Full Text HD-93-06

NETWORK OF PEDIATRIC PHARMACOLOGY RESEARCH UNITS

NIH GUIDE, Volume 21, Number 40, November 6, 1992

RFA:  HD-93-06

P.T. 34, AA

Keywords: 
  Pharmacology 
  Children (Patients) 
  Infants 
  Adverse Effects 


National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  February 15, 1993
Application Receipt Date:  April 13, 1993

PURPOSE

The National Institute of Child Health and Human Development (NICHD)
plans to support a cooperative Network of Pediatric Pharmacology
Research Units (PPRU) to serve as a resource for studies of drug action
and disposition in infants and children.  These studies will be
conducted by pediatric clinical pharmacologists, either cooperatively
with investigators at other units in the network, collaboratively with
pharmaceutical companies, or independently with other support.  The
ultimate goal of studies conducted by the network is to provide the
clinical data on drugs necessary for U.S. Food and Drug Administration
(FDA) approval for use in children.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention goals of "Healthy People 2000," a
PHS-led national activity for setting priorities.  This Request for
Applications (RFA), Network of Pediatric Pharmacology Research Units,
is related to the priority areas of food and drug safety and maternal
and infant health.  Copies of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0, or Summary Report:  Stock No.
017-001-00473-1) are available through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-783-3238).

ELIGIBILITY REQUIREMENTS

PPRU cooperative clinical agreement (U01) awards will be made to
children's hospitals or their equivalent or to educational institutions
with accredited medical schools, within the United States.  Each PPRU
must become an identifiable unit within its institution, its Principal
Investigator reporting to the chief of pediatrics or the chairperson of
the pediatrics department.  The applicant institution must also meet
the standard eligibility requirements for research grants established
in the Public Health Service Grants Policy Statement #(OASH) 90-50,000,
Rev. 10/1/90.

There must be at the applicant institution an ongoing program of
excellence in clinical pharmacology, with an emphasis on pediatric
applications.  The quality of this program must be evident from the
receipt by its staff of research support in peer-reviewed competition,
or from their consistent record of publication in peer-reviewed
research journals.  In addition, the applicant institution must have
available a sufficient number of eligible research subjects in the
pediatric age groups:  newborns, infants, children, pre-adolescents,
and adolescents.  This is an essential component of the network and
must be spelled out in detail in the application.

MECHANISM OF SUPPORT

The funding mechanism to be used to assist the scientific community in
undertaking this program of research in clinical pharmacology will be
a cooperative clinical agreement (U10) between the participating units
and the NICHD.  The U10 award will provide support for laboratory and
administrative resources to assist the research community in carrying
out clinical therapeutic research protocols.  The major difference
between a cooperative agreement and a traditional research grant is the
substantial scientific involvement of NICHD staff beyond the levels
normally required for program stewardship of grants.

Cooperative clinical agreements (U01) are assistance mechanisms and are
subject to the same administrative requirements as grants.

FUNDS AVAILABLE

It is expected that up to four applications will be funded, within the
total direct cost limit of $1,000,000 available for the first year.
Therefore, the maximum direct cost request (first year) for individual
applications should not exceed $250,000.  This level of support is
dependent on the receipt of a sufficient number of applications of high
scientific merit.  Although this program is provided for in the
financial plans of the NICHD, awards pursuant to this RFA are
contingent upon the availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

Federal law and the regulations of the FDA require that drugs be tested
for safety and efficacy before they are approved for clinical use.
This testing must take place in all populations in which the drug will
be employed.  Since both the qualitative and quantitative aspects of
pharmacodynamics and pharmacokinetics are different in immature
individuals, studies must be conducted in infants and children before
a drug can be approved for use with them.  For the purposes of this
RFA, the term children is used to mean human beings during their
prenatal and postnatal stages of development, from fetal life through
adolescence.

Several practical problems discourage the testing of drugs in children.
These include the unforeseeable nature of some clinical responses in
immature individuals; the possibility of catastrophic unanticipated
reactions; the threat of effects on growth or health long after
completion of the drug administration; the difficulty in predicting
efficacious blood levels by extrapolation from data obtained in adults;
the ethical problems of conducting nontherapeutic research in children;
the awkwardness of procedures for obtaining informed consent or assent
in older children; the lack of a suitable infrastructure for the
conduct of pediatric pharmacology research; the high cost of pediatric
studies; and the absence of a financial incentive for the
pharmaceutical industry to conduct pediatric pharmaceutical trials if
children are a minority of the population for which the drug might be
prescribed.

The result of these practical problems and the regulatory requirements
is that more than three-quarters of the drugs marketed in the United
States, including many of the most useful agents in modern therapy, are
not approved as safe and effective for use in children.  Since the
provision of pediatric care without the use of these agents would be
unacceptable, they are commonly administered "off-label" (without
specific FDA approval) by pediatricians, anesthesiologists, general
practitioners, surgeons, and others.  Under these conditions the child
is at risk of an inadequate therapeutic response or some unanticipated
adverse reaction.  Physicians can face medicolegal actions as a result
of such accidents, but they can also risk suit for failure to utilize
an effective drug for a child's illness, even if that drug does not
have specific FDA approval for use in children.

This dilemma must be resolved if children are to receive the full
benefits of contemporary therapeutics.  Modern pediatric pharmacology
is a sophisticated clinical discipline capable of carrying out the
studies necessary for the safe and ethical evaluation of drugs in
children.  Pursuit of such studies, however, is limited by the scarcity
of available facilities in which to follow children receiving drugs and
collect data in a systematic way, as well as the small number of
qualified clinical investigators interested in this problem. In order
to assist the pediatric community in carrying out these needed studies,
the NICHD is issuing this RFA.

Objectives and Scope

The objective of the PPRU Program is to increase the number and variety
of medications that are FDA-approved for use in children, with the
ultimate goal that all drugs prescribed for children be labeled for
such usage.  This is to be accomplished by providing resources for
pediatric pharmacokinetic and pharmacodynamic research through the
establishment of a Network of Pediatric Pharmacology Research Units
(PPRU).

Each PPRU will have four specific aims:

(1) To participate with other units in the network and with NICHD staff
assistance in collaborative clinical trials of drugs in children
through protocols determined by consensus;

(2) To provide a locus for the conduct of pre-marketing and
post-marketing clinical trials in children by qualified clinical
pharmacologists working in collaboration with proprietary
pharmaceutical firms;

(3) To conduct independent, investigator-initiated studies on the
pharmacodynamics and pharmacokinetics of drugs in children; and

(4) To provide an environment in which pediatricians and others can
gain supervised experience in pediatric clinical pharmacology.

It is expected that most of the studies conducted in the PPRU network
will be clinical and pediatric.  Nevertheless, pre-clinical studies may
sometimes be conducted (with other support) in a Unit's core laboratory
if these are important as preliminaries or adjuncts to clinical
projects.  Similarly, limited clinical studies in adults may sometimes
justify PPRU support if they are necessary for adapting existing
protocols to children.

Components of a PPRU

A.  Principal Investigator and Administrative Staff

The Principal Investigator (PI) of a PPRU must be an established
pediatric clinical pharmacologist, preferably holding independent
peer-reviewed grant or contract support, actively publishing in the
field, and familiar with academic and proprietary research in
pharmacology and pharmacokinetics.  The PI is responsible for
developing and maintaining the PPRU as an institutional and national
resource and for general oversight, appointing the members of the
institutional advisory committee (see below) and (with advisory
committee advice) the associate clinical pharmacologist and other
members of the Unit staff.  It is expected that the PI will be active
in conducting research within the Unit and in negotiating support from
proprietary pharmaceutical organizations.  The PI will assist other
investigators in conducting PPRU research protocols.  The PI will
attend the meetings of the Network Steering Committee (see below) and
participate in its deliberations.  The PI may be supported for up to 25
percent time and effort in the program, and may be assisted by a
part-time secretary (25 percent time and effort).

The PI is expected to hold final authority and responsibility for the
care of PPRU patients, reporting only to the chief of pediatrics or the
chairperson of the pediatrics department, even though the regular care
of the patients may be in the hands of other investigators or house
officers.  The PI must therefore be state-licensed as a physician and
board-certified in pediatrics.

B.  Local Advisory Committee

This group will play an important part in the operations of the PPRU
program. It should comprise from three to five members of the host
institution faculty in addition to the PI, either users or non-users of
the Unit, appointed for defined terms.  Members should all be sensitive
from experience or training to the special needs of children
participating in research.  They should all be qualified for the
committee's principal activities, evaluating protocols to be conducted
on the Unit for scientific merit and recommending to the PI priorities
for the use of unit resources.  The committee also has the
responsibility of examining the qualifications of candidates for the
associate clinical pharmacologist and other PPRU positions and
reporting their recommendations to the PI.

C.  Clinical Facility

A designated physical site where the clinical research is to be
performed is required.  To allow optimal opportunities for
collaboration among units in the network, it is desirable that each
PPRU have both an inpatient and an outpatient capability.  These could
be provided by a pediatric metabolic ward and outpatient clinic, a
General Clinical Research Center (GCRC) funded by the NIH National
Center for Research Resources and suitable for admitting children and
caring for them as outpatients, or some other unit similarly equipped
for conducting pediatric clinical research.

Applicant institutions that wish to identify the GCRC as a site for
conducting PPRU research should include with the application a letter
of agreement from the GCRC program director or PI.

D.  Core Laboratory

A funded PPRU may include a core laboratory dedicated to performing
specialized analyses and/or data management functions for studies
conducted in the Unit.  This should not include procedures routinely
performed for a fee in institutional laboratories or available in the
laboratories of the investigators utilizing the unit.  Each proposed
protocol should end with an estimate of staff time and required
hospital ancillary costs that will be made necessary by pursuit of the
protocol.  (These costs should not be included in the overall requested
Unit budget, since they will be distributed over all the network
participants in that protocol.)  For studies performed in collaboration
with pharmaceutical firms, those firms should pay the fees for
research-related clinical determinations.   For investigator-initiated
studies in which pharmaceutical firms do not participate, these costs
must be supported from sources other than the PPRU funding.

The core laboratory may be staffed by a PPRU-supported doctoral-level
core laboratory director (maximum 25 percent time and effort) and a
core laboratory technician (maximum 50 percent time and effort), if the
science proposed so warrants. Core laboratory consumable expenses and
equipment maintenance costs, up to a maximum of $20,000 annually, may
be supported if justified.

The core laboratory director, who reports to the PI, should have
responsibility for quality control in that laboratory.  The time and
effort of the PI may also be devoted to developing new methods for
protocols being conducted with PPRU support and to standardizing
procedures to be carried out for PPRU network collaborative protocols.
In addition, the core laboratory director is responsible for the care
and maintenance of the laboratory equipment, and will cooperate with
the PI in assisting other investigators in their use of the Unit.

The equipment used in the core laboratory should be primarily that
available to the investigators or obtainable from institutional
resources.  Nevertheless, new equipment up to a maximum cost of $50,000
over the first four years of the award may be requested in a PPRU
cooperative agreement application, with appropriate justification.

As an occasional courtesy, determinations that are available in the
core laboratory  may be performed for non-PPRU protocols, at the
discretion of the PI and core laboratory director.  For consistent or
recurrent non-PPRU usage, or for drug company-initiated protocols being
pursued on the units, there should be appropriate reimbursements from
non-PPRU sources for core laboratory equipment maintenance, supplies,
and personnel time, as well as for data management costs.  These
reimbursements, which must be used to offset unit costs, should be
reported as grant-related income.

E.  Investigators

Any person with pediatric privileges at the grantee institution is
eligible to utilize the PPRU resources for studies of drug efficacy or
metabolism, supported from independent research funds, if the protocols
have been approved and prioritized by the local PPRU Advisory
Committee.  These individual investigator protocols must not delay or
interfere with pursuit of the collaborative studies that are the Units
primary responsibility.  For investigators inexperienced in clinical
pharmacology, the PI is expected to provide advice and guidance.
Clinical pharmacists are encouraged to participate in PPRU research in
collaboration with physicians who bear the responsibility for patient
care.

F.  Research Plan

The scientific program at each PPRU should comprise three areas of
investigation.  The first priority will be the collaborative protocols
agreed upon by the Network Steering Committee (see below); the second
will be protocols performed for and with pharmaceutical companies; and
the third will be the Unit's own investigator-initiated research
protocols.

For the inter-PPRU collaborative work, applicant institutions are asked
to provide one or two examples of drug evaluation studies that they
would propose to the Network Steering Committee (see below).  These
examples should be drafts (up to 1,500 words) for consideration by
other participants in the program, but should include enough detail
(proposal, rationale, significance, procedures, resources required, end
points, power calculations, and discussion of feasibility) to allow
reviewers of the application to evaluate them for scientific merit.

For the collaborative work with industry, each applicant may include
one or two examples of previous studies conducted with pharmaceutical
organizations on the development of drugs for use in children.
Alternatively, a protocol proposed for pursuit with industry
participation may be presented, if a letter of interest from the
proprietary organization is included.

For the independent investigator work, each PPRU application should
include one or two examples of research protocols on pharmacokinetics
or pharmacodynamics in children that participating investigators intend
to pursue if the PPRU is funded.  These protocols should be presented
in fewer than 1,500 words.  Each should include a clearly identified
hypothesis, brief background information, and a narrative of the
procedures to be employed. They should include details of statistical
design and enough additional specific material as necessary for a fair
scientific review.  In addition, each protocol should provide a brief
justification of its need for PPRU resources.

G.  Nurse Coordinator

A qualified nurse coordinator is one of the most important assets of a
PPRU.  The nurse coordinator reports to and takes direction from the
PI, whether or not he or she is a member of the institution's nursing
service.  The nurse coordinator (in cooperation with the associate
clinical pharmacologist) carries out as many parts of the research
protocols as possible, dovetailing schedules for maximum efficiency and
instructing and supervising the other nursing staff in those operations
or procedures for which he or she is unavailable.  He or she is
responsible for data collection and organization, unless the latter
responsibility is assigned to a data coordinator (see below).  One or
more individuals may be supported in the nurse coordinator position, at
a total of one full-time equivalent (100 percent time and effort).

H.  Associate Clinical Pharmacologist

Units may request support for salaries and fringe benefits for this
position (maximum 50 percent time and effort).  The associate clinical
pharmacologist may be a physician who is fully trained in pediatrics,
has completed subspecialty training, and wishes to gain experience in
the conduct of pediatric pharmacology research under the guidance and
supervision of the PI or some other appropriate person.  Alternatively,
the associate clinical pharmacologist may be a non-physician holding
the Pharm.D. degree who has had special training in pediatric
pharmacology and wishes to obtain additional supervised clinical
experience.  Support for the associate clinical pharmacologist from the
PPRU is for research time and effort only, except that if this person
is a licensed physician he or she may assist the PI in supervising
patient care in the Unit.  A qualified individual may be supported for
up to two years as an associate clinical pharmacologist at a PPRU.

I.  Data Coordinator

Each PPRU application should include information about the data
management system to be used in the unit.  The system must be
satisfactory not only for support of local PPRU activities, but also
for participation in collaborative studies being performed by the
network, since each PPRU will serve in turn as the data coordinating
center for collaborative protocols.  If justified by the volume of work
expected, a data coordinator may be supported (up to 25 percent time
and effort) by a PPRU grant.  This person will organize the data in
preparation for transmission to other PPRUs when appropriate.  These
functions are critical to the success of the network.

SPECIAL REQUIREMENTS

Terms and Conditions of Awards

The following terms and conditions of award are in addition to, and not
in lieu of, otherwise applicable OMB administrative guidelines, HHS
grant administration regulations at 45 CFR Part 74, and other HHS, PHS,
and NIH grant administration policies and procedures.  The specific
terms and conditions pertaining to the nature and scope of the
interaction between NICHD staff and the participating PPRUs will be
incorporated into the Notice of Grant Award and will be in addition to
the customary programmatic and financial negotiations that occur in the
administration of grants.

Awardee Responsibilities

Each PI will have primary responsibility to define objectives and
approaches and to plan, conduct, analyze, and publish results,
interpretations, and conclusions of his/her studies.  For network
collaborative protocols, this responsibility will be shared with other
network members and the project coordinator.  The awardees retain
custody of and primary rights to the data developed under those awards,
subject to government rights of access, consistent with current HHS,
PHS, and NIH policies.  Awardees must be willing to participate and
collaborate with other awardees and with NICHD staff.

NICHD Responsibilities

The Project Coordinator (Medical Officer, Endocrinology, Nutrition and
Growth Branch, NICHD) will assist in the identification of important
areas for study; in the development of collaborative protocols; in the
review and evaluation of each stage of study protocols before
subsequent stages are started; and in the reporting of results to the
scientific community.

Network Steering Committee Responsibilities

The Network Steering Committee (NSC) will consist of the PIs of the
funded units and the Project Coordinator, NICHD, and will be chaired by
an (non-voting) outside chairperson selected by the members.  The
committee will meet at least quarterly to review and select protocols
to be performed collaboratively by the network and to exchange
information on progress.

The Steering Committee will collaboratively establish rules governing
publication, analysis and inter-unit sharing of data.

Arbitration Procedures

Whenever agreement between an awardee and NICHD staff cannot be reached
on programmatic and scientific issues that arise after the award, an
arbitration panel will be formed.  The panel will consist of one person
selected by the PI, one person selected by the NICHD Project
Coordinator, and a third person selected by these two members.  The
decision of the arbitration panel, by majority vote, will be binding.
These special arbitration procedures in no way affect the awardee's
right to appeal an adverse action in accordance with PHS regulations at
42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

Other Application Requirements

A Safety Monitoring Committee will monitor the data from each ongoing
collaborative clinical trial and advise on the safety of its
continuation. This committee, to be selected by the Steering Committee,
will include expertise in clinical trial design, pharmacology,
epidemiology, statistics, and medical ethics.

The availability of a pharmacy capable of supporting clinical research
activities and experienced in the preparation of materials for
randomized clinical trials should be documented.

An explicit statement of the applicants' preparedness to participate in
PPRU network clinical trials according to the terms of the RFA should
be in the application, and evidence of a long-term institutional
commitment to the needs of the PPRU is required.  This may take various
forms, including (but not limited to) the waiver of facility fees or
bed costs for use of an outpatient clinic or research ward for patients
on protocol; equipment and space for a core laboratory; released time
for faculty to perform clinical pharmacology research in children;
and/or funding for support personnel.

Allowable Budgetary Items and Supportable Activities

Allowable costs in NIH cooperative agreements are governed by rules set
forth in the Public Health Service Grants Policy Statement and as
stated on the Notice of Grant Award.  Under these rules the PI may
exercise flexibility to meet unexpected requirements by rebudgeting or
requesting approval to rebudget among categories within the total
direct cost budget of the PPRU (as shown on the Notice of Grant Award),
within the ceilings set in these guidelines.

PPU grants are for five years, at a maximum level of $250,000 in direct
costs for the first year, with annual increments of 4 percent
thereafter.  They are renewable through competing continuation
applications, provided funds are available.  Items supportable through
a PPRU cooperative agreement award may include:

1.  Administration.  Personnel:  Principal investigator (maximum 25
percent time and effort); secretary (maximum 25 percent time and
effort).  Administrative Support Services:  supplies, duplication
costs, telephone.  Travel:  PI to meetings of the NSC.

2.  Core Laboratory.  Personnel:  Core laboratory director (maximum 25
percent time and effort); core laboratory technician (maximum 50
percent time and effort).  Equipment:  Maximum of $50,000 total cost,
distributed over the first four years of the award.  Supplies:
Appropriate for unit participation in collaborative protocols and for
support of specialized analyses for investigator-initiated studies on
the Unit

Other:  Maintenance costs on equipment purchased by the award or
otherwise dedicated to Unit use.

The maximum allowable total annual amount for supplies plus other in
the core laboratory is $20,000.

3.  Research Services Core.  Personnel:  Nurse Coordinator (maximum 100
percent time and effort); Associate
Clinical Pharmacologist (maximum 50 percent time and effort); Data
Coordinator
(maximum 25 percent time and effort).

The following items are not fundable through a PPRU grant:

Costs of clinical care, such as patient bed costs, outpatient visit
fees, and clinical laboratory determinations.  These costs must be paid
by the pharmaceutical companies for protocols performed on their
initiative or by third-party carriers or other sources for
investigator-initiated protocols. For Network protocols for which
necessary ancillary costs cannot be paid from other sources, the NICHD
will provide administrative supplements.

Travel to scientific meetings or for any other purpose except for the
PI to attend meetings of the NSC.

Laboratory costs (outside the core laboratory) for projects being
performed by
investigators using the Unit.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF FEMALES AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements are required to include minorities and females
in study populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study.
Special emphasis must be placed on the need for inclusion of minorities
and females in studies of diseases, disorders and conditions which
disproportionately affect them.  This policy is intended to apply to
males and females of all ages.  If females or minorities are excluded
or inadequately represented in clinical research, particularly in
proposed population-based studies, a clear compelling rationale must be
provided.

The composition of the proposed study population must be described in
terms of gender or racial/ethnic group, together with a rationale for
its choice.  In addition, gender and racial/ethnic issues must be
addressed in developing a research design and sample size appropriate
for the scientific objectives of the study.  This information must be
included in the form PHS 398 in Sections 1-4 of the Research Plan and
summarized in Section 5, Human Subjects.  Applicants are urged to
assess carefully the feasibility of including the broadest possible
representation of minority groups.  However, NIH recognizes that it may
not be feasible or appropriate in all research projects to include
representation of the full array of United States racial/ethnic
minority populations (i.e., Native Americans [including American
Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks,
Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues cannot
be identified or linked to individuals are excluded.  However, every
effort should be made to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
females or minorities in a study design is inadequate to answer the
scientific question(s) addressed and the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and reflected in assigning
the priority score to the application.

All applications for clinical research support submitted to NIH are
required to address these policies.  NIH funding components will not
award cooperative agreements that do not comply with these policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 15, 1993, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the 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 subsequent applications, the information
that it contains is helpful in planning for the review of applications.
It allows NICHD staff to estimate the potential review workload and to
avoid possible conflict of interest in the review.

The letter of intent is to be sent to:

Ephraim Y. Levin, M.D.
Endocrinology, Nutrition and Growth Branch
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
Executive Plaza North, Room 637
Bethesda, MD  20892
Telephone:  (301) 496-5593

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone
301/496-7441.

The RFA label available in the PHS 398 application form must be affixed
to the bottom of the face page of the application.  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 2a of the face page of
the application form and the YES box must be marked.

Applicants should follow the instructions included with PHS Form 398
except where these are at variance with instructions in this RFA.
Since the generic guidelines were not prepared specifically to be used
for PPRU cooperative agreement applications, considerable flexibility
in application format will be tolerated.  Applicants should take care,
however, that adequate information is provided to allow reviewers to
evaluate the application on the basis of the review criteria listed
below.  Since applicants will be proposing at least two research plans,
the individual and the collaborative, the standard 25-page limit will
not apply.  For questions related to application format, applicants may
contact one of the individuals under INQUIRIES.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies in one package to:

Division of Research Grants
National Institutes of Health
Room 240, Westwood Building
Bethesda, MD  20892**

In addition to the application and copies mailed to the Division of
Research Grants, two copies of the application must also be sent to:

Susan Streufert, Ph.D.
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E01
Bethesda, MD  20892

Applications must be received by April 13, 1993.  If an application is
received after that date, it will be returned to the applicant.

REVIEW CONSIDERATIONS

Applications will be reviewed by the Division of Research Grants for
completeness and by NICHD staff for responsiveness to the RFA.  An
incomplete or non-responsive application will be returned to the
applicant.  Responsive applications may be subjected to a triage by a
peer-review group to determine the scientific merit relative to the
other applications received in response to this RFA.  The NICHD will
withdraw from competition those applications judged to be
noncompetitive and notify the applicants and institutional business
officials.

Applications considered responsive to this RFA will be reviewed for
technical merit by an Initial Review Group convened by the scientific
review staff of the NICHD solely to evaluate these applications.
Criteria for the initial review are described below.  Following review
by the Initial Review Group, applications will be evaluated by the
National Advisory Child Health and Human Development (NACHHD) Council
for program relevance and policy issues before awards are made.

REVIEW CRITERIA

The following are the review criteria for the evaluation of PPRU
applications:

Qualifications of the core of experienced investigators in clinical
pharmacology who have independent competitively-earned research
support, a record of research productivity, and a demonstrated interest
in pharmacological research in children.

An explicitly stated willingness by these investigators to generate
protocols to perform on the unit, propose protocols to the NSC for
collaborative pursuit, and collaborate with pharmaceutical firms in
testing useful drugs in children is required.

Suitability of the proposed clinical locus for the Unit in the
applicant institution or its affiliated hospital, such as a pediatric
metabolic ward and outpatient clinic, a GCRC with staff accustomed to
conducting studies in children, or some unit similarly staffed and
equipped.

Availability of a suitable population to participate as research
subjects in PPRU studies.

Qualifications of the PI for the duties described in this RFA.

Scientific quality and relevance of the sample protocols proposed for
pursuit in the Network and in the local PPRU.

Evidence of previous successful research collaborations with industry
or of efforts to arrange future collaborations.

Nature, facilities, functions, and probable value to the research of
any proposed core laboratory.

Adequacy of data management resources available to support PPRU
protocols.

Evidence of institutional commitment to the long-term activities of the
PPRU network.

Composition of the proposed local advisory committee and its proposed
procedures for evaluating protocols, monitoring ongoing research on the
Unit, and recommending candidates for the associate clinical
pharmacologist and other PPRU positions.

Qualifications of the nurse coordinator proposed for support from the
Unit and/or the criteria to be used in selecting a person for this
position.

Qualifications of the associate clinical pharmacologist (if any)
proposed for support from the Unit and/or the criteria to be used in
selecting a person for this position.

AWARD CRITERIA

The anticipated date of award is September 30, 1993.  Awards will be
made on scientific merit as determined by peer review.  The
availability of appropriate study populations, the extent of
investigator experience, adequacy of equipment and facilities, and
program balance will also be taken into account.

Timetable

Letter of Intent Receipt Date:  February 15, 1993
Application Receipt Date:       April 13, 1993
Initial Review Date:            July 1993
Review by NACHHD Council:       September 1993
Earliest Possible Award Date:   September 30, 1993

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Ephraim Y. Levin, M.D.
Endocrinology, Nutrition and Growth Branch
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 637
Bethesda, MD  20892
Telephone:  (301) 496-5593

Direct inquiries regarding fiscal matters to:

E. Douglas Shawver
Supervisory Grants Management Specialist
Office of Grants and Contracts
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 505
Bethesda, MD  20892
Telephone:  (301) 496-1303

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.865, Research for Mothers and Children.  Awards are made under
authorization of the Public Health Service Act, Section 301 (42 USC
421), and administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74.  This program is not
subject to the intergovernmental review requirements of Health Systems
Agency review.

.

Return to RFAs Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.