AMENDMENT #01 OF SOLICITATIONS FOR SUBCLINICAL CARDIOVASCULAR
  DISEASE STUDY, NHLBI HC-98-07, NHLBI HC-98-08, NHLBI HC-98-09, NHLBI
  HC-98-10, NHLBI HC-98-11, NHLBI HC-98-12
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  1. AMENDMENT OF SOLICITATION NUMBERS: NHLBI HC-98-07, NHLBI HC-98-08,
 NHLBI HC-98-09, NHLBI HC-98-10, NHLBI HC-98-11, NHLBI HC-98-12
  
  2. AMENDMENT #01
  
  3. AMENDMENT DATE: NOVEMBER 26, 1997
  
  4. RFP ISSUE DATE: NOVEMBER 4, 1997
  
  5. ISSUED BY: National Institutes of Health
                  National Heart, Lung, and Blood Institute
                  Contracts Operations Branch
                  Rockledge Building, <SC 7902
                  6701 Rockledge Drive
                  Bethesda, MD 20892-7902
  
  6. NAME AND ADDRESS OF CONTRACTOR:
  
     To all recipients of RFP Numbers:  NHLBI HC-98-07, NHLBI HC-98-08, NHLBI HC-98-09,
NHLBI HC-98-10, NHLBI HC-98-11, NHLBI HC-98-12
  
  7. This amendment revises various sections of the RFPs as shown
       below:
  
  *******************************************************************
   
  Correction to Note under Table 1 regarding components of
  examinations
  
  A repeat retinal artery photography examination should not be
  planned for, and the timing of the repeat imaging examinations is
  incorrect in the note but correct in the Figure.  The Note should be
  modified to read as follows:
  
  "Note: . . . For planning purposes, follow-up examinations are of 
  three types: Approximately every 6 months, phlebotomy; approximately
  every 12 months, endothelial function and vascular stiffness; and
  periodically, a repeat imaging measure, including repeat EBCT (once,
  in Year 6); repeat ultrasound (once, in Year 7); and repeat MRI
  (once, in Year 8)."    
  
  Correction to Table 1 and Figure 1 regarding timing of morbidity and
  mortality follow-up
  
  The Figure indicates that Morbidity and Mortality Follow-up begins
  on September 1, 2000, whereas the Table indicates that it will begin
  on March 1, 2000.  The correct date is March 1, 2000.  Morbidity and
  mortality follow-up will need to begin as soon as the first
  participants have been screened.  The Table indicates that Morbidity
  and Mortality Follow-up will end on February 28, 2007, whereas the
  Figure indicates that it will end on September 30, 2008.  The
  correct date is September 30, 2008. 
  
  Correction to examination components
  
  In each RFP, Table 2. Examination Components, b.ii. should read:
  "Enhanced grey-scale and Doppler ultrasound of carotid artery".
  
  Correction to Work Statement for Ultrasound Reading Center
  
  The Ultrasound Reading Center should also plan to read scans of the
  brachial artery conducted during assessment of vascular reactivity. 
  In Section 3. SPECIFIC REQUIREMENTS AND TASKS, modify a. as follows
  (underlined text has been added):
  
     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 6 re-examinations.  The protocol will specify the
  techniques to measure wall thickness and lesion  characteristics as
  well as potential physiological characteristics in the carotid and
  brachial arteries in examinations not to exceed 30 minutes each of
  participants' time (examination  time).
    
  Add the following section:
  
  During the comprehensive examination (September 1, 2000 - August 31,
  2002) and in Years 4-9 (September 30, 2001 - March 31, 2007), read
  images from the brachial artery recorded during and after forearm
  blood flow occlusion, and measure changes in vessel diameter. 
  Assume that 4,500 participants will be measured seven times each.
  
  
  
  Regarding goals for recruitment of racial/ethnic groups:
  
  In the section entitled "TECHNICAL EVALUATION CRITERIA/METHOD OF
  REVIEW" it states:
    
  "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 least 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."
  
  The statement regarding the expectation for inclusion of at least
  10% from each of two racial/ethnic groups refers to all
  racial/ethnic groups, including non-Hispanic whites.  For example,
  it would be acceptable to propose including 90% non-Hispanic whites
  and 10% of another racial ethnic group.  Offerors should be aware,
  however, of the final statement in the above paragraph that allows
  NHLBI to select offerors, in part, based on their contributions to
  overall study goals regarding racial/ethnic composition.
  
  
  Regarding the term "OMB"
  
  The term "OMB" mentioned in the Introduction to each Work Statement
  refers to the federal Office of Management and Budget.  All NIH
  research protocols involving information collection are submitted
  for a clearance process through the Office of Management and Budget
  via the NIH Office of Extramural Research prior to actual
  recruitment of participants.  This office reviews questionnaires to
  assess, assure adequate justification for, and minimize the burden
  to research subjects.  
  
  
  Regarding the use of electron-beam computed tomography
  
  There are several sections of the RFPs that address the use of
  electron-beam computed tomography and other methods to initially
  screen participants for subclinical cardiovascular disease.  In each
  Work Statement Introduction, it states 
  
  "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 maybe 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."  
  
  In the Work Statement for the Field Center (RFP NIH-NHLBI-HC-98-08),
  section b.1.(3)(a), it states
  
  "Electron-beam computed tomography of the heart, or equivalent
  baseline screening method or combination of measurements, to
  identify persons at very high risk for clinical cardiovascular       
  disease events.  The proposed baseline screening method must be
  demonstrated to accurately         predict coronary events across a
  broad age range 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."
  
  This statement is followed by the note:
    
  "[Justification must be provided for the proposed screening 
  strategy to identify the high risk group, documenting expected 
  clinical cardiovascular disease event rates among those who screen 
  positive, compared to those who screen negative.]"
  
  These statements, while citing EBCT as a possible screening tool
  that would be likely to fulfill the research goals, indicate that
  measures other than EBCT may be proposed and that any proposed
  measure must be justified.  This language allows for the careful
  consideration of research developments that may occur from the time
  of the release of the RFP to the time of protocol development.
  
  While the protocol for the screening examination will be developed
  by the Steering Committee, the Field Centers need not all use the
  same protocol.   For example, some centers might use EBCT, while
  others might use carotid ultrasound and/or other noninvasive methods
  to assess risk for cardiovascular disease.
  
  Access to a facility conducting electron-beam computed tomography
  (EBCT) of the heart or a comparable non-invasive measure of
  subclinical disease 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 or other method for screening.  However, it is anticipated
  that only one such request may be fulfilled among the six to eight
  Field Centers.
  
  Regarding criteria for determining partial funding for an EBCT
  scanner
  
  In each Work Statement, under Special Requirements, it states:
  
  "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."  
  
  Criteria for partial funding of an EBCT scanner include availability
  of a scanner within a reasonable distance or with reasonable access
  for the proposed Field Center and the availability of alternate
  screening technologies.  In addition, overall cost considerations
  will be taken into account, and partial funding for a scanner is not
  guaranteed.
  
  
  Regarding the question of handling of two or more proposals from the
  same institution
  
  Multiple proposals from the same institution will be treated by the
  initial review group as separate, independent proposals.   However,
  if more than one proposal is judged to be competitive, the NHLBI
  will carefully examine issues related to institutional capacity to
  support both contracts; burden on local resources, including
  potential participants and clinical facilities; overlap of
  commitment among involved investigators; and funding overlap.  It is
  in the best interest of institutions with multiple proposals to
  resolve issues of potential overlap and conflict prior to submission
  of proposals.
  
  ******************************************************************
  
  8. The hour and date specified for receipt of offers is NOT
       extended.  If you submit a proposal, please acknowledge that
       your proposal is based on the original RFP and this amendment. 
       Failure of this acknowledgment in your proposal may result in
       rejection of your offer.
  
  9A.     NAME AND TITLE OF CONTRACTING OFFICER (type or print):
  
     Cheryl A. Jennings, Contracting Officer
  
  9B.     UNITED STATES OF AMERICA
  
     BY (Signature of Contracting Officer)
     /signed/
  
  9C.     DATE SIGNED: November 26, 1997
  
  END OF AMENDMENT