BILIARY ATRESIA CLINICAL RESEARCH CONSORTIUM

Release Date:  June 28, 2001

RFA:  RFA-DK-02-008

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  October 16, 2001
Application Receipt Date:       November 28, 2001

PURPOSE

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
invites cooperative agreement applications for participation in a 
collaborative clinical research consortium to establish a database of clinical 
information and serum and tissue samples from children with biliary atresia 
and idiopathic neonatal hepatitis to facilitate and perform clinical, 
epidemiological and therapeutic research in these two important pediatric 
liver diseases.  

Jaundice and hyperbilirubinemia that extents beyond the immediate newborn 
period is usually due to either biliary atresia or idiopathic neonatal 
hepatitis. Biliary atresia, although a rare disease, is the most common reason 
for liver transplantation in children.  Its etiology, however, remains elusive 
and its optimal management is still unsettled.  Idiopathic neonatal hepatitis 
can resemble biliary atresia clinically but is usually a self-limited illness 
that does not lead to cirrhosis or the need for liver transplantation.  The 
cause of neonatal hepatitis is also unknown; however, it appears to be non-
infectious in etiology.  There are too few new cases of biliary atresia and 
neonatal hepatitis seen each year at a single pediatric liver disease center 
to allow for intensive analyses of risk factors or to critically assess 
different means of diagnosis and treatment. Thus, a collaborative consortium 
of pediatric hepatology and transplant centers is needed to gather sufficient 
data and adequate numbers of serum and tissue samples in a prospective manner 
to facilitate research and generate hypotheses on the pathogenesis and optimal 
treatment modalities of biliary atresia and neonatal hepatitis.  

The objective of this Request for Applications (RFA) is to establish and 
maintain the infrastructure required for accrual of sufficient numbers of 
patients with biliary atresia and neonatal hepatitis to do adequately powered 
studies.  Eight to ten Clinical Centers (CCs) and a Data Coordinating Center 
(DCC) will be necessary to meet this objective.  

This is a one-time solicitation to support a Clinical Research Consortium for 
five years.

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 Request for Applications (RFA), 
Biliary Atresia Clinical Research Consortium, is related to one or more of the 
priority areas.  Potential applicants may obtain a copy of "Healthy People 
2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government. Racial/ethnic minority individuals, women, 
and persons with disabilities are encouraged to apply as Principal 
Investigators.

All current policies and requirements that govern the research grant programs 
of the National Institutes of Health (NIH) will apply to grants awarded under 
this RFA.  Among the disciplines and expertise that may be appropriate for 
this program are hepatology, pediatrics, transplantation, neonatology, 
genetics, epidemiology, physiology, pharmacology, therapeutic development, and 
clinical trials management. 

A DCC will be a part of this Biliary Atresia Clinical Research Consortium.  In 
order to ensure that data analysis is done independently of data acquisition, 
the DCC cannot have the same Principal Investigator as a CC. Within the 
Consortium an institution may apply for both a CC and the DCC, but each must 
have separate principal investigators and submit a separate application with a 
specific plan of how the independent operation of each unit of the CC and DCC 
will be maintained.

MECHANISM OF SUPPORT

This RFA will use the NIH cooperative clinical research (U01) award mechanism 
of support, an “assistance” mechanism (rather than as “acquisition” mechanism) 
in which substantial NIH scientific and/or programmatic involvement with the 
awardee is anticipated during performance of the activity.  Under the 
cooperative agreement, the NIH purpose is to support and stimulate the 
recipients’ activity by involvement in the activity and otherwise working 
jointly with the award recipients in a partner role, but it is not to assume 
direction, prime responsibility, or a dominant role in the activity.  Details 
of the responsibilities, relationships and governance of the study to be 
funded under cooperative agreements are discussed below under “Terms and 
Conditions of Award.”

FUNDS AVAILABLE 

The NIDDK intends to commit approximately $2 million in total costs (direct 
plus Facilities and Administrative (F & A) costs) in FY 2002 to fund up to ten 
Clinical Center applications and one Data Coordinating Center application in 
response to this RFA.  Applicants for the Clinical Centers may request a 
project period up to five years and a budget for total costs (direct plus F & 
A) of up to $125,000/year.  Applicants for the Data Coordinating Center may 
request a project period up to five years and a budget for total costs (direct 
plus F & A) of up to $750,000/year.  Because the nature and scope of the 
research proposed in response to this RFA may vary, it is anticipated that the 
size of an award may vary in all years.  Future year costs will be distributed 
based on the recommended protocols, database development, epidemiological 
studies, pilot studies or planning studies for future clinical trials.

Although the financial plans of the NIDDK provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications. At this time, 
it is not known if this RFA will be reissued. 

RESEARCH OBJECTIVES

Background

Biliary atresia is a rare disease occurring in 1/10,000 to 1/15,000 live 
births in the United States, resulting in 250 to 400 new cases/year. It is 
considered the most serious digestive disease affecting children and the most 
common reason for liver transplantation in childhood.  Biliary atresia is 
marked by a progressive, inflammatory obliteration of the extrahepatic biliary 
tree resulting in decreased bile flow and signs and symptoms of biliary 
obstruction starting soon after birth. Untreated, the resulting obstruction in 
bile flow leads to cholestasis, progressive fibrosis, and, ultimately, 
cirrhosis.  The operation known as hepatoportoenterostomy developed by Kasai 
in Japan was introduced in 1959 and remains today the mainstay of management 
of biliary atresia. This operation can restore bile flow, particularly if 
performed within the first 8 weeks of life.  Nevertheless, it is not curative 
and two-thirds of children will still require a liver transplant, including 
one-third before the age of two years.  Very little new knowledge about the 
pathogenesis, etiology, timely diagnosis, or optimal treatment strategies of 
biliary atresia has emerged in the last three decades.  

Neonatal hepatitis resembles biliary atresia clinically, but has a different 
pathogenesis and course.  It is an inflammatory disease of the liver of 
unknown cause that occurs during the neonatal period or early infancy.  The 
signs and symptoms of neonatal hepatitis are similar to those of biliary 
atresia and the differential diagnosis can be difficult.  Importantly, 
however, neonatal hepatitis is characterized by inflammation and giant cell 
transformation of hepatocytes in the liver without injury or destruction of 
the extrabiliary tree.  Neonatal hepatitis tends to be self-limited and rarely 
leads to cirrhosis or liver transplantation.  Viruses (such as hepatitis A, B 
and C, rubella, and cytomegalovirus) transmitted by the mother in the 
perinatal period can also cause hepatitis in the neonate.  But the etiology of 
most cases of neonatal hepatitis remains unclear, and the disease may not be 
due to a virus.  Most infants with neonatal hepatitis recover with minimal 
liver scarring; however, 20% will develop chronic liver disease that 
progresses to cirrhosis requiring liver transplantation.  

A longitudinal cohort study of patients with biliary atresia and neonatal 
hepatitis will help accelerate clinical research and progress in understanding 
the pathogenesis of biliary atresia and neonatal hepatitis by more carefully 
defining its natural history and by providing a mechanism to investigate 
better means of diagnosis and of treatment.  The rarity of these two diseases 
and the difficulty in timely diagnosis makes it difficult to accumulate an 
adequate number of patients followed for an adequate period of time in one 
center.  Furthermore, a common and coordinated approach to evaluation and 
therapy will reduce the number of patients needed at each CC.  Also, the 
Biliary Atresia Clinical Research Consortium mechanism will help pool the 
necessary clinical expertise and administrative resources to facilitate the 
conduct of multiple and novel therapeutic trials in a timely, efficient 
manner.  This, in turn, will promote rapid dissemination of research findings 
to health care professionals. 

Research Scope  

The objective of this RFA is to establish a consortium of pediatric clinical 
research centers and a data coordinating center with expertise in biliary 
atresia and neonatal hepatitis that will accelerate advances in the 
understanding, diagnosis and clinical management of these rare, pediatric 
liver diseases.  

Five specific areas of research have been identified as critical to advancing 
the science and treatment of biliary atresia.  They are:  

1) Identification of the etiology of biliary atresia focusing on 
environmental, genetic, virologic, and immunologic risk factors; 

2) Development of rapid and sensitive means for diagnosis of biliary atresia 
and discrimination from other forms of neonatal cholestasis including 
idiopathic neonatal hepatitis; 

3) Definition of the natural history of biliary atresia; 

4) Definition of the optimal regimens and timing for medical and surgical 
interventions; and 

5) Identification of risk factors for progression of disease and 
complications, including factors that affect the success of liver 
transplantation.

The Consortium should initially focus upon development of a clinical database 
of patients with biliary atresia and neonatal hepatitis.  An essential first 
step will be to develop common definitions, nomenclature and terms for the 
clinical diagnosis of biliary atresia and neonatal hepatitis.  In particular, 
histological criteria for the diagnosis as well as standard diagnostic 
algorithms are needed.  Also important are clinical definitions, means of 
assessing symptoms and quality of life, standardized forms and questionnaires, 
and agreed upon essential information for the diagnosis and characterization 
of a patient cohort.  The database can also include control subjects and 
family members for genetic studies.  The database should be designed to 
address specific questions and to provide appropriate reagents or patient 
populations for clinical or laboratory investigation. The Biliary Atresia 
Clinical Research Consortium should also provide the preliminary data and 
background for further investigator-initiated research.  For instance, the 
Consortium might generate a pilot study of therapy and clinical information to 
allow the investigators to submit a separate application for a full-scale 
clinical trial (R01).  The Consortium also is expected to interact with basic 
and laboratory research investigators with interest in these diseases by 
providing reagents, serum or DNA specimens and other resources to help assess 
hypotheses on the pathogenesis, prevention or treatment of the disease.  The 
Consortium can also provide a focus for training in clinical investigation.

THESE ARE EXAMPLES ONLY.  APPLICANTS SHOULD NOT FEEL LIMITED TO THE SUBJECTS 
MENTIONED ABOVE AND ARE ENCOURAGED TO SUBMIT OTHER TOPICS PERTINENT TO THE 
OBJECTIVES OF THE RFA.  It is not the intent of the Consortium to provide 
support for only one or two protocols that run for the entire five years. 
Multiple trials or clinical and epidemiological investigations will be 
conducted, possibly two to four a year, some large and some small.  It is 
anticipated that in the initial one or two years, trials and investigations 
will be selected from the studies proposed by the successful CCs in their 
applications. 

Each CC within the Consortium should propose a research plan that includes the 
structure of a large database as well as two clinical research protocols as 
models that could be used in the Consortium environment.  The protocols should 
demonstrate knowledge of the diseases and experience in treating and following 
patients with biliary atresia and neonatal hepatitis.  Each protocol should 
require sufficient subjects to necessitate the use of a Consortium with multi-
center participation.  Applicants should indicate knowledge of the number of 
patients required for each study based on sample size calculations.  One 
protocol must be a short-term study (one year or less) and one a long-term 
study (one to three years).  The research plan should follow the instructions 
in the PHS 398 application form (revised 4/98; 
http://grants.nih.gov/grants/funding/phs398/phs398.html).  For the overall 
structure and factors that are included in the common database of patients 
include a justification for necessary information on patients to be included.  
For each of the two protocols include a description in approximately two pages 
of the rationale, research aims, outcome measures, and study design.  In 
addition, provide a description of the proposed patient populations with an 
estimate of the expected distribution of male and female patients, ages, and 
assurances of the applicant's access to the patient populations. 

The CC principal investigator should indicate for each protocol how many 
patients meeting proposed criteria are available in his/her CC and how many 
will be required from the entire Consortium (all of the CCs).  In the 
discussion of outcome measures, it will be important to indicate appropriate 
objective measures of primary and secondary outcome.  The CC principal 
investigators are encouraged to explore, within the context of their proposed 
protocols, new technologies to monitor disease progression and response to 
therapy.

All projects must be completed within the five-year duration of this research 
program.

Organization of the Clinical Research Consortium

The Biliary Atresia Clinical Research Consortium will be a cooperative 
consortium of eight to ten CCs and one DCC.  CCs will be responsible for 
proposing data to be collected for the database, protocols, participating in 
their overall development, conducting the research, and disseminating research 
findings. All individual CCs will be required to participate in a cooperative 
and interactive manner with one another and with the DCC in all aspects of the 
Biliary Atresia Clinical Research Consortium.  The DCC will support 
development of a database of clinical information, serum and tissue samples, 
protocol development, provide sample size calculations, statistical advice, 
questionnaires, and data analysis; support manuscript preparation; and provide 
overall study coordination and quality assurance, including coordination of 
the activities of the Data and Safety Monitoring Board, the Steering Committee 
and other standing committees.  Applicants for the DCC should also propose a 
Specimen Core (serum and tissue) facility for central storage of specimens.  
This specimen core will not be awarded until the Steering Committee has met 
and approved its structure and duties.

Governance

A Steering Committee will be the main governing body of the Biliary Atresia 
Clinical Research Consortium. At a minimum, the Steering Committee will be 
composed of the principal investigators of each CC in the Consortium, the 
principal investigator of the DCC and the NIDDK Project Scientist.  The first 
meeting of the Steering Committee will be convened by the NIDDK Project 
Scientist.  By the end of the second meeting of the Steering Committee, the 
NIDDK will name a study Chairperson from one of the CCs to oversee and guide 
Steering Committee activities.  The Steering Committee will meet as often as 
three to six times during the first 12 months of the study, and two to four 
times thereafter.  All major scientific decisions will be determined by a 
majority vote of the Steering Committee.  Each CC, the DCC, and the NIDDK 
Project Scientist will have one vote.  The Steering Committee will have 
primary responsibility for the general organization of the Biliary Atresia 
Clinical Research Consortium, finalizing common clinical protocols, 
facilitating the development of a standardized nomenclature, diagnostic 
criteria, histological definitions, and necessary components to the common 
database on patients.  The Steering Committee will be responsible for the 
conduct and monitoring of studies and reporting study results.  Topics for 
investigational and treatment protocols will be proposed and prioritized by 
the Steering Committee.

For each investigational or therapeutic protocol, one CC will take the lead 
responsibility for drafting the protocol, although the Steering Committee will 
provide input and will be responsible for assuring development of a common 
protocol to be implemented by the CCs.  

Subcommittees of the Steering Committee will be established as necessary.  For 
example, a Publications Committee would be helpful to facilitate the process 
for authorship selection and to supervise preparation of manuscripts.
 
An independent Data and Safety Monitoring Board (DSMB) will be established by 
the NIDDK to review protocols and monitor patient safety and performance of 
each study.  As a part of its responsibilities, the Data and Safety Monitoring 
Board will submit recommendations to the NIDDK regarding the continuation of 
each study. 

Each investigational or therapeutic protocol will be implemented in a minimum 
of two and optimally in all of the CCs, depending on the number of patients 
and investigational expertise needed for the study.  As specific protocols are 
developed, support will depend on the availability of funds and will be 
provided on a per patient basis.  All the CCs must be willing to pursue this 
funding arrangement for each new protocol conducted.
 
Clinical protocols must be approved by local institutional review boards and 
the Biliary Atresia Clinical Research Consortium Data and Safety Monitoring 
Board before initiation.  The exact number of protocols supported in the five-
year program will depend on the nature and extent of the investigations 
proposed by the Steering Committee.  Databases will be developed; 
epidemiological studies and other clinical studies may be performed.  Planning 
may be done for large clinical trials that would be submitted as separate R01s 
if further funding were necessary.  The Biliary Atresia Clinical Research 
Consortium investigators are also encouraged to seek out separate funding for 
special projects and to develop collaboration with laboratory and basic 
research investigators to draw upon the resources (clinical data, serum, 
tissue, DNA) made available by the Biliary Atresia Clinical Research 
Consortium Database.  Any specific collaboration involving the resources of 
the Biliary Atresia Clinical Research Consortium will require approval by the 
Steering Committee.

SPECIAL REQUIREMENTS

Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator(s) as well as the 
institutional official at the time of award. These special Terms of Award are 
in addition to and not in lieu of otherwise applicable OMB administrative 
guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, 
the NIH Grant Policy statement.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01 an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during 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 this concept, the dominant role and prime responsibility for 
the activity resides with the awardee(s) for the project as a whole, although 
specific tasks and activities in carrying out the studies will be shared among 
the awardees and the NIDDK Project Scientists.

1) Awardees Rights and Responsibilities

o The awardee(s) will have lead responsibilities in all aspects of their 
protocols, including any modification of study design, conduct of the study, 
quality control, data analysis and interpretation, preparation of 
publications, and collaboration with other investigators, unless otherwise 
provided for in these terms or by action of the Steering Committee.  
Modifications and ancillary protocols will be approved by the Steering 
Committee and the Data and Safety Monitoring Board.

o Awardees will retain custody of and have primary rights to their data 
developed under these awards, subject to Government rights of access 
consistent with current HHS, PHS, and NIH policies.  The collaborative 
protocol and governance policies will call for the continued submission of 
data centrally to the DCC for a collaborative database; the submission of 
copies of the collaborative data sets to each principal investigator upon 
completion of the study; procedures for data analysis, reporting and 
publication; and procedures to protect and ensure the privacy of medical and 
genetic data (if any) and records of individuals.  The NIDDK Project 
Scientist, on behalf of the NIDDK, will have the same access, privileges and 
responsibilities regarding the collaborative data as the other members of the 
Steering Committee.

o The Data Coordinating Center will be involved in collaborations with the 
NIDDK and the Clinical Centers during all phases of the trial and will 
maintain the Specimen Core facility.  Thus, the awardee is expected to work 
cooperatively with Clinical Centers and sponsoring organizations in a 
multicenter trial and oversee the implementation of and adherence to a common 
protocol, as well as assure quality control of the data collected and storage 
of collected tissue specimens.  In addition to organizing and attending 
regular meetings, the Data Coordinating Center will be expected to maintain 
close communications with the NIDDK Project Scientist and the Principal 
Investigators of the Clinical Centers.
 
o Awardees are encouraged to publish and to publicly release and disseminate 
results, data and other products of the study, concordant with the study 
protocol and governance and the approved plan for making data and materials 
available to the scientific community and the NIDDK.  However, during or 
within three years beyond the end date of the project period of NIDDK support, 
unpublished data, unpublished results, data sets not previously released, or 
other study materials or products are to be made available to any third party 
only with the approval of the Steering Committee.

o Support or other involvement of industry or any other third party in any 
study performed by the Consortium-- e.g., participation by the third party; 
involvement of project resources or citing the name of the project or the 
NIDDK support; or special access to project results, data, findings or 
resources -- may be advantageous and appropriate.  However, except for 
licensing of patents or copyrights, support or involvement of any third party 
will occur only following notification to, and concurrence by, NIDDK.

o Upon completion of the project, the DCC is expected to put all study 
intervention materials and procedure manuals into the public domain and/or 
make them available to other investigators, according to the approved plan for 
making data and materials available to the scientific community and the NIDDK, 
for the conduct of research at no charge other than the costs of reproduction 
and distribution.

2) NIDDK Staff Responsibilities

The NIDDK will name a Project Scientist from within the Division of Digestive 
Diseases and Nutrition whose function will be to assist the Steering Committee 
in carrying out the study.  The Project Scientist will have one vote for all 
key study group subcommittees.  The Project Scientist will have substantial 
scientific-programmatic involvement in quality control, interim data analysis, 
safety monitoring, and final data analysis and interpretation, preparation of 
publications, and coordination and performance monitoring.  The dominant role 
and prime responsibility for these activities resides with the awardees for 
the project as a whole, although specific tasks and activities in carrying out 
the studies will be shared among the awardees and the NIDDK Project Scientist.

The NIDDK reserves the right to terminate or curtail the study (or an 
individual award) in the event of (a) failure to develop or implement a 
mutually agreeable collaborative protocol, (b) substantial shortfall in 
participant recruitment, follow-up, data reporting, quality control, or other 
major breach of the protocol, (c) substantive changes in the agreed-upon 
protocol with which NIDDK cannot concur, (d) reaching a major study endpoint 
substantially before schedule with persuasive statistical significance, or (e) 
human subject ethical issues that may dictate a premature termination.

3) Collaborative Responsibilities

The Steering Committee, composed of each of the Principal Investigators of the 
DCC and the CCs, the NIDDK Project Scientist, and the Chairman of the Steering 
Committee, will be the main governing board of the studies.  This committee 
will have the primary responsibility for approval of the common protocols, 
facilitating the conduct of participant follow-up, monitoring completeness of 
data collection and timely transmission of data to the DCC, and reporting the 
study results.  It will also be responsible for establishing study policies in 
such areas as access to patient data, ancillary studies, publications and 
presentations, and performance standards.  Each member of the Steering 
Committee will have one vote and all major scientific decisions will be 
determined by a majority vote of the Steering Committee.  A Chairperson will 
be chosen from among the Steering Committee members (but not the NIDDK Project 
Scientist or Data Coordinating Center Principal Investigator), or 
alternatively, from among experts in the field of liver diseases who are not 
participating directly in the study.  Subcommittees will be established on 
topics such as ancillary studies, publications and presentations, quality 
control, recruitment, protocol adherence, among others.  

Each Consortium CC Awardee and the DCC Awardee agree to the governance of the 
study through the Steering Committee.  The Steering Committee voting 
membership shall consist of the Principal Investigators of the CCs and the 
DCC, and the NIDDK Project Scientist.  Meetings of the Steering Committee will 
ordinarily be held by telephone conference calls or in the Washington DC 
Metropolitan Area. 

The NIDDK Project Scientist (and the other cited NIDDK scientists) may work 
with awardees on issues coming before the Steering Committee and, as 
appropriate, other committees, e.g., issues of recruitment, intervention, 
follow-up, quality control, standards and methods, adherence to protocol, 
assessment of problems affecting the study and potential changes in the 
protocol, interim data and safety monitoring, final data analysis and 
interpretation, preparation of publications, and development of solutions to 
major problems such as insufficient participant enrollment.  Regardless of the 
number of NIH staff participating in technical advisory roles, the NIDDK will 
be limited to one vote on the Steering Committee.

4) Arbitration

Any disagreement that may arise in scientific/programmatic matters (within the 
scope of the award), between award recipients and the NIDDK may be brought to 
arbitration.  An arbitration panel will be composed of three members one 
selected by the Steering 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 
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 at 45 
CFR part 16, or the rights of NIDDK under applicable statutes, regulations and 
terms of the award.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of  
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43). 

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

DATA AND SAFETY MONITORING IN CLINICAL TRIALS

Applicants are directed to the full text of the NIH Policies regarding Data 
and Safety Monitoring and Reporting of Adverse Events that are found in the 
NIH Guide for Grants and Contracts Announcements at the following web 
sites:  http://grants.nih.gov/grants/guide/notice-files/not98-084.html; 
http://grants.nih.gov/grants/guide/notice-files/not99-107.html; 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html

All applicants receiving an award under this RFA must comply with the NIH 
policy cited in these NIH Announcements and any other data safety and 
monitoring requirements found elsewhere in this RFA.

The following is a brief summary of the Data and Safety Monitoring and Adverse 
Event Reporting Requirements:

Data and Safety Monitoring (DSM) is required for every clinical trial.  
Monitoring must be performed on a regular basis and the conclusions of the 
monitoring reported to the extramural Program Director.

The DSM plan is established at the time the protocol is developed and must be 
approved by both the Institutional Review Board (IRB) and the NIH and be in 
place before the trial begins.  If the protocol will be developed during the 
research funded under this RFA, a general description of the Data and Safety 
Monitoring plan must be submitted as part of the proposal and will be reviewed 
by the initial review group.  If the protocol has been developed and is 
included as part of the submitted proposal, the complete and specific data and 
safety monitoring plan must be submitted as part of the proposal.

Monitoring plans, at a minimum, must include the prompt reporting of adverse 
events to the IRB, Food and Drug Administration and the NIH.  The frequency of 
reporting of the conclusions of the monitoring activities should also be 
described in the plan.  The overall elements of each plan may vary depending 
on the size and complexity of the trial.  Examples of monitoring activities to 
be considered are described in the NIH Policy for Data and Safety Monitoring 
at http://grants.nih.gov/grants/guide/notice-files/not98-084.html.

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.  This policy announcement is found in the NIH Guide for Grants and 
Contracts Announcement dated June 5, 2000, at the following website:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

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:
http://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.

LETTER OF INTENT

Prospective applicants are asked to submit, by October 16, 2001, a letter of 
intent that includes a descriptive title of the proposed research; the name, 
address, and telephone number of the Principal Investigator; the identities of 
other key personnel and participating institutions; whether the application is 
for a CC or the DCC; 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 a subsequent application, the information that it 
contains allows NIDDK staff to estimate the potential review workload and 
avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. Francisco Calvo at the address 
listed under INQUIRIES, below.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: 
GrantsInfo@nih.gov.

Application Requirements

Applicants must describe plans to accommodate the stated program requirements, 
criteria, and staff involvement.  Applicants must address points discussed in 
the SPECIAL REQUIREMENTS section of this RFA.

1.  Clinical Center Applications

Each CC within the Consortium should propose a research plan that includes the 
structure of a large database as well as two clinical research protocols as 
models that could be used in the Consortium environment.  The protocols should 
demonstrate knowledge of biliary atresia and neonatal hepatitis.  Each 
protocol should require sufficient subjects to necessitate the use of a 
Consortium with multi-center participation.  Applicants should indicate 
knowledge of the number of patients required for each study based on sample 
size calculations.  One protocol must be a short-term study (one year or less) 
and one a long-term study (one to three years).  For the overall structure and 
factors that are included in the common database of patients include a 
justification for necessary information on patients to be included.  For each 
of the two protocols include a description in approximately two pages of the 
rationale, research aims, outcome measures, and study design.  In addition, 
provide a description of the proposed patient populations with an estimate of 
the expected distribution of male and female patients, ages, and assurances of 
the applicant's access to the patient populations. 

The CC principal investigator should indicate for each protocol how many 
patients meeting proposed criteria are available in his/her CC and how many 
will be required from the entire Consortium (all of the CCs).  In the 
discussion of outcome measures, it will be important to indicate appropriate 
objective measures of primary and secondary outcome.  The CC principal 
investigators are encouraged to explore, within the context of their proposed 
protocols, new technologies to monitor disease progression and response to 
therapy.  Funding for the relevant technology should be presently available 
for each protocol proposed.  It will also be important to include strategies 
to assure adherence to therapy as part of the protocol.

To promote development of a collaborative program, the issues discussed below 
need to be addressed in each application for a CC within the Biliary Atresia 
Clinical Research Consortium.  This material is in addition to the submission 
of a research plan, as described in the section entitled Research Scope.

The following specific criteria should be addressed:

o Qualifications and experience.  Applicants for CCs must demonstrate 
experience and expertise to conduct clinical studies in biliary atresia and 
neonatal hepatitis. This must include documentation of experience in the 
diagnosis and management of patients with biliary atresia and neonatal 
hepatitis.  

o Study population.  CCs must demonstrate a history of evaluating and managing 
children with biliary atresia and neonatal hepatitis.  The CC should discuss 
the number of patients with biliary atresia and neonatal hepatitis seen and 
followed at the center in the previous five years that might have been 
eligible to enroll in the clinical database as well as in specific treatment, 
investigational or diagnostic protocols.   Approximately half of the patients 
enrolled in the Biliary Atresia Clinical Research Consortium should be 
females.    The applicant for a CC in the Consortium must include a 
description of the children seen with biliary atresia and neonatal hepatitis 
by sex, age categories, and ethnic/racial distribution, as well as recruitment 
source. Patient access may be developed by establishing links with other 
groups outside the CC's institution. If outside links are proposed, there must 
be a well described plan to link the individual CCs with community health care 
providers such as HMOs, clinics, or private practice physicians to ensure 
adequate numbers patients for clinical studies of therapeutic agents and 
management strategies.  Applicants for a CC from institutions that have a 
General Clinical Research Center (GCRC) funded by the NIH National Center for 
Research Resources are encouraged to identify the GCRC as a resource for 
conducting the proposed research.  If so, a letter of agreement from either 
the GCRC Project Coordinator or Principal Investigator should be included with 
the application.

o Willingness to participate in Biliary Atresia Clinical Research Consortium.  
The principal investigator should state his/her general support of 
collaborative research and interaction with the NIDDK, the other CCs, and the 
DCC through the Consortium concept.  Applicants should discuss their 
willingness, and that of the institutions involved, to pursue a per patient 
basis (capitation) of operational costs for each protocol. CCs must be able to 
interact with the DCC to transmit and edit data and should discuss their 
capability to participate in a distributed data entry system.

o Institutional resources for patient care and follow-up including personnel, 
space, and special laboratory facilities should be described.

2. Data Coordinating Center Applications

A separate complete application is required from institutions applying to be 
the DCC for the Biliary Atresia Clinical Research Consortium.  Applicants for 
the DCC component are not required to be a clinical site within the 
Consortium, though applicants for clinical sites may also submit an 
application to be the DCC. 

Applicants must describe plans to achieve the stated “Objectives and Scope,” 
”Special Requirements,” and “Terms and Conditions of Award” stated in this 
RFA.  In addition, applicants should document their willingness to participate 
on the Steering Committee and appropriate subcommittees, work cooperatively 
with other members of the Steering Committee, and follow the common protocol 
established cooperatively by the Steering Committee.  Applicants must also 
address the following responsibilities of the DCC:  

o Participation in the design of the final protocol and development of the 
manual of operation, data collection forms, and questionnaires; 

o Development and implementation of systems for communication among Steering 
Committee members, and among study sites; 

o Data collection, editing, processing, analysis, and reporting;

o Monitoring of adherence to the protocol and of data quality; and 

o Establishment of procedures that insure the safety and confidentiality of 
all records.

Data management and quality control procedures must be detailed.  Methods for 
assuring privacy and maintaining confidentiality should be included.  There 
must be a data and safety management plan.  Applicants must state their plans 
for the reporting of results that examine differences in treatment effects 
across these subgroups (see section, “Inclusion of Women and Minorities in 
“Research Involving Human Subjects”).

Applications may not exceed 25 pages for sections a - d, excluding appendices, 
which may contain copies of pertinent forms or examples of correspondence 
useful for coordinating tasks.

The following specific criteria should be addressed:

o Qualifications and experience.  The applicant for a DCC must demonstrate 
experience in the area of in coordinating multi-center clinical trials and 
epidemiological studies in all phases: protocol and manual of operations 
development, staff training in study procedures, research instrument 
development, data collection and management, quality assurance, data analysis, 
distributed data entry, electronic communications, administrative management 
and coordination. Specific experience in coordinating or monitoring studies of 
liver disease is not required, but the applicant may wish to include a 
hepatologist or hepatic pathologist in the application as a key collaborator 
and advisor.

o Study design and management. DCC proposals should discuss the applicant's 
familiarity and experience with various aspects of study design that would be 
important in developing clinical protocols, for example: eligibility criteria; 
baseline and outcome measures; methods of randomization; important 
considerations for making sample size and power calculations; methods and 
frequency of data collection and entry; monitoring accuracy of data 
collection; quality control procedures including training and certification 
for multiple protocols, some of which may occur simultaneously; managing 
labeling and handling of serum and tissue samples (see below); and plans for 
statistical analysis. The DCC proposal should also describe their familiarity 
with model plans for managing the Data and Safety Monitoring Board. 

o The applicant for the DCC should delineate how laboratory specimens will be 
handled.  NIDDK anticipates that some clinical outcome measures may be 
centrally assessed.  Laboratories responsible to the DCC will manage specimens 
and laboratory studies as required by the Steering Committee.  The costs of 
performing specific laboratory tests will be budgeted as a part of the per 
patient costs of each CC. The costs of specimen shipment as well as laboratory 
data acquisition and management will be a part of the budget of the DCC. 

The DCC does not need to prepare two protocols.  

BUDGET AND RELATED ISSUES

Applicants should complete the budget information as directed in the PHS 398 
application form. 

1.  Clinical Center Applications 
 
CCs should consider the following additional issues regarding budgets.  The 
underlying concept of the Biliary Atresia Clinical Research Consortium is that 
a core effort is essential to maintain the infrastructure required to perform 
multiple clinical trials or clinical studies.  Based on this approach, it is 
estimated that the individual CCs will require a minimum level of effort to 
sustain the organizational aspects of the Clinical Research Consortium.  
Therefore, individual CCs should submit requests for a CORE BUDGET.  It is 
anticipated that this core budget will cover a minimum ten percent effort for 
the principal investigator, and a small percent effort for other key personnel 
(nurse, technician, clinic coordinator, secretary), and travel costs for two 
people to attend three Biliary Atresia Clinical Research Consortium meetings a 
year in Bethesda, MD.  These costs should be justified appropriately in 
budgets and may be distributed into subcontracts.  Escalation is allowed at 
three percent for future years.

In addition to the core budget, each CC will be provided funds for 
implementation of protocols.  The precise number of protocols conducted will 
be determined by the Biliary Atresia Clinical Research Consortium Steering 
Committee and will depend on availability of funds.  It is anticipated that 
after the first year, two to four protocols may be active each year.  CCs may 
request PATIENT CARE costs.  This amount should be placed in the patient care 
category.  Patient care costs may be escalated at three percent for future 
years.  Allowable total costs for each CC  (core costs, costs per patient to 
conduct the protocols, and indirect costs) will vary.  However, the maximum 
total costs for each Consortium to implement the protocols (including CCs and 
DCC and Specimen Core) are $125,000 per year.  

The CCs are requested to present the following information:

o For each year, each CC should include the core budget costs and patient care 
costs.  Estimated protocol implementation costs for Year 1 should be based on 
the two proposals presented in the applicants’ research plan.  A table should 
be included showing estimated costs per patient for conducting each protocol. 
Total cost for implementation of both protocols should not exceed $125,000.

The budget for each clinical protocol should be developed on a cost per 
patient basis and include all direct and any applicable facilities and 
administrative costs. Costs of drugs or laboratory tests should be part of the 
per patient cost of conducting a protocol.  The clinical protocol should 
identify the potential source(s) for any drugs or substances that are being 
considered for clinical protocols that are currently unavailable commercially.  
Investigators should only prepare budgets for their own CC to conduct the 
proposed study or trial, and not for the entire Biliary Atresia Clinical 
Research Consortium.  The CC should state the total number of patients 
required by the entire Consortium to complete each proposed study or trial.  
The yearly budget for each CC should include the number of patients available 
for the proposed protocol at that CC.  A budget based on the costs per patient 
for recruiting and maintaining the specified number of subjects at the 
applicant's center should be included for each protocol. 

Note that ongoing annual budgets for protocols will be based on the protocols 
approved by the Biliary Atresia Clinical Research Consortium Steering 
Committee and will be funded through a per patient basis (capitation) funding 
mechanism.  The individual CCs will be expected to project patient enrollment 
for a specific protocol during a specified time frame; continuation and level 
of funding for each CC will be based on actual recruitment and overall 
performance. 

The Biliary Atresia Clinical Research Consortium awards will be subject to 
administrative review annually.

2.  Data Coordinating Center Applications

Applicants for the DCC should prepare budgets for five 12-month periods (not 
to exceed $750,000 total cost per year) that roughly correspond with the 
standard coordinating center responsibilities outlined in other sections of 
this RFA.  In the first year, DCC applicants should include all costs 
associated with the organization of all administrative aspects of the Biliary 
Atresia Clinical Research Consortium to be developed and with the initiation 
of one protocol to be developed and started.  For subsequent years, applicants 
may assume that two to four protocols a year will be active, i.e. either in 
the protocol development, implementation, or analysis and writing phase. DCC 
should include costs for managing the Data and Safety Monitoring Board 
including the cost of meeting three times/year in Bethesda.  Approximately 
$20,000 for the whole 5 years should be budgeted for managing the Data and 
Safety Monitoring Board.

The DCC will be subject to administrative review annually. It is expected that 
all protocols will be performed in a manner consistent with United States Food 
and Drug Administration guidelines.

The RFA label available in the PHS 398 (rev. 4/98) 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 sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

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

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be 
sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD  20892-5452
Telephone:  (301) 594-8897
FAX:  (301) 480-3505

Applications must be received by November 28, 2001.  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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIDDK.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NIDDK in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the NIDDK National Advisory Council or Board.

Review Criteria

All applications will be reviewed according to the criteria listed below.  The 
reviewers will be asked to evaluate the following aspects of the application 
in order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  Each of these criteria will 
be addressed and considered in assigning the overall score, weighting them as 
appropriate for each application.  Note that the application does not need to 
be strong in all categories to be judged likely to have major scientific 
impact and thus deserve a high priority score.

o Significance:  The application should address the problem outlined in the 
RFA.  The application should demonstrate how the study will advance scientific 
and/or medical knowledge.

o Approach:  The adequacy of the proposed conceptual framework, design, 
methods, and analyses.  The  acknowledgement of  potential problem areas and 
the consideration of alternative tactics.

Since the final study design(s) will be developed collaboratively by the 
Steering Committee for the protocols, the peer review group will focus on 
evidence that the applicant has carefully thought about the issues involved 
and possesses the knowledge necessary to contribute meaningfully to the final 
design, including understanding of the scientific, ethical, and practical 
issues underlying the proposed study.

o Innovation:  The applicant should demonstrate how the project challenges 
existing paradigms or develops new methodologies or technologies.

o Investigator:  The investigator should be appropriately trained and well 
suited to carry out this work.  The proposed study should be appropriate to 
the experience level of the principal investigator and other researchers (if 
any).  There should be evidence of prior experience in working collaboratively 
to carry out a clinical study or standard protocol as well as evidence of 
willingness to work cooperatively on the Steering Committee to develop and 
follow a unified protocol.

o Environment:  The environment in which the work will be done should 
contribute to the probability of success. The proposed protocol should take 
advantage of unique features of the scientific environment and employ useful 
collaborative arrangements. There should be evidence of institutional support.

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o The adequacy of plans to include both genders, minorities and their 
subgroups as appropriate for the scientific goals of the research.  Plans for 
the recruitment and retention of subjects will also be evaluated.

o The reasonableness of the proposed budget and duration in relation to the 
proposed research

o The adequacy of the proposed protection for humans or the environment, to 
the extent they may be adversely affected by the project proposed in the 
application.  The initial review group will also examine the safety of the 
research environment.

1.  Clinical Center Applications

Review of CC applicants also will be based on the following specific criteria:

o Scientific and technical merit of the proposed approach to managing the 
requirements of the study as outlined in the RFA.

o Staff Qualifications:  Specific competence and previous experience of 
professional, technical, and administrative staff relevant to the operation of 
a CC in the proposed study. 

o Recruitment Capability:  Evidence of successful experience in recruitment 
and retention of research subjects in multicenter clinical trials. Evidence of 
ability to recruit, enroll, and maintain minority subjects in a randomized 
trial or other clinical studies at the proposed center.  This includes 
documentation of access to an adequate patient population for the proposed 
protocols. 

o Resources:  Documented adequacy of the proposed facility, space, and 
resources for the work proposed.  This includes evidence of an appropriate 
organizational structure and institutional support.

o Data and Sample Management:  Adequacy of plans to ensure accurate collection 
and timely transmission of study data to the DCC and patient samples to the 
Specimen Core.  Documented experience in meticulous and expeditious handling 
of laboratory specimens and study data.

o Knowledge of Problems:  Demonstrable knowledge of the potential problems 
associated with the conduct of this study and possible solutions.

o Cooperative Experience: Evidence of prior experience in working 
collaboratively in carrying out a developed study protocol.  Evidence of 
willingness to work cooperatively in this study.

o Collaborations between CCs within the Biliary Atresia Clinical Research 
Consortium.  For those applicants that propose collaborative efforts between 
two groups to form a single CC, additional factors to be considered would 
include the advantages of the collaboration in terms of cost, recruitment, or 
facilities; the commitment of the participants to the collaboration; and the 
adequacy of plans to coordinate efforts.

2.  Data Coordinating Center Applications.

Review of DCC applicants also will be based on the following specific 
criteria:

o Understanding of the scientific, statistical, logistical, and technical 
issues underlying multi-center studies, including issues relating to treatment 
and management of liver disease, and knowledge necessary to resume a 
leadership role in the area of study design, statistics, logistics, data 
acquisition and management, handling of laboratory specimens, quality control, 
data analysis, and Consortium coordination.

o Adequacy of the proposed plans for acquisition, transfer, management, and 
analysis of data, quality control of data collection and monitoring, and 
overall coordination of the Biliary Atresia Clinical Research Consortium 
activities.

o The expertise, training, and experience of the investigators and staff, 
including the administrative abilities of the Principal Investigator and co-
investigators, and the time they plan to devote to the effective coordination 
of the Biliary Atresia Clinical Research Consortium.

o The administrative, supervisory, and collaborative arrangements for 
achieving the goals of the program, including willingness to cooperate with 
the principal investigator of the Administrative Core, the principal 
investigators of the CCs and the NIDDK.

o Facilities, equipment, and organizational structure to effectively 
coordinate the Biliary Atresia Clinical Research Consortium activities in 
implementing the protocols, providing for specialized laboratory testing, and 
collecting data.

o Appropriateness of the budget for the work proposed.

Schedule

Letter of Intent Receipt Date:    October 16, 2001
Application Receipt Date:         November 28, 2001
Peer Review Date:                 March 2002
Council Review:                   May 2002
Earliest Anticipated Start Date:  July 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific and technical merit of the application for a Clinical Center or a 
Data Coordinating Center.

o The multi-disciplinary nature of the proposed studies (CC).

o Demonstration of expertise to manage, design and coordinate multicenter 
clinical trials that include handling and storage of laboratory specimens 
(DCC).

o The quality of response to the special requirements stated in this RFA. 

o Relevance to the overall programmatic balance and priorities of the NIDDK 
and sufficient compatibility of features proposed in the research plan and 
qualifications of the investigators to make a collaborative program within the 
Biliary Atresia Clinical Research Consortium a reasonable likelihood. 

o Availability of funds.

o Access to patients including children and minority individuals.

o A demonstrated willingness on the part of the investigators to work as part 
of the Biliary Atresia Clinical Research Consortium and with the NIDDK Project 
Scientist.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Patricia Robuck, Ph.D., M.P.H.
Director, Clinical Trials Program
Division of Digestive Diseases and Nutrition, NIDDK
6707 Democracy Blvd.
Room 675, MSC 5450
Bethesda, MD  20892-5450
Telephone:  (301) 594-8879
FAX:  (301) 480-8300
Email: pr132q@nih.gov

Direct inquiries regarding review issues to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD  20892-5452
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: fc15y@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Sharon Bourque
Grants Management Specialist
Division of Extramural Affairs, NIDDK
6707 Democracy Blvd.
Room 719, MSC 5456
Bethesda, MD  20892-5456
Telephone:  (301) 594-8846
FAX:  (301) 480-3504
Email: sb114m@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.848.  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 and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.


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