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BARIATRIC SURGERY CLINICAL RESEARCH CONSORTIUM
 
RELEASE DATE:  November 1, 2002
 
RFA: DK-03-006 (Reissued as RFA-DK-08-501)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov) 

LETTER OF INTENT RECEIPT DATE:  February 18, 2003

APPLICATION RECEIPT DATE:  March 18, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Organization of the Bariatric Surgery Clinical Research Consortium
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria 
o Reference List
o Required Federal Citations:

PURPOSE OF THIS RFA 
 
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
invites applications for establishment of a Bariatric Surgery Clinical 
Research Consortium (BSCRC)to focuses on bariatric surgery and its role in 
the understanding and treatment of obesity and its complications. Bariatric 
surgery involves reducing the size of the gastric reservoir, with or without 
a degree of associated malabsorption, with a goal of inducing weight loss 
among patients with extreme obesity.(American Society for Bariatric Surgery, 
2001) The objective of this Request for Applications (RFA) is to establish 
and maintain a Bariatric Surgery Clinical Research Consortium consisting of a 
group of between four and six interactive Clinical Centers (CCs) and a Data 
Coordinating Center (DCC).  The goal of the BSCRC is to facilitate 
coordinated clinical, epidemiological, and behavioral research in the field 
of bariatric surgery, through the cooperative development of common clinical 
protocols and a bariatric surgery database to collect information from 
participating CCs. This is a one-time solicitation to support a Clinical 
Research Consortium for five years.

RESEARCH OBJECTIVES

A. Background

Obesity is increasing at alarming rates in the US, with more than 25% of adult 
Americans now considered obese (BMI>30).(U.S.Department of Health and Human 
Services, 2001)  Of even more concern, there are large increases in the 
prevalence of higher levels of obesity (Class II, BMI 35-39.9 and Class III 
BMI >40).(Flegal, K. M., Carroll, M. D., Kuczmarski, R. J., & Johnson, C. L., 
1998)  In some minority populations, such as African American women ages 40-
60, the percentage of individuals with a BMI >40 exceeds 10%.(Flegal, K. M., 
Carroll, M. D., Kuczmarski, R. J., & Johnson, C. L., 1998)   Along with this 
increase in the prevalence of obesity has come a rise in the incidence and 
prevalence of obesity-related co-morbid condition, such as type 2 
diabetes.(Harris, M. I. et al., 1998)   Although prevention of overweight and 
obesity remains the primary public health goal, more effective treatments for 
those who are already obese are crucial.  

Numerous studies have shown that obesity treatments using behavioral therapy 
to improve diet and physical activity levels can lead to weight losses of 
approximately five to ten percent over four to six months.(Wadden, T. A. & 
Foster, G. D., 2000) With such weight losses come improvements in obesity-
related co-morbidities, such as hypertension, dyslipidemia, hyperinsulinemia, 
and progression to diabetes. (Knowler, W. C. et al., 2002)  However, these 
improvements are not maintained if weight is regained, and in a majority of 
cases, rebound in weight gain above the pre-intervention weight is the 
ultimate outcome.  Therefore, better means to induce substantial weight loss 
in the extremely obese population, as well as to maintain weight loss over the 
longer term, are treatment goals.  The most effective means currently 
available to induce substantial weight loss, with long-term maintenance of 
much of that weight loss, is through bariatric surgery.

A 1991 NIH Consensus Conference found that gastric restrictive or bypass 
surgery could be considered in well-informed and motivated patients with 
severe obesity (BMI >40) or less severe obesity (BMI >35) with high-risk co-
morbid conditions.(1992) It was noted that insufficient data were available on 
which to base recommendations for patient selection using objective clinical 
features alone, and that additional research was needed to determine 
predictive factors. 

Since 1991, bariatric surgical procedures have become established modalities 
in the treatment of extreme obesity.  It is estimated that 40,000 bariatric 
surgical procedures were carried out in the US in 2001, with many more 
predicted in 2002.(NIDDK Working Group on Bariatric Surgery Executive Summary, 
2002) Although systematic long-term follow-up across multiple sites is 
lacking, individual researchers have published case series with excellent 
follow-up.(Pories, W. J. et al., 1995; Brolin, R. E., 2001)  These studies 
suggest that bariatric surgery can have a long-lasting outcome on some co-
morbid conditions, particularly type 2 diabetes.  The Swedish Obese Subjects 
(SOS) is an ongoing non-randomized multi-center trial investigating the long-
term effects of surgically induced weight loss on obesity-related morbidity 
and mortality,(Sjostrom, C. D., Peltonen, M., Wedel, H., & Sjostrom, L., 2000) 
and may answer some, but not all, questions regarding the health impact of 
bariatric surgery.  One limitation of this study is that most procedures were 
restrictive in nature, with more limited weight loss than is common with 
gastric bypass procedures.

Some of the research questions posed by the Consensus Panel in 1991 remain 
unanswered a decade later. These include the mechanisms whereby surgical 
treatment produces weight reduction, mechanisms of improvement in co-morbid 
risk factors or disease, safety and efficacy of bariatric surgery in defined 
subgroups, safety and efficacy of differing bariatric surgical procedures, and 
impact of bariatric surgery on subsequent pregnancy.  The panel also noted the 
need for improved reporting of surgical results, and clearer outcomes 
assessment, including psychosocial outcomes.  The importance of including 
meaningful control or comparison groups was also noted, although challenges in 
obtaining truly comparable groups were acknowledged. 

In 2001, NIDDK, in conjunction with the American Society for Bariatric 
Surgery, sponsored a workshop on Research Considerations in Obesity 
Surgery,(Kral, J. G. et al., 2002) which provided an update on bariatric 
surgery and posed research questions that might be answered by future studies. 
Some of the research topics proposed included the impact of bariatric surgery 
on subsequent pregnancy, impact of age on outcomes, and the effect of 
operations with greater malabsorptive potential on nutritional status. In May 
2002, NIDDK convened a Working Group on Research in Bariatric Surgery that 
brought together investigators from a variety of disciplines to assist NIDDK 
in identifying areas of scientific opportunity pertaining to bariatric surgery 
and its impact on obesity and co-morbid conditions.  A number of topics were 
identified as research opportunities, including using bariatric surgery as a 
model to understand underlying pathophysiology of obesity-related diseases, 
and evaluation of the safety and efficacy of bariatric surgical procedures, 
including their impact on weight loss, co-morbid conditions, psychosocial 
status, quality of life, and economic factors.  Studies looking at both short-
term and long-term outcomes were felt to be critical. The need for refining 
phenotyping to better predict outcomes, and hence improve risk/benefit ratio 
of an individual patient was also considered essential.  A consortium of 
centers performing bariatric surgical procedures on large numbers of patients 
would permit collaborative studies in more basic areas, including studies on 
energy balance, nutrient absorption, physiology and metabolism, and the 
genetics of severe obesity.  Establishing a bariatric surgery database, to 
collect hypothesis-driven data on multiple variables of clinical and 
scientific interest was considered a potential strength of such a 
collaboration, which could provide information on clinically important 
predictors and outcomes, as well as economic and quality of life data.  

A Bariatric Surgery Clinical Research Consortium (BSCRC) will accelerate 
clinical research and progress in understanding the pathogenesis of severe 
obesity and its complications, as well as in understanding the risks and 
benefits of bariatric surgery as a treatment modality.  Use of standardized 
definitions, clinical protocols, and data collection instruments will enhance 
the ability to provide meaningful evidence-based recommendations for patient 
evaluation, selection, and follow-up care.  Also, the BSCRC will help pool the 
necessary clinical expertise and administrative resources to facilitate the 
conduct of multiple and novel clinical studies in a timely, efficient manner.  
This, in turn, will promote rapid dissemination of research findings to health 
care professionals. 

B. Research Scope

1. Study Goals and Objectives

The objective of this Request for Applications (RFA) is to establish and 
maintain a Bariatric Surgery Clinical Research Consortium consisting of a 
group of interactive Clinical Centers (CCs) and a Data Coordinating Center 
(DCC).  The goal of the BSCRC is to facilitate coordinated clinical, 
epidemiological, and behavioral research in the field of bariatric surgery. 
CCs and the DCC will work cooperatively to develop common clinical protocols, 
as well as to develop and implement a database to collect information from 
participating clinical centers.  It is anticipated that the BSCRC will carry 
out one or more studies per year during the five year period, ranging from 
small pilot studies to larger studies (such as studies on quality of life or 
economic factors).

The Bariatric Surgery Clinical Consortium should provide the preliminary data 
and background for further investigator-initiated research.  For example, the 
Consortium might investigate metabolic and endocrine changes with bariatric 
surgery, generating information to allow the investigators to submit a 
separate application for a full-scale clinical investigation through the RO1 
mechanism. The Consortium also is expected to interact with basic and 
laboratory research investigators with interest in these diseases by providing 
laboratory specimens, tissues, or opportunities to assess hypotheses on the 
pathogenesis, prevention or treatment of obesity and its co-morbid conditions.  
The Consortium can also provide a focus for training in clinical 
investigation.

2. Study Timeline

During the first 10-12 months, investigators will collaboratively develop the 
protocols, with IRB and other approvals obtained by the end of the first 
year.  Database development and implementation will also take place during 
this phase (Phase 1).  Short-term and longer-term studies, as described 
below, will be instituted during years 2-4 (Phase 2), with continued follow-
up, study analysis, and close out during the final year (phase 3).  All 
projects must be completed within the five-year duration of this research 
program.

3. Research Approaches

a.  Database
 
The Consortium will initially focus upon development of a clinical database of 
patients undergoing bariatric surgery, including elements of medical history, 
physical examination, and laboratory results.  Development of the database 
will necessitate agreement on standardized definitions, means of assessing 
symptoms and quality of life, standardized forms and questionnaires, time-
points for data collection, and agreed-upon essential information for the 
characterization of a patient cohort. The database may also include control 
subjects and family members for genetic studies. The database should be 
designed so that the information collected is based on the need to answer 
specific scientific questions. 

Each CC must provide a brief description of their suggestions for a database, 
including which data they believe should be acquired in the database, a 
discussion of the pros and cons of various non-surgical control groups, as 
well as discussion of the types of scientific questions such a database might 
answer.

The DCC must propose a research plan that includes the structure of a large 
database and an information core that they believe should be collected on all 
participants that are prospectively enrolled, including potential and actual 
bariatric surgical patients and non-surgical control patients. 

b. Clinical Studies

The BSCRC will carry out one or more clinical studies each year, with a mix of 
short-term and longer-term studies. These nature and content of these studies 
will be developed by the steering committee during the first year of funding.

So that NIDDK can better evaluate the potential range of studies that might 
be developed by the BSCRC, this application requires that each CC propose a 
research plan that includes two clinical research protocols as models that 
could be used in the Consortium environment. IT IS SUGGESTED THAT EACH 
PROTOCOL PROPOSAL BE APPROXIMATELY THREE PAGES IN LENGTH, INCLUDING TABLES OR 
FIGURES. The protocols must demonstrate knowledge of the fields of bariatric 
surgery and extreme obesity, and the research questions should reflect the 
unique opportunities provided by large and sustained weight losses due to 
surgical treatment.  Each clinical protocol must require sufficient subjects 
to necessitate the use of a Consortium with multicenter participation.  
Applicants must indicate 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) focusing on the pathophysiology of an obesity-related co-morbid 
condition or the impact of bariatric surgery on appetite, nutrient 
metabolism, and/or energy expenditure. The other protocol must propose a 
longer-term study (one to three years). All projects must be completed within 
the five-year duration of this research program.  CC and DCC applicants will 
not include a Data and Safety Monitoring Plan (DSMP) for these protocols 
within this application. The DSMP will be developed by the DCC, and approved 
by the Steering Committee and Data Safety Monitoring Board (DSMB) prior to 
the implementation of any clinical protocols.  The CCs must state a 
willingness to follow the Data and Safety Monitoring Plan that is developed 
and approved. 

THESE ARE EXAMPLES ONLY.  APPLICANTS SHOULD NOT FEEL LIMITED TO THE SUBJECTS 
MENTIONED BELOW AND ARE ENCOURAGED TO SUBMIT OTHER TOPICS PERTINENT TO THE 
OBJECTIVES OF THE RFA. It is anticipated that in the initial one or two years, 
trials and investigations will be selected (with modifications) from the 
studies proposed by the successful CCs in their applications, but 
investigators should not anticipate that the studies they propose as part of 
this application will necessarily be included, with or without modification, 
in the final research plan.

Short-term study (one year or less)

o Studies evaluating the short-term impact of bariatric surgery on an obesity-
related co-morbid condition, such as non-alcoholic steatohepatitis

o Studies investigating the impact of bariatric surgery on appetite, nutrient 
absorption, nutrient metabolism, or energy expenditure

o Studies investigating the effects of surgically-induced weight loss on beta 
cell function and insulin resistance

o Studies evaluating changes in neuroendocrine or gastrointestinal hormones 
with surgically induced weight loss

Longer-term study (one to three years)

o Studies investigating predictors of successful weight loss

o Studies investigating impact of surgery on obesity-related co-morbid 
conditions

o Studies investigating the impact of bariatric surgery on fitness, body 
composition, or long-term energy balance

o Studies evaluating predictors of risk or adverse outcomes following 
bariatric surgery 

o Studies of behavioral, psychosocial, and economic outcomes of bariatric 
surgery

As a part of each protocol proposal (within the 3 pages), please submit a 
SAMPLE PATIENT CARE BUDGET for the first year in which the protocol would be 
implemented.  A table must be included for each protocol showing estimated 
costs per patient for conducting the protocol. Investigators must only prepare 
budgets for their own CC to conduct the proposed study or trial, and not for 
the entire BSCRC.  The CC must state the total number of patients required by 
the entire Consortium to complete each proposed study or trial.  The sample 
budget for each CC must 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 must be included for each protocol. Budget requests for per-patient 
costs should be based on the two specific protocols proposed in the 
application and reflect anticipated costs for simultaneous implementation of 
these protocols in the first year.  Funding may not be requested for the 
purchase of expensive equipment.  

The budget for each clinical protocol must be developed on a cost per 
patient basis and include all direct and any applicable facilities and 
administrative costs. Therefore, a per capita cost for each of these studies 
proposed should be included in the budget proposal. Patient care costs for 
both protocols combined are limited to $100,000 (total costs) per year. 
Patient care costs should include costs of carrying out the proposed study at 
your institution, including any medications, imaging, clinical evaluations, 
and laboratory studies or tissue analyses that you do not propose to be 
centrally assessed (costs of laboratory or other sample analysis that are 
centrally assessed, as well as costs for shipment and storage of samples will 
be included in the DCC budget). ROUTINE (NON-RESEARCH RELATED) PATIENT CARE 
COSTS, SUCH AS ROUTINE LABORATORY AND IMAGING EVALUATIONS, MAY NOT BE INCLUDED 
IN THE BUDGET; NOR MAY THE COSTS RELATED TO THE SURGICAL PROCEDURE ITSELF 
(INCLUDING PREOPERATIVE, POSTOPERATIVE, AND FOLLOW-UP CARE) BE INCLUDED.  
APPLICATIONS INCLUDING SURGICAL OR ROUTINE PATIENT CARE COSTS IN THE SAMPLE 
BUDGET WILL BE RETURNED WITHOUT REVIEW. 

This is a sample budget only.  On the actual budget page, you should note 
patient care costs of $100,000 total costs per year for each of the five 
years, and need not provide budget details. Note that Core costs, as opposed 
to Patient Care costs, will be submitted as part of the regular budget on the 
budget page, with appropriate level of detail.  

ORGANIZATION OF THE BARIATRIC SURGERY CLINICAL RESEARCH CONSORTIUM 

The BSCRC will consist of the following components:  the NIH, four to six CCs, 
a DCC, a Steering Committee and its subcommittees, a Data and Safety 
Monitoring Board (DSMB), and other committees as needed.  The responsibilities 
of each component of the BSCRC are described in the Terms and Conditions of 
Award.

NIDDK.  The NIDDK will be responsible for organizing and providing support for 
the BSCRC and will be involved substantially with the awardees as a "partner", 
consistent with the Cooperative Agreement mechanism.  A designated NIDDK 
Project Scientist, who will also serve as Program Director, will monitor 
subject recruitment and study progress, ensure disclosure of conflicts of 
interest and adherence to NIDDK policies. The NIDDK Project Scientist, 
together with the NIDDK Grants Management Specialist, will be responsible for 
fiscal management of the network, including calculation of capitation budget 
rates and awards.  The NIDDK will appoint the Chairperson of the Steering 
Committee and all members of the DSMB.
	
Clinical Centers. 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 BSCRC (see Terms and Conditions of Award).

Data Coordinating Center (see Terms and Conditions of Award). 

Study Governance

Steering Committee. A Steering Committee will be the main governing body of 
the BSCRC (see Terms and Conditions of Award). 
An Executive Committee comprised of the Study Chair and Co-Chair, the 
Principal Investigator of the Coordinating Center, and the NIDDK Project 
Scientist also will be convened to effect management decisions required 
between Steering Committee meetings, as needed for efficient progress of the 
trial. 
For each investigational protocol, one CC or subcommittee will take the lead 
responsibility for drafting the protocol, with the assistance of the DCC, 
although the Steering Committee will provide input and will be responsible for 
assuring development of a common protocol to be implemented by the CCs.  The 
final decision of which common protocol(s) will first be implemented will be 
determined by a vote of the entire steering committee, and will be subject to 
additional review by the DSMB and NIDDK.

Other 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, and a Database Subcommittee would supplement the activities of 
the Steering Committee and propose the content and structure of the database.
 
Data Safety and Monitoring Board. 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 DSMB will submit recommendations to the NIDDK regarding 
the continuation of each study. The DSMB will be responsible for final 
approval of the Data Safety Monitoring Plan developed by the DCC. 

Each investigational 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 participating CCs must be willing to 
accept this funding arrangement for each new protocol conducted.
 
Clinical protocols must be approved by local institutional review boards, the 
Steering Committee, the BSCRC Data and Safety Monitoring Board, and the NIDDK 
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.  A database 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 is 
necessary.  The BSCRC 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 BSCRC.  Any specific collaboration 
involving the resources of the BSCRC will require approval by the Steering 
Committee.

MECHANISM OF SUPPORT
 
This RFA will use NIH cooperative agreement (UO1) award mechanism. The NIH 
UO1 is a cooperative agreement award mechanism in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award"    

This RFA is a one-time solicitation. The total project period for applications 
submitted in response to this RFA will be five years. 
 
The anticipated award date is September 30,2003 

This RFA uses just-in-time concepts. Modular budgets will not be used.  
Follow the instructions for non-modular research grant applications.

FUNDS AVAILABLE 
 
It is anticipated that between four and six awards for CCs and one award for a 
DCC will be made under this RFA. NIDDK intends to commit approximately 3 
million dollars in total costs to the Bariatric Surgery Research Consortium 
per year. Total costs include Direct Costs and Facility and Administrative 
Costs, also called indirect costs or overhead.  It is anticipated that the 
award for the DCC will be no more than $1.2 million total costs per year. The 
amount awarded to each CC per year may vary, but will be limited to no more 
than $300,000 total costs/CC/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 will also 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. AWARDS MADE TO A PARTICULAR CENTER UNDER THIS RFA WILL DEPEND IN PART 
ON THE PROTOCOLS CARRIED OUT BY THE BSCRC AND MAY BE MORE OR LESS THAN THE 
REQUESTED BUDGET. FUNDS WILL NOT BE AVAILABLE TO SUPPORT THE COSTS OF THE 
SURGERY ITSELF, PRE- OR POST OPERATIVE CARE, OR ROUTINE PATIENT CARE COSTS.

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 applications of outstanding scientific 
and technical merit.  Designated funding levels are subject to change at any 
time prior to final award, due to unforeseen budgetary, administrative, or 
scientific developments. 

ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic institutions only. This geographic constraint will be necessary 
because of the need for close communication among members of the program, the 
requirement for frequent steering committee meetings, and site visits for data 
verification.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   

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 surgery, internal medicine, nutrition, behavioral science, 
and clinical trials management.

A DCC will be a part of this BSCRC.  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 (i.e., confidentiality of the study-wide data) of each unit of the 
CC and DCC will be maintained. In addition, there should be no overlap in 
personnel between the CC and DCC.
 
SPECIAL REQUIREMENTS 
 
Only CCs that are currently conducting bariatric surgical procedures may 
apply.  To be eligible, a CC (including affiliated hospitals participating in 
the study) must have performed a minimum of 100 bariatric surgical procedures 
during 2002, and must have a minimum of two surgeons performing bariatric 
surgery who confirm willingness to collaborate with the Consortium.  Evidence 
of experience with laparoscopic bariatric surgery is also a requirement. 

The BSCRC will be a collaborative effort that will require frequent 
interactions of awardees among themselves and with the NIDDK. Applicants must 
explicitly indicate their willingness to:

o Participate in Steering Committee meetings (expected to occur approximately 
6 times during the first year and 3 times per year in subsequent years, in or 
near Bethesda, MD), site visits required by the NIDDK, and regular telephone 
conference calls,

o Cooperate with other awardees in the development and design of 
research protocols,

o Abide by common definitions; common methods for patient selection 
and enrollment; and common protocols, procedures, tests, and reporting 
forms as chosen by majority vote of the Steering Committee, 

o Actively seek to implement each consortium-wide protocol approved by 
the DSMB and the NIDDK,

o Comply with study policies and quality assurance measures approved 
by the Steering Committee,

o Agree to oversight of the study by a Data and Safety Monitoring 
Board (DSMB),

o Accept awards for the support of research based on per-patient 
(capitated) rates and the actual numbers of subjects enrolled, 
followed, and completing the study (Clinical Centers only),

o Transmit study data to the Data and Coordinating Center in a timely 
and accurate manner (Clinical Centers only),

o Report all adverse events in accordance with procedures established 
by the Steering Committee and NIDDK policies,

o Cooperate with other awardees in the publication of study results 
and the eventual release to the scientific community of study 
procedures and other resources, 

o Accept the Cooperative Agreement Terms and Conditions of Award given 
below.

Cooperative Agreement Terms and Conditions of Award

The cooperative agreement is an award instrument establishing an "assistance" 
relationship (in contrast to an "acquisition" relationship) between NIDDK and 
a recipient, in which substantial NIDDK scientific and/or programmatic 
involvement with the recipient is anticipated during performance of the 
activity.  The NIDDK purpose is to support and/or stimulate the recipient's 
activity by involvement in and facilitation of the activity in a "partner" 
role. The dominant role and prime responsibility for the planned activity 
reside with the awardees for the project as a whole, although specific tasks 
and activities in carrying out the activity will be shared among the awardees 
and NIDDK Project Scientist.  The terms and conditions below elaborate on 
these interactions and responsibilities, and the awardee agrees to these 
collaborative actions toward achieving the project objectives.  It is 
anticipated that these terms and conditions will enhance the relationships 
among the awardees and with the NIDDK Project Scientist, and will facilitate 
the successful conduct and completion of the study.  These agreements will be 
in addition to, and not in lieu of, the relevant NIH procedures for grants 
administration.  The terms will be as follows:

1) Awardees Rights and Responsibilities

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. Modifications will 
be approved by the Steering Committee and the Data and Safety Monitoring 
Board.

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. 

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 or 
contract with the Central Laboratory.  The DCC will also coordinate with the 
NIDDK Biosample Repository, if it is available and chosen by the NIDDK as the 
study repository. If the NIDDK Biosample Repository is not available or is not 
chosen as the sample repository by the NIDDK at the time the study is in the 
protocol development phase, the DCC will be required to maintain or contract 
with a repository for central storage and distribution of serum, tissue, and 
other samples.  In addition, the DCC will coordinate with the NIDDK Data 
Repository, if it is available, to prepare the data for eventual archiving and 
distribution. Thus, the awardee is expected to work cooperatively with 
Clinical Centers and sponsoring organizations 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 (including conference calls), the 
Data Coordinating Center will be expected to maintain close communications 
with the NIDDK Project Scientist, NIDDK Database Coordinator, and the 
Principal Investigators of the Clinical Centers.
 
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. 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.

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. Indeed, NIH policy requires that investigators make unique 
research resources readily available for research purposes to qualified 
individuals within the scientific community after publication [NIH Grants 
Policy Statement (http://grants.nih.gov/grants/policy/nihgps; Principles and 
Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining 
and Disseminating Biomedical Research Resources:  Final Notice, December 1999 
(http://www.ott.nih.gov/policy/rt_guide_final.html)].  It is expected that the 
specimens and data collected in projects funded by this RFA will eventually be 
made available to the broader scientific community, after the proprietary 
period.

This RFA has a special requirement that applicants acknowledge in a "Sharing 
Plan" in the proposal that they will share the specimens and data collected 
with the wider scientific community, through eventual transfer of these 
materials to the NIDDK Central Biosample and Data Repositories or through 
another mechanism determined by NIDDK.  A data sharing plan as approved, after 
negotiation with the applicant when necessary, will be a condition of the 
award.  Evaluation of the Non-competing Grant Progress Report (PHS 2590) will 
include assessment of the effectiveness of research resource release.

2) NIDDK Staff Responsibilities

The NIDDK will be responsible for organizing and providing support for the 
BSCRC and will be involved substantially with the awardees as a "partner", 
consistent with the Cooperative Agreement mechanism.  A designated NIDDK 
Project Scientist, who will also serve as Program Director, will monitor 
subject recruitment and study progress, ensure disclosure of conflicts of 
interest and adherence to NIDDK policies. The NIDDK Project Scientist, 
together with the NIDDK Grants Management Specialist, will be responsible for 
fiscal management of the network, including calculation of capitation budget 
rates and awards.  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.  
NIH staff will also participate in key subcommittees. The NIDDK will appoint 
the Chairperson of the Steering Committee and all members of the DSMB.
	
The NIDDK reserves the right to terminate or curtail the Consortium (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
Clinical Centers. 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 BSCRC. The Principal Investigator at each Clinical Center will 
have primary responsibility for study design and implementation, including 
subject recruitment and safety.  With the assistance of Co-Investigators as 
appropriate, the Principal Investigator will hire and supervise relevant 
personnel, obtain Institutional Review Board (IRB) approval for BSCRC 
protocols, oversee data collection and adherence to quality assurance 
measures, and prepare budgets and annual reports.  

Data Coordinating Center. The DCC will support protocol development, provide 
sample size calculations, statistical advice, questionnaires, and data 
analysis; support development, implementation, and maintenance of a database 
of clinical information, serum, and tissue samples; develop the data safety 
and monitoring plan, support manuscript preparation; and provide overall study 
coordination and quality assurance, including coordination of the activities 
and meetings (including conference calls) of the Data and Safety Monitoring 
Board, the Steering Committee and other standing committees. The DCC will 
prepare protocols for submission to the DSMB, and prepare confidential data 
analyses and reports for the DSMB. The DCC will be responsible for the 
preparation of the Data and Safety Monitoring Plan that will be submitted to 
the DSMB and the Steering Committee for their approval prior to the 
implementation of any study protocols.  The Data Coordinating Center will be 
responsible for acquiring and administering subcontracts for a central 
laboratory. Examples of the types of centralized laboratory functions that may 
be required include analyses such as blood lipid and lipoprotein subtypes, 
glycosylated hemoglobin, and insulin levels. Costs for shipping, processing, 
and analysis must be included in the DCC budget. 

Specimens, including serum, tissue, and possibly DNA, will be stored in a 
specimen repository. It is anticipated that the  Central NIDDK Biosample 
Repository will be used as a repository for the BSCRC, and the DCC will be 
required to coordinate with the NIDDK repository if it is selected by NIDDK as 
the study repository. Costs for shipment of specimens and specimen storage in 
a repository, whether or not it is the Central NIDDK Biosample Repository, 
must be included in the DCC budget. If the NIDDK Biosample Repository is not 
available or chosen as the sample repository by the NIDDK at the time the 
study is in the protocol development phase, the DCC will be required to 
maintain or contract with a different repository for central storage and 
distribution of serum, tissue, and other samples.  

No subcontract(s) will be awarded until the Steering Committee has met and 
approved their structure and duties.  The DCC must also propose how it would 
identify subcontractors for a central laboratory and a repository through a 
competitive process. 
 
The DCC will be subject to annual administrative review.

Steering Committee. A Steering Committee will be the main governing body of 
the BSCRC. 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 various study results.  It will also be responsible for 
establishing study policies in such areas as access to patient data, 
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 an appropriate scientific field who is 
not participating directly in the study.  Subcommittees may be established on 
topics such as database development, protocol development, publications and 
presentations, core measures, quality control, recruitment, and 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 Bethesda, MD area. 

The NIDDK Project Scientist (and other NIH 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.
Executive Committee. An Executive Committee comprised of the Study Chair and 
Co-Chair, the Principal Investigator of the Coordinating Center, and the 
NIDDK Project Scientist also will be convened to effect management decisions 
required between Steering Committee meetings, as needed for efficient 
progress of the trial. 
Data Safety and Monitoring Board. 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 DSMB will submit recommendations to the NIDDK regarding 
the continuation of each study. The DSMB will be responsible for final 
approval of the Data Safety Monitoring Plan developed by the DCC. 

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.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  A website on the NIDDK homepage 
containing information pertaining to this RFA is located at 
http://www.niddk.nih.gov/fund/crfo/faqsforbscrc.htm. Answers to frequently 
asked questions and other information updates concerning this RFA posted on 
the site as they are developed.  Applicants are strongly encouraged to visit 
this website on a regular basis in the course of preparing their 
applications.

Inquiries may fall into three areas:  scientific/research, peer review, and 
financial or grants management issues:

o Direct your questions about scientific/research issues that are not 
addressed by the website to:

Susan Z. Yanovski, M.D.
Director, Obesity and Eating Disorders Program
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 665, MSC 5450
Bethesda, MD  20892-5450
Telephone:  (301) 594-8882
FAX:  (301) 480-8300
Email: [email protected]

o Direct your questions about peer review issues that are not addressed by 
the website to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  [email protected]

o Direct your questions about financial or grants management matters that are 
not addressed by the website to:

Ms. Sharon Bourque
Grants Management Specialist
Division of Extramural Affairs
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 719, MSC 5456
Bethesda, MD  20892-5456
Telephone:  (301) 594-8846
FAX:  (301) 480-3504
Email:  [email protected] 
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone:  (301) 594-8885
FAX:  (301) 480-3505

SUBMITTING AN APPLICATION

A. Submission Instructions

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: [email protected].
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application must be 
sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  [email protected]

APPLICATION PROCESSING: Applications must be received by the application 
receipt date listed in the heading of this RFA.  If an application is received 
after that date, it will be returned to the applicant without review.
 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an Introduction addressing the previous critique.

B. Application Requirements

1. CC and DCC Applications
Applicants must describe plans to accommodate the stated program 
requirements, criteria, and staff involvement.  Applicants must address 
points discussed in the RESEARCH OBJECTIVES and SPECIAL REQUIREMENTS sections 
of this RFA.  In addition, applicants must address the following issues that 
are important to the successful development of a collaborative program:  
willingness to participate on the Steering Committee and appropriate 
subcommittees, to work cooperatively with other members of the Steering 
Committee, and to follow the common protocols established by the Steering 
Committee.

This RFA has a special requirement that applicants acknowledge in a "Sharing 
Plan" in the proposal that they will share the specimens and data collected 
with the wider scientific community, through eventual transfer of these 
materials to the NIDDK Central Biosample and Data Repositories or through 
another mechanism determined by NIDDK.  

The  application should follow the instructions in the PHS 398 application 
form http://grants.nih.gov/grants/funding/phs398/phs398.html. Applications for 
both the CC and the DCC may not exceed 25 pages for sections a-d, excluding 
appendices. This page limit includes protocol descriptions.

Clinical Center Applications

The applicant must submit two clinical research protocols as models that could 
be used in the Consortium environment, as described in the section entitled 
"Research Scope." 

For each of the two protocols include a description, in approximately three 
pages, of the rationale, research aims, outcome measures, and study design.  
In addition,(within the three pages) provide a description of the proposed 
patient populations with an estimate of the expected distribution of male and 
female patients, ages, racial and ethnic distribution, approximately and 
assurances of the applicant's access to the patient populations. The CC 
principal investigator must 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, appropriate objective measures of primary and secondary 
outcome must be indicated. Include, within the three pages, a sample patient 
care budget for the first year in which the protocol would be implemented, in 
tabular form, for the above protocols, as described under "Research Scope."  
This sample budget should show patient care costs ONLY for each protocol, on 
a capitated basis (See Research Scope).  Total patient care costs for both 
protocols combined must not exceed $100,000/year. 
 
Each CC must also provide a brief description of their suggestions for a 
database, including which data they believe should be acquired in the 
database, a discussion of the pros and cons of various non-surgical control 
groups, as well as discussion of the types of scientific questions such a 
database might answer.

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

o Qualifications and experience.  Applicants for CCs must demonstrate 
experience and expertise to conduct clinical studies in bariatric surgical 
patients. This must include documentation of experience in the pre-operative, 
operative, and post operative care of extremely obese patients undergoing 
bariatric surgical procedures, as well as on-going support and follow-up for 
post surgical patients. Include a short description of your procedures for 
short-term and long-term patient follow-up.  A minimum of 100 bariatric 
surgical procedures during 2002 at the applicant institution or its affiliated 
hospitals participating in the study is required. An institution (including 
its affiliated hospitals participating in the study) must have a minimum of 
two surgeons who perform bariatric surgical procedures and who confirm 
willingness to collaborate with the Consortium.  Evidence of experience with 
laparoscopic bariatric surgery is also a requirement. Experience with more 
than one type of bariatric surgical procedures (for example, gastric bypass, 
vertical banded gastroplasty, biliopancreatic diversion, laparoscopic banding, 
etc.), while not required, is encouraged.  

o Clinical Center population.  CCs must discuss the number of patients with 
extreme obesity who are potential candidates for bariatric surgery each year, 
the number evaluated, and the number undergoing the procedures, including age 
range, gender, and racial/ethnic distribution, as well as the recruitment 
source. Because of the lack of data on the safety of bariatric surgical 
procedures in pediatric populations, children and adolescents under age 18 
will not be included in this protocol; however, it is expected that patients 
between the ages of 18 and 21 would be studied, if they are appropriate 
surgical candidates.

o 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 must be included with the application.

o Willingness to participate in a BSCRC.  The principal investigator must 
state his/her general support of collaborative research and interaction with 
the NIDDK, the other CCs, and the DCC through the Consortium concept.  
Applicants must discuss their willingness, and that of the institutions 
involved, to accept 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 must discuss their capability to participate in a distributed data 
entry system.

o CC applicants will not include a Data Safety Monitoring Plan (DSMP) within 
this application. The DSMP will be developed by the DCC, and approved by the 
Steering Committee and DSMB prior to the implementation of any clinical 
protocols.  The CCs must state a willingness to follow the Data and Safety 
Monitoring Plan that is developed and approved.

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

o Each CC must provide a plan for which data they believe should be included 
in the database, including a discussion of the pros and cons of various non-
surgical control groups, and a discussion of the types of scientific questions 
such a database might answer.

Applications for a DCC:

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 
obese patients or surgical procedures is not required, but the applicant may 
wish to include a surgeon or obesity specialist in the application as a 
collaborator or advisor.

The DCC must propose a research plan that includes the structure of a large 
database and an information core that they believe should be collected on all 
participants that are prospectively enrolled, including potential and actual 
bariatric surgical patients and non-surgical control patients. 

o Study design and management. DCC proposals must 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 must also describe their familiarity 
with development of data safety and monitoring plan and administrative support 
of a Data and Safety Monitoring Board. 

o The applicant for the DCC must 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. 

o DCC applicants will not include a DSMP within this application. The Data 
and Safety Monitoring Plan will be developed by the DCC, and approved by the 
Steering Committee and DSMB prior to the implementation of any clinical 
protocols.  The DCC must state their willingness to develop the Data and 
Safety Monitoring Plan once clinical protocols are developed.

C. Budget and Related Issues

Applicants must complete the budget information as directed in the PHS 398 
5/01 rev) application form.  The applicants shall not submit budget 
information in modular format and cost projections must adequately correspond 
to the scope of research proposed. 

Applications for CCs: 

For each year, each CC must include the core budget costs (not to exceed 
$200,000 total costs) and patient care costs (not to exceed $100,000 total 

Core Budget

The underlying concept of the BSCRC 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 must 
submit requests for a CORE BUDGET not to exceed $200,000 total costs per year. 
Escalation of costs is allowed at 3%/year in future years, but must not exceed 
$200,000 in any year.

It is anticipated that this core budget will cover a maximum of 30% effort for 
the combined leadership (Principal Investigator and any Co-Investigators).  It 
should also include a Clinical Coordinator at 50% effort, Secretarial/Data 
Entry Support at 30% effort, and other necessary supplies and equipment. 
During the first year, the core budget should also include travel costs for 
two people to attend six BSCRC meetings in Bethesda, MD ($1500/person/meeting 
or $9000 per person, $18,000 total). In subsequent years, budget sufficient 
travel funds for two people to attend three BSCRC meetings in Bethesda, MD 
($1500/person/meeting or $4500 per person, $9000 total.

Patient Care Budget

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 BSCRC Steering Committee and will depend on availability 
of funds.  It is anticipated that after the first year, one or more protocols 
will be active each year.  CCs may request PATIENT CARE costs to be used on a 
per patient basis (capitation).  This amount must be placed in the patient 
care category.  Escalation is allowed at 3%/year in future years, but must not 
exceed $100,000 total costs in any year. Therefore, the maximum total costs 
for each CC to implement the protocols are $100,000 per year. Routine (non-
research related) patient care costs, such as routine laboratory and imaging 
evaluations, may not be included in the budget; nor may the costs related to 
the surgical procedure itself (including preoperative, postoperative, and 
follow-up care be included. 

Because actual patient care costs related to protocols will vary with the 
protocols developed by the Steering Committee, APPLICANTS SHOULD LIST $100,000 
TOTAL COSTS/YEAR IN THE BUDGET SECTION UNDER "PATIENT CARE COSTS" AND SHOULD 
NOT PROVIDE BUDGET DETAILS.  However, a proposed "sample budget" for patient 
care costs during the first year in which a protocol would be implemented 
should be included in the body of the application along with the protocol 
description (see Research Scope). 

o Note that ongoing annual budgets for protocols will be based on the 
protocols approved by the BSCRC 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. Patient care costs will 
be adjusted on a yearly basis based on the protocols developed and the number 
of patients entered by each center.

The BSCRC awards will be subject to administrative review annually.

DCC Budget:

Applicants for the DCC must prepare budgets for five 12-month periods (not to 
exceed $1.2 million 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 must include all costs associated 
with the organization of all administrative aspects of the BSCRC to be 
developed and with the initiation of one protocol to be developed and started.  
For subsequent years, applicants may assume that one or more protocols a year 
will be active, i.e. either in the protocol development, implementation, or 
analysis and writing phase. The DCC budget must include costs for 
administrative support of the Data and Safety Monitoring Board (including 
yearly face-to-face meetings and semi-annual telephone calls) and the cost of 
face-to-face steering committee meetings up to six times during the first year 
and three times/year in subsequent years in Bethesda, MD, exclusive of travel 
and per diem for CC investigators, as well as telephone conference calls of 
the executive committee and subcommittees. It should also include the costs of 
developing and maintaining, the bariatric surgery database.  

The DCC budget must also include the cost of shipping and analysis of serum 
and tissue specimens that are to be assessed by the Central Laboratory, as 
well as shipment and storage of serum, tissues, and other samples in a 
repository, which may be administered through a subcontract from the DCC or 
through the NIDDK Biosample Repository. The DCC should include in their 
budget, as examples, the costs involved in central analysis of a lipid profile 
(Total Cholesterol, HDL Cholesterol, and Triglycerides) as well as serum 
insulin and glycosylated hemoglobin.  While the actual award may vary, the DCC 
may estimate $300,000 total costs/year for consortium/contractual agreements 
with a central laboratory and/or sample and data repositories, including costs 
of shipping.

The DCC will be subject to administrative review annually. All protocols must 
be performed in a manner consistent with United States Food and Drug 
Administration guidelines.

APPLICATIONS NOT CONFORMING TO THESE GUIDELINES WILL BE CONSIDERED 
UNRESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT FURTHER REVIEW.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the (IC).  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 (IC) in accordance with the review criteria stated below.  As 
part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the National Diabetes and Digestive and 
Kidney Diseases Advisory Council. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The criteria of Significance, Approach, and Innovation will relate primarily 
to the two protocols submitted as a part of this application, as well as to 
the recommendations for information to be acquired in the database.  The 
protocol and database descriptions are being requested in order to allow 
reviewers to evaluate the scientific thinking of the investigators, and their 
likely ability to contribute to protocol and database development.  The 
actual protocols and database will be developed by the Steering Committee, 
after study funding. 
  
The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your 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.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider 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.

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, CC and DCC 
applications will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for humans, animals, 
or the environment, to the extent they may be adversely affected by the 
project proposed in the application. CC and DCC applicants will not include a 
DSMP, for these protocols within this application. The Data and Safety 
Monitoring Plan will be developed by the DCC, and approved by the Steering 
Committee and DSMB prior to the implementation of any clinical protocols.  
The CCs must state a willingness to follow the Data and Safety Monitoring 
Plan that is developed and approved.  The DCC must state their willingness to 
develop the Data and Safety Monitoring Plan once clinical protocols are 
developed.

o INCLUSION:  The adequacy of plans to include subjects from both genders, 
all racial and ethnic groups (and subgroups), and children as appropriate for 
the scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below)

o DATA SHARING:  The adequacy of the proposed plan to share data. A data 
sharing plan will be developed by the DCC, but all applicants (CC and DCC) 
must acknowledge in a "Sharing Plan" in the proposal that they will share the 
specimens and data collected with the wider scientific community through 
eventual transfer of these materials to the NIDDK Central Biosample and Data 
Repositories or through another mechanism determined by NIDDK.

o BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.  Note that the actual budget 
for each CC and the DCC will be determined when the protocols are developed 
after funding.  The Sample Patient Care Budget proposed in the protocols is 
an example only.

o OTHER REVIEW CRITERIA:  

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 BSCRC: 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.

DCC:

Considerations for the review of applications for the DCC for the BSCRC 
include the following issues:

o Understanding of the scientific, statistical, logistical, and technical 
issues underlying multi-center studies, including conduct of clinical studies 
in surgical patients, and knowledge necessary to assume 
to lead in the area of study design, statistics, logistics, data acquisition 
and management, identification of and coordination with central laboratories 
and serum/tissue/data repositories, 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 BSCRC activities.

o Plans for data sharing and access through coordination with NIDDK Biosample 
and Data Repository or another mechanism determined by NIDDK.

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 BSCRC.

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

o Facilities, equipment, and organizational structure to effectively 
coordinate the BSCRC activities in implementing the protocols, providing for 
specialized laboratory testing, and data collection. 

o Experience in developing a Data Safety and Monitoring Plan for multisite 
clinical trials. 

o Expertise in setting up and managing databases

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:     February 18, 2003
Application Receipt Date:          March 18, 2003
Peer Review Date:                  June/July 2003
Council Review:                    September, 2003
Earliest Anticipated Start Date:   September 30, 2003

AWARD CRITERIA

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

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

REFERENCE LIST

Gastrointestinal surgery for severe obesity: National Institutes of Health 
Consensus Development Conference Statement (1992). Am J Clin Nutr 55:615S-
619S.
NIDDK Working group on bariatric surgery: Executive Summary (2002).
American Society for Bariatric Surgery (2001). Rationale for the surgical 
treatment of morbid obesity. 
http://www.asbs.org/html/rationale/rationale.html [On-line]. 
Brolin, R. E. (2001). Gastric bypass. Surg Clin North Am 81:1077-1095.
Flegal, K. M., Carroll, M. D., Kuczmarski, R. J., & Johnson, C. L. (1998). 
Overweight and obesity in the United States: prevalence and trends, 1960-
1994. Int J Obes Relat Metab Disord 22:39-47.
Harris, M. I., Flegal, K. M., Cowie, C. C., Eberhardt, M. S., Goldstein, D. 
E., Little, R. R., Wiedmeyer, H. M., & Byrd-Holt, D. D. (1998). Prevalence of 
diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. 
adults. The Third National Health and Nutrition Examination Survey, 1988-1994 
[see comments]. Diabetes Care 21:518-524.
Knowler, W. C., Barrett-Connor, E., Fowler, S. E., Hamman, R. F., Lachin, J. 
M., Walker, E. A., & Nathan, D. M. (2002). Reduction in the incidence of type 
2 diabetes with lifestyle intervention or metformin. NEJM 346:393-403.
Kral, J. G., Brolin, R. E., Buchwald, H., Pories, W. J., Sarr, M. G., 
Sugerman, H. J., & Wolfe, B. M. (2002). Research considerations in obesity 
surgery. Obes Res 10:63-64.
Pories, W. J., Swanson, M. S., MacDonald, K. G., Long, S. B., Morris, P. G., 
Brown, B. M., Barakat, H. A., deRamon, R. A., Israel, G., & Dolezal, J. M. 
(1995). Who would have thought it? An operation proves to be the most 
effective therapy for adult-onset diabetes mellitus. Ann Surg 222:339-350.
Sjostrom, C. D., Peltonen, M., Wedel, H., & Sjostrom, L. (2000). 
Differentiated long-term effects of intentional weight loss on diabetes and 
hypertension. Hypertension 36:20-25.
U.S. Department of Health and Human Services. The Surgeon General's call to 
action to prevent and decrease overweight and obesity.  2001. Rockville, MD, 
U.S. GPO, Washington, DC. Ref Type: Pamphlet
Wadden, T. A. & Foster, G. D. (2000). Behavioral treatment of obesity. Med 
Clin North Am 84(vii):441-61.

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: 
Research components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous data 
management, quality assurance, and auditing procedures.  In addition, it is 
NIH policy that all clinical trials require data and safety monitoring, with 
the method and degree of monitoring being commensurate with the risks (NIH 
Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, 
June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are 
available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm 
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998. Because of the lack of data on the 
safety of bariatric surgical procedures in pediatric populations, children 
and adolescents under age 18 will not be included in studies carried out by 
the BSCRC; however, it is expected that patients between the ages of 18 and 
21 would be studied, if they are appropriate surgical candidates.  

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy 
requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at 
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 must 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

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

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 
2010," a PHS-led national activity for setting priority areas. This RFA is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.848,and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284)and 
administered under NIH grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm  and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92 

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



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