RFP No. NHLBI HC-98-10 Subclinical Cardiovascular Disease Study,
  Ultrasonography Reading Center
  
  This RFP consists of three Sections:
  
  I. Streamlined Technical RFP
  II.     Specific RFP Instructions and Provisions
  III.    Applicable RFP REFERENCES
  
  ******************************************************************
  I. Streamlined Technical RFP
  
  A. Solicitation Form/Cover Letter
  
  Purchase Authority: 95-83, as amended
  
  RFP No. NHLBI HC-98-10
  
  Title:  Subclinical Cardiovascular Disease Study:
          Ultrasonography Reading Center
  
  Issued by:   Cheryl A. Jennings
               Contracting Officer
               NIH/NHLBI
               Contracts Operations Branch
               Rockledge Building, MSC 7902
               6701 Rockledge Drive
               Bethesda, MD 20892-7902
  
  DATE ISSUED: November 4, 1997
  
  DATE PROPOSAL DUE: January 28, 1998, 4:30 P.M. (EST)
  
  SMALL BUSINESS SET-ASIDE: X NO     YES     SIC Code: 8733
  
  Ladies and Gentlemen:
  
  This Streamlined Technical RFP consists of this combined
  solicitation form and cover letter, and four additional components,
  as follows:  
  
     B.   Work Statement with Project Background;
     C.   Reports/Deliverables;
     D.   Special Requirements; and
     E.   Evaluation Factors for Award, including Technical 
          Evaluation Criteria.
  
  These components contain the technical information required for the
  submission of a proposal for this acquisition.  
  
  In addition, there are two other sections to this specific RFP.  The
  section entitled "Specific RFP Instructions and Provisions"
  contains, for example, the address for delivery of your proposal, as
  well as other provisions that provide specific information for this
  RFP.  The section entitled "Applicable RFP REFERENCES" identifies
  those items resident on the Gopher directory that are applicable to
  this RFP.  
  
  Although these documents contain sufficient information for you or
  your organization to submit a proposal, if you intend to submit a
  proposal in response to this RFP, IT IS ESSENTIAL THAT YOU
  IMMEDIATELY NOTIFY Cheryl A. Jennings OF THE NHLBI CONTRACTING
  OFFICE AT THE FOLLOWING INTERNET ADDRESS: cj19f@nih.gov
  
  IF YOU DO NOT NOTIFY THE CONTRACTING OFFICE OF YOUR INTENT, YOU WILL
  NOT RECEIVE NOTICE OF AMENDMENTS TO THE RFP.  HOWEVER, ALL
  AMENDMENTS WILL BE POSTED ON THE NIH GOPHER.
  
  The original and thirty (30) copies of your technical proposal and
  the original and six (6) copies of your business proposal must be
  received by the Contracting Officer no later than January 28, 1998,
  at 4:30 p.m. local time (EST) at the address listed in the item
  entitled "Packaging and Delivery of Proposals" in the file entitled
  "Specific RFP Instructions and Provisions" found under the directory
  for this RFP.  Also, refer to that file for the item entitled
  "Proposal Intent Response Sheet."  Please complete this form and
  deliver it to the address indicated therein on or before December 5,
  1997.  This will allow us to expedite preparations for the peer
  review of proposals.  
  
  You are reminded that the "Technical Proposal Cover Sheet" must be
  completed in full detail and used as the cover sheet for each copy
  of your technical proposal (a copy of this form is contained in this
  NIH Gopher under the FORMS, FORMATS, AND ATTACHMENTS subdirectory
  found in C. RFP REFERENCES.)  This information will be used to
  ensure that there will be no conflict of interest when selecting
  review committee members.  Also, your proposal must be organized and
  submitted in accordance with the "Technical Proposal Table of
  Contents" found in Section II, Paragraph I.of this RFP.
  
  NOTE; IF YOUR PROPOSAL IS NOT RECEIVED BY THE CONTRACTING OFFICER OR
  DESIGNEE AT THE PLACE AND TIME SPECIFIED, THEN IT WILL BE CONSIDERED
  LATE.  THE PHSAR CLAUSE 352.215-10, "LATE PROPOSALS, MODIFICATIONS
  OF PROPOSALS, AND WITHDRAWALS OF PROPOSALS," is incorporated into
  this RFP.  
  
  If you have any additional questions regarding this RFP, please
  contact Cheryl A. Jennings through the Internet using the electronic
  mail address listed above or telephone 301-435-0345 or facsimile
  301-480-3430.  COLLECT CALLS WILL NOT BE ACCEPTED.
  
  Sincerely,
  
  /s/
  
  Cheryl A. Jennings
  Contracting Officer
  
  ******************************************************************
  I. Streamlined Technical RFP
  ==================================================================
  
  WORK STATEMENT WITH PROJECT BACKGROUND
  
  PROJECT BACKGROUND
  
  1. A general description of the required objectives and desired
       results
  
  The Field Studies and Clinical Epidemiology Scientific Research
  Group, Epidemiology and Biometry Program, Division of Epidemiology
  and Clinical Applications, NHLBI proposes to initiate a prospective
  observational study of the characteristics of subclinical
  cardiovascular disease (disease detected non-invasively before it
  has produced signs and symptoms) that predict progression to
  clinically overt cardiovascular disease in a diverse and
  representative population-based sample of men and women aged 35-84. 
  The specific objectives of the study are:
  
     a.   To determine characteristics related to progression of
            subclinical to clinical cardiovascular disease;
  
     b.   To identify factors related to newer measures of
            subclinical disease and examine relationship of new to
            established measures; and
  
     c.   To develop population-based methods, suitable for
            application in future screening and intervention studies,
            for identifying asymptomatic persons at highest risk of
            clinical events. 
  
  2. Background information helpful to a clear understanding of the
       requirements and how they evolved
  
  To further the study of the relationship between risk factors and
  atherosclerosis and to avoid the biases involved in relying solely
  on clinical disease outcomes, objective and unbiased measures of
  cardiovascular disease (CVD) have been introduced in NHLBI-initiated
  epidemiologic studies of CVD etiology.  Two well-developed examples
  include echocardiography and carotid ultrasound.  The observation
  that risk of subsequent cardiovascular events and mortality
  increased 1.5 to 2-fold per 50 gm/m of echocardiographically-defined
  left ventricular mass in Framingham led to inclusion of
  echocardiographic LV mass assessment in several population samples. 
  Development and validation of duplex ultrasound imaging as a measure
  of atherosclerosis provided for the first time a method for
  visualizing the atherosclerotic process at the level of the vessel
  wall and suitable for application in population-based studies.
    
  Use of carotid ultrasound in the Atherosclerosis Risk in Communities
  (ARIC) Study has demonstrated strong relationships of carotid wall
  thicknesses to clinical CVD and to traditional CVD risk factors such
  as age, sex, lipids, hypertension, smoking, diabetes, obesity and
  dietary fat.  Using the powerful nested case-control design, in
  which atherosclerosis cases and non-atherosclerotic controls are
  selected from the entire population distribution of wall thickness,
  ARIC has also demonstrated strong associations of carotid
  atherosclerosis with Lp(a) and Lp(a) phenotypes, antibodies to
  infectious agents, fibrinolytic factors and inflammatory factors,
  cellular adhesion molecules, homocysteine levels, and dietary
  magnesium and antioxidants.  
  
  Carotid ultrasound and echocardiography were also included in the
  Cardiovascular Health Study (CHS) and were quickly demonstrated to
  bear strong relationships with overt CVD in this older population
  sample, to be associated with many conventional CVD risk factors,
  and to be strong predictors of subsequent overt cardiovascular
  events.  More importantly, short-term risk of clinical events was
  shown to be low to non-existent in the absence of subclinical
  disease.
  
  Subclinical disease measures have thus enhanced studies of CVD risk
  by examining the early stages of CVD in an objective manner free of
  biases related to severity, diagnostic suspicion, or completeness of
  medical investigation.  Because subclinical disease is asymptomatic
  and previously unknown to participants, it is unlikely to have any
  direct impact on health behavior, such as lifestyle modification or
  medication use, which may limit the detection of risk relationships
  with clinical disease.  In addition, the continuous nature of most
  subclinical measures greatly increases power to detect risk
  associations compared to discrete measures, such as presence or
  absence of clinical events.  Most importantly, subclinical measures
  now permit the epidemiologic investigation of CVD risk to focus on
  the biology of CVD rather than on vagaries in its diagnosis.  
  Application of non-invasive measures in ongoing prospective,
  population-based studies has demonstrated a surprisingly high
  prevalence of subclinical disease.  Atherosclerotic plaque is
  extremely common in the extracranial carotid arteries of U.S. men
  and women older than 45 years and can be detected in subjects at low
  risk as defined by traditional risk factors.  Coronary calcium, a
  specific marker for coronary atherosclerosis, is present in 10% of
  women and 30% of men aged 30-39 and increases in prevalence with
  age.  One-sixth of men and nearly one-fifth of women in Framingham
  have echocardiographically defined left ventricular hypertrophy, and
  over 30% of persons over age 65 in CHS have MRI-defined cerebral
  infarcts.  
  
  Standardized measures of retinal arteriovenous nicking, which are
  strongly associated with hypertension and cerebral infarction, are
  present in 14% of middle-aged ARIC participants.  Quantitative
  retinal arteriolar narrowing increases across the entire range of
  blood pressure, even in persons receiving effective antihypertensive
  therapy, and may provide an integrated measure of duration and
  severity of hypertension.  
  
  Risk associated with subclinical disease measures has been shown to
  be graded and continuous (similar to risk associated with
  conventional CVD risk factors such as hypertension and cholesterol)
  rather than demonstrating a threshold level at which risk increases
  sharply.  This suggests that interventions yielding even modest
  reductions in levels of subclinical disease should be explored for
  their potential impact on reducing CVD risk.  To design such
  interventions, factors contributing to the development and
  progression of subclinical disease must be identified.  
  
  The recognition that plaque rupture is a key event in coronary
  thrombosis and that plaques that rupture tend to be subcritical
  stenoses associated with lipid-laden lesions has shifted the focus
  of etiologic research to factors leading to formation and rupture of
  unstable plaque, such as inflammation and impaired endothelial
  function.  Inflammatory and infectious factors have long been known
  to be associated with CVD in epidemiologic studies and recognition
  of the importance of plaque rupture provides a plausible mechanism
  for this relationship.  Continued research on inflammation and CVD
  risk in populations thus provides a promising avenue for elucidating
  mechanisms of plaque rupture.  It also exemplifies the cyclical and
  complementary nature of risk factor identification in population and
  experimental studies, progressing from clinical events at the
  population level to the tissue and cellular level experimentally,
  and back to the tissue and population level in studies of
  subclinical disease.
  
  Results of the proposed study will be applicable to clinical
  practice by identifying subclinical disease measures that best
  predict risk and by suggesting new interventions for preventing
  progression of subclinical to clinical disease.  This information
  can be used to target subgroups who should undergo aggressive risk
  factor modification or other treatment.  Some findings may be
  directly applicable to clinical practice, others may be used to
  design clinical trials or optimize interventions, and still others
  may lead to research resulting in new methods of intervention.
  
  Having demonstrated that subclinical disease measures are powerful
  discriminators of persons at high risk, three key research questions
  emerge with both etiologic and potential therapeutic implications: 
  
  1) How does subclinical disease progress to clinical disease? 
  
  Although short-term risk of clinical events appears to be extremely
  low in the absence of subclinical disease, clinical events occur
  within 2.5 years in less than 10% of persons over age 65 with clear
  evidence of subclinical disease defined by a variety of techniques. 
  Progression of subclinical disease to clinical events thus does not
  appear to be inevitable, and a critical unanswered question related
  to subclinical disease is the identification of factors promoting or
  retarding this progression.  
  
  2) What are the correlates of newer measures of subclinical disease,
  and how are newer measures related to existing measures in
  population-based samples? 
  
  A variety of techniques for assessing subclinical disease have been
  introduced in the past several years and further refinements are
  under active development.  Newer techniques permit imaging of the
  coronary bed and of lesion characteristics potentially indicative of
  high-risk plaque, allowing plaque biology to be studied in vivo on a
  population basis.  Examination of correlates of these newer
  measures, such as inflammatory, hemostatic and genetic markers, is
  essential to understanding their etiology, their relationship to
  existing subclinical disease measures, and their progression to
  clinical events.
  
  3) What is the most parsimonious combination of subclinical disease
  measures that reliably identifies high risk persons for targeted
  interventions? 
  
  Current risk stratification algorithms identify persons with a high
  relative risk of disease, many of whom will never develop clinical
  events.  Existing subclinical measures similarly identify many who
  do not develop events in the short term, and refinement of these
  measures is needed to provide effective targeting of interventions. 
  Inclusion and comparison of multiple measures of subclinical disease
  will permit development of a hierarchy of measures allowing cost-effective screening and risk stratification of individuals.  
  
  Recent developments in measurement of cardiovascular structure and
  function make the imaging of subclinical disease and measuring
  functional aspects of the vasculature in population-based studies
  feasible and accurate, providing specific, detailed information that
  relates more directly to pathology.  Improved gray-scale ultrasound
  imaging of the carotid arteries and aorta, for example, can identify
  plaque characteristics related to rupture and thrombosis (such as
  echolucency and heterogeneity) associated with a 4-6-fold increased
  risk of acute myocardial infarction. Coronary calcium quantified by
  electron-beam computed tomography (EBCT) has correlations of >0.90
  or greater with histological coronary plaque area, identifies
  persons with 5- to 20-fold increased risk for CHD events, and is
  thus the best available noninvasive technique for quantifying
  subclinical coronary atherosclerosis.  Vascular stiffness and
  endothelial function are additional new noninvasive measures of
  early functional changes in the vasculature with strong
  relationships to existing disease, risk factor exposure, and
  effective treatment.  
  
  This study will include a substantial proportion of previously
  understudied minority groups whose prevalence of risk factors and
  increased CHD risk related to specific risk factors has been shown
  or hypothesized to differ from that of the majority population.  The
  prevalence of coronary heart disease differs among racial and ethnic
  groups in the United States of America.  African Americans,
  composing approximately 12% of the U.S. population, tend to have
  higher CHD rates than whites, particularly among women.  Prevalence
  of coronary calcification has been suggested to differ in blacks and
  whites, though population-based data are relatively sparse and
  clinical data are inconsistent.  Hispanic populations, composing
  about 8% of the U.S. population, tend to have lower rates of
  clinical disease despite high risk factor levels, although data are
  not consistent in this regard.  Pacific Islanders/Asians
  (particularly Chinese- and Japanese-Americans and immigrants from
  southeast Asia), composing about 3% of the U.S. population, have
  lower morbidity and mortality rates than whites.  This group,
  particularly Pacific Asian women, has not been well-represented in
  population-based studies to date.  Study of relatively low risk
  populations, especially those with comparable levels of subclinical
  disease, may provide clues to prevention of disease in other ethnic
  groups.
  
  In addition, levels of risk factors for cardiovascular disease
  differ among racial or ethnic groups.  While it is clear that
  smoking, diabetes, hypertension, obesity, hyperlipidemia, low
  socioeconomic status and psychosocial stress are detrimental in all
  groups, the distributions of several risk factors and their
  associations with disease differ among groups.  Notable examples of
  differences in distributions include higher blood pressure and rates
  of hypertension in blacks, higher levels of HDL-cholesterol in black
  men, higher levels of Lp(a) in blacks, and higher rates of obesity
  and diabetes in Hispanics and blacks compared to whites.  
  
  Although data on subclinical disease in minorities are much more
  limited, initial ARIC and CHS data suggest greater carotid
  atherosclerosis in blacks than whites; limited data in Hispanics
  suggest slightly less carotid atherosclerosis than whites.  Data in
  American Pacific Islanders/Asians are virtually nonexistent.  The
  marked disparity in end-organ disease among black hypertensives,
  which remains unexplained by differing levels of blood pressure or
  treatment, suggests that subclinical disease indicators may be
  useful in distinguishing racial/ethnic variations related to
  vascular and end-organ biology from those due primarily to
  psychosocial and cultural differences. 
  
  While some of these differences may be biological, evidence of true
  biological differences in disease pathogenesis among racial/ethnic
  groups has been relatively slim.  Differences in environmental,
  behavioral and psychosocial conditions may be at least as important
  in disease development and progression, but have been inadequately
  examined in relationship to subclinical disease and its progression
  to clinical events.  Substantial differences in use of invasive
  procedures, which have consistently been shown to be less frequently
  utilized in minority than majority populations, have not been
  explored in relationship to objective subclinical disease measures
  rather than subjectively measured symptoms or signs.  For these
  reasons, adequate racial/ethnic diversity in studies of subclinical
  disease is essential.
  
  WORK STATEMENT:
  
  INTRODUCTION
  
  The Subclinical Cardiovascular Disease Study is a study of the
  characteristics of subclinical cardiovascular disease (disease
  detected non-invasively before it has produced clinical signs and
  symptoms) that predict progression to clinically overt -
  cardiovascular disease in a diverse and representative population-based sample of men and women aged 35-84.  Eighteen thousand
  participants will be recruited from the Field Centers and screened
  for evidence of subclinical coronary atherosclerosis, using
  electron-beam computed tomography (EBCT) or another noninvasive
  measure of subclinical disease, and for coronary risk factors.  To
  allow for the expected continued rapid evolution of subclinical
  disease measures in the next few years, the choice of the most
  appropriate screening measure will be made during final protocol
  development in collaboration with study investigators.  A
  combination of measures, potentially involving multiple arterial
  beds, and biochemical tests may be utilized or a single method may
  be most appropriate.  One such measure at present appears to be
  coronary calcium scores by EBCT, but an alternative method or
  combination of methods may be proposed.  The proposed alternate
  method or combination of methods must be demonstrated to accurately
  predict coronary events or be correlated with angiographic or
  pathologic evidence of coronary artery disease, be reproducible, and
  be noninvasive and otherwise feasible for use in a multicenter
  population-based study.  The final protocol will be reviewed and
  approved by an outside advisory panel of diverse expertise,
  including special expertise on imaging methodology and subclinical
  disease.  
  
  A sample of those at highest risk for coronary heart disease events,
  within defined age-, sex- and ethnicity-strata and an age-, sex-,
  ethnicity-, center-matched sample of participants representing the
  normal spectrum of subclinical coronary disease will be reexamined
  in more depth approximately six months later for other evidence of
  subclinical disease and for characterization of possible precursors
  of disease events.  Because the study will provide examination
  results to participants and their physicians, there is expected to
  be a significant amount of clinical intervention in individuals,
  depending on the severity of the disease, the acceptance of the test
  results by the medical community, and the aggressiveness of the
  individual treating physicians.  The study will collect information
  on the nature and magnitude of such interventions to control for
  them in analyses.  Approximately 15% of the highest risk
  participants will be selected for this comprehensive examination and
  follow-up.  Assuming that a large proportion of these high risk
  participants will be referred for an intervention that substantially
  modifies their risk, the effective sample size after accounting for
  the intervention effect is assumed to be 10%, rather than 15%.  All
  participants will be followed for identification and
  characterization of cardiovascular disease events, including acute
  myocardial infarction and other forms of coronary heart disease,
  stroke, and congestive heart failure; mortality; and for any
  cardiovascular disease interventions received. 
  
  A timeline for the study is provided in Table 1 and Figure 1..  A
  list of exam components is in Table 2.  
  
  The study will involve six to eight Field Centers, a Coordinating
  Center (which will subcontract for a Central Lipid Laboratory), a
  Special Laboratory Center; and separate Reading Centers for 
  Ultrasonography, Magnetic Resonance Imaging, and Electron Beam
  Computed Tomography (EBCT).  Principal Investigators from each of
  these 11-13 sites plus the NHLBI Project Officer form the study
  Steering Committee.
  
  Eighteen thousand men and women aged 35 to 84 will be recruited for
  an initial examination in this prospective study.  The broad age
  range will permit analysis of important interactions between age and
  risk factor-subclinical disease relationships and between age and
  subclinical disease-event relationships.  The large total number is
  necessary to ensure the accrual of a sufficient number of coronary
  heart disease events over a 5-6 year morbidity and mortality follow-up period.  Initial recruitment will be population-based with the
  goal of enrolling approximately 50% minority participants, including
  roughly equal numbers of non-Hispanic blacks, Hispanics, and Pacific
  Islanders/Asians.  
  
  There will be an initial 18-month protocol planning, OMB clearance,
  training,  and pilot testing period.  This will be followed by a
  two-year screening examination for all participants to identify the
  highest risk groups in age-race/ethnicity-gender-specific strata.  A
  subsample of participants at the highest end of the subclinical
  disease distribution for their age, race/ethnicity and gender group
  and a random sample from the remainder of the distribution will
  undergo a comprehensive examination within 6 months of screening. 
  The comprehensive examination will include more detailed measures of
  large and small vessel disease as described below.  The numbers of
  participants in these subsamples will be determined during protocol
  development, based on the estimated power to conduct analyses of
  risk factors for subclinical disease progression and development of
  clinical events and for comparing the high risk subsample and random
  sample to identify relationships between risk factors and
  subclinical disease.  For purposes of power and sample size
  estimation, each subgroup was assumed to be 10% of the total cohort,
  with oversampling of the high-risk group to compensate for medical
  and surgical intervention, as stated above.  The remaining
  participants (those not in either subsample) will not be
  periodically re-examined as is typically done in traditional
  epidemiologic studies; rather, they will be contacted annually for
  ascertainment of morbidity and mortality only.
  
  For the high risk and random sample subgroups, follow-up
  examinations at periodic intervals (e.g., 6-12 months) will focus on
  biochemical and other factors more proximally associated with
  events.  Smaller subsets of particular interest may be selected to
  undergo more frequent follow-up or specialized examinations
  particularly for subclinical disease.  The timing and composition of
  repeat subclinical disease measures will depend on the temporal
  nature of the measurement in its relation to clinical outcomes,
  demonstrated reliability of the measurement techniques in this
  population, the relationships found among measures, and the specific
  measures found most likely to progress to clinically overt events. 
  The subsamples will also be followed for morbidity and mortality for
  a 5-6 year period, to allow accrual of a sufficient number of fatal
  and nonfatal events for completion of study objectives 1 and 3
  (related to risk of clinical events).  The original cohort of 18,000
  will also be followed for events, to allow relationships between
  screening variables and events to be analyzed.  Completion of
  morbidity and mortality follow-up for the study will be followed by
  a period of final data analysis and study close-out, although
  initial data analysis is expected to begin using data from the
  baseline screening examination.  The total contract period is 10
  years.  
  
  Table 1. Timeline for Subclinical Disease Study 
  
  Activity                         Time period                           
  Protocol development           September 1,1998--August 31,1999                                                          (12 months)
  
  OMB clearance                    March 1,1999--August 31,1999
                                 (6 months)
  
  Protocol review                  September 1,1999--February 29, 2000
  (September 1999)
  Training                         (6 months)
  Pilot testing
  
  
  Baseline screening examination   March 1,2000--February 28, 2002                                                              (24 months)
  
  Comprehensive examination of   September 1,2000--August
  31,2002high risk subgroup and random  (24 months)       
  sample     
  
  Follow-up of high risk subgroup  March 1,2001--February 28, 2007  
  and random sample for changes  (72 months)
  in subclinical disease and 
  measurement of possible clinical 
  disease precursors
  
  Follow-up of original cohort     March 1,2000--February 28, 2007
  and subgroups for morbidity    (84 months)
  and mortality
                              
  Close-out                        March 1,2007--August 31, 2008    
                                 (12 months)
  
  Note: Some activity periods overlap.  Follow-up periods for
  morbidity and mortality and for repeat examinations for individual
  study participants are, on average, shorter than the total periods
  specified.  For planning purposes, follow-up examinations are of
  three types: Approximately every 6 months, phlebotomy; approximately
  every 12 months, endothelial function and vascular stiffness; repeat
  EBCT (once, beginning in Year 5); repeat ultrasound (once, beginning
  in Year 6); repeat retinal photography (once, beginning in Year 6);
  and repeat MRI (once, beginning in Year 7).    
  
  *Study Years are designated as follows: 
  
   Year 1, September 1, 1998 - August 31, 1999
   Year 2, September 1, 1999 - August 31, 2000
   Year 3, September 1, 2000 - August 31, 2001
   Year 4, September 1, 2001 - August 31, 2002
   Year 5, September 1, 2002 - August 31, 2003
   Year 6, September 1, 2003 - August 31, 2004
   Year 7, September 1, 2004 - August 31, 2005
   Year 8, September 1, 2005 - August 31, 2006
   Year 9, September 1, 2006 - August 31, 2007
   Year 10, September 1, 2007 - August 31, 2008
  
  
  Figure 1. Timeline for the Subclinical Cardiovascular Disease Study
  
  Year |  1  |  2  |  3  |  4  |  5  |  6  |  7  |  8  |  9  | 10  |
  
  Month 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/ 3/ 9/
  Year  98 99 99 00 00 01 01 02 02 03 03 04 04 05 05 06 06 07 07 08 08
         |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |
         .     .     .     .     .     .     .     .     .     .     .
  Develop.     .     .     .     .     .     .     .     .     .     .
  proto-
  col    |-----|     .     .     .     .     .     .     .     .     .
         .     .     .     .     .     .     .     .     .     .
  OMB 
  clearance |--|     .     .     .     .     .     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Revise 
  protocol     .     .     .     .     .     .     .     .     .     .
  pilot/
  training     |--|  .     .     .     .     .     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  MRI 
  protocol     
  pilot/
  training     .  |--|     .     .     .     .     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Screening      
  examination  .  |-----------|  .     .     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Comprehensive   
  examination  .     |-----------|     .     .     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Follow up    
   phlebotomy  .     .  |--|--|--|--|--|--|--|--|--|--|--|--|  .     .
               .     .     .     .     .     .     .     .     .     .
  Follow up    
  examination  .     .     |-----|-----|-----|-----|-----|--|  .     .
               .     .     .     .     .     .     .     .     .     .
  Follow up 
  EBCT         .     .     .     .     |-----|     .     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Follow up US .     .     .     .     .     |-----|     .     .     .
               .     .     .     .     .     .     .     .     .     .
  Follow up MRI.     .     .     .     .     .     |-----|     .     .
               .     .     .     .     .     .     .     .     .     .
  Morbidity/   
  mortality 
  follow up    .     |-----------------------------------------------|
               .     .     .     .     .     .     .     .     .     .
  Analysis/    
  publication  .     .     .  |--------------------------------------|
               .     .     .     .     .     .     .     .     .     .
  Close-out    .     .     .     .     .     .     .     .  |--------|
  
  
  
  Table 2.  Examination Components
  
  Data to be collected is approximated by the following list of
  components, which may be modified during protocol development, for
  the approximate following number of participants:
  
  a. Baseline screening examination (N=approximately 18,000):
  
   I.   Demographic information (age, sex, race, ethnicity,
          education) [Note: This information should also be obtained
          on people who decline participation (non-participants), as
          feasible.]
   ii.  Anthropometry (height and weight), blood pressure, and
          smoking history
   iii. Medical history [Note: Selected medical history information
          should also be obtained on non-participants, as feasible.]
   iv.  Electrocardiogram
   v.   Fasting whole blood, serum, plasma, and special blood and
          tissue collection (e.g., DNA)
   vi.  Electron beam computed tomography (EBCT) results, and/or
          results of screening for high risk, as specified in the
          protocol
  
  b. Comprehensive examination and periodic follow-up examinations
       (N=approximately 2,700 high risk and 1,800 random sample
       subgroups):
  
   I.   Repetition of selected screening examination components
   ii.  Enhanced grey-scale and Doppler ultrasound of  artery
   iii. Measures of arterial compliance (stiffness)
   iv.  Measurement of endothelial function
   v.   MRI measures of cardiac and vascular morphology and function
   vi.  Retinal photographs producing measures of vascular and other
          morphological characteristics of retinal anatomy
   vii. Resting and exercise-induced ankle-arm blood pressure index
   viii.Newly identified risk factors for cardiovascular disease
     including but not
     necessarily limited to measures of lipoprotein and fatty acid
       metabolism, homocysteine, thrombosis/hemostasis, antioxidation
       biochemical moieties, infectious agents, markers of immune and
       inflammatory response, and biochemical markers of endothelial
       function
   ix.  Indicators of blood viscosity
   x.   Genetic material
  
  [Note: For planning purposes, use the following schedule for follow-up examinations in both the high risk and random sample subgroups:
  
   (1)  Approximately every 6 months (March 1, 2002 - February 28,
          2007) phlebotomy to remeasure hemostatic and thrombotic
          factors, indicators of inflammation, and other factors that
          may enhance prediction of clinical events;
   (2)  Approximately annually (March 1, 2002 - February 28, 2007)
          measurement of endothelial function and vascular stiffness;
          and
   (3)  In order to measure progression of subclinical disease, one
          repeat examination of each of the following: in Year 5
          (September 1, 2002 - August 31, 2003), EBCT of the heart; in
          Year 6 (September 1, 2003 - August 31, 2004),
          ultrasonography of the carotid arteries; and in Year 7
          (September 1, 2004 - August 31, 2005), MRI of the heart and
          aorta.]
  
  c. Follow-up for morbidity (cardiovascular disease, including
       myocardial infarction, stroke, and congestive heart failure)
       and mortality:
  
   i.   Dates of deaths and hospitalizations
   ii.  Interview data from participants and relatives and other
          informants
   iii. Hospital discharge diagnosis and ICD9 codes
   iv.  Classification of events as determined by the Morbidity and
          Mortality Committee
   v.   Data collected from physician questionnaires
   vi.  Data collected from hospital inpatient and outpatient
          records
   vii. Information on cardiovascular disease interventions as
          determined by the Morbidity and Mortality Committee 
  
  
  *****************************************************************
  
  1. GENERAL REQUIREMENTS AND TASKS 
  
  
  [Note: Throughout this statement of work, the terms "Contractor" and
  "Ultrasound Reading Center" and "Ultrasonography Reading Center" are
  used interchangeably.
  
  2. GENERAL REQUIREMENTS AND TASKS:
   a.   Coordinate, at the direction of the Steering Committee and
          in collaboration with the Coordinating Center and Field
          Centers, the development of protocols for ultrasound
          examinations and measurements at each of 6 to 8 Field
          Centers, and ultrasound reading and information abstraction
          at the Reading Center in accordance with the study design.
  
  [Note: For planning purposes, plan for 7 Field Centers.]
  
   b.   Coordinate, at the direction of the Steering Committee and
          in collaboration with the Coordinating Center and Field
          Centers, the development of scores for morphological and
          physiological measurements from ultrasound examination. 
          These scores will be used both as predictors and as outcome
          variables of cardiovascular risk and disease.  The scores
          must be appropriate to the statistical distribution features
          characterizing a general population, most members of whom
          are clinically asymptomatic.  Include suggested technical
          measurements and scoring procedures in the proposal.
   c.   Train and certify technicians according to the Field Center
          measurement protocol.  Include initial training and
          certification, annual recertification, and training and
          certification of new technicians due to turnover.  Include
          orientation training to measurement protocol methods for
          professional staff from the Coordinating Center with quality
          assurance responsibilities.
   d.   Train and certify ultrasound readers at the Reading Center
          and orient professional staff from the Coordinating Center
          with quality assurance responsibilities according to the
          reading and information abstraction protocol.  Include
          initial training, certification, and orientation, annual
          recertification, and training, certification, and
          orientation of new readers and quality assurance staff due
          to turnover.
   e.   Conduct pilot tests of the ultrasound protocols during the
          protocol development/pilot testing phase in collaboration
          with Field Centers and the Coordinating Center.
  
  [Note: The protocol for the baseline screening examination will be
  completed before completion of the protocol for the comprehensive
  examination, and clearance from the Office of Management and Budget
  (OMB) for the screening examination will be initiated before
  clearance for the comprehensive examination.   After draft protocols
  have been developed and approved by the Steering Committee, staff
  are to be centrally trained for each examination.  Pilot testing for
  the screening examination and for the comprehensive examination will
  be conducted after training is complete and OMB clearance for each
  examination has been obtained.  Pilot testing will consist of
  performing the examination, according to the draft Manual of
  Operations, in at least 20 volunteers per Field Center, who are not
  study participants.  The pilot tests are to include transmission of
  images to the appropriate reading centers.  Final modifications to
  the Manuals of Operations are to be made based on the pilot test
  results at the direction of the Operations Committee.]
  
   f.   Perform readings of ultrasound measurements during the
          screening examination for those Field Centers using
          ultrasonography to identify the high risk subgroup, and
          during the comprehensive subsample examination and one
          follow-up re-examination for all Field Centers at a time to
          be determined during protocol development (approximately
          four years after the comprehensive examination), including
          quality assurance activities.  
  
  [Note: For planning purposes, assume measurements will be conducted
  at two Field Centers for the baseline screening examination (i.e.,
  approximately 5,140 participants over two years).  Assume the total
  number of participants at all Field Centers for the comprehensive
  and follow-up examinations will be 4,500 at each examination (2,700
  high risk and 1,800 random sample).]
  
   g.   Participate in administrative and other activities to
          include, but not necessarily be limited to, visiting Field
          Centers annually during exam cycles  and as needed in
          support of quality assurance activities of the Coordinating
          Center; participate in the Steering Committee and
          subcommittees, particularly the Imaging Committee, as
          determined by the Steering Committee; and participate in
          preparation of reports and manuscripts  and in publication
          of results related to use of the ultrasound data.
  
  3. SPECIFIC REQUIREMENTS AND TASKS:
   a.   Develop, at the direction of the Steering Committee and in
          collaboration with the Coordinating Center and Field
          Centers, a final protocol for ultrasound examinations during
          the screening examination, and the subsample comprehensive
          examination and one re-examination.  The protocol will
          specify the techniques to measure wall thickness and lesion
          characteristics as well as potential physiological
          characteristics in the carotid arteries in an examination
          not to exceed 30 minutes of participants' time (examination
          time).
  
  [Note: For planning purposes, assume that each Field Center will
  have a Toshiba SSH-160A echocardiography machine.]
  
     Images will include two to three longitudinal views centered on
       the largest lesion or at the bifurcation in the right and left
       internal carotid arteries, and a single lateral view of the
       distal 10 mm of each common carotid artery.
     The examination will be sufficient to permit the following
       measurements to be made at the Ultrasound Reading Center:
     i. Quantitative measurements:
        (1)  Vessel interfaces; including near and far wall
               adventitia-periadventitia, media-adventitia, lumen-intima of both common carotid arteries, both carotid
               bulbs, and both internal carotid arteries.
        (2)  Wall thicknesses; including mean and maximum intimal-medial thickness of near and far walls of both common
               carotid arteries, both carotid bulbs, and both internal
               carotid arteries.
        (3)  Minimum residual lumen of the common and internal
               carotid arteries.
        (4)  Vessel width; including mean and maximum width of the
               common carotid arteries, carotid bulbs and internal
               carotid arteries. 
        (5)  Doppler frequency shift or velocity at point of maximum
               disease in the assessment of stenosis.
        (6)  Lesion characteristics such as homogeneity, density,
               and regularity of surface.
     ii.  Suggest, and, at the direction of the Steering Committee,
            develop and coordinate other proposed imaging methods for
            assessing subclinical cardiovascular disease.
  [Note: This list of core measurements is subject to modification
  either after the Ultrasound Reading Center contract is awarded as a
  result of protocol development, and/or before award, as a result of
  recommendations, capabilities and proposed costs of potential
  contractors.  In response to the RFP, in addition to addressing the
  list of core measurements, recommended deletions from or additions
  to the list may be suggested.  In addition, other methods for making
  measurements of subclinical disease may be suggested, as techniques
  emerge during the study, with scientific justification.  Any new
  suggestions for imaging or modifications to the protocol must be
  justified.
  For each of the measures listed above and for any additional
  measures recommended, the methods to be used for measurement and
  coding, as well as expertise and experience with the proposed
  methods should be described in response to the RFP.  Issues of
  measurement reproducibility and burden to participants and Field
  Center staff should be included.  Budget estimates must be provided
  for the interpretation of core measurements alone, with separate
  estimates provided for any additional components proposed.  Types of
  equipment and expertise needed at each Field Center in order to
  accomplish the proposed measurements should be specified.  Any
  additional components suggested should be ranked in terms of scien-
  tific importance, ease and reproducibility of measurement, and cost
  (including cost in time and equipment to Field Centers).]
     iii. Prepare Web-ready Field Center Manuals of Operations for
            distribution to interested parties, and prepare hard
            copies of Manuals for distribution to and use by the Field
            Centers, the Coordinating Center, and the Project Office.
   b.   Develop, at the direction of the Steering Committee, a final
          protocol for ultrasound readings as a means to identify
          those at highest risk for CVD (for the baseline screening
          examination) and to fully characterize carotid
          atherosclerosis (for the comprehensive examination).
  
   [Note: The proposal should detail the proposed reading method. 
  The proposal should   describe any offline analysis systems to be
  used, and should provide data on validity and   reproducibility of
  proposed reading methods.]
  
     i. The readings will measure characteristics listed in
          section a.i. above.
     ii.  Prepare Web-ready Reading Center Manuals of Operations for
            distribution to interested parties, and prepare hard
            copies of Manuals for distribution to the Coordinating
            Center and the Project Office.
     iii. Demonstrate accuracy and reliability on an ongoing basis,
            as described in the next section.
   c.   In collaboration with Coordinating Center staff as part of
          an overall quality assurance     program, train and oversee
          quality control monitoring of measurements from the Field           Centers' ultrasound technicians in details of the ultrasound
          examination.  Training should include a meeting at the
          Ultrasound Reading Center with all Field Center technicians
          and     supervisors during the protocol development/pilot
          testing phase, followed by on-site      calibration and
          monitoring at each Field Center during the pilot phase.
  [Note: For proposal purposes assume the Field Center ultrasound
  technicians will have general experience in vascular ultrasound, 
  but need training in specific details of this study.  Assume each
  Field Center will have a physician-ultrasonographer on site to
  supervise performance of ultrasound studies and to contribute to
  protocol development, quality assurance, and data analysis.  For
  proposal purposes, assume the Field Centers are located as follows:
  two in Boston, two in Chicago, two in Houston, and one in Los
  Angeles.]
     i. Train and certify technicians during the protocol
          development/pilot testing phase, and retrain and recertify
          technicians as needed during examination phases in
          performance of high quality studies in accordance with the
          final ultrasound measurement protocol.
  
  [Note: Specific detailed plans for this training, including proposed
  curriculum and number of studies to be performed by technicians in
  training must be included in the proposal.]
  
     ii.  Train and certify new technicians when turnover occurs.
   d.   As part of an overall quality assurance program in
          collaboration with Coordinating Center staff, train and
          certify the ultrasound readers in interpretation of studies
          and reading   conventions developed in the final ultrasound
          protocol.
     i. Train and certify initially, and retrain and recertify as
          needed during the entire study        period.
     ii.  Train and certify new readers when turnover occurs.
   e.   In collaboration with Coordinating Center staff, oversee and
          evaluate a pilot study at each Field Center during the
          protocol development/pilot testing phase.
     i. Perform measurements in 20 volunteers twice at each Field
          Center, according to the protocol developed in item a.
          above and transmit all data to the Coordinating Center as
          part of the protocol development/pilot testing phase.
     ii.  A system of assessment for data/image quality will be
            developed and applied for each examination of each subject
            throughout the study.
     iii. For the purposes of planning, assume there will be two
            technicians at each of seven field centers. Assume there
            will be two readers at the Ultrasound Reading Center, each
            of whom will initially read half, or 140, of the pilot
            images. Assume each reader will re read 40 of these images
            for the purposes of assessment of intra reader
            variability, and will read 40 of the other reader's first
            reading as a test of inter reader variability. This will
            be a total of 440 images processed and read during the
            pilot test.
     iv.  During these pilot studies, and throughout all periods of
            data collection, inter- and intra-individual variation
            among technicians and readers will be assessed and limits
            of acceptability will be defined.  The Ultrasound Reading
            Center will 1) collaborate with Coordinating Center staff
            in the analysis of pilot data and of continuing quality
            control data, 2) report results to the Steering Committee,
            and 3) design and implement necessary corrective actions.
   f.   Perform readings, information abstractions, and
          interpretations for the baseline screening examination, the
          comprehensive examination, one follow-up examination,
          including quality assurance activities.
     i. Read approximately 5,480 studies from the baseline
          screening examination (5,140 primary readings and 340
          quality control readings) from March 1, 2000 to February
          28, 2002.
        (1)  Include each reader re reading 50 of his/her own
               readings for the purpose of assessing intra reader
               variation, and reading 50 of the other reader's
               readings to assess inter reader variation.
    
  [Note: Assessment of intra-reader variability should be performed
  with each new reader or within each examination period, as
  appropriate.]
  
     ii.  Read approximately 4,900 studies during the comprehensive
            examination period (4,500 primary readings and 405 quality
            control readings) from September 1, 2000 to August 31,
            2002.
        (1)  Include each reader re reading 50 of his/her own
               readings for the purpose of assessing intra reader
               variation, and reading 50 of the other reader's
               readings to assess inter reader variation.
        (2)  Include 100 readings from the baseline screening
               examination to assess reader drift.
     iii. Between March 1, 2004 and June 30, 2004, re-read images of
            100 subjects from the previous examination for the purpose
            of assessing measurement drift over time.  Transmit the
            results to the Coordinating Center.  In collaboration with
            the Quality Assurance Committee, assess whether drift has
            occurred and implement necessary corrective action.
     iv.  Read approximately 4,440 studies during one follow-up
            examination (4,060 primary readings and 380 quality
            control readings) from September 1, 2004 to August 31,
            2005.  Include each reader re reading 50 of his/her own
            readings for the purpose of assessing intra reader
            variation, and reading 50 of the other reader's readings
            to assess inter reader variation.  
     v. Transmit all measurement data for a given participant to
          the Coordinating Center in an agreed-upon format within
          thirty days of receipt of measurements from a Field
          Center.
   g.   Design, implement, and support a quality assurance program
          in collaboration with Coordinating Center staff.  This will
          include the development of written standard     operating
          procedures (SOPs) and quality control activities, and the
          monitoring of performance to ensure uniformity of data coll-
          ection among all Field Sites throughout all data collection
          periods, including the assessment and control of temporal
          drift.  Report results of monitoring to the Steering
          Committee or a designated subcommittee.
     i. Develop written SOPs as reflected in Manuals of Operation
          for documentation and records keeping; for logs of
          incidents reflecting unusual circumstances related to
          measurements, readings, errors, or any other information
          that may be of utility in providing perspective; for
          measurement quality control activities; and for any other
          activity identified in the protocol development/pilot
          testing phase.
     ii.  In conjunction with the Coordinating Center, develop
            quality control procedures and performance standards to
            ensure that measurements from each technician at each
            Field Center conform to protocol requirements.   Recommend
            specific actions to be taken when performance standards
            are not met should be outlined in the proposal.
   
  [Note: Propose methods for the selection of measurements to be
  duplicated, and provide estimates of reasonable turnaround time for
  comparisons to be completed.  Specify frequency and type of feedback
  to be provided.  Propose methods for identifying and resolving any
  substantial disagreements between readers.]
  
     iii. Visit each Field Center once during the training and pilot
            testing phase and once a year during examination years to
            ensure protocol adherence.
     iv.  Maintain calibration, suggesting appropriate methods, of
            Field Center equipment and monitor necessary maintenance.
   h.   Subordinate Tasks
     i. Participate in the Steering Committee and its
          subcommittees, particularly the Imaging Committee, as
          needed.
     ii.  Participate in publication of ultrasound data.
  
  [Note: Capability for data analysis will be available at the
  Coordinating Center.  Provide discussion of expertise and commitment
  to this activity, and the scientific questions believed to be most
  important.  Make specific reference to types of information to be
  collected or proposed for future collection in the overall study. 
  Describe relations to be explored between these data and the
  ultrasound information in proposals for at least five (5)
  manuscripts.]
  
     iii. Prepare and present to the Steering Committee two
            Ultrasound Manuals of Operation: one for measurement
            (reading) of ultrasound data for the Ultrasound Reading
            Center and one for performing the ultrasound examinations
            for the Field Centers, in draft and final form for NHLBI
            approval, prior to training Field Center staff. Prepare in
            Web-ready format for distribution to interested parties.
     iv.  Cooperate in providing up-to-date lists of publications
            and presentations coming from the Ultrasound Reading
            Center for a data base to be managed by the Coordinating
            Center.
     v. Participate in ancillary studies and substudies, as
          desired, feasible, and recommended by the Steering
          Committee.
  
  [Note: Investigators may propose ancillary studies and substudies to
  be conducted in one or more study Centers.  A substudy is an
  investigation which, although not part of the core exam protocol,
  will yield additional information related to study objectives.  An
  ancillary study is a study not funded by contract funds.  Substudies
  and ancillary studies may include all or a subgroup of the cohort at
  a given center, and may involve additional interviews or
  examinations of study participants as well as analysis of blood or
  tissue samples, tapes, or images collected previously.  
  Ancillary studies and substudies are subject to the same policies,
  reviews and approvals as the core protocol.  Substudies involving
  additional participant burden will require OMB clearance. 
  Investigators proposing substudies will also prepare a request for
  OMB clearance for the substudy; or, for case-control studies, a
  request for exemption from OMB review.  Examples of such submissions
  will be provided on request.
  
  Ancillary study data, collected under a grant mechanism, are not
  required to become part of the public use data set; however, these
  data will be incorporated into the study data set after an
  appropriate period of time (generally 12 months after completion of
  data collection).  Investigators conducting ancillary studies are to
  be viewed as collaborating investigators of the primary study, with
  appropriate access to the full data set and to analytic resources of
  the study.
  
  Ancillary studies and substudies will be evaluated by the Steering
  Committee.  Highest priority will be given to studies which:  1)
  have the highest scientific merit, 2) do not interfere with the main
  study objectives, 3) produce the least burden on participants, 4)
  have objectives directly related to the study, and 5) require the
  unique characteristics of the cohort.  
  For all substudies and ancillary studies, the contractor shall
  define the hypotheses to be investigated and the methodology to be
  used, and should estimate the cost and burden on participants. 
  Study data collection must not interfere with the conduct of the
  core examination.  All substudies in the proposal should be
  distinctly identified, with separate descriptions and estimates of
  costs.  Ancillary studies and substudies may be proposed before
  and/or after contract award as scientific opportunities arise.  All
  studies must be approved by the Steering Committee, the Monitoring
  Board and the NHLBI Project Office before initiation.]
  
     vi.  Enter and edit the results from study ultrasonograms and
            blind duplicates into a computer, using software designed
            in cooperation with the Coordinating Center, and transmit
            the information to the Coordinating Center within 30 days
            of receipt of the images.  
  
  
  ********************************************************************
  
  C. REPORTS/DELIVERABLES
  
  1. REPORTS
  
   a.   Semi-annual progress reports (3 copies), indicating general
          progress in study activities and administrative issues;
          personnel with FTE level for the reporting period; changes
          in personnel; specific problems encountered or anticipated
          and attempts to resolve such problems; and progress in
          publications activities, including an updated list of
          ongoing and completed manuscripts (not to exceed 4 pages).
  
   b.   Quarterly financial reports (3 copies).  Use form NIH 2706.
   
   c.   A final report, due on or before expiration of the contract
          on August 31, 2008 (10 copies), documenting and summarizing
          the results of the entire contract work, including
          recommendations and conclusions based on both the general
          experience and the special viewpoint of the center not to
          exceed ten (10) pages.
     
   d.   With the final report, a summary (not to exceed 200 words)
          of salient results achieved during the performance of the
          contract (3 copies).
  
  2.    DELIVERABLES
  
                                                Delivery
  Item #     Description       Quantity    Schedule       Information
  
  1.         Draft Field       16-20       August 1, 1999 Field Centers
     Center Manual                              (2 copies each)
     Of Operations                              Coordinating 
                                                Center 
                                                (2 copies)
                                                Project Office
                                                (2 copies)
  
  2.         Field Center   16-20          September 1,1999 Same as 1.
     Manual of                                  Above
     Operations
  
  3.         Draft Reading  16-20          September 1,1999 Same as 1.
     Center Manual                              Above
     of Operations
  
  4.         Reading Center 16-20          September 1,1999 Same as 1.
     Manual of                                  Above
     Operations
  
  5.         Training          16-20       October 1, 1999     Same as 1.
     Materials for                              Above
     Field Centers
  
  6.         Reading Center 1         30 days after  Coordinating
     Results                Receipt of     Center;
                               Field Center     Project Office
                               Data             as requested
  
  7.         Orientation    4         October 1, 1999     Coordinating
     Materials on                          Center 
     Field Center                          (2 copies)
     Procedures for                             Project Office
     Coordinating                          (2 copies)
     Center
  
  8.         Site Visit        5           30 days after  Coordinating
     Report                    Site Visit       Center
                                                (2 copies)
                                                Project Office
                                                (2 copies)
                                                Contracts Office
                                                (1 copy)
  
  9.         Raw Data          1           As requested   Project Office
  
  10.             Manuscripts         10 copies 4 weeks before Publications
                               Submission       Committee
                                                (1 copy per
                                                Member)
                                                Project Office
                                                (2 copies)
  
  11.             Abstracts    10 copies   2 weeks before Same as 9.
                               Submission       Above
  
  11.             Semi-annual         3         February 28-29 Project Office
     Progress                  August 31        (2 copies)
     Report                                     Contract Office
                                                (1 copy)
  
  12.             Financial           3         Quarterly      Contract Office
     Reports                               (3 copies)
  
  13.             Final Report 10          August 21, 2008     Project Office
     and Summary                                (2 copies)
                                                Contract Office
                                                (8 copies)
  
  *****************************************************************
  
  D. SPECIAL REQUIREMENTS (as applicable)
  
  Clearance of all forms used during participant recruitment, interim
  contact, and clinic examinations and scans that represent a burden
  of time to the participant must be cleared by the Office of
  Management and Budget (OMB) prior to use in the study. 
  
  Human Subject Certification by the local institution's IRB must be
  obtained prior to participant contact.  Additionally, a study
  certificate of confidentiality at each field center will be obtained
  to protect genetic information from disclosure.  
  
  Access to a facility conducting electron-beam computed tomography
  (EBCT) of the heart is desirable.  The facility must be able to
  accommodate the participants for this study during the required time
  frame and in a manner feasible for the conduct of the study.  The
  facility should be accessible to the participants during convenient
  hours.  Alternative methods for identifying high risk participants
  may be proposed or a request may be made for partial funding of a
  scanner.  However, it is anticipated that only one such request may
  be fulfilled among the six to eight Field Centers.  Computer
  hardware and software which may be needed for data transfer and
  communication between the Field Centers and the Coordinating Center
  selected in response to the RFP will be provided by the Coordinating
  Center; a need for comparability between the Coordinating Center and
  the Field Centers has been factored into the estimated costs.  
  
  The Contractor shall supply all materials and facilities for the
  conduct of this study, except for the Toshiba SSH-160A
  ultrasonography machine, which will be furnished by the Government
  to each of the Field Centers.
  
  Availability of genetic material and data related to genetic
  assessments for further research and development shall be handled in
  accordance with the NHLBI policy in effect at the time of award.  It
  is expected that this policy will be made available for discussion
  with offerors in the competitive range.
  
  Industry/Third Party contributions shall be processed in accordance
  with Federal regulations and NHLBI policy.
   
  
  
  ****************************************************************
  TECHNICAL EVALUATION CRITERIA/METHOD OF REVIEW
  
  The technical proposal will receive paramount consideration in the
  selection of the contractor for this procurement.  The evaluation
  will be based on the demonstrated capabilities of the prospective
  contractors in relation to the needs of the project as set forth in
  the RFP.  The merits of each proposal will be evaluated carefully,
  based on the thoroughness and feasibility of the technical approach
  taken.  
  
  Although cost is not a specific evaluation criterion, it will be
  assessed.  In the event that the technical evaluation reveals that
  two or more offerors are approximately equal in technical ability,
  then the estimated cost may become significant in determining
  award(s).  In any event, the Government reserves the right to make
  an award to the best advantage of the Government, cost and other
  factors considered. 
  
  This research project involves human subjects.  Offerors must make
  every effort to seek out and include (a) study goal of 50% women
  within each racial/ethnic minority group aged 35-84, and (b)overall
  study goal of 50% U.S. racial/ethnic minority populations of roughly
  equal numbers of non-Hispanic blacks, Hispanics, and Pacific
  Islanders/Asians.  A major goal of this solicitation is to have good
  representation of women and of minority populations.  The numbers of
  women and minority participants may vary from center to center
  depending on local population composition and other characteristics
  that influence access to care.  However, each Field Center is
  expected to include at lest 10% from each of two racial/ethnic
  groups.  The NHLBI reserves the right to make awards under this RFP
  in a manner that accomplishes the overall recruitment goals for
  women and minorities.  Thus, a higher ranked proposal may be passed
  over for a lower ranked proposal if the lower ranked proposal is
  needed to fulfill recruitment goals.  
  
  Where inclusion of proper representation of women and/or minority
  populations is not feasible, the offeror must submit with the
  technical proposal a clear justification.  The NHLBI will review
  this justification in light of the research design and desired women
  and minority representation in the proposal study.  If the rationale
  is not considered acceptable by the Government and the offeror is
  included in the competitive range, the offeror will be afforded the
  opportunity to further discuss and/or clarify its position during
  discussions and in the best and final offer (BAFO).  If the
  offeror's exclusion position is still considered unacceptable by the
  Government after discussions, the proposal may not be considered
  further for award.  
  
  As an agency of the U.S. Public Health Service, the National Heart,
  Lung, and Blood Institute is responsible for sponsoring research
  programs and for disseminating information that will serve to
  improve the health of the population of the United States. 
  Therefore the recruitment into this program of foreign populations
  that have significantly different social, cultural and economic
  conditions could substantially alter the study results.  As a
  result, the award of contracts for performance as Field Centers
  under this program shall be made only to offerors who are located in
  the United States of America.  Proposals received from offerors
  located outside of the United States of America will not be
  considered for contract award.
  
  Proposals submitted in response to this solicitation will be
  reviewed by a peer group of scientists under the auspices of the
  Review Branch, Division of Extramural Affairs, NHLBI, and
  subsequently by a review group within NHLBI.
  
  TECHNICAL EVALUATION CRITERIA SPECIFIC TO THE REQUIREMENT:
  
  1. Adequacy of plans and demonstrated capacity for fulfilling the
       Ultrasound Reading Center functions outlined in the statement
       of work. These include plans and protocols for ultrasound
       measurements at the Field Centers and for information
       processing, coding, and interpretation at the Reading Center;
       and evidence the proposed reading methods and instrumentation
       provide the best and most valid measures in a population
       comprised of a large proportion of clinically asymptomatic
       individuals.
                                                (25 points)
  
  2. Adequacy of plans and documented ability for developing,
       maintaining, and modifying quality assurance activities in
       collaboration with the Coordinating Center. This includes
       development of written standard operating procedures;
       appropriate training and certification of all Field Center,
       Coordinating Center, and Ultrasound Reading Center staff to
       implement the ultrasound measurement protocol; and monitoring
       of reliable and accurate measurement performance at Field
       Centers and the Ultrasound Reading Center.
                                                (20 points)
  
  3. Expertise and experience of Ultrasound Reading Center senior
       staff in arterial ultrasonography, and their willingness and
       ability to take appropriate leading roles in protocol
       development, collaboration and coordination among centers,
       quality assurance activities, and scientific data analysis and
       publication.
                                                (20 points)
  4. The adequacy of plans and documented ability for data
       management, including detailed plans to assure accurate
       transmission of data from Field Centers to the Ultrasound
       Reading Center, and from the Ultrasound Reading Center to the
       Coordinating Center.
                                                (20 points)
  5. The adequacy of the administrative structure, support staff,
       and institutional support. This includes the availability of
       adequate facilities and equipment, including technical
       hardware, and the ability to develop, maintain, and modify
       technical software, hardware, and operational procedures as
       necessary.
                                                (15 points)
  
  ******************************************************************
  THE REMAINDER OF THIS GOPHER RFP CONSISTS OF THE FOLLOWING SECTIONS:
  
  II.        Specific RFP Instructions and Provisions, and
  III.       Applicable RFP REFERENCES
  *******************************************************************
  II.        Specific RFP Instructions and Provisions
  ==================================================================
  NOTICE TO OFFERORS: This attachment contains proposal instructions
  and information which are specifically related to this acquisition. 
  The information provided below is only a portion of the instructions
  and notices required for the submission of a proposal.  References
  to additional, more general, information and forms regarding
  proposal preparation are contained under Applicable RFP REFERENCES.
  Listing of Contents:
  A. Proposal Intent Response Sheet (submit prior to proposal
       submission)
  B. Packaging and Delivery of Proposal
  C. Privacy Act System of Records
  D. SIC Code and Small Business Size Standard
  E. Number and Type of Award(s)
  F. Estimate of Effort
  G. Service of Protest
  H. Travel Requirements for Solicitation Purposes
  I. Technical Proposal Table of Contents
  J. Reference Materials
  K. Other Provisions
   1.  ROTC Access and Federal Military Recruiting on Campus
   2.  Continued Ban on Funding of Human Embryo Research
  ******************************************************************
  A. PROPOSAL INTENT RESPONSE SHEET
  
  RFP No. NHLBI HC-98-10; TITLE OF RFP: Subclinical Cardiovascular
  Disease Study: Ultrasonography Reading Center
  
  PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL.  FURNISH THE
  INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY December 5,
  1997.  YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL GREATLY
  ASSIST US IN PLANNING FOR PROPOSAL EVALUATION.
  ===================================================================
  I INTEND TO SUBMIT A PROPOSAL
  ===================================================================
  COMPANY/INSTITUTION NAME:
  
  ADDRESS:
  
  
  PROJECT DIRECTOR'S NAME:
  TITLE:
  
  TELEPHONE NUMBER:
  
  NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS (include
  Subcontractors and Consultants):
  
  
  
  ===============================================================
  RETURN TO:
   Review Branch            or    FAX TO:  Dr. James Scheirer
   NIH, NHLBI                              301-480-3541
   Attention: Dr. James Scheirer
   Rockledge Building, Room 7220
   6701 ROCKLEDGE DR   MSC 7924
   BETHESDA MD 20892-7924
  
  B. PACKAGING AND DELIVERY OF THE PROPOSAL
  
  Your proposal shall be organized as specified in Section C.1.,
  "Standard RFP Instructions and Provisions."  Shipment and marking
  shall be as indicated below.
  
  EXTERNAL PACKAGE MARKING
  In addition to the address cited below, mark each package as
  follows:
  
  "RFP NO. NHLBI HC-98-10
  TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"
  
  NUMBERS OF COPIES
  The number of copies required of each part of your proposal are as
  specified below.
  
  TECHNICAL PROPOSAL ONLY
  ORIGINAL* AND Thirty (30) COPIES
  
  BUSINESS PROPOSAL
  ORIGINAL* AND Six (6) COPIES
  
  COPIES TO:
  If hand-delivered or delivery service-
  
  Review Branch                            
  Division of Extramural Affairs      
  National Heart, Lung, and Blood Institute
  Rockledge Building, Room 7091
  6701 Rockledge Drive   MSC 79924
  Bethesda, MD 20817-7924
  
  If using U.S. Postal Service-
  
  Review Branch                            
  Division of Extramural Affairs      
  National Institutes of Health
  National Heart, Lung, and Blood Institute
  6701 Rockledge Drive   MSC 79924
  Bethesda, MD 20892-7924
  
  *THE ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING.
  
  NOTE: The U.S. Postal Service's "Express Mail" is delivered a
  Rockville, Maryland address.  Any package sent to this address via
  this service will be held at a local post office for pick-up.  The
  Government is not responsible for picking up any mail at a local
  post office.  If a proposal is not received at the place, date, and
  time specified herein, it will be considered a "late proposal."
  
  GOVERNMENT NOTICE FOR HANDLING PROPOSALS
  
  An Offeror shall place this notice on top of each copy of the
  technical proposal.
  
  "This proposal shall be used and disclosed for evaluation purposes
  only, and a copy of this Government notice shall be applied to any
  reproduction or abstract thereof.  Any authorized restrictive
  notices which the submitter places on this proposal shall also be
  strictly complied with.  Disclosure of this proposal outside the
  Government for evaluation purposes shall be made only to the extent
  authorized by, and in accordance with, the procedures in HHSAR
  paragraph 315.608-72."
  
  (For information regarding authorized restrictive notices, offerors
  should refer to the "Confidentiality of Proposals" section of the
  STANDARD RFP INSTRUCTIONS AND PROVISIONS subdirector of the RFP
  REFERENCES director of the Gopher RFP.)
  
  C. PRIVACY ACT SYSTEM OF RECORDS
  
  This procurement action requires the field centers to do one or more
  of the following:  design, develop, or operative a system of records
  on individuals to accomplish an agency function in accordance with
  the Privacy Act of 1974.  Public Law 93-579, December 31, 1974 (5
  USC 552a) and applicable agency regulations.  All data except
  personal identifiers will be transmitted to the NHLBI by
  coordinating center.  All data collected will be used only for group
  analyses, and information on individually identifiable participants
  will not be sent to the NHLBI or disseminated or used in
  publications or presentations.  The field centers will be required
  to keep the records confidential and protect the individual's
  privacy.  The data may be used only by the contractor, the study
  chairman, and the NHLBI.
  
  The most recent Publication of Notices of Systems of Records upon
  award will be applicable.  The current Privacy Act System of Records
  applicable to this project is identified as follows:
  NIH NHLBI 09-25-0126, Clinical Research: Epidemiology and
  Biometrics, HHS/NIH/NHLBI, as set forth in the Federal Register Vol.
  60. No. 13, January 20, 1995. 
  
  D. SIC CODE AND SMALL BUSINESS SIZE STANDARD
  
  NOTE: The following information is to be used by the offeror in
  preparing its Representations and Certifications (See Section C.4 of
  the Gopher RFP, specifically in completing the provisions entitled,
  SMALL BUSINESS PROGRAM REPRESENTATIONS (OCT 1995), FAR 52.2219-1:
  
  The standard industrial classification (SIC) code for this
  acquisition is 8733.
  
  The small business size standard is $5,000,000.
  
  THIS REQUIREMENT IS NOT SET-ASIDE FOR SMALL BUSINESS.  However, the
  FAR requires in every solicitation (except for foreign acquisitions)
  the inclusion of the SIC and corresponding size standard which best
  describes the nature of the requirement in the solicitation.  
  
  E.  NUMBER AND TYPE OF AWARD(S)
  
  It is anticipated that a single award will be made from this
  solicitation and that award will be made on or about September 7,
  1998. 
  
  It is anticipated that the award from this solicitation will be a
  multiple-year cost reimbursement, completion type contract with a
  period of performance of ten (10) years, and that incremental
  funding will be used [see paragraph (6) of Business Proposal
  Instructions, in the "Standard RFP Instructions and Provisions" of
  the Gopher RFP.]
  
  F.  ESTIMATE OF EFFORT
  
  It is estimated that percent effort to be provided per year is as
  indicated below.
                Yr.1 Yr.2 Yr.3 Yr.4 Yr.5 Yr.6 Yr.7 Yr.8 Yr.9 Yr.10
  PI/Proj.Dir.   10   10   10   10   10   10   10   10   10   10
  Other
  Investigators  10   75  150   125  10   10  100   10   10   10
  Other           0   10   15    10   10   10   10  15   10    0
   
  All staffing levels should be accompanied by specific justifications
  as to the type and hours of work expected to be performed by all
  personnel. Offerors will be required to propose levels of commitment
  whether compensated or donated effort, necessary to complete the
  work described in their proposals.  It is expected that realistic
  levels of effort will be proposed such that an offeror's
  understanding of the work will be apparent.  
  
  G.  SERVICE OF PROTEST
  
  In accordance with FAR 52.233-2 SERVICE OF PROTEST (NOV 1988):
  (a) Protests, as defined in Section 33.101 of the Federal
  Acquisition Regulation, that are filed directly with an agency, and
  copies of any protests that are filed with the General accounting
  Office (GAO) or the General Services Administration Board of
  Contract Appeals (GSBCA), shall be served on the Contracting Officer
  (addressed as follows) by obtaining written and dated acknowledgment
  of receipt from:
  
   Mr. Robert R. Carlsen
  
   Hand-Carried Address:
  
     National Institutes of Health
     National Heart, Lung, and Blood Institute
     Contracts Operations Branch
     II Rockledge Center, Room 6122
     6701 Rockledge Drive, MSC 7902
     Bethesda, MD 20817
  
   U.S. Postal Service:
  
     National Institutes of Health
     National Heart, Lung, and Blood Institute
     Contracts Operations Branch
     II Rockledge Center, Room 6122
     6701 Rockledge Drive, MSC 7902
     Bethesda, MD 20892-7902
  
  The copy of any protest shall be received in the office designated
  above on the same day a protest is filed with GSBCA or within one
  day of filing a protest with GAO.
  
  H.  TRAVEL REQUIREMENTS FOR SOLICITATION PURPOSES
  
  Investigators should plan to travel to Bethesda, Maryland for all
  Steering Committee and Monitoring Board meetings.  Travel to Field
  Centers for site visits and two scientific meetings should be
  planned within the continental United States; however, for planning
  purposes, assume that these meetings will also be in Bethesda. 
  Assume that each trip will be two (2) days long.  Annual trips for
  the Ultrasonography Reading Center--plan for two (2) trips in the
  first year and five (5) in the second year, ten (10) trips in the
  third and seventh years and four (4) in all other years.
  
  I.  TECHNICAL PROPOSAL TABLE OF CONTENTS
  IMPORTANT: Technical proposals submitted in response to this RFP
  MUST NOT EXCEED 25 PAGES, however, this limitation does not include
  the cover sheet, table of contents, abstract or copies of biosketch
  or appendices.  Please number each page of text.  Type density and
  size must be 10-12 points.  If constant spacing is used, there
  should be no more than 15 cpi, whereas proportional spacing should
  provide an average of no more than 15 cpi.  There must be no more
  than six lines of text within a vertical inch.  
  
  The technical proposal should be organized as follows:
  
  1. TECHNICAL PROPOSAL COVER SHEET (Format in the NIH Gopher RFP
       under "FORMS, FORMATS, ATTACHMENTS").................Page 1
  2. TECHNICAL PROPOSAL TABLE OF CONTENTS.................Page 2
  3. ABSTRACT.............................................Page 3
   State the proposal's broad, long-term objectives and specific
     aims.  Briefly and concisely describe the research design and
     methods for achieving these goals.  DO NOT EXCEED one page in
     providing the abstract.  Identify the RFP Number, Institution
     and Principal Investigator on the abstract.  
  
  4. TECHNICAL PLAN (LIMIT 25 PAGES)
   Refer to Technical Proposal Instructions, Standard RFP
     Instructions and Provisions, Gopher RFP for more detail.
  
   a.  WORK STATEMENT
       1.  Objectives...................................Page #
       2.  Approach.....................................Page #
       3.  Methods......................................Page #
       4.  Schedule.....................................Page #
  
   b.  Personnel 
       1.  List of all Personnel on the project, including
           Subcontractors, Consultants/Collaborators, by
           name, title, department and organization.
  
       PROVIDE NARRATIVE FOR:
       2.  Principal Investigator/Project Director......Page #
       3.  Other Investigators..........................Page #
       4.  Additional Personnel.........................Page #
   [NOTE: For personnel, include a two-page biosketch under
     APPENDICES below.]
  
   c.  FACILITIES, EQUIPMENT AN OTHER RESOURCES........Page #
  
   List/describe all facilities, equipment and other resources
     available for this project.
  
   D.  OTHER CONSIDERATIONS.............................Page #
   (Use specifically titled subparagraphs, as applicable.)
  
  5. OTHER SUPPORT........................................Page #
   Include form "summary of Current and Proposed Activities."  All
     key personnel must be listed on this form.  It is located in
     the NIH Gopher RFP under "FORMS, FORMATS, & ATTACHMENTS."
  
  6. HUMAN SUBJECTS AND MINORITY AND GENDER ISSUES NOT OTHERWISE
       ADDRESSED............................................Page #
  
  7. TECHNICAL PROPOSAL COST INFORMATION..................Page #
   (Form located in the NIH Gopher RFP under "FORMS, FORMATS, &
     ATTACHMENTS.")
  
  8. LITERATURE CITED....................................Page #
  
  9. APPENDICES...........................................Page #
   List each Appendix and identify the number of pages for each
     one.  Appendices must be clear and legible, and easily located.
  ,End form - Technical Proposal Table of Contents
  **********************************************************             
  J.  REFERENCE MATERIALS
  
  Protocols and Manuals of Operation from the Cardiovascular Health
  Study, the Atherosclerosis Risk in Communities Study, and the
  Coronary Artery Risk Development in Young Adults Study will be made
  available in a reading room upon request of the Contracting Officer.
  
  K.  OTHER PROVISIONS
  
  1. ROTC ACCESS AND FEDERAL MILITARY RECRUITING ON CAMPUS
  
  Section 514 of the FY 1997 Appropriations Act prohibits NIH from
  providing contract funds to educational institutions that the
  Secretary of Defense determines have a policy or practice
  (regardless of when implemented) that either prohibits, or in effect
  prevents (1) the maintaining, establishing, or operation of a unit
  of the Senior Research Officer Training Corps at the covered
  educations entity; or (2) a student at the covered educational
  entity from enrolling in a unit of the Senior Research Officer
  Training Corps at another institution of higher education.
  
  Further, contract funds may not be provided to educational
  institutions that have a policy or practice that prohibits or
  prevents (1) entry to campuses, or access to students (who are 17
  years of age or older on campuses, for purposes of Federal military
  recruiting; or (2) access by military recruiters for purposes of
  Federal military recruiting to information pertaining to students
  (who are 17 years of age or older) enrolled at the covered
  educational entity.
  
  2. CONTINUED BAN ON FUNDING OF HUMAN EMBRYO RESEARCH
  
  Section 512 of the Fiscal Year 1997 Appropriations Act contains
  language identical to that contained in the Fiscal Year 1996
  Balanced Budget Down payments Act (P.L. 104-99) that prohibits NIH
  from using appropriated funds to support human embryo research. 
  Contract funds may not be used for (1) the creation of a human
  embryo or embryos for research purposes; or (2) research in which a
  human embryo or embryos are destroyed, discarded, or knowingly
  subjected to risk or injury or death greater than that allowed for
  research on fetuses in utero under 45 CFR 46.208(a)(2) and Section
  498(b) of the Public Health Service Act (42 U.S.C.289g(b)).  The
  term "human embryo or embryos" include any organism, not protected
  as a human subject under 45 CFR 46 as of the date of the Act, that
  is derived by fertilization, parthenogenesis, cloning or any other
  means from one or more human gametes.  
  ******************************************************************
  III.       Applicable RFP REFERENCES
  ==================================================================
  This section identifies the items located in the Gopher direct at
  URL gopher://gopher.nih.gov:70/11/res/rd-rfp/rfppref.c "RFP
  REFERENCES" that are applicable to this RFP.
  
  1.  The entire file entitled "STANDARD RFP INSTRUCTIONS AND
  PROVISIONS" is applicable to this RFP, except as otherwise may be
  modified by the inclusion of an item from the "OPTIONAL RFP
  INSTRUCTIONS AND PROVISIONS" below.
  
  2.  The following items are applicable from the file entitled
  "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS":
   (1)LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF
  PROPOSALS, PHS 352.215-10
  
   (2) HUMAN SUBJECTS
   (3) SMALL, SMALL DISADVANTAGED AND WOMEN-OWNED SMALL BUSINESS
  SUBCONTRACTING PLAN, FAR 52.219-9 [NOTE: A Subcontracting Plan is
  not due with the initial proposal.  The Contracting Officer will
  notify offerors if a plan becomes due.]
   (4) INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
  SUBJECTS.
  
  3. The following items are applicable from the subdirector entitled
  "FORMS, FORMATS, AND ATTACHMENTS":
  
  APPLICABLE TO TECHNICAL PROPOSAL:
  (1) Technical Proposal Cover Sheet
  (2) Technical Proposal Cost Information, Dec 1988
  (3) Summary of Current and Proposed Activities, July 1995
  
  APPLICABLE TO BUSINESS PROPOSAL:
  (4) Contract Pricing Proposal, SF-1411, (Rev. 10/9995)
  (5) Proposal Summary an Data record, NIH-2043 (Rev. 6/82)
  (6) Business Proposal Cost Information
  (7) Disclosure of Lobbying Activities, OMB SF-LLL4.
  (8) Representations and Certifications are applicable.  A completed
  copy must be submitted with offeror's business proposal.  This form
  can be found in the Gopher System [URL
  gopher;//gopher.nih.gov:70/00/res/rd-rfp/rfpref.c/reps_cer.gph].
  
  TO BECOME CONTRACT ATTACHMENTS:
  (9) Invoice/Financing Requests Instructions for NIH Cost-Reimbursement Type Contracts, NIH(RC)-1, (Rev. 5/97)
  (10) Instructions for Completing Form NIH 2706 (Financial Report)
  (11) Procurement of Certain Equipment, NIH(RC)-7
  (12) NIH Women and Minority Policy
  (13) Protection of Human Subjects - Assurance
  Identification/Certification/Declaration, OF 310
  
  OTHER - TO BE SUBMITTED:
  
  (14) Certificate of Current Cost or Pricing Data, NIH-1397, to be
  submitted with the Best and Final Offer, as directed by the
  Contracting Officer.
  (15) Subcontracting Plan to be submitted as directed by the
  Contracting Officer, after the competitive range is determined.
  
  4.  The "sample Contract Format-General" is applicable.
  *************************************************************
  End of document