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. ******************************************************************** ******************************************************************** 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) ******************************************************************** ******************************************************************** 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. ******************************************************************** ******************************************************************** 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. ****************************************************************** 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 ******************************************************************** ******************************************************************** 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 .