applications will be returned to the applicant without
further consideration. And, if the application is not responsive to
the RFA, CSR staff may contact the applicant to determine whether to
return the application to the applicant or submit it for review in
competition with unsolicited applications at the next appropriate NIH
review cycle.
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:
o Receive a written critique
o 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 and assigned a priority score
o Receive a second level review by the National Diabetes and Digestive
and Kidney Diseases Advisory Council.
REVIEW CRITERIA
REVIEW CRITERIA FOR COORDINATING CLINICAL CENTERS
General: The ability to regionally recruit sufficient numbers of
subjects for randomization, to provide the proposed frequent
hemodialysis therapy, to provide cost data, and to document adherence
to the protocol in a large number of dialysis sites will be key review
criteria.
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? 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 and Analysis Coordinating Center. Knowledge of the possible
problems associated with the conduct of clinical 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 design of the trial?
Staff Qualifications: Documented specific competence and relevant
experience of professional, technical, and administrative staff
pertinent to the operation of a Coordinating Clinical Center are
required. Documented experience in nephrology, and specifically in the
field of ESRD and clinical trial methodology is 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 sufficient 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.
REVIEW CRITERIA FOR A DATA AND ANALYSIS 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?
How does the applicant propose to collect and analyze dialysis cost
data? Experience in developing protocols, developing web-based
technology for data collection, establishing and maintaining large
databases for data from the Coordinating 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? 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 and Analysis
Coordinating Center to take the lead in developing a cooperative
relationship among the Coordinating 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?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o PROTECTIONS: The adequacy of the proposed protection for humans,
animals, or the environment, to the extent they may be adversely
affected by the project proposed in the application.
o INCLUSION: The adequacy of plans to include subjects from both
genders, all racial and ethnic groups (and subgroups), and children as
appropriate for the scientific goals of the research. Plans for the
recruitment and retention of subjects will also be evaluated. (See
Inclusion Criteria included in the section on Federal Citations, below)
o DATA SHARING: The adequacy of the proposed plan to share data.
o BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: February 14, 2003
Application Receipt Date: March 14, 2003
Peer Review Date: June/July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 30, 2003
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 Programmatic priorities.
REQUIRED FEDERAL CITATIONS
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:
Research components involving Phase I and II clinical trials must
include provisions for assessment of patient eligibility and status,
rigorous data management, quality assurance, and auditing procedures.
In addition, it is NIH policy that all clinical trials require data and
safety monitoring, with the method and degree of monitoring being
commensurate with the risks (NIH Policy for Data Safety and Monitoring,
NIH Guide for Grants and Contracts, June 12, 1998:
https://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:
It is the policy of the NIH that women and members of minority groups
and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification
is provided indicating that inclusion is inappropriate with respect to
the health of the subjects or the purpose of the research. This policy
results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).
All investigators proposing clinical research should read the AMENDMENT
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a
complete copy of the updated Guidelines are available at
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition
of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language
governing NIH-defined Phase III clinical trials consistent with the new
PHS Form 398; and updated roles and responsibilities of NIH staff and
the extramural community. The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must provide a description of plans to
conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy that children (i.e., individuals
under the age of 21) must be included in all human subjects research,
conducted or supported by the NIH, unless there are scientific and
ethical reasons not to include them. This policy applies to all initial
(Type 1) applications submitted for receipt dates after October 1,
1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
https://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:
NIH policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has
provided guidance at
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
this award.
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. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet
site.
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 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.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.849 and is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and administered under NIH grants policies described
at https://grants.nih.gov/grants/policy/policy.htm and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products. In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a
facility) in which regular or routine education, library, day care,
health care, or early childhood development services are provided to
children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.