Subject: NIHGUIDE - Vol. 19, No. 39, November 2, 1990 - RFA DK-91-02
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 31 Oct 90 15:32 EST

Hi Paul,
    Please post this one to the NIHListserver as:
RFADK-91-02.110290
   Thanks.  dottie
 
CLINICAL TRIAL PLANNING GRANT
FOR DIGESTIVE AND NUTRITIONAL DISEASES
 
RFA AVAILABLE:  DK-91-02
 
P.T. 34; K.W. 0755015, 0715085, 0715135, 0710095
 
National Institute of Diabetes and Digestive and Kidney Diseases
 
Application Receipt Date:  January 22, 1991
 
PURPOSE
 
The Division of Digestive Diseases and Nutrition of the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites
applications for Planning Grants (R21) to support the development of
single center or multicenter clinical trials in digestive and
nutritional diseases.  Areas of particular importance include obesity,
inflammatory bowel disease, irritable bowel syndrome, helicobacter
pylori, primary biliary cirrhosis, and sclerosing cholangitis.  It is
anticipated that three planning grant awards will be made.
 
BACKGROUND
 
Recent advances in basic biomedical research have provided new insights
into the pathogenesis of many nutritional and digestive diseases.  These
advances have led to new possibilities for therapeutic intervention in
these diseases.  New therapies or interventions are best evaluated in
prospective, randomized controlled clinical trials.  However, the
planning, design, conduct, and analysis of clinical trials are
difficult.  Each step in the process requires major commitment of effort
and time, financial support, and multidisciplinary expertise.  As a
consequence, opportunities can be lost to identify and rigorously
evaluate important new therapeutic possibilities.
 
In the area of digestive diseases and nutrition there are several
diseases or conditions that warrant studies of new therapeutic
interventions.  Digestive and nutritional diseases or conditions of
importance for which there are currently no satisfactory long-term
therapies include severe obesity, inflammatory bowel disease, irritable
bowel syndrome, primary biliary cirrhosis, and sclerosing cholangitis.
These are important conditions that affect many Americans and cause
considerable morbidity and mortality.  Primary biliary cirrhosis, for
example, is an autoimmune disease of the liver that largely affects
women and leads slowly but inexorably to cirrhosis and death from liver
failure.  Primary biliary cirrhosis is the leading single indication for
liver transplantation in adults.  Despite these features, there is
currently no therapy of proven benefit for primary biliary cirrhosis.
In recent years, several small clinical trials in primary biliary
cirrhosis have reported some benefit of several agents including
ursodeoxycholic acid, chlorambucil, cyclosporine A, methotrexate,
prednisone, and colchicine.  While results from several of these studies
have been promising, they have not been convincing enough to provide
firm guidance for therapy of patients with this important disease.  It
is obvious, however, that one or several of these agents could be
adequately evaluated in a proper, large, multicenter randomized
controlled trial.
 
Clinical Trial Planning Grants have been designed to aid investigators
in designing clinical trials in important areas of digestive and
nutritional diseases.  These Planning Grants will support the
development of a clinical trial research plan.  This grant also provides
a means for early peer review of the rationale and need for the trial.
 
OBJECTIVES AND SCOPE
 
The overall goal of this Request for Applications (RFA) is to encourage
experienced clinical investigators in digestive and nutritional diseases
to undertake prospective, randomized, controlled, single-center or
multicenter trials in the treatment of digestive and nutritional
diseases.
 
The NIDDK Clinical Trial Planning Grant has been designed to help
support the extensive planning that should precede any well-designed
single-center or multicenter clinical trial.  The grant provides a
mechanism for early peer review of the rationale and need for the trial
as well as support for the development of a detailed Manual of
Procedures.  In addition, a limited number of patients can be recruited
to test the operational aspects of the trial.
 
It is expected that this Planning Grant RFA will be followed by a
program announcement within twelve months from the funding of grants in
response to this initial RFA, for applications to perform single-center
or multicenter clinical trials.  Applications in response to this latter
announcement will be required to provide detailed information regarding
the rationale, experimental design, protocols and procedures, analytical
techniques, facilities and environment, adequacy of the proposed
administrative procedures, and collaborative arrangements for the trial.
A well documented Manual of Procedures will also need to be part of the
latter submission.  The actual funding of a single-center or multicenter
clinical trial will be contingent on the excellence and feasibility of
the proposed trial, programmatic needs, and on the availability of
designated funds.
 
PREPARATION OF THE APPLICATION
 
General instructions for the preparation of applications contained in
Grant Application Form PHS 398 (Revised 10/88) are to be used in
preparing Planning Grant (R21) applications.  Item 2 should state "RFA #
DK-91-02 Clinical Trial Planning Grant for Digestive and Nutritional
Diseases."
 
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  In such a case, a letter of agreement from either the GCRC
program director or principal investigator should be included with the
application.
 
ELIGIBILITY REQUIREMENTS
 
All applicants must be qualified nutritionists, gastroenterologists,
hepatologists, or surgeons, with the demonstrated ability to recruit
adequate numbers of patients.  Applicants for a Planning Grant for a
multicenter clinical trial must have demonstrated expertise in the many
complex features of conducting a multicenter study.  If participating
centers are proposed, they must have an adequate patient load and
demonstrate ability to adhere to clinical trial protocols and
procedures.  All applicants are responsible for obtaining and
maintaining the appropriate Investigational New Drug Application from
the Food and Drug Administration and the appropriate assurance and
certification from their Institutional Review Boards on Human Subjects.
Only costs that are not usual costs for the normal care of patients
entered in the trial may be requested as research costs to the grant
application.
 
The NIH places special emphasis on the need for inclusion of minorities
and women in studies of diseases which disproportionately affect them
and also requires that applicants give added attention, where feasible
and appropriate, to their inclusion in other clinical studies.  For
proposed population-based studies that include neither women nor
minorities, a clear rationale for not including them must be provided.
In attempting to include either group in a particular study, attention
must be paid to such issues as research design and sample size.
 
TERMS OF THE AWARD
 
Applications for single-center or multicenter clinical trial Planning
Grants should request up to 1 year duration and a maximum of $50,000 in
direct cost.  Three Planning Grants may be awarded.  Funding decisions
will be based in part on relative merit recommendation of the IRG and in
part on programmatic needs as determined by the National Diabetes and
Digestive and Kidney Diseases Advisory Council and by the staff of the
Division of Digestive Diseases and Nutrition.  The award of applications
submitted in response to this RFA is contingent on the actual
availability of funds and receipt of applications deemed worthy of
support by the accepted NIH peer review process.
 
REVIEW PROCEDURES
 
All applications submitted in response to this RFA will be evaluated for
scientific and technical merit by an initial review group convened for
this purpose by the Division of Extramural Activities, NIDDK.
 
REVIEW CRITERIA
 
In evaluating a Clinical Trial Planning Grant Application, the Initial
Review Group (IRG) will consider the criteria outlined below.  The
greatest weight will be given to Items I, IV and V.
 
 I.Rationale
 
     A. Clinical importance of the disease or condition being studied.
     B. Rationale for therapy being applied.
     C. Ethical considerations of treatment.
 
II.Experimental Design
 
     A. Merit of the study design.
     B. Appropriateness of intervention groups.
     C. Plans to minimize bias through randomization, statification,
choice of controls, and masking of treatment or results.
     D. Identification of appropriate primary and secondary outcomes for the tr
     E. Recognition of possible problems inherent in the design and the
        adequacy of plans for dealing with them.
 
III. Experimental Procedures and Plans for Patient Participation
 
     A. Quality of plans (even if broadly described) for recruitment and
        retention of patients, identification of eligibility and
exclusion criteria, and standardization and maintenance of quality
        control among participating centers.
     B. Patient protection, including informed consent and monitoring
data for safety and efficacy.  Plans for early termination if it
becomes necessary.
     C. Documentation of potential availability of patients at each of
        the participating centers.
     D. Plans for the preparation of a Manual of Procedures that must be
        submitted with any future application for actual conduct of the
        randomized controlled trials.
 
 IV. Plans for Data Analysis
 
     A. Rationale and validity of sample size.
     B. General methods to be used for data analyses.
 
  V. Planned Preliminary Studies
 
     A. Suitability for providing the necessary supporting data.
     B. Feasibility particularly in conducting preliminary studies.
     C. Provisions not made for needed preliminary information.
 
 VI. Investigators
 
     A. Professional credentials of the organizers indicating experience
        in such areas as:
 
        1.  The problem under study
        2.  Clinical trial administration
        3.  Methodology
        4.  Adequate and similar patient recruitment potential of
            participants
        5.  The proposed procedures.
 
     B. Professional credentials of the participating center
investigators in the clinical problem and in clinical trial
participation.  Verification of the cooperating investigators and their
institutions should be included.
 
VII. Budget
 
      The budget should be itemized on page 4 and justified on page 5 of the
      application.  The total direct cost budget may not exceed $50,000 and
      may not exceed a 12-month period.  Examples of typical use of these
      funds include:
 
     A. Travel expenses of personnel assisting in preparation of the Manual
        of Procedures
     B. Secretarial assistance
     C. Consultant fees
     D. Preliminary studies to refine trial procedures, document
recruitment
        potential, etc.
     E. Office supplies
     F. Communication expenses.
 
METHOD OF APPLYING
 
The regular research grant application form PHS-398 (revised 10/88) must
be used.  The RFA label available in the application kit must be affixed
to the bottom of the face page.  Failure to use this label could result
in delayed processing of your application.  There will be a single
receipt date of January 22, 1991.  Applications received after that date
will be returned.  Earliest possible funding will be December 1991.
 
Submit a signed, typewritten original of the application, including the
Checklist and four (4) signed, exact photocopies, in one package to:
 
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda MD 20892**
 
IMPORTANT:  At time of submission, two (2) additional copies of the
application should be sent under separate cover to:
 
CHIEF, REVIEW BRANCH
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Room 406, Westwood Building
Bethesda MD 20892
 
Applications must be received by January 22, 1991.  If an application is
received after that date, it will not be accepted and will be returned.
 
Potential applicants should write or phone the individual listed below
for the full RFA document.
 
Tommie S. Tralka
Director, Clinical Trials Program
Division of Digestive Diseases and Nutrition
Westwood Bldg., Rm 3A-15
5333 Westbard Ave.
Bethesda, MD 20892
Telephone:  (301) 496-9717
 
This program is described in the Catalog of Federal Domestic Assistance
No. 93,848, Digestive Diseases and Nutrition.  Awards will be made under
the authority of the Public Health Service Act, Title III, Section 301
(Public Law 78-410, as amended; 42 USC 241) and administered under PHS
grant policies and Federal Regulations 42 CFR Part 52 and CFR Part 74.
This program is not subject to the intergovernmental review requirements