RFP No.       NIH-NHLBI-HC-97-10
  
Title:      Magnesium in Coronaries (MAGIC)
  
Issued by:    Donna Berkowitz
                      Contracting Officer
                      National Institutes of Health
                      National Heart, Lung, and Blood Institute
                      Contracts Operations Branch
                      TWO ROCKLEDGE CENTER RM 6122    
                      6701 ROCKLEDGE DR MSC 7902
                      BETHESDA MD 20892-7902
  
  
DATE ISSUED: July 21, 1997
  
PROPOSAL DATE DUE:   September 8, 1997 at 4:30 p.m. EST
  
  
Ladies and Gentlemen:
  
  You are invited to submit a proposal in accordance with the 
requirements of this RFP NIH-NHLBI-HC-97-10 titled "Magnesium in 
Coronaries (MAGIC)."  The Government anticipates the awarding one, 
three year, cost-reimbursement type contract as a result of this 
RFP.
  
  The documents included with this electronic RFP package are as 
follows:
  
  I.   Streamlined RFP
  
       a.   Introduction, Background and Work Statement (Attachment
1)
  
       b.   Deliverables and Reporting Requirements (Attachment 2)
  
       c.   Evaluation Factors for Award (Attachment 3)
  
  II.  Specific RFP Instructions and Provisions (Attachment 4)
  
  III. Applicable RFP References (Attachment 5)
  
  In addition to this directory which provides access to this 
streamlined RFP, there are five other subdirectories in the Gopher 
System [URL gopher://nih.gov:70/11/res/rd-rfp/rfpref.c] under "RFP 
References" which must be retrieved, in whole or in part, in order 
to submit a proposal.  The identity of these additional documents 
are detailed in Attachment 5 (Applicable RFP References) of this 
RFP.  If you are unable to download any of these documents, please 
contact Peggy Mills, Contract Specialist.  Ms. Mills may be reached
at the numbers provided below.
  
  The attachments listed above represent all the necessary
information   required for the submission of a proposal for this
acquisition.  Following proposal submission and review, additional
information  will be requested by the Contracting Officer from all
offerors which  comprise the competitive range.
  
  The original and twenty (20) copies of your technical proposal and 
the original and eight (8) copies of your business proposal must be 
received by the Contract Specialist no later than September 8, 1997, 
at 4:30 p.m. EST at the address listed in Attachment 4, Item 7.
  
  BE ADVISED THAT YOUR TECHNICAL PROPOSAL SUBMITTED IN RESPONSE TO 
THIS RFP IS SUBJECT TO A 25 PAGE LIMIT (excluding required sample  
protocols and consent forms, and appendices).  The format and
content of your  TECHNICAL PROPOSAL along with page limitation
information is  detailed in the "Technical Proposal Table of
Contents/Format," Attachment 4, Item 11.
  
  In addition, 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 the NIH Gopher under the FORMS, FORMATS, AND 
ATTACHMENTS subdirectory found in "RFP REFERENCES.")  New policies 
require submission of more detailed information than what has been 
previously required.  It is important that you list all professional 
personnel and organizations named in the proposal who have any role 
in the proposed work, including:  staff of the primary organization 
(offeror), subcontractors, collaborating organizations, and 
consultants.  Organizational affiliation(s) must be indicated for 
every person named.  You may use additional sheets, as needed, 
following the format shown in the Technical Proposal Cover Sheet. 
This information will be used to ensure that there will be no 
conflicts of interest when selecting review committee members.
  
Your attention is further directed to the "Proposal Intent" form 
contained in Attachment 4, Item 12.  Please complete this form and 
return it to this office on or before August 4, 1997.  This will 
allow us to expedite preparations for the peer review of proposals.
  
  Funds are not presently available for this requirement.  The 
Government's obligation under a resulting contract is contingent 
upon availability of appropriated funds from which payment for 
contract purposes can be made.
  
  If you intend to submit a proposal in response to this RFP, it is 
essential that you immediately notify Peggy Mills, Contract 
Specialist, from the NHLBI Contracting Office at the following 
Internet address: 
  
                 pm39m@nih.gov
  
  If you fail to notify the Contracting Office of your interest, you 
will not receive notification of amendments issued to this RFP.  
However, all amendments will be posted on the NIH Gopher and/or the 
NIH Home Page.  Also, please note the requirement for submission of
a Proposal Intent Response sheet later in this RFP.  
 
If you have any additional questions regarding this RFP, please
contact Peggy Mills, Contract Specialist by facsimile (301)
480-3430, by phone (301) 435-0351 or by electronic mail at the
address above. Collect calls will not be accepted.
  
  
  Sincerely,
  
    /s/
  
  Donna Berkowitz
  Contracting Officer
  National, Heart, Lung, and Blood Institute
  
  
  Attachments:  1 - 5
  
  
  
  
  
  *****************************************************************
  *****************************************************************
  RFP-NIH-NHLBI-HC-97-10  
  
  I.  STREAMLINED RFP
  
ATTACHMENT  1: INTRODUCTION, BACKGROUND, AND WORK STATEMENT
  
  
  INTRODUCTION
  ------------
  
  This proposed study will determine whether early treatment with
intravenous magnesium of  patients with suspected acute myocardial
infarction (presenting with  ST elevation on the ECG) and who are at
(relatively) high risk for  mortality, reduces all-cause 30 day
mortality. Secondary endpoints will be followed also for a 30 day
mortality and include the development of cardiogenic shock, 
ventricular fibrillation, congestive heart failure, and conduction 
delay that requires the placement of a temporary pacemaker.  
  This study will be a randomized, placebo-controlled, double blind
trial which will include approximately 10,400 patients with acute 
myocardial infarction. Patients who do not receive thrombolytic 
therapy or primary angioplasty (PTCA) will be randomized if they can 
begin their magnesium infusion within 6 hours of the onset of 
symptoms.  Patients 65 years of age or older undergoing reperfusion
therapy  (either with thrombolytics or PTCA) will be eligible
provided  magnesium can be administered before or at the same time
as the  reperfusion therapy.  Patients will be stratified at
randomization  based on whether or not they receive reperfusion.
  
  Details of the study design include patient entry criteria, 
randomization procedures, and analyses which will be incorporated 
into a protocol developed by the successful respondent to this 
request for proposals in conjunction with consultants, and  the
National Heart, Lung, and Blood Institute (NHLBI) staff.
  
  
  BACKGROUND
  ----------
  
  Mortality in acute MI
  
  The management of patients with acute myocardial infarction (MI)
has  improved dramatically over the last three decades.  Advances in
the  general coronary care unit environment, treatment with beta 
blockers, and aggressive attempts at reperfusion have all 
contributed to a reduction in mortality from acute MI.(1)  Large 
randomized trials have demonstrated that aggressive reperfusion 
strategies in conjunction with aspirin can reduce mortality in 
patients with suspected acute MI to an average of 6.5%-7.5%.(2)   
However, the mortality rate remains high in two particular subgroups 
of patients: those who do not receive thrombolysis (11.5%-13%) or 
those over 65 years who do receive thrombolytics (13.5%-24%).(2,3)  
  
  Recently, attention has turned to additional adjunctive 
pharmacologic treatment with agents such as magnesium, nitrates, and 
angiotensin converting enzyme inhibitors to determine their 
potential for reducing mortality further.  Of these, magnesium 
appears to be particularly promising.  It is safe, even in the hands 
of physicians who have no prior experience with it and it is easily 
administered and readily available in any hospital in the United 
States.  Further, if it has the expected benefit in the high risk 
groups described, it would become an unusually cost-effective 
intervention, costing less than $2,500 per year of life saved.  
  Potential cardioprotective effects of intravenous magnesium in
acute  MI.
  
  Supplemental administration of magnesium very early after the
onset  of acute myocardial infarction is supported by abundant data 
indicating potential cardioprotective effects of magnesium.(4-6)   
Magnesium is considered to be "nature's physiologic calcium 
blocker."(6)  This is because it protects myocytes against calcium 
overload by inhibiting calcium influx which is particularly 
important at the time of reperfusion.  In experimental models of 
ischemia and reperfusion, agents inhibiting calcium influx improved 
post-ischemic recovery of mechanical function when given prior to or 
at the time of reperfusion.  On the other hand, little improvement 
in mechanical function was observed if such agents were given 15-20 
minutes after the onset of reperfusion.(7)  Reduced serum magnesium 
may also be responsible for a maladaptive increase in coronary tone 
and an increased response to vasoconstrictors.
  
  In the setting of acute myocardial infarction, when increased
serum  magnesium might be beneficial, there is actually a decline in
free  magnesium.  This comes about because of a sharp rise in free
fatty  acids brought about by catecholamine induced lipolysis at the
onset  of chest pain, that results in a completing of magnesium in
the form  of insoluble soaps.  Thus, although total body magnesium
does not  decrease, magnesium available in a free form that is
capable of  exerting a cardioprotective effect declines.  Hence,
there is a  strong theoretical rationale for supplemental magnesium 
administration in this setting.
  
  Need for a new clinical trial of intravenous magnesium in acute
MI.
  
  Review of RCT experience:  Since 1984, at least 10 randomized 
control trials (RCTs) of intravenous magnesium for acute MI have 
been reported.  Several statistical models exist for pooling the 
data from multiple RCTs in a meta-analysis and estimating the 
treatment effect of magnesium.  It is important to review the 
essential features of these models in order to place the RCT 
findings in proper perspective.  The fixed effects model assumes 
that the RCTs are sampled from a homogenous group of trials.  Under 
the homogeneity assumption, each RCT provides an estimate of the 
true treatment effect and differences between the estimates from the 
various RCTs are due only to experimental error (within-trial 
variability).  The random effects model assumes the RCTs are 
heterogeneous and that differences between their estimates of the 
treatment effect are due both to experimental error (within-trial 
variability) and real differences among the trials such as trial 
design and characteristics of the patients enrolled (between-trial 
variability).(8)  The random effects model is generally favored
since  heterogeneity that cannot be explained by experimental error
often  exists among the RCTs, and this model takes such
heterogeneity into  account in estimation and hypothesis testing.(9) 
 
  Meta-analyses of the 7 RCTs published between 1984-199l provided
an  estimated odds ratio (OR) for mortality of magnesium treated 
patients of 0.44 (0.27-0.71) using the fixed effects model and 0.45 
(0.23-0.86) using the random effects model.(10,11)  The Leicester 
Intravenous Magnesium Intervention Trial (LIMIT-2), published in 
1992, reported a 24% reduction in mortality with magnesium treatment 
(P<0.04), confirming the benefit of magnesium in reducing mortality 
in MI and inspiring many clinicians to advocate magnesium treatment 
programs in their coronary care units.(12)  The magnesium treated 
patients in LIMIT-2 experienced a 25% lower incidence of congestive 
heart failure in the coronary care unit, suggesting that magnesium 
exerts its beneficial effects, at least in part, via a direct 
protective action on the myocardium. Given the potent predictive 
power of left ventricular function on survival following MI one 
would anticipate that magnesium-treated patients in LIMIT-2 would 
have a lower long-term mortality.  This hypothesis appears to have 
been confirmed by the recent long-term follow up report from LIMIT-2 
showing a 21% lower rate of ischemic heart disease related mortality 
in the magnesium group over a median follow up of 2.7 years.(13) 
The  LIMIT-2 investigators have recently examined the mortality
rates  over a 5 year follow up, and continue to document the same
long term  benefit of magnesium administered in the acute phase of
infarction.   (14)   The absence of any loss of the mortality
benefit of magnesium  over the long term is consistent with a
significant myocardial  protective effect achieved during the
critical period of myocardial  reperfusion.
  
  The results of ISIS-4 seemed to contradict the results of the
above  studies.  A total of 58,043 patients were enrolled in ISIS-4,
29,009  allocated to magnesium and 29,034 to control. There were
2,196  deaths (7.6%) by 35 days in the magnesium group and 2,079
deaths  (7.2%) in the control group (OR 1.06[0.99-1.13]) suggesting
no  mortality benefit of magnesium administration and even the 
possibility of slight harm.(15)   The findings of ISIS-4 have
triggered  considerable controversy over the reasons why it produced
a null  effect for magnesium in reducing mortality in suspected
acute MI.(16,17)
  
  When ISIS-4 is added to the preceding 8 RCTs the fixed effects
model  (driven heavily by the large sample size of ISIS-4) indicates
no  beneficial effect of magnesium (OR= 1.02 [0.96-1.09])while the 
random effects model that takes into account the heterogeneity among 
these trials suggests that magnesium may reduce mortality (OR= 
0.69[0.47-1.02]).(18)  Thus, the random effects model suggests that 
one must search for possible sources of differences between ISIS-4 
and the preceding trials.  Two important differences that appear to 
be acting in concert to bias ISIS 4 towards a null effect of 
magnesium include:
  
  1. A low control group mortality rate.  The control group
mortality  in ISIS-4 was only 7.2%.  This was probably the result of
the  combination of extensive use of thrombolysis (70% of patients)
and  antiplatelet agents (94% of patients) combined with the
enrollment  of intrinsically low-risk patients (only 28% were over
70 years of  age, 17% had a history of a prior MI, 14% had clinical
CHF, and 2%  had SBP <100 mm Hg).  Incremental mortality reducing
effects of  magnesium are difficult to detect against a low
background control  mortality rate.  The inability of ISIS 4 to
detect any overall  benefit of magnesium also apply to specific
subgroups such as the  17,325 patients who did not receive
thrombolytics.  ISIS 4 had less  than 60% power to detect even a 10%
reduction observed in the 9.3%  control mortality in this subgroup. 
A detailed analysis relating  the mortality rate in the control
group and the treatment effect of  magnesium observed in the
clinical trials published before ISIS-4  shows clearly that the
benefit of magnesium therapy increases as the  control group
mortality increases. Using this  relationship, it was predicted that
trials with a control group  mortality rate of about 7% would show
no benefit of magnesium  therapy, precisely the result observed in
ISIS-4(17,18).  Of note, the  LIMIT-2 trial observed a control group
mortality of 10.3% that was  reduced to 7.8% with magnesium. The
ISIS-4 control group mortality  was thus below that of the magnesium
treated group in LIMIT-2.
  
  This analysis is consistent with the results of the latest RCT 
recently reported by Shechter and colleagues.(19)  They randomized
194  patients with acute MI considered unsuitable for thrombolysis
to  control (N=98) or intravenous magnesium (N=96).  In addition to
the  standard contraindications to lytic therapy, reasons for
exclusion  from thrombolysis included either presentation after 6
hours and/or  age greater than 70 years. 
  
  Shechter et al (19) reported 17 deaths (17.3%) in the placebo
group and  4 deaths (4.2%) in the magnesium group corresponding to
an OR of  0.21 (0.07-0.64).  Consistent with the hypothesis that
magnesium  helps reduce mortality by a direct myocardial protective
effect are  the data on the causes of death in this latest study. In
the placebo  group, 11 patients died from cardiogenic shock, 2 from 
electromechanical dissociation, 2 from myocardial rupture and 1 from 
cardiac arrest.  In contrast, in the magnesium group 1 patient died 
from cardiogenic shock, 1 from myocardial rupture, and 2 from 
electromechanical dissociation.  Particularly noteworthy are the 
findings in the subset of 77 patients over the age of 70, a group 
expected to have a high short-term mortality from acute MI. Indeed, 
10 of the 44 elderly patients treated with placebo died (23%) while 
only 3 of the 33 elderly patients treated with magnesium died (9%, 
p=0.09).  Also, in this especially high risk subgroup, the incidence 
of congestive heart failure was reduced from 25% in the placebo 
patients to 18% in the magnesium patients.
  
  2. Magnesium was administered late in ISIS-4. The ISIS-4 protocol 
required that acute phase treatments for MI, including lytic 
therapy, were administered prior to randomization and initiation of 
study drug therapy (i.e. magnesium). By design, therefore, magnesium 
could not be administered in the "early" lytic phase (e.g. first 
hour).(15)  Although the time from onset of symptoms to
randomization  was recorded in ISIS-4, time from randomization to
actual  administration of magnesium was NOT recorded. The median
time to  randomization from the onset of chest pain for all patients
was 8  hours; in the subset of patients who did not receive
thrombolytic  therapy (30% of trial patients) the median time to
randomization  from onset of chest pain was QUITE prolonged at 12
hours. No further  details of the distribution of time to
randomization have been  reported by the ISIS-4 investigators. In an
effort to answer these  concerns, they conducted a retrospective
survey of a 1,000 randomly  selected patients. This revealed that
among those receiving  thrombolytics only about 50% received
magnesium within the two hours  following the start of thrombolytic
therapy. LIMIT-2 randomized  patients a median of 3 hours from the
onset of chest pain, and in  Schechter's study19 of nonthrombolytic
treated patients, the average  time from chest pain to initiation of
treatment was about 7 hours in  both the treatment and placebo
groups (a full five hours earlier  than in the non thrombolized
group in ISIS-4) Attempts at subgroup  analyses in ISIS-4 also
suffer from a critical lack of precise  information on the actual
time of administration of magnesium. Thus  although no apparent
benefit of magnesium was seen in the 23,000  patients randomized
within six hours of the onset of chest pain, or  among the 17,000
who did not receive thrombolytic therapy (including  9,000
randomized within 12 hours), since most of these patients  received
magnesium several hours after randomization, one cannot be 
confident that reperfusion (pharmacologically induced or 
spontaneous) took place in the presence of a raised serum magnesium 
level in any subgroup. Experimental attempts aimed at ameliorating 
cellular calcium overload have shown that calcium antagonists must 
be administered before reperfusion or during a critical window of 
only a few minutes following reperfusion in order to minimize 
contractile dysfunction. Calcium flux inhibitors, such as magnesium, 
administered too late after reperfusion appear to be
ineffective.(20,21)
  
  The same observations pertain to the subset of patients alluded to 
by the ISIS-4 Investigators who were randomized within six hours of 
symptoms onset and had a high multivariate prognosis score. In the 
absence of details on the timing of administration of magnesium, 
with particular reference to the elapsed time from onset of 
thrombolytic therapy, even in high risk subgroups, the findings of 
the ISIS-4 study remain compatible with the hypothesis that early 
administration of magnesium (particularly before reperfusion occurs) 
is associated with a reduction in mortality from acute myocardial 
infarction.
  
  Conclusion:
  
  The implications of these observations are that, to prevent
calcium  overload of reperfused myocytes, a loading dose of
magnesium should  be administered before thrombolytic therapy and
during the period  when spontaneous reperfusion is most likely to
occur in patients not  receiving thrombolytics. The design of ISIS-4
did not permit these  conditions to be met.  Further, prior studies
suggest that the low  risk profile that characterized the ISIS-4
patients would have been  likely to preclude obtaining much
additional benefit. The results of  the small trial reported by
Shechter et al (19) strongly support the  view that high risk MI
patients benefit from early treatment with  magnesium infusion. 
However, definitive proof requires the larger  sample size proposed
in this study.
  
  References
  
  1.  de Vreede J J M, Gorgels A P M, Verstraaten G M P, Vermeer F, 
Dassen W R M, Wellens H J J. Did Prognosis After Acute Myocardial 
Infarction Change During The Past 30 years? A Meta-analysis. J Am 
Coll Cardiol 1991;18:698-706.
  
  2.   Fibrinolytic Therapy Trialists'(FTT) Collaborative Group. 
Indications for Fibrinolytic Therapy in Suspected Acute Myocardial 
Infarction: Collaborative Overview of Mortality and Major Morbidity 
Results From All Randomized Trials of More Than 1000 Patients. 
Lancet 1994;343:311-322.
  
  3.   Rogers W, Bowlby L, Chandra N, French W, Gore J, Lambrew C, 
Rubison R, Tiefenbrunn A. Weaver W. Treatment of Myocardial 
Infarction in the United States(1990-1993).  Observations from the 
National Registry of Myocardial Infarction. Circulation 
1994;90:2103-2114.
  
  4.  Arsenian M A. Magnesium and Cardiovascular Disease. Progress
in  Cardiovascular Diseases 1993:35:271-310. 
  
  5.  Flink E B, Brick J E, Shane S R. Alterations of Long-chain
Free  Fatty Acid and Magnesium Concentrations in Acute Myocardial 
Infarction. Arch Intern Med 1981;141:441-3.
  
  6.  Woods K L. Possible Pharmacological Actions of Magnesium in 
Acute Myocardial Infarction. Br J Clin Pharmacol 1991;32:3-10.
  
  7.  du Toit E F, Opie L H. Modulation of Severity of Reperfusion 
Stunning in the Isolated Rat Heart by Agents Altering Calcium Flux 
at Reperfusion. Circ Res 1992;70:960-967.
  
  8.  DerSimonian R, Laird N. Meta-analysis in Clinical Trials. 
Controlled Clinical Trials 1986:7:177-188.
  
  9.  National Research Council. Combining information: Statistical 
Issues and Opportunities for Research.  Washington, D.C.: National 
Academy Press, 1992:1-217.
  
  10.  Teo K K, Yusuf S, Collins R, Held P H, Peto R. Effects of 
Intravenous Magnesium in Suspected Acute Myocardial Infarction: 
Overview of Randomized Trials. Br Med J 1991;303:1499-503.
  
  11.  Antman E M, Lau J, Kupelnick B, Mosteller F, Chalmers T C. A 
Comparison of Results of Meta-analyses of Randomized Control Trials 
and Recommendations of Clinical Experts: Treatments for Myocardial 
Infarction. J Amer Med Assoc 1992:268:240-248.
  
  12.  Woods K L, Fletcher S, Roffe C, Haider Y. Intravenous
Magnesium  Sulphate in Suspected Acute Myocardial Infarction:
Results of the  Second Leicester Intravenous Magnesium Intervention
Trial (LIMIT-2).  Lancet 1992;339: 1553-8.
  
  13.  Woods K L, Fletcher S. Long-term Outcome After Intravenous 
Magnesium Sulphate in Suspected Acute Myocardial Infarction: The 
Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). 
Lancet 1994;343:816-9.
  
  14.  Woos KL.  Personal Communication.
  
  15.  ISIS-4: A Randomized Factorial Trial Assessing Early Oral 
Captopril, Oral Mononitrate, and Intravenous Magnesium Sulfate in 
58,050 Patients with Suspected Myocardial Infarction. Lancet 1995; 
669-85.
  
  16.  Domanski M J, Friedman L M. Relative Role of Meta-analysis
and  Randomized Controlled Trials in the Assessment of Medical
Therapies.  Am J Cardiol 1994;74:395396.
  
  17.  Woods K L, Fletcher S. Magnesium and Myocardial Infarction. 
Lancet 1994;343:1565-66.
  
  18.  Antman EM. Randomized Trials of Magnesium in Acute Myocardial 
Infarction: Big Numbers Do Not Tell the Whole Story. Am J Cardiol 
1995;75:391-93.
  
  19.  Shechter M, Hod H, Kaplinsky E, Chouraqui P, Rabinowitz B.  
Magnesium as Alternative Therapy in Patients with Acute Myocardial 
Infarction Who Are Not Candidates for Thrombolytic Therapy.  Am J 
Cardiol 1995;75:321-323.
  
  20.  Opie L H. Myocardial Stunning - Are Calcium Antagonists
Useful?  Cardiovascular Drugs and Therapy 1994;8:533-541.
  
  21.  Leor JL, Kloner RH.  Does Magnesium Have a Place in the
Therapy  of Acute Myocardial Infarction?  Significance of Early vs.
Late  Reperfusion.  J Am Coll Cardiol, 1995 (February) 189A.
  
  
  WORK STATEMENT
  --------------
  
  Independently and not as an agent of the Government, the
Contractor  shall furnish all the necessary services, qualified
personnel,  material, equipment, and facilities, not otherwise
provided by the  Government as needed to perform the Statement of
Work below.
  
  I. GENERAL DESCRIPTION OF REQUIREMENTS
  
  A.  The anticipated performance period for the MAGIC study is
April 1,  1998 through March 31, 2001.  Throughout the period of
performance,  the Contractor shall provide appropriate personnel
with expertise in  cardiology to:
  
  1.  Participate fully in all Steering Committee and other study 
meetings;
  
  2.  Take lead responsibility in particular scientific areas for 
protocol development, data analysis and publication preparation;
  
  3.  Work cooperatively with other study investigators, and the
NHLBI  Program Office staff in all aspects of the study;
  
  4.  Be involved and closely familiar with data collection and 
quality control activities at own Clinical Center; and
  
  5.  Contribute to committees established by the Steering Committee 
as needed (e.g. Mortality and Morbidity Classification Committee, 
Publications Committee, etc.).
  
  B.   Throughout the period of performance, the Contractor shall:
  
  1.  Work with selected experts and NHLBI staff in the development
of  the protocol, forms, and a detailed Manual of Operations for the 
study.  The contractor shall be responsible for distribution of the 
forms and Manual of Operations.  This manual,  and all forms shall 
be updated and distributed as necessary during the conduct of the 
study.
  
  2.  Work with NHLBI staff and the Steering Committee in the 
selection of qualified clinical investigators.  Develop criteria for 
selection of clinical investigators early in Phase I.  Criteria for 
selection shall, at a minimum, include evidence of an adequate 
patient population; evidence of successful management of the subject 
population; evidence of institutional support; and previous 
experience with clinical trials.  Potential clinical investigators 
will be identified through mailings to appropriate organizations and 
professional associations such as the American College of 
Cardiology.
   
  3.  Establish procedures for data entry.
  
  4.  Train the clinical staff in proper procedures and data 
collection for the study.
  
  5.  Develop a system of random assignment of each patient eligible 
and willing to participate in the trial and make the necessary 
arrangements for randomization at the individual clinical 
investigator settings.
  
  6.  Monitor patient recruitment and provide weekly enrollment 
reports to the NHLBI  during the recruitment period.  This report 
shall include data on minorities and women randomized, as well as a 
log of those screened.
  
  7.  Accumulate and maintain appropriate data files.  Maintain 
confidentiality and security of the data files.
  
  8.  Provide on-going quality control and management procedures,
such  as verification of data entered and analyzed, and reentry of a
small  sample of the data set.
  
  9.  Provide continuous medical and technical support for 
randomization emergencies (24 hour on-call physician).
  
  10.  Monitor quality control and performance of the clinical 
investigators, and prepare reports on these and related matters as 
stated in the study protocol. The contractor shall assume the 
responsibility of reviewing, on a regular basis, the quality of all 
data transmitted by the clinical investigators.
  
  11.  Develop appropriate methods of analysis and presentation of 
data collected during the course of the study.
  
  12.  Prepare quarterly technical and statistical reports and
charts  for distribution to the NHLBI as appropriate. These reports
shall  include a description of the activities during the reporting
period,  including subcontract activities.  The narrative portion of
the  report, as well as the charts, shall include how progress in
the  particular quarter compares with the target progress predicted
for  that quarter.  The contractor shall identify any problems that
have  arisen and how they have been or will be resolved.  Activities 
planned for the ensuing reporting period shall be discussed.  The 
report and the progress chart are due 15 calendar days after the end 
of each quarter.
  
  a.  The progress chart shall serve as the basis for assessing the 
actual progress during the particular reporting period.  Any 
deviation from the progress chart shall be explained and corrective 
measures shall be discussed.  If necessary, the progress chart shall 
be readjusted to reflect the true progress achieved and future work 
to be performed.  The first annual report shall be submitted within 
three months after the effective date of the contract and quarterly 
thereafter.  Specific dates are in Article F.1. of the contract.
  
  13.  Prepare interim technical and statistical reports for 
presentation to the Data and Safety Monitoring Board (DSMB).
  
  14.  Monitor adverse effects.
  
  15.  Prepare reports of the study for publication in collaboration 
with the investigators and the NHLBI.
  
  16.  Coordinate, arrange, participate in, and provide any 
information necessary for regular clinical investigator meetings, 
and prepare and distribute minutes of each meeting and any other 
correspondence necessary.
  
  17.  Obtain clearances required by the Paperwork Reduction Act
from  the Office of  Management and Budget. 
 
  18.  Obtain single project assurance numbers from the Office for 
Protection from Research Risks, National Institutes of Health, DHHS 
on each clinic before randomizing patients from that clinic.
  
  II. SPECIFIC REQUIREMENTS AND TASKS
  
  In addition to performing the requirements included above under 
"General Description of Requirements," the contractor shall perform 
the following specific tasks and requirements in the proposed 
timetable described below:
  
  Phase I - (Planning) April 1, 1998 - September 30, 1998 (6 Months)
  
  a.  Develop a detailed Study Protocol and Manual of Operations for 
the conduct of this multi center clinical study. The contractor
shall  be responsible for organizing meetings of the Protocol
Planning  Group, including paying for travel costs of approximately
ten people  for three meetings.  In addition, the contractor shall
be  responsible for organizing one Planning Review Committee meeting
for  ten people.
  
  b.  Assume responsibility for developing, pretesting, reproducing, 
and distributing  appropriate reporting forms.
  
  c.  Prepare and present the study protocol to the NHLBI Project 
Officer, Contracting Officer, and the MAGIC Planning Review 
Committee within five months after the effective date of  the 
contract.  
  
  d.  An external peer review panel established by the NHLBI will
make  a recommendation regarding final approval of the MAGIC study 
protocol.  The Contractor shall not begin work on Phase II activity 
until written approval has been received from the Contracting 
Officer.  The progress for the study shall be periodically reviewed 
by the Data and Safety Monitoring Board.
  
  e.  Provide staff to coordinate the conduct of the study as
outlined  in the Study Protocol and Manual of Operations. 
  
  f.  In conjunction with NHLBI staff, select clinical investigators 
who are capable of carrying out the protocol according to criteria 
developed (See B.2. above).
  
  g.  Prepare a training video and other training materials and 
distribute these items to a maximum of 300 Investigators.
  
  h.  Organize the drug distribution to the clinical sites. The
NHLBI  will make arrangements for the drug to be provided at no cost
to the  study.
  
  I.  develop administrative procedures necessary for reimbursement
of  clinical investigators for accepted data forms.  Investigators
will  receive a fixed fee for each completed and accepted patient 
randomized data form and another fixed fee for each completed and 
accepted patient follow-up data form.
  
  NOTE:  THE REIMBURSEMENT TO CLINICAL INVESTIGATORS FOR  ACCEPTABLE 
DATA FORMS SHALL BE PAID FOR UNDER THE CONTRACT; HOWEVER, THESE 
COSTS SHALL BE IDENTIFIED AS AN ITEM NOT SUBJECT TO INDIRECT COSTS.  
A GENERAL AND ADMINISTRATIVE RATE TO COVER THE COST OF HANDLING 
CLINIC REIMBURSEMENT MAY BE PROPOSED.  OFFERORS MUST SUGGEST A 
REASONABLE REIMBURSEMENT FEE TO BE PAID TO CLINICAL SITES FOR 
RANDOMIZATION AND FOLLOW-UP ALTHOUGH THE FEE WILL BE SUBJECT TO 
NEGOTIATION.  NOTE THAT REIMBURSEMENT WILL ONLY BE PROVIDED FOR 
RANDOMIZED PATIENTS.  STAFF PAID UNDER THE CONTRACT WILL BE 
RESPONSIBLE FOR HANDLING REIMBURSEMENT ACTIVITIES. ROUTINE PATIENT 
CARE COSTS ARE TO BE ASSUMED BY THIRD PARTY OR OTHER NORMAL  
PAYMENT PROCEDURES.  CALCULATION OF FEES SHOULD BE BASED ON   
ADDITIONAL EFFORT REQUIRED FOR PURPOSES OF THE STUDY.
  
  Phase II - (Recruitment and Follow-up) October 1, 1998 - September 
30, 2000 (24 Months)
  
  Approximately 10,400 patients will be randomized over 24 months,
by  at least 200 sites.
  
  a.  Randomly assign patient to treatment groups and monitor
patient  recruitment in the study.
  
  b.  Assume responsibility for prompt accumulation, entry, and 
editing of study data.
  
  c.  Communicate with the clinical investigators concerning
missing,  delayed, incomplete, or erroneous data.
  
  d.  Monitor patient recruitment and provide weekly enrollment 
reports to the NHLBI  during the recruitment period.  This report 
shall include data on minorities and women randomized, as well as a 
log of those screened.
   
  e.  Prepare interim statistical reports quarterly and as needed to 
monitor study progress, quality of data, clinical investigator 
performance (enrollment, protocol compliance, form completion), 
complications, and adverse reactions.     
  
  f.  Arrange for one meeting for all Investigators at the clinical 
sites (approximately 250-300 people) at the location of a National 
Scientific Meeting; arrange for two DSMB meetings for ten people at 
each meeting. Record, produce and distribute minutes for all 
meetings and conference calls.  
  
  g.  Prepares reports on patient recruitment, status of data 
collection, quality control, and matters relating to any other data 
to be discussed at the clinical investigators meeting, Steering 
Committee and DSMB Meetings or conference calls. (Note:  For 
estimating purposes, assume 1 DSMB Meeting in each year of Phase II 
for 10 people.)
  
  h.  Begin analysis activities from the start of data collection 
through the end of Phase III.
  
  Phase III - (Analysis) October 1, 2000 - March 31, 2001 (6 months) 
  Completion of data collection analysis and manuscript preparation 
will take place.
  
  a.  Finalize data collection from clinical investigator units.
  
  b.  Continue analysis of study data.
  
  c.  Arrange a meeting for approximately eight person (contractor) 
trips.
  
  d.  Work with clinical investigators including NHLBI staff in the 
preparation of reports and scientific manuscripts.
  
  e.  Submit a draft copy of the final written report of the entire 
MAGIC study to NHLBI for approval one month prior to the contract 
completion date.  The final report shall summarize the work 
performed and results obtained for the entire contract period of 
performance.  This report shall be in sufficient detail to describe 
comprehensively the results achieved.  The contractor shall submit, 
with the final report, a summary (not to exceed 200 words) of 
salient results achieved during the performance of the contract.  
The final version of this written report shall be submitted to the 
NHLBI  by the expiration date.
  
  f.  Prepare a final data tape for delivery to the NHLBI one month 
prior to contract  completion date.
  
 
********************************************************************
 
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  RFP-NIH-NHLBI-HC-97-10
  
  ATTACHMENT  2: DELIVERABLES AND REPORTING REQUIREMENTS
  
  
  DELIVERABLES AND REPORTING REQUIREMENTS
  ______________________
  
  The Contractor shall submit to the Contracting Officer and to the 
Project Officer technical progress reports covering the work 
accomplished during each reporting period. These reports are subject 
to technical inspection and requests for clarification by the 
Project Officer. These shall be brief and factual and prepared in 
accordance with the following format:
  
  A.  TECHNICAL REPORTS
  
  In addition to those reports required by SECTION I and other 
terms of this contract, the Contractor shall prepare and submit  the
following reports in the manner stated below:
  
  (1) WEEKLY RECRUITMENT REPORTS.  Upon initiation of the study 
protocol, the Contractor shall  submit recruitment reports every 7 
days to the Clinical Trials  Center.  These reports shall include 
the number of patients recruited, describe the progress of 
recruitment activities, and describe registry enrollment of study 
subjects as defined by the study protocol and manual of operations.  
In these reports, the Contractor shall submit information about the 
inclusion of women and members of minority groups and their 
subpopulations.
  
  (2) MONTHLY RECRUITMENT AND FOLLOW-UP REPORTS.  During Phase II,
the  contractor will submit monthly follow-up reports to the
Clinical  Trials Center. These reports shall describe the progress
of  the  clinical trial indicating the number of patients that were
seen  initially and in follow-up.  The report shall indicate which
data  were collected and whether the patient was seen within the
window  defined by the study protocol.  
  
  (3)  SEMI-ANNUAL TECHNICAL PROGRESS REPORTS - by the fifteenth 
working day of the month following the end of each six month period, 
the Contractor shall submit the Semi-Annual Technical Progress 
Report.  Such reports shall include the following specific 
information:
  
  a. A cover page that lists the contract number and title, the
period  of performance being reported, the Contractor's name and
address,  the author(s), and the date of submission;
     
  b. SECTION I - An introduction covering the purpose and scope of
the  contract effort;
      
  c. SECTION II - A description of overall progress plus a separate 
description for each task or other logical segment of work on which 
effort was expended during the report period. The description shall 
include pertinent data and/or graphs in sufficient detail to explain 
any significant results achieved and preliminary conclusions 
resulting from analysis and scientific evaluation of data 
accumulated to date under the project;
       
  d. SECTION III - Substantive performance; a description of current 
technical or substantive performance and any problems encountered 
and/or which may exist along with proposed corrective action.  Each 
clinical study should be reported separately according to the number 
assigned by the Project Officer.  An explanation of any difference 
between planned progress and actual progress, why the differences 
have occurred and if behind planned progress what corrective steps 
are planned;
       
  e. An anticipated work plan for the next six months; and
    
  f. Pre-prints, reprints of papers and abstracts shall be submitted 
along with the report.
  
  Semi-Annual Technical Progress Reports are not due for periods  in
which an annual or final report is due.
  
  (4)  ANNUAL REPORTS - On the anniversary date of the contract, the 
Contractor shall submit an annual Technical Progress Report. Such 
reports shall detail, document, and summarize the results of the 
entire contract work for the period covered and shall include 
information regarding numbers of women and minority subjects 
enrolled in trials. These reports shall be in sufficient detail to 
explain comprehensively the results achieved. Also to be included in 
the report is a summary of work proposed for the next reporting 
period. Specific requirements, in any, are set forth in the Work 
Statement.  A one page summary of each ongoing and completed 
protocol shall also be submitted at this time.  Pre-prints, reprints 
of papers and abstracts not submitted in the semi-annual technical 
progress report shall be submitted.
      
  An annual report will not be required for the period when the
final  report is due.
  
  (5)  DRAFT FINAL REPORT A draft final report shall be submitted to 
the NHLBI for approval 30 calendar days before the expiration date.  
Upon approval, a final version of the report shall be submitted to 
the NHLBI which is due on or before the expiration date of the 
contract.  This report shall be no more than five pages in length, 
documenting and summarizing the results of the entire contract work, 
including recommendations and conclusions.
  
  (6)  FINAL REPORT - By the expiration date of the contract, the 
Contractor shall submit a comprehensive Final Report.  These final 
reports shall detail, document and summarize the results of the 
entire contract period of performance. These reports shall be in 
sufficient detail to explain comprehensively the results achieved.  
Pre-prints, reprints of papers and abstracts not included previously 
shall be submitted.
    
  (7)  SUMMARY OF SALIENT RESULTS - With the annual and final
reports  the Contractor shall submit a summary (not to exceed 200
words) of  salient results achieved during performance of the
contract.
    
  (8)  OTHER REPORTS - The Contractor shall submit to the Project 
Officer and or the Contracting Officer:
  
  a.  A draft version and upon approval, a final version of the
study  protocol, prepared in collaboration with the Steering
Committee and  the NHLBI Project Office.
  
  b.  A draft version and upon approval, a final version of the
Manual  of Operations, prepared in collaboration with the Steering
Committee  and the NHLBI Project Office.
  
  c.  Data shall be documented, regularly updated and delivered in
SAS  format to Steering Committee members and the Project Office as 
directed by the Project Officer.
  
  d.  Reports shall be provided as needed for Steering Committee 
meetings, DSMB Meetings,  NHLBI meetings, etc.  Special reports 
needed may include protocol amendments, training materials, OMB 
forms-clearance submission, etc. 
  
  e.  Minutes of Steering Committee meetings, etc. shall be
delivered  to the Project Office and Contracting Office within ten
working days  after the meeting concludes. 
   
  NOTE TO OFFERORS: OMB forms submission is required if a clinical 
exemption from the Paperwork Reduction Act is not obtained.
     f.  Draft OMB forms submission, as well as the final OMB forms 
submission shall be finalized in Phase I.
  
  B. If the Contractor becomes unable to deliver the reports 
specified hereunder within the period of performance because  of
unforeseen difficulties, notwithstanding the exercise of  good 
faith and diligent efforts in performance of the work,  the
Contractor shall give the Contracting Officer immediate  written
notice of any anticipated delays with reasons.
    
  C.  Technical Report Distribution
  
  Copies of the technical reports shall be submitted as follows:
  
  ITEM, NUMBER OF COPIES, AND DUE DATE 
  
  (a) Draft Protocol, 2 copies to Project Officer (PO), 1 copy to 
Contracting Officer (CO), four months after the effective date of 
the contract.
  
  (b) Draft Manual of Operations, 2 copies to PO, 1 copy to CO, four 
months after the effective data of the contract.
  
  (c) Final Protocol, 3 copies to PO, 1 copy to CO, five and one
half  months after the effective date of the contract.
  
  (d) Final Manual of Operations, 3 copies to PO, 1 copy to CO, five 
and one-half months after the effective date of the contract.       
  (e)  Data Required by the study, 1 copy to PO, delivered as
directed  by the PO.
  
  (f) Quarterly financial reports, 2 copies to CO, quarterly by the 
15th of the month following the end of the reporting period.
  
  (g)  Semi-annual progress reports, 1 copy to PO, 1 copy to CO, 
within 15 days after the t-month reporting period ending September 
30 and March 31 each year.
  
  (h)  Weekly Enrollment Reports, 2 copies to PO, 1 copy to CO, due 
weekly.
  
  (I)  Minutes of Committee, 2 copies to PO, 1 copy to CO, due 10
days  after each meeting. 
  
  (j)  Minority Reporting, 1 copy to PO, 1 copy to CO, submit with 
Annual Report.
  
  (k)  Edited Data Tape documentation for use, 1 copy to PO, due on 
expiration date and as directed by the PO.
  
  (l)  Annual Reports, 2 copies to PO, 1 copy to CO.
  
  (m)  Draft Final Report, 3 copies to PO, 1 copy to CO, due 30 
calender before the contract expires.
  
  (n)  Final Report, copies to PO, 1 copy to CO, due by the contract 
expiration date.
       
  (o) Monthly ENROLLMENT REPORTS, 2 copies to PO, 1 copy to CO, due 
monthly, 10 days after the end of each month.
  
  THE DELIVERABLES SPECIFIED ABOVE SHALL BE DELIVERED TO:
  
  Project Officer, MAGIC Study               
  Leader, Scientific Research Group     
  National Heart, Lung, and Blood Institute            
  Rockledge Building II       
  6701 Rockledge Drive, MSC 7936   
  Bethesda, MD 20892-7936          
  (For courier delivery, use zip code 20817)
  
  AND
  
  Contracting Officer, MAGIC Study
  ECA Contracts Section
  National Heart, Lung,  and Blood Institute  
  Rockledge II Building
  6701 Rockledge Drive, MSC 7902
  Bethesda, MD 20892-7902
  (For courier delivery, use zip code 20817)
  
    
 
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  RFP-NIH-NHLBI-HC-97-10
  
  ATTACHMENT  3: EVALUATION FACTORS FOR AWARD
  
  EVALUATION FACTORS FOR AWARD
  ____________________________
      
  
  1.  GENERAL
  
  Offerors should ensure that their proposal addresses the 
requirements in the Statement of Work and Deliverables to achieve 
the best possible evaluation.
  
  The evaluation will be based on the demonstrated capabilities of
the  offerors in relation to the needs of the project as set forth
in the  RFP.  The merits of the proposals will be evaluated
carefully, based  on the thoroughness and feasibility of the
technical approach taken. 
    
  The proposals will be evaluated according to the following
criteria.   The peer review group will provide narrative statements
on strengths  and weaknesses and recommendations on the
acceptability of the  proposals. 
  
  2.  TECHNICAL EVALUATION CRITERIA
  
  Proposals submitted in response to this solicitation will be 
reviewed by a peer group of scientists under auspices of the Review 
Branch, Division of Extramural Affairs, NHLBI, and subsequently by a 
review group within NHLBI.  Technical quality will be paramount.  If 
proposals are substantially equal technically, then cost may become
the discriminating factor. The Government reserves the right to make
an award to the best advantage of the Government, technical
approach, cost and other factors considered.
  
  The proposals will be assessed according to the following criteria 
and weight factors:
 
  a.  Personnel             Weight:   40 points
          
  The offeror demonstrates the qualifications and availability of 
proposed personnel including:
  
          Professional, technical, and administrative staff with
experience pertinent to the            development of  protocols and
management of  multi center clinical trial in cardiovascular         
  disease or other randomized prospective clinical trials of similar
complexity.
          Medical and scientific staff with expertise in clinical
cardiology, management of myocardial infarction, congestive heart
failure, data collection, data monitoring, quality control,     
management of side effects and adverse reactions to medical therapy,
data analysis, and            preparation of scientific reports and
manuscripts.
  
          Experience in analysis and interpretation of medical data
for purposes of ensuring patient safety, particularly with regard to
management of myocardial infarction.
  
  b.  Technical Approach     Weight:  30 points
  
  The offeror demonstrates the following:
  
          Suitability of proposed approach to protocol development
and implementation of study protocol, including accessing and
overseeing clinical investigators with the ability to enroll and
follow, as per protocol, adequate numbers of patients including
women and minority patients.
  
          Suitability of the proposed data management and data
analysis plan (adequacy of the technical approach).
  
          Adequacy of the proposed methods of coordination,
monitoring, and central management of all activities required by the
study protocol, including procedures, randomization of patients,
coordination of data collection, and specialized tests.
  
  c.  Institutional Experience and Facilities      Weight: 30 points
  
          The offeror demonstrates the following:
  
          Adequacy of the organizational and administrative
structure of the proposed program and institutional commitment to
the program.
  
          Prior participation by the institution in multi center
clinical trials in cardiovascular diseases or other randomized
prospective clinical trials of similar complexity, both in the
collection of data from multiple clinical sites as well as
experience in monitoring the quality and timeliness of such data.
  
          Availability and adequacy of the proposed facilities,
equipment, and space.
  
  100 points        TOTAL
  
  3.   EVALUATION OF MINORITY GROUP AND GENDER REPRESENTATION
       (NIH 3185) (JUL 1994)
  
  This research project involves human subjects.  NIH Policy
requires  that woman and members of minority groups and their
sub-populations  must be included in the study population of all NIH
supported  biomedical and behavioral research projects involving
human  subjects, unless a clear and compelling rationale and
justification  are provided that inclusion is inappropriate with
respect to the  health of the subjects or the purpose of the
research.  Where inclusion of women and minority populations is not
feasible, a  detailed rationale and justification for exclusion of
one or both  groups from the study population must be submitted with
the  technical proposal.  The NIH will review the exclusion
rationale to  determine if it is appropriate with respect to the
health of the  subjects and/or the purpose of the research.  If the
rationale is  not considered acceptable by the Government and you
are included in  the competitive range, you will be afforded the
opportunity to  further discuss and/or clarify your position during
discussions or  include women and minorities in your best and final
(BAFO) offer.  If your  exclusion position is still considered
unacceptable by the  Government after discussions, your proposal may
not be considered  further for award.
  
  This policy results from the NIH Revitalization Act of 1993
(Section  492B of Public Law 103-43).  All investigators proposing
research  involving human subjects should read the "NIH Guidelines
for  Inclusion of Women and Minorities as Subjects in Clinical
Research",  which have been published in the Federal Register of
March 28, 1994  (FR 59 14508-14513) and the NIH Guide for Grants and
Contracts, Vol.  23, No.11, March 18, 1994.
  
  
 
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********************************************************************
  RFP-NIH-NHLBI-HC-97-10
  
  ATTACHMENT 4: SPECIFIC RFP INSTRUCTIONS AND PROVISIONS
  
  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 in Attachment 5,
"Applicable RFP  References."
  
  1.  ESTIMATE OF EFFORT
  
  It is expected that a completion type contract will be awarded  as
a result of this RFP.  To assist you in the preparation of your 
proposal, the Government considers the total direct labor effort to 
be approximately 994%.  This estimate is furnished for  your
information only and is not to be considered restrictive for 
proposal purposes.  As further assistance, it is estimated that the 
above total labor effort is constituted as follows:
  
       Phase I: (6 Months), Effort
  
       Principal Investigator, 25%
       Co-Principal Investigator, 10%
       Program Manager, 80%
       Statistician, 10%
       Programmer, 5%
       Consultant, 5%
       Nurse Consultant, 5%
       Data Entry, 2%
       Clerical Support, 50%
       Total 192%
  
       Phase IIa: Recruitment (12 Months), Effort
  
       Principal Investigator, 25%
       Co-Principal Investigator, 10%
       Program Manager, 80%
       Statistician, 10%
       Programmer, 25%
       Consultant, 5%
       Nurse Consultant, 20%
       Data Entry, 60%
       Clerical Support,  50%
       Total 285%
  Phase IIb: Recruitment (12 Months), Effort
  
       Principal Investigator, 25%
       Co-Principal Investigator, 10%
       Program Manager, 80%
       Statistician, 10%
       Programmer, 25%
       Consultant, 5%
       Nurse Consultant, 20%
       Data Entry, 60%
       Clerical Support,  50%
       Total 285%
  
       Phase III: Analysis (6 Months), Effort
       
       Principal Investigator, 25%
       Co-Principal Investigator, 10%
       Program Manager, 80%
       Statistician, 25%
       Programmer, 25%
       Consultant, 5%
       Nurse Consultant, 10%
       Data Entry, 2%
       Clerical Support, 50%
       Total 232%
  
  *  Effort in the above chart was based on 100% effort = 2,080   
hours per year, which includes holidays and other paid  absences.  
If you are using a different base, please state the work year used 
in your proposal.  The above level of effort is the Government's 
estimate of the effort that will be necessary to satisfactorily 
accomplish the objective of these studies.
  
  2. TRAVEL REQUIREMENTS FOR SOLICITATION PURPOSES
  
  For estimating purposes, assume all meetings will be held in 
Bethesda, Maryland, and will require two days for traveling.  
Offerors should be prepared to cover all travel expenses with the 
exception of Government employees.  Proposed travel estimates should 
be based on the following:
  
  Phase I - 3 Planning Meetings for 10 people; 1 DSMB Meeting for 10 
people
  Phase IIa - 2 DSMB Meetings for 13 People
  Phase IIb - 1 DSMB Meeting for 13 People
  Phase III - 8 Contractor Trips for 1 person
  
  The Clinical Coordinator will be certified in study operations
after  the study protocol has been recommended for approval by the
Data and  Safety Monitoring Board and before Phase II begins.
  
  3.  PAPERWORK REDUCTION ACT
  
  The objective of this clinical trial is to evaluate whether early 
treatment of patients with suspected myocardial infarction reduces 
30-day mortality.  Protocol development must be expeditious if field 
work is to begin 6 months after contract award.  The Paperwork 
Reduction Act is applicable to this procurement; however, a Clinical 
Exemption is expected.  If a clinical exemption is not granted, the 
contractor shall be responsible for preparing the necessary 
documentation for OMB approval of the study forms.   
  
  4.  SIC CODE AND SMALL BUSINESS SIZE STANDARD (NIH 3150) (JUN
1988)
  
  Note:  The following information is to be used by the offeror in 
preparing its Representations and Certifications (See Attachment 5, 
Item 4. of this RFP.), specifically in completing the provision 
entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (OCT 1995), FAR 
52.219-1:
  
  a)  The standard industrial classification (SIC) code for this 
acquisition is 8733.
  
   (b) (1) The small business size standard is $5,000,000.
  
       (2)  The small business size standard for a concern which
submits an offer in its own name, other than on a construction or
service contract, but which proposes to furnish a product which it
did not itself manufacture, is $5,000,000.
  
    (c)  This requirement is NOT Set-Aside for Small Business. 
However, the Federal Acquisition Regulation (FAR) requires in every 
solicitation (except for foreign acquisitions) the inclusion of the 
Standard Industrial Classification (SIC) Code and corresponding size 
standard which best describes the nature of the requirement in the 
solicitation.
  
  5.  NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984)
  
  It is anticipated that one (1) award will be made from this 
solicitation and that award will be made on or about April 1, 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 3 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].
  
  6.  PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994)
  
  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. NIH-NHLBI-HC-97-10"
  
            "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"
  
  
     Number of Copies:
     -----------------
  
       Technical Proposal: ORIGINAL* AND 20 COPIES
       Business Proposal:  ORIGINAL* AND 8 COPIES
  
  
     If hand delivered or delivery service:
     --------------------------------------
  
  NIH, NHLBI
  Review Branch
  II Rockledge Centre, Room 7220
  6701 Rockledge Drive
  Bethesda, MD 20817
  
  If using U.S. Postal Service:
  NIH, NHLBI
  Review Branch 
  II Rockledge Centre, MSC 7924
  6701 Rockledge Drive
  Bethesda, MD 20892-7924
  
  *  THE ORIGINALS MUST BE READILY ACCESSIBLE FOR DATE STAMPING
      PURPOSES
  
  NOTE:  The U.S. Postal Service's "Express Mail" does not deliver
to  the Rockville, Maryland address.  Any package sent to the
Rockville  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" and handled in accordance with PHSAR
352.215-10 LATE  PROPOSALS, MODIFICATIONS OF PROPOSALS AND
WITHDRAWALS OF PROPOSALS  (NOV 1986).
  
  7.   GOVERNMENT NOTICE FOR HANDLING PROPOSALS  
    
  An Offeror shall place this notice on top of each copy of its 
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 subdirectory of the
RFP  REFERENCES directory of the Gopher RFP).
    
  8.  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 Carlsen
  
                 Hand-Carried Address:
  
                      National Institutes of Health
                      National Heart, Lung, and Blood Institute
                      Contracts Operations Branch
                      TWO ROCKLEDGE CTR RM 6122    
                      6701 ROCKLEDGE DR MSC 7902
                      BETHESDA MD 20817
  
                 U.S. Postal Service:
  
                      National Institutes of Health
                      National Heart, Lung, and Blood Institute
                      Contracts Operations Branch
                      TWO ROCKLEDGE CTR RM 6122    
                      6701 ROCKLEDGE DR MSC 7902
                      BETHESDA MD 20892-7902
  
  (b)  The copy of any protest shall be received in the office 
designated above on the same day a protest is filed with the GSBCA 
or within one day of filing a protest with the GAO.
  
    9.  PRIVACY ACT SYSTEM OF RECORDS
  
  This procurement action requires the clinical sites to do one or 
more of the following: design, develop, or operate 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 the clinical trials 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 clinical 
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 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
  
  All records (manual and automated) will be disposed of in
accordance  with instructions to be furnished by the Government on
or before  expiration of the contract. The Privacy Act System of
Records Notice  that applies to this RFP.
  
10.  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 education
entity; or (2) a student at the covered educational entity from
enrolling in a unit of the senior Reserve 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.
11.  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 payment Acts I (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 CFR46.208(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 45CFR 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.
  
12.  TECHNICAL PROPOSAL TABLE OF CONTENTS/FORMAT
  
  IMPORTANT:  Technical proposals submitted in response to this  
RFP MUST NOT EXCEED 25 PAGES, however, this limitation does not 
include copies of the requested sample protocols, consent forms, and
Appendices.  PAGES SUBMITTED IN EXCESS OF THIS LIMIT WILL BE DELETED
AND WILL  NOT BE REVIEWED.  PLEASE NUMBER EACH PAGE. The front side
of a  page equals one page (front and back of a page equals two
pages).  Type density and size must be 10 to 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:
  
 SECTION #                                                    PAGE #
  
     1.  TECHNICAL PROPOSAL COVER SHEET (Format in the NIH Gopher
RFP under "FORMS, FORMATS, ATTACHMENTS").......................... 1
  
     2.  TECHNICAL PROPOSAL TABLE OF CONTENTS .................... 2
  
     3. ABSTRACT.................................................. 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. The abstract is used by the Scientific Review
Administrator in making review assignments.  DO NOT EXCEED one page
in providing the abstract.  Identify the RFP Number, Institution and
Principal Investigator on the abstract.
  
     4.  TECHNICAL PLAN 
Refer to Technical Proposal Instructions, Standard RFP Instructions
and Provisions, Gopher RFP for more detail)
  
           a. WORK STATEMENT (Items 1 through 4 below are not to
exceed 25 pages)
                1.Objectives...................................... 4
                2. Approach..................................... ___
                3. Methods ..................................... ___
                4. Schedule .................................... ___
           b. PERSONNEL (List by name, title, department and
organization, and detail each person's qualifications and role in
the Project); provide narrative for:
  
                1. Principal Investigator/Project Director ..... ___
                2. Other Investigators ......................... ___
                3. Additional Personnel (technical support/
                   subcontractors/consultants) ................. ___
  
[Note: Include a two page biosketch under Section 9--APPENDICES
below.]
          
           c.  FACILITIES, EQUIPMENT, AND OTHER RESOURCES.......     
List/describe all facilities, equipment, and other resources
available for this project.
           
            d.  OTHER  CONSIDERATIONS..........................     
 
                1.   SAMPLE PROTOCOLS AND CONSENT FORMS [Note:
Include in Section 9--APPENDICES below.]
                2.OTHER ITEMS (use specifically titled
subparagraphs, as applicable)
     5.  OTHER SUPPORT.........................................      
Include the 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 GENDER ISSUES NOT OTHERWISE
ADDRESSED.....................................................      
     7.  TECHNICAL PROPOSAL COST INFORMATION (form located in the
NIH Gopher RFP under "FORMS, FORMATS, & ATTACHMENTS ")........      
     8.  LITERATURE CITED
     9.  APPENDICES...........................................       
Appendices and items 4b. through 8. above do not have a page
limitation, except as is inherent in each format to be used, and
each biosketch is limited to two pages.  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>
  ******************************************************************
  
  13.  PROPOSAL INTENT RESPONSE SHEET
  
  
  RFP No.:  NHLBI-HC-97-10
  
  TITLE OF RFP: MAGNESIUM IN CORONARIES (MAGIC) STUDY
  
  PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL.  FURNISH THE 
INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY August 4, 1997.  
YOUR EXPRESSION OF INTEREST IS NOT BINDING BUT WILL GREATLY ASSIST 
US IN THE PLANNING FOR PROPOSAL EVALUATION.
  
 
===================================================================
  
  I INTEND TO SUBMIT A PROPOSAL
  
 
===================================================================
  
  COMPANY/INSTITUTION NAME:                                          
 
                                                                     
  
  ADDRESS:                                                           
 
  PROJECT DIRECTOR'S NAME:                                           
 
     TITLE:                                                         
  
  TELEPHONE NUMBER:                                  
  
ELECTRONIC MAIL (E-MAIL) ADDRESS:
  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
  II Rockledge Centre, MSC 7924 
  6701 Rockledge Drive
  Bethesda, MD  20892-7924
  
  <End form - Proposal Intent>
 
********************************************************************
 
********************************************************************
  
  RFP-NIH-NHLBI-HC-97-10 
  
  ATTACHMENT 5: APPLICABLE RFP REFERENCES
  
  III. APPLICABLE RFP REFERENCES
  ------------------------------
  
  This section identifies the items located in the Gopher directory
at  URL gopher://gopher.nih.gov:70/11/res/rd-rfp/rfpref.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 subdirectory 
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. 10/95)
        (5) Proposal Summary and Data record, NIH-2043 (Rev. 6/82)
        (6) Business Proposal Cost Information
        (7) Disclosure of Lobbying Activities, OMB SF-LLL 4.  
        (8)The Representations and Certifications are applicable and
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, JUN 1992
        (10) Instructions for Completing Form NIH 2706 (Financial
Report)
        (11) Procurement of Certain Equipment, NIH(RC)-7
        (12) Research Patient Care Costs, NIH(RC)-11
        (13) NIH Women and Minority Policy
        (14) Protection of Human Subjects - Assurance
Identification/Certification/Declaration,  OF 310
  
       OTHER - TO BE SUBMITTED
       ----------------------------------------------------------
  
        (15) Certificate of Current Cost or Pricing Data, NIH-1397,
to  be submitted with the Best and Final Offer, as directed by the
Contracting Officer.
        (16) 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
.