| Request for Proposal No.: | NIH-NHLBI-HC-99-04 |
| Issue Date: | December 15, 1998 |
| Issued By: | Lisa T. O'Neill Contracting Officer NIH/NHLBI Contracts Operations Branch II Rockledge Centre, RM 6122 6701 Rockledge Drive, MSC 7902 Bethesda, Maryland 20892-7902 |
| Purchase Authority: | Public Law 95-83, as amended |
| Small Business Set-Aside: | No; SIC Code 8731 |
| Proposal Due Date: |
March 15, 1999, 4:00 PM (Eastern Time) |
Ladies and Gentlemen:
The National Heart, Lung, and Blood Institute (NHLBI) is soliciting proposals to initiate an epidemiological study of the prevalence, genetic and environmental determinants , and potential clinical, personal and societal impact of iron overload and hereditary hemochromatosis in a multi-center, multiethnic, primary care based sample of 100,000 adults. This RFP NHLBI-HC-99-04, is specifically for all interested Field Centers. This Streamlined Technical Request For Proposal (RFP) consists of this combined solicitation form and cover letter (PART A), and five attachments, as follows: Attachments:
Attachments A., B. and C. contain the technical information required for the submission of a proposal for this acquisition. Attachment D., titled "Specific RFP Instructions and Provisions" contains, for example, the proposal intent response form and the address for delivery of your proposal. The section titled "Applicable RFP References" lists those items in the "Streamlined RFP References" directory that apply to this RFP, including forms that can be downloaded and are required for the submission of a proposal. If you are unable to download any of the applicable documents, please contact the Contracting Officer listed above for assistance.
Although sufficient information to submit a proposal is provided, if you intend to submit a proposal in response to this RFP, it is essential that you immediately notify Ms. Lisa O'Neill, Contracting Officer, at the following Internet address:
If you fail to notify the Contracting Officer of your organizations interest, you will not receive notice of amendments which may be issued for this RFP, and this could impact your proposal preparation. However, please note that all amendments will be posted on the NIH RFP WEB SITE. Your attention is further directed to the "Proposal Intent Response Sheet" contained in Attachment D. Please complete this form and return it to this office on or before 1/29/99. This will allow us to expedite preparations for the peer review of proposals.
The Business and Technical proposals must be separate from one another in the proposal package. The Business proposal must be signed by an authorized official of your organization and must contain a detailed breakdown of costs by year for each cost category. The basis for costs must be explained and supporting documentation must be submitted with the proposal. (See "STANDARD RFP INSTRUCTIONS and PROVISIONS" in the RFP homepage for more detail on the Business proposal requirements. Your proposal (Business and Technical) must be received no later than March 15, 1999, at 4:00 p.m. local time at the address and quantity specified in Attachment D titled "Packaging and Delivery of Proposals". NOTE: IF YOUR PROPOSAL IS NOT RECEIVED BY THE CONTRACTING OFFICER OR DESIGNEE AT THE PLACE AND TIME SPECIFIED, THEN IT WILL BE CONSIDERED LATE AND HANDLED IN ACCORDANCE WITH THE PHS CLAUSE 352.215-10 TITLED, "LATE PROPOSALS, MODIFICATIONS OF PROPOSALS, AND WITHDRAWALS OF PROPOSALS".
Offers will be valid for 120 days unless a different period is specified by the offeror on the form titled, "Proposal Summary and Data Record, NIH 2043" also located at the site for FORMS, FORMATS, AND ATTACHMENTS. If you have any additional questions regarding this RFP, please contact Mrs. O'Neill through the Internet using the electronic mail address listed above or phone (301) 435-0345, fax (301) 480-3430. COLLECT CALLS WILL NOT BE ACCEPTED.
SUBMISSION OF PROPOSALS USING FACSIMILE OR ELECTRONIC MAIL IS NOT AUTHORIZED.
Sincerely Yours,
Lisa T. O'Neill
Contracting Officer
ATTACHMENTS
ATTACHMENT A
BACKGROUND AND WORK STATEMENT
The Genetic Epidemiology Scientific Research Group, Epidemiology and Biometry Program, Division of Epidemiology and Clinical Applications, NHLBI, in conjunction with the Blood Diseases Program, Division of Blood Diseases and Resources, NHLBI, and the Ethical, Legal and Social Implications Research Program, Division of Extramural Research, NHGRI, propose to initiate an epidemiologic study of the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample of 100,000 adults. This information will be used to determine the feasibility and potential individual and public health benefits and risks of primary care-based screening and intervention for iron overload and hereditary hemochromatosis. The specific objectives of the study are to:
The project duration is planned for five years.
Hereditary iron overload, or hemochromatosis, is a common inherited disorder among Caucasians, with an estimated prevalence of 0.25-0.50%, though it is mistakenly believed by many to be quite rare. The disease is insidious in onset, and many or even most individuals diagnosed with this disorder are not identified until advanced organ damage is present. However, in the absence of anemia, which can be caused by tissue damage from iron in late stages of the disease, it is relatively easy to treat the disorder by removing the excess iron through repeated phlebotomy. Evidence suggests that early diagnosis and treatment can prevent disease manifestations and enable normal life expectancy. The discovery of the HFE C282Y and H63D variants in the HLA gene region on chromosome 6 provides an opportunity for early and rapid genetic identification of individuals at risk for development of hereditary hemochromatosis. Much remains to be learned about the penetrance and expression of these alleles, including their relevance to the full spectrum of clinical disease. To date, the HFE alleles appear predominantly associated with disease mainly in populations of Caucasian descent. While 80-90% of Caucasian hemochromatosis patients have HFE abnormalities, there are hetero- and homozygotes that do not manifest any evidence of disease, or manifest disease at different ages and with different outcomes, implying the existence of other genetic or environmental factors. Similarly, not all hemochromatosis patients have HFE abnormalities. Other genes yet to be discovered are also likely to be involved in pathogenesis of iron overload and familial hemochromatosis in non-Caucasian populations as well. This project is intended to examine the genetic and environmental determinants and correlates of iron overload and hereditary hemochromatosis in diverse populations.
Increases in body iron may be due to increased absorption (hemochromatosis), increased oral intake of non-therapeutic iron, unneeded iron therapy, or multiple blood transfusions in the absence of bleeding. The excess iron is deposited in body tissues, and can reach toxic levels leading to organ damage. The toxicity can affect most tissues and organs, but particularly the liver, causing cirrhosis; the endocrine system, causing diabetes, hypogonadism, and sometimes hypoparathyroidism; and the heart, causing arrhythmias and cardiomyopathy.
Iron overload and hereditary hemochromatosis have not been as extensively studied in non-Caucasian racial/ethnic groups as they have in Caucasians. The toxicity of excess iron in non-Caucasians appears to be similar to that in Caucasians, but the prevalence of iron overload is unknown and while a genetic contribution to that overload is suspected it has not been proven in all groups. It has long been assumed that iron storage disease in populations of sub-Saharan Africa is due to increased iron absorption from beer brewed in iron pots, but more recent information suggests there is also a hereditary component to that accumulation of iron. However, iron overload among Africans does not appear to be due to HFE abnormalities, nor to other genes in the HLA region at all. Primary iron overload has been reported in African Americans but it remains to be determined whether or not this is linked to HFE or other genetic factors. Iron overload has been reported in Asian populations, but the frequency and genetic contributions (if any) are not known. In some studies where HFE variants have been found in non-Caucasians, additional genetic testing has suggested that Caucasian admixture may have been involved. Hispanic-Americans appear to have a frequency of iron overload similar to non-Hispanic Caucasians, although further study of the genetic and environmental correlates is warranted. There has been almost no study of iron overload and hereditary hemochromatosis in Native American populations.
Hemochromatosis may be suitable for detection and intervention through primary care or population-based screening strategies because: 1) it is relatively common; 2) it is asymptomatic in its early stages; 3) screening methods are reliable; 4) standard diagnostic methods are widely available in developed countries and relatively inexpensive; 5) it is easily treatable; and 6) if untreated, the subsequent burden of morbidity and mortality is substantial. The feasibility and benefits of such programs remain to be assessed, however, since the prevalence of the disorder and the factors related to its phenotypic expression (such as the optimal age for reliable detection and effective intervention) are unknown. Other questions needing to be addressed include public acceptability of screening and testing; sensitivity and specificity of the screening methods, particularly in non-Caucasians; optimal timing and setting of screening and testing; as well as the benefits and costs and/or other burdens associated with screening and testing.
A major objective of the proposed project is to gather information needed to develop recommendations regarding possible primary care- or population-based screening for hemochromatosis. Estimating the burden of preventable illness from unrecognized hemochromatosis is one of the most important of these needs. Comparing the relative value and acceptability of diagnosis and screening by genotype vs phenotype is also important. In particular, differences by racial/ethnic group, age and other characteristics will need to be examined. Some of these issues, such as appropriate thresholds for transferrin saturation screening, may be resolved during the proposed study's planning phase, while others will constitute key research questions to be addressed by the study itself.
The Iron Overload and Hereditary Hemochromatosis Study is a multi-center study of the prevalence and genetic and environmental determinants of iron overload and hereditary hemochromatosis in a diverse and representative primary care-based sample of men and women aged 25 and older. One hundred thousand patients undergoing routine screening or testing involving a blood draw will be recruited from five to seven Field Centers and screened for transferrin saturation levels. Cost-effective population-based strategies for recruitment will also be considered. A repeat fasting transferrin saturation screen in conjunction with a serum ferritin assay will be used to identify potential case' participants with confirmed elevated transferrin saturation levels and matched random control' participants with confirmed non-elevated transferrin saturation levels.
In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40% of the 100,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. The panel of genotypes to be assayed will reflect the state of knowledge at the time this phase of the study is conducted. In particular, any newly discovered variants related to iron overload and hemochromatosis in non-Caucasian populations, such as for iron overload among Africans, will be included. The results of the genotyping will not directly impact the selection of case and control participants; case/control selection will be based only on the transferrin saturation/serum ferritin screen results. It is likely that many HFE genotype positive persons will have confirmed elevations of transferrin saturation and thus may get selected as confirmed elevated transferrin saturation case participants. Genotype positive persons with non-elevated transferrin saturation levels, who are not randomly selected as controls, will constitute a third group and undergo the same intensive studies as cases and controls.
A random sample of the individuals being recruited to participate in the genotyping subgroup will be surveyed to determine their knowledge and attitudes about, interest in, and support for such screening programs. Both qualitative and quantitative measures will be employed. Efforts will be made to ascertain reasons for refusal and related information from those who decline participation. An addition 2000 primary care patients will be selected to participate in a substudy comparing phenotype- versus genotype-based screening and testing methods.
Following these transferrin and random subgroup genotyping screens, a comprehensive clinical examination will be conducted in the confirmed elevated transferrin saturation potential case participants, the genotype-positive participants, and the confirmed non-elevated control participants to assess iron stores, distinguish between primary and secondary causes of iron overload and to examine the associated hepatic, endocrinologic, hematologic and cardiovascular disease correlates and sequelae of hemochromatosis. A detailed family and medical history will be obtained. Examination participants not previously genotyped will undergo genotyping, with a panel of genotypes as described above, for use in association analyses. The genotype-positive participants will receive counseling on their results. The examination will also include an extended ELSI assessment of issues related to genetic screening and testing and diagnosis of disease. Data will be collected on the participants' acceptability of genetic testing, their experience with screening, their understanding and interpretation of their results, and on the impact this information is having on their own lives as well as those of their family members. Specific components of the comprehensive clinical examination will be determined during protocol development. Follow-up ELSI assessments will examine issues such as impact of the screening program on relationships with family members, and any experiences with stigmatization and discrimination.
A family study, using comprehensive clinical examinees as probands, will seek to identify modifier genetic variants related to the expression of iron overload and hereditary hemochromatosis disorders via genome scanning and assessment of linkage. Identification of new genetic variants, particularly in minorities, is also of great interest, but it is possible this study will not achieve sufficient power to do so. Proposed efforts to improve the power, such as combining data from other studies, will be considered. The family study ELSI assessment will examine family members' experiences with the screening program, the impact of this information on their lives and relationships, and any experiences with stigmatization and discrimination.
A repository of blood specimens will be established to permit additional studies of genetic and environmental factors relating to iron overload. This will require careful attention to the details of informed consent. For some later studies, the specimens may be anonymized.
The study will involve five to seven Field Centers, a Coordinating Center (which will subcontract for any necessary Reading Centers such as an ECG Reading Center), and a Central Laboratory (which may subcontract for novel assays and/or the genome-wide scan). Principal Investigators from each of these seven to nine Centers plus the NHLBI Project Officer form the Steering Committee. A Data Safety and Monitoring Board (DSMB) will be appointed by NHLBI to oversee the project and make recommendations on various aspects (e.g., protocol approval, participant safety, project activation, and later milestones). The DSMB is expected to meet initially to review the "final" protocol, to meet routinely (annually) during the study, and to meet on an ad hoc basis when needed for major protocol revisions or for the evaluation of unexpected results.
Time lines for the study are provided in Table 1 and Figure 1, and a list of probable exam components is shown in Table 2. Protocol planning, informed consent form design, OMB clearance, training and pilot testing will occupy the first twelve months of the study. The initial transferrin saturation screen will then be conducted over a two year period. The repeat fasting transferrin saturation/serum ferritin screen will follow shortly, preferably within one to two months of the initial screen of each participant. Appropriate threshold values for each of the screens should be proposed, with discussion of specificity and sensitivity issues and expected numbers of participants meeting these criteria. It should be recognized that the confirmed elevated transferrin saturation group will be much smaller in number than the initial group of 100,000 screenees. As these confirmed elevated transferrin saturation participants and confirmed non-elevated control participants are identified, scheduling for the comprehensive clinical examination will begin. These examinations will also take place over a two year period, overlapping the transferrin saturation screen period. Similarly, as examinees with hereditary hemochromatosis are identified, recruitment of relatives for the family study will begin. During the last year of the study, follow-up of comprehensive clinical examinees will be performed. Depending on when the examination is performed, the follow-up interval will be between one and three years. Concurrently, final data analysis and study close-out will be completed, although initial data analysis is expected to begin much earlier using data from the initial transferrin saturation screen and random subgroup study.
The initial 100,000 screenees will include roughly equal numbers of men and women aged 25 and older. Individuals requiring repeated blood transfusions for treatment of other conditions will be excluded. Since iron accumulation increases with age, this broad age span will lead to inclusion of participants with a wide range of iron overload states and related sequelae to be studied. Screening of children and adolescents, however, is not expected to be productive because iron overload is generally not detectable until at least the third or fourth decades of life. In addition, there is evidence that juvenile hemochromatosis is genetically distinct from adult hemochromatosis, and has a different pattern of clinical sequelae. Inclusion of slightly younger adults, that is those 25 and older, will enable analysis of gene and environmental interactions related to the penetrance of HFE and other hemochromatosis-related gene expression during the age span when iron overload is developing but before such interactions may be confounded by hemochromatosis-related organ damage. The initial screenees should represent a range of racial and ethnic groups, with the goal of enrolling approximately 40-50% minority participants. To enable comparisons within as well as across Field Centers, each Center's sample is expected to enroll from two or more racial/ethnic groups, one of which may be non-Hispanic Caucasians. For Field Centers with two racial/ethnic groups in the study, each group is expected to comprise 20% or more of that Center's study population. For Field Centers with three or more racial/ethnic groups, at least two of the groups are expected to each comprise 20% or more of the study population at the Center. Selection of Field Centers will be partly governed by the need to achieve the overall racial/ethnic and gender targets for the study as a whole.
Clinical sites will be expected to assess the clinical, personal, and societal impact of the screening program. During planning, a common approach to this assessment will be developed and implemented. The development of guidelines for informed consent and the protection of individual rights or prerogatives is an important component of this study. All clinical sites will thus be asked to address issues of consent, protection against discrimination, confidentiality, etc. Public policy implications of screening programs that identify risk or disease states in which much about the natural history of the disease remains unknown, but for which existing medical interventions appear to substantially reduce risk or morbid states, are of interest, but may be beyond the scope of the main study. Offerors are thus encouraged to propose and participate in substudies and ancillary studies, as described in task 3.e. below, to address the broader ethical, economic and health policy issues related to the possible implementation of such screening programs, or other issues related to iron overload and hemochromatosis.
Ethical considerations mandate that subjects found to have evidence of iron overload or deficiency be treated to prevent or attempt to reverse clinical disease. Accordingly, offerors must be prepared to refer those patients to appropriate sources of standard clinical care for follow-up and/or treatment as indicated, which will not be supported by this research program. Although not a primary goal of the program, differences in the response to treatment by genotypes will be sought through follow-up procedures. Study-wide guidelines for treatment, including assessment of family members as guidelines warrant, will be developed and recommended to care providers of cases detected through the study. The final, detailed protocol will be developed and approved by a Steering Committee-appointed subcommittee, reviewed by the Data and Safety Monitoring Board and approved by the NHLBI/NHGRI staff.
Table 1. Time line for the Iron Overload and Hereditary Hemochromatosis Study
| Activity | Time period |
|---|---|
| Protocol Development | September 30, 1999 - September 30, 2000 (12 months) |
| OMB Clearance | April 1, 2000 - September 30, 2000 (6 months) |
| Training, Pilot Testing Protocol Modification |
July 15, 2000 - September 30, 2000 (2.5 months) |
| Initial Transferrin Saturation Screen | October 1, 2000 - September 30, 2002 (24 months) |
| Random Subgroup Genotyping Initial ELSI Assessment |
October 1, 2000 - September 30, 2002 (24 months) |
| Repeat Transferrin Saturation Screen Serum Ferritin Assay |
October 1, 2000 - September 30, 2002 (24 months) |
| Comprehensive Clinical Examination Genotyping, Extended ELSI Assessment |
January 2, 2000 - September 30, 2003 (33 months) |
| Family Study, ELSI Assessment | March 1, 2001 - September 30, 2003 (31 months) |
| Follow-up for ELSI, Morbidity and Mortality |
January 2, 2001 - September 30, 2004 (45 months) |
| Final Data Analysis and Close-out | October 1, 2003 - September 30, 2004 (12 months) |
[Note: Some activity periods overlap. Since participant eligibility for screens and examinations following the initial screen is dependent on laboratory or other diagnostic results, some activity periods are on average shorter than the total periods specified.]
Study years are designated as follows:
| Year 1, September 30, 1999 - September 30, 2000 | Year 4, October 1, 2002 - September 30, 2003 |
| Year 2, October 1, 2000 - September 30, 2001 | Year 5, October 1, 2003 - September 30, 2004 |
| Year 3, October 1, 2001 - September 30, 2002 |
Figure 1. Time line for the Iron Overload and Hereditary Hemochromatosis Study
|---Year 1---|---Year 2---|---Year 3---|---Year 4---|---Year 5---|
Protocol
Development |------------|
OMB Clearance |-----|
Screening Exam |-------------------------|
Random Sample Genotyping* |-------------------------|
Case/control Intensive Exam* |------------------------------|
Family Study* |------------------------|
Case Follow-up* |--------------------------------------------|
Analyses |---------------------------------------------------------|
Publications |--------------------------------------------|
|---Year 1---|---Year 2---|----Year 3---|---Year 4---|---Year 5---|
*includes Ethical, Legal, and Social Implications (ELSI) assessment.
Table 2. Examination Components
Data to be collected is approximated by the following list of components, which may be modified during protocol development, for the approximate following number of participants (across all Field Centers):
------------
| |
| 100,000* |
| |
------------
1. Initial Transferrin Saturation |
Screen (TS1) [Random Subgroup**; ---------------(1)--------------
Genotyping Initial ELSI***] | |
------------ -------------
| | | |
| 2,500 | | 97,500 |
2. Repeat Transferrin | TS1+ | | TS1- |
Saturation Screen (TS2) ------------ -------------
| |
------(2)------ (2)
| | |
-------------- -------------- ---------------
| | | | |Random Sample|
| 1,750 | | 750 | | 1,000 |
| TS1+ TS2- | | TS1+ TS2+ | | TS1- TS2- |
-------------- -------------- ---------------
3. Clinical Assessment, | |
Extended ELSI***, Geno- ------(3)------ (3)
typing | | |
------------ -------------- ---------------
| 250 | | 500 | | 1,000 |
| 2° Iron | |1°Iron Over-| | TS1- TS2- |
| Overload | | load CASES | | CONTROLS |
------------ -------------- ---------------
4. Family Study (4 or more |
members per case) (4)
|
-------------
| 2000 |
| Family |
| Members |
-------------
* All numbers after the initial 100,000 are estimates and may change during the protocol development or as cases are identified during the course of the study.
** During step 1, a random subgroup of 20-40% participants will have additional blood drawn for candidate gene testing concurrent with transferrin saturation assays. Any genotype-positive (for example, HFE C282Y/C282Y or HFE C282Y/H63D) individuals not otherwise selected for steps 2-4 will be invited to participate in these steps (although not shown above).
***Ethical, Legal, and Social Implications assessment. An initial ELSI assessment will be conducted in a random subgroup at the beginning of step 1. All step 3, and a subset of step 4 participants will undergo an extended ELSI assessment. A follow-up assessment will be conducted in the hemochromatosis cases (not shown above).
Independently, and not as an agent of the Government, the contractor shall furnish the necessary services, qualified personnel, equipment, facilities, and materials, not otherwise provided by the Government. [Note: Throughout this statement of work, the terms "Contractor" and "Field Center" are used interchangeably.] Specifically, throughout the period of performance, the Contractor shall provide appropriate senior personnel with expertise in the epidemiology of iron overload and hereditary hemochromatosis; clinical hepatic, endocrinologic, hematologic and cardiovascular disease; genetic epidemiology; genetic counseling; the ethical, legal and social implications (ELSI) of genetic screening and testing; laboratory measurements; and clinical epidemiology study management to:
The Field Center contract will be awarded for a five year duration with Phases I, II, III, and IV described below:
[Note: See time lines and flowchart in Table 1 and Figures 1 and 2 for overview of phases, tasks and study design. A list of examination components is in Table 2.]
[Note: For planning purposes, assume the Offeror will be represented on the Steering Committee and three subcommittees and that Steering Committee meetings will take place in Bethesda, Maryland. Assume there will be 4 two-day Steering Committee meetings during the first year, 3 during the second year, and 2 each year thereafter. DSMB and Subcommittee meetings will generally take place in conjunction with Steering Committee meetings, but in the first year assume one additional meeting may need to take place separately.]
[Note: It is anticipated that a total of 100,000 participants will be recruited among five to seven Field Centers for an initial transferrin saturation screen. For purposes of the proposal, assume that 20,000 participants will be recruited by each of five Field Centers. Concurrent with this screen, a genotyping screen is expected to be performed on a 20-40% random subgroup, and an initial ELSI assessment on a 2-4% random subgroup. Following the initial screen, approximately 3,600 participants are expected to participate in a repeat transferrin saturation screen, with approximately 1,800 participants continuing on to a comprehensive clinical examination, and approximately 560 participants and 2240 of their family members are expected to participate in a family study. A morbidity, mortality and ELSI follow up of the comprehensive clinical examinees, for up to two years, is also planned. An additional 2,000 participants will participate in an ELSI-related substudy comparing acceptability of genotype vs phenotype screening methods (with approximately half of the participants in each of the two groups).]
[Note: While a core informed consent form will be developed for use across Field Centers, it is recognized that local IRBs may require modifications for a particular Field Center.]
[Note: The Offeror should plan pilot testing to include components of the initial and repeat transferrin saturation screens, the comprehensive clinical examination, and initial and extended ELSI assessments. The protocol for the initial transferrin saturation screen and ELSI assessment will likely require clearance from the Office of Management and Budget (OMB). The Coordinating Center will coordinate the effort to produce the OMB clearance packet, with assistance from the other Centers as needed. After draft protocols have been developed and approved by the Steering Committee, staff are to be centrally trained for each screen or examination component. Pilot testing will be conducted after training is complete and OMB clearance has been obtained, and will consist of performing the study components, according to the draft Manual of Operations, in approximately 10-20 non-study participant volunteers per Field Center. Repeat measurements should be planned for any examination component for which reproducibility is in question. The pilot tests also are to include shipping blood specimens as specified by the protocol. As the initial transferrin saturation assays are likely to be conducted on-site, rather than at the Central Laboratory, each Field Center's laboratory will need to obtain study certification documenting the ability to conduct standardized assays as specified in the protocol.]
[Note: It is anticipated that a total of 100,000 participants will be recruited among five to seven Field Centers. For purposes of the proposal, assume that 20,000 participants will be recruited by each Field Center. It is further expected that approximately 50% of the cohort will be women and that approximately 40-50% of the cohort will be minority participants. Each Field Center is expected to enroll from two or more racial/ethnic groups, one of which may be non-Hispanic Caucasians. Field Centers with two racial/ethnic groups are expected to ensure that each group comprise at least 20% of the Center's study population. Field Centers with three or more racial/ethnic groups in the study are expected to ensure that at least two of the groups comprise 20% or greater of the Center's study population.]
[Note: It is assumed that the primary care patient is already undergoing routine screening, testing or examination involving a blood draw, so only minimal additional effort for recruitment, informed consent, and phlebotomy tasks is required. If this is not the case, the Offeror should describe the additional steps and costs needed to complete these tasks. Cost-effective strategies for recruitment of population-based participants may also be proposed.]
[Note: Attempts should be made to obtain information on reasons for refusal from those declining to participate in the study.]
[Note: For planning purposes, assume the initial transferrin saturation assay will be performed on-site, at a laboratory meeting certification specifications as determined by the Steering and Laboratory Committees.]
[Note: Offerors should propose and provide justification for appropriate threshold values for elevated transferrin saturation levels (including, as necessary, age-, gender- and/or ethnic-specific values) and numbers of participants estimated to meet this criterion. Responses should address the design outlined in Table 2 and Figure 2, and if alternate designs are proposed, separate budgets should be provided.
While the focus of this study is on hereditary hemochromatosis and thus on elevated transferrin saturation levels and iron overload, it is recognized that this screen may also identify individuals with possible iron deficiency. Offerors should also propose threshold values for low levels of transferrin saturation that would trigger referral to primary care provider and procedures for appropriate follow-up outside of the study. Iron-deficient participants are eligible for selection into the control sample to provide as broad a comparison group as possible.
The actual threshold values to be used in the study, and thus the potential number of participants eligible for subsequent phases of this study, will be determined by the Steering Committee during protocol development.]
[Note: The Offeror may propose plans for combining this and subsequently described stages of informed consent with that for the initial transferrin saturation screen.]
[Note: Items (f) and (g) are not traditional elements of ELSI assessments, but are included as these responses may impact the ELSI responses for this particular study. The survey instruments utilized by the NHGRI-NCI-NIMH-NINR-sponsored Cancer Genetics Studies Consortium may serve as a guideline in the planning of the quantitative assessment. A qualitative ELSI assessment is outlined in task b.iii.(2) below.]
[Note: It is anticipated that the genotyping will be performed centrally. Offerors should propose and justify the variants to be tested, and estimate the number of participants expected to be genotype-positive. These participants will be invited to participate in the comprehensive clinical examination and family study, regardless of their outcome on the initial or repeat transferrin saturation assay. It is anticipated that variants to be tested will reflect the state of knowledge at the time this phase of the study is conducted.]
[Note: All participants will receive pre-test counseling via the informed consent process. Participants with genotypes considered at risk of disease at the time this phase of the study is conducted will also receive post-test counseling.]
[Note: It is expected that these substudies will be conducted in a subset of the five to seven Field Centers. For planning purposes, assume that two Centers will be chosen and each will enroll half of the participants described.]
[Note: Offeror should propose and justify methods to be used. These methods may include qualitative or semi-structured interviews, focus groups, or other appropriate in-person methods. Qualitative issues include, but are not limited to, perceived susceptibility to a condition; perceived severity of the seriousness of developing a condition; perceived benefits of interventions to reduce morbidity or mortality; and perceived barriers to undertaking some preventive behavior.]
[Note: Repeat transferrin saturation and serum ferritin assays will be conducted at the Central Laboratory.]
[Note: Offerors should propose and provide justification for methods to select appropriate threshold values for confirmed elevated transferrin saturation and serum ferritin levels (including, if necessary, age-, gender- and/or ethnic-specific values) and numbers of participants estimated to meet these criteria. Responses should address the design outlined in Table 2 and Figure 2, and if alternate designs are proposed, separate budgets should be provided. Standardized criteria for all Field Centers will be developed during protocol planning and approved by the Steering Committee. These participants will be considered iron overload cases for the comprehensive examination. Genotype-positive participants will be invited to participate in the comprehensive examination, regardless of repeat transferrin saturation assay and serum ferritin assay results.]
[Note: It is expected that 1,000 control participants will be recruited across the Field Centers. Controls will be matched to cases by Center, at a minimum. For purposes of the proposal, assume that 200 control participants will be selected at each Field Center. Offerors should propose and justify appropriate sampling scheme to result in randomly-selected control participants, and other criteria beyond Center, if any, for matching controls to cases.]
[Note: Use threshold values for confirmed transferrin saturation and serum ferritin levels as defined above in Task 2.b.iii(4). These participants will be considered controls during the comprehensive examination.]
[Note: Offerors should provide justification for proposed questionnaires and measures.]
[Note: Unless otherwise determined during protocol development, all assays will be conducted at the Central Laboratory.]
[Note: The CBC will be conducted locally. The Offeror should propose, with justification, appropriate components of CBC to be included.]
[Note: The erythrocyte sedimentation rate will be conducted locally, in conjunction with the CBC.]
[Note: Blood shall be drawn for low temperature (-70°C) long-term storage at the Central Laboratory. For planning purposes, plan that approximately 90 ml of blood will be drawn into 10 tubes and aliquotted into 30 microvials for shipping to the Central Laboratory and long-term storage.]
[Note: Offerors should propose and justify non-invasive and any invasive procedures proposed for inclusion in the comprehensive clinical examination, including, as appropriate, any decision-tree algorithms to be used. Participants' primary care provider may wish to conduct additional procedures outside the study protocol; Offerors should discuss options to obtain these data when possible. Protocol-performed assessments must be standardizable among multiple examinees and across Field Centers; hence Offerors should carefully describe proposed measures and methods for assuring standardization and quality control. During protocol development, a common standardized protocol will be agreed upon, and approved by the Steering Committee, reviewed by the DSMB and approved by the NHLBI/NHGRI staff.]
[Note: Offerors should propose definitions of primary and secondary iron overload and hereditary hemochromatosis based on results of above screens and comprehensive clinical examination.]
[Note: It is expected that this substudy will be conducted in a subset of the five to seven Field Centers. For planning purposes, assume that two Centers will be chosen and each will enroll half of the participants described. Offeror should propose and justify methods to be used. These methods may include qualitative or semi-structured interviews, focus groups, or other appropriate in-person methods. Qualitative issues include, but are not limited to, perceived susceptibility to a condition; perceived severity of the seriousness of developing a condition; perceived benefits of interventions to reduce morbidity or mortality; and perceived barriers to undertaking some preventative behavior.]
[Note: Offerors should discuss logistical issues related to geographical location of family members and examination of family members not part of the primary care organization used to ascertain the probands. Advantages and disadvantages of including family members regardless of age should also be discussed.]
[Note: It is expected that this substudy will be conducted in a subset of the five to seven Field Centers. For planning purposes, assume that two Centers will be chosen and each will enroll half of the participants described. Offeror should propose and justify methods to be used. These methods may include qualitative or semi-structured interviews, focus groups, or other appropriate in-person methods. Qualitative issues include, but are not limited to, perceived susceptibility to a condition; perceived severity of the seriousness of developing a condition; perceived benefits of interventions to reduce morbidity or mortality; and perceived barriers to undertaking some preventative behavior.]
[Note: If there are insufficient numbers of families/family members in a particular race/ethnic group to achieve adequate statistical power for linkage analyses, strategies for supplementing families/family members, for instance remote blood collections or including families from other studies, will be considered.]
[Note: The follow-up interval will vary depending on when the comprehensive clinical examination is performed, ranging from approximately one to three years.]
[Note: It is expected that this substudy will be conducted in a subset of the five to seven Field Centers. For planning purposes, assume that two Centers will be chosen and each will enroll half of the participants described. Offeror should propose and justify methods to be used. These methods may include qualitative or semi-structured interviews, focus groups, or other appropriate in-person methods. Qualitative issues include, but are not limited to, perceived susceptibility to a condition; perceived severity of the seriousness of developing a condition; perceived benefits of interventions to reduce morbidity or mortality; and perceived barriers to undertaking some preventative behavior.]
[Note: The proposal should include brief descriptions of at least five potential manuscript topics that could be first-authored by the Offeror. It is anticipated that abstracts and manuscripts proposed for presentation or publication will be submitted to the Publications Committee and the NHLBI Project Office in advance for review and approval, as outlined in the section on Deliverables. Due to overlapping interest and expertise, manuscript writing groups will likely include members from several, most or all Centers.]
Throughout the period of performance the Contractor shall participate in other activities related to the successful completion of the project, as specified by the Steering Committee and/or NHLBI Project Office. These include, but are not necessarily limited to the following:
[Note: Investigators may propose ancillary studies and substudies to be conducted in one or more study Centers. A substudy is an investigation which, although not part of the core exam protocol, is funded by Contract funds, and will yield additional information related to study objectives. An ancillary study is a study not funded by contract funds. Substudies and ancillary studies may include all or a subgroup of the cohort at a given center, and may involve additional interviews or examinations of study participants as well as analysis of blood or tissue specimens, tapes, or images collected previously.
Ancillary studies and substudies are subject to the same policies, reviews and approvals as the core protocol. Substudies involving additional participant burden will likely require OMB clearance. Investigators proposing substudies will also prepare a request for OMB clearance for the substudy; or, for case-control studies, a request for exemption from OMB review. Examples of such submissions will be provided on request.
Ancillary study data will be incorporated into the study data set after an appropriate period of time (generally 12 months after completion of data collection). Investigators conducting ancillary studies are to be viewed as collaborating investigators of the primary study, with appropriate access to the full data set. However, use of analytic resources of the study will require additional support from the ancillary study investigators.
Ancillary studies and substudies will be evaluated by the Steering Committee. Highest priority will be given to studies which: 1) have the highest scientific merit, 2) do not interfere with the main study objectives, 3) produce the least burden on participants, 4) have objectives directly related to the study, and 5) require the unique characteristics of the study participants.
For all substudies and ancillary studies, the contractor shall define the hypotheses to be investigated and the methodology to be used, and should estimate the cost and burden on participants. Study data collection must not interfere with the conduct of the core examination. All substudies in the proposal should be distinctly identified, with separate descriptions and estimates of costs. Ancillary studies and substudies may be proposed before and/or after contract award as scientific opportunities arise. All studies must be approved by the Steering Committee, reviewed by the Data and Safety Monitoring Board, and approved by the NHLBI Project Office before initiation.]
ATTACHMENT B
DELIVERABLES/REPORTING REQUIREMENTS
The following table provides an overview of deliverables:
| Item # |
Description | Quantity | Delivery Schedule | Delivery Information |
|---|---|---|---|---|
| 1. | Draft consent forms | 2 | February 15, 2000 | Project Office |
| 2. | Materials for OMB package | 1 | March 15, 2000 | Coordinating Center |
| 3. | Final consent forms | 2 | March 15, 2000 | Project Office |
| 4. | Draft sections of Manuals of Operations |
15-21 | July 1, 2000 | Coordinating Center |
| 5. | Training Materials | 15-21 | July 1, 2000 | Coordinating Center |
| 6. | Data from pilot testing | 20 | August 20, 2000 | Coordinating Center Central Laboratory |
| 7. | Laboratory certification data | 2 | August 20, 2000 | Coordinating Center Central Laboratory |
| 8. | Final sections of Manuals of Operations |
1 | September 1, 2000 | Coordinating Center |
| 9. | Screen and Examination Data |
1 | Weekly | Coordinating Center |
| 10. | Laboratory Specimens | 1 | Weekly | Central Laboratory |
| 11. | Clinical reports on findings | 1 | Within 3 months of comprehensive examination | Participant and/or health care provider |
| 12. | Progress report | 3 | September 30 Yearly |
Project Office (2 copies) Contracts Office (1 copy) |
| 13. | Abstracts | 8-10 | 2 weeks prior to submission | Publications Committee (1 copy per member) Project Office (2 copies) |
| 14. | Manuscripts | 8-10 | 4 weeks prior to submission | Publications Committee (1 copy per member) Project Office (2 copies) |
| 15. | Raw data | 1 | As requested | Project Office |
| 16. | Financial Reports | 3 | Quarterly | Contracts Office (Form NIH 2706) |
| 17. | Clinical Research Study Populations Report | 2 | Annually | Contracts and Project Office |
| 18. | Final report and summary | 10 | September 30, 2004 | Project Office (2 copies) Contracts Office (1 copy) |
ATTACHMENT C
EVALUATION FACTORS FOR AWARD WITH TECHNICAL EVALUATION CRITERIA AND OTHER INFORMATION
The technical proposal will receive paramount consideration in the selection of the contractor for this procurement. The evaluation will be based on the demonstrated capabilities of the prospective contractors in relation to the needs of the project as set forth in the RFP. The merits of each proposal will be evaluated carefully, based on the thoroughness and feasibility of the technical approach taken. Although cost is not a specific evaluation criterion, it will be assessed. In the event that the technical evaluation reveals that two or more offerors are approximately equal in technical ability, then the estimated cost may become significant in determining award(s). In any event, the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered.
This research project involves human subjects. Offerors must make every effort to seek out and include (a) study goal of 50% women within each racial/ethnic minority group aged 25 and older, and (b) overall study goal of 40-50% U.S. racial/ethnic minority populations. Screening of children and adolescents, however, is not expected to be productive because iron overload is generally not detectable until at least the third or fourth decades of life. In addition, there is evidence that juvenile hemochromatosis is genetically distinct from adult hemochromatosis, and has a different pattern of clinical sequelae. Inclusion of young adults, that is those 25 and older, will enable analysis of gene and environmental interactions related to the penetrance of HFE and other hemochromatosis-related gene expression during the age span when iron overload is developing but before such interactions may be confounded by hemochromatosis-related organ damage. A major goal of this solicitation is to have good representation of women and of minority populations. The numbers of women and minority participants may vary from center to center depending on local population composition and other characteristics that influence access to care. However, each Field Center is expected to include two or more racial/ethnic groups, one of which may be non-Hispanic whites. For Field Centers with two racial/ethnic groups, each group is expected to comprise at least 20% of the Center's study population. For Field Centers with three or more racial/ethnic groups, at least two of the groups are expected to each comprise 20% or greater of the Center's study population. The NHLBI reserves the right to make awards under this RFP in a manner that accomplishes the overall recruitment goals for women and minorities. Thus, a higher ranked proposal may be passed over for a lower ranked proposal if the lower ranked proposal is needed to fulfill recruitment goals. While this solicitation focuses on primary-care based Field Centers, cost-effective population-based strategies for recruitment of participants will also be considered.
This program is to be conducted in a population sample representative of persons with access to primary medical care and as such will under-represent persons without access to care. The National Health Interview Survey and other sources have demonstrated that persons without access to medical care are younger, have fewer years of education and lower incomes, and are more often male and non-white than persons in pre-paid health plans, Medicare/Medicaid, or fee-for-service care settings. Offerors will be expected to demonstrate the representativeness of their proposed samples to persons having access to medical care, not to the general U.S. population.
Where inclusion of representation of women and/or minority populations, as described above, is not feasible, the offeror must submit with the technical proposal a clear justification. The NHLBI will review this justification in light of the research design and desired women and minority representation in the proposal study. If the rationale is not considered acceptable by the Government and the offeror is included in the competitive range, the offeror will be afforded the opportunity to further discuss and/or clarify its position during discussions. If the offeror's exclusion position is still considered unacceptable by the Government after discussions, the proposal may not be considered further for award.
As an agency of the U.S. Public Health Service, the National Heart, Lung, and Blood Institute is responsible for sponsoring research programs and for disseminating information that will serve to improve the health of the population of the United States. Therefore the recruitment into this program of foreign populations that have significantly different social, cultural and economic conditions could substantially alter the study results. As a result, the award of contracts for performance as Field Centers under this program shall be made only to offerors who are located in the United States of America or Canada. The award of contracts for Coordinating Center and Central Laboratory is open to offerors from the United States of America only. Proposals received from offerors located outside of the United States of America or Canada will not be considered for contract award.
Proposals submitted in response to this solicitation will be reviewed by a peer group of scientists under the auspices of the Review Branch, Division of Extramural Affairs, NHLBI, and subsequently by a review group within NHLBI.
Past performance is not an evaluation criterion but it will be considered when determining contractor responsibility using the information required by the "Qualifications of the Offeror" portion of the "Standard RFP Instructions and Provisions" of the RFP References Directory.
TECHNICAL EVALUATION CRITERIA
The evaluation criteria are used by the technical evaluation committee when reviewing the technical proposals. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes.
Total possible points: 100
ATTACHMENT D
SPECIFIC RFP INSTRUCTIONS AND PROVISIONS
NOTICE TO OFFERORS: This section 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 E. titled, "Applicable RFP References".
An index of the specific RFP instructions and provisions, which apply, follow:
RFP No. NHLBI-HC-99-04 (Field Centers)
TITLE OF RFP: "Iron Overload and Hereditary Hemochromatosis Study--Field Centers"
FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY 1/29/99. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL ASSIST US IN PLANNING FOR PROPOSAL EVALUATION.
I INTEND TO SUBMIT A PROPOSALCOMPANY/INSTITUTION NAME:
ADDRESS:
PROJECT DIRECTOR'S NAME:
TITLE:
TELEPHONE NUMBER:
NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS (include Subcontractors and Consultants):
______________________________________________________
______________________________________________________
RETURN TO:
Review Branch, NIH, NHLBI, 6701 Rockledge Drive, MSC 7924, Bethesda, MD 20892
ATTN: Dr. James Scheirer
or FAX TO: Dr. James Scheirer at (301) 480-3541
Your proposal shall be organized as specified in the "Standard RFP Instructions and Provisions." Shipment and marking shall be as follows:
EXTERNAL PACKAGE MARKINGIn addition to the address cited below, mark each package as follows:
"RFP NO. NHLBI-HC-99-04TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"
The number of copies required of each part of your proposal are:
TECHNICAL PROPOSAL: ORIGINAL* AND Twenty-five (25) COPIES
BUSINESS PROPOSAL: ORIGINAL* AND Six (6) COPIES
DELIVER PROPOSAL TO:
If hand delivered or delivery service:Review Branch, National Heart Lung and Blood Institute, Rockledge Building, Room 7091 6701 Rockledge Drive MSC 7924 Bethesda, MD 20817-7924
If using U.S. Postal Service:
Review Branch, Division of Extramural Affairs, National Institutes of Health National Heart, Lung, and Blood Institute, 6701 Rockledge Drive MSC 7924 Bethesda, MD 20892-7924*THE ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING.
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."
This procurement action requires the Contractor 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. Violation of the Act may involve the imposition of criminal penalties.
The Privacy Act System of Records Notice that applies to this RFP was published in the Federal Register dated April 7, 1997, Vol. 62, No. 66.. This most recent notice will be incorporated into any contract resulting from this RFP. If you would like a copy, please contact the Contracting Officer identified in the cover letter to this RFP.
NOTE: The following information is to be used by the offeror in preparing its Representations and Certifications, specifically in completing the provisions entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS, FAR 52.219-1:
The standard industrial classification (SIC) code for this acquisition is 8731.
The small business size standard is 500 employees.
THIS REQUIREMENT IS NOT SET-ASIDE FOR SMALL BUSINESS. However, the FAR requires in every solicitation (except for foreign acquisitions) the inclusion of the SIC code and corresponding size standard which best describes the nature of the requirement in the solicitation.
It is anticipated that multiple awards will be made from this solicitation and that award will be made on September 30, 1999.
It is anticipated that the awards made from this solicitation will be a multiple-year cost reimbursement, completion type contract with a period of performance of 60 months, and that incremental funding will be used.
To assist you in the preparation of your proposal, the Government considers the effort to perform this work each year over the five year performance period. This following estimate is furnished for the offeror's information only and is not to be considered restrictive for proposal purposes.
| Labor Category | Level of Effort (full-time equivalents) |
||||
|---|---|---|---|---|---|
| Year 1 |
Year 2 | Year 3 | Year 4 | Year 5 | |
| Principal Investigator | .2 | .2 | .2 | .2 | .2 |
| Other Investigators | .4 | .2 | .2 | .2 | .2 |
| Other | .95 | 11 | 12 | 3 | 2 |
All staffing levels proposed should be accompanied by specific justifications as to the type and hours of work expected to be performed by all personnel. Offerors will be required to propose levels of commitment whether compensated or donated effort, necessary to complete the work described in their proposals. It is expected that realistic levels of effort will be proposed such that an offeror's understanding of the work will be apparent.
In accordance with FAR 52.233-2 SERVICE OF PROTEST (NOV 1988):
(a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General accounting Office (GAO) shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from:
Mr. Robert R. Carlsen Hand-Carried Address: National Institutes of Health, National Heart, Lung, and Blood Institute, Contracts Operations Branch, II Rockledge Center, Room 6122, 6701 Rockledge Drive, MSC 7902 Bethesda, MD 20817
U.S. Postal Service: National Institutes of Health, National Heart, Lung, and Blood Institute, Contracts Operations Branch, II Rockledge Center, 6701 Rockledge Drive, MSC 7902 Bethesda, MD 20892-7902
The copy of any protest shall be received in the office designated above within one day of filing a protest with GAO.
Please number each page of text. Type density and size must be 10-12 points. If constant spacing is used, there should be no more than 15 cpi, whereas proportional spacing should provide an average of no more than 15 cpi. There must be no more than six lines of text within a vertical inch.
The technical proposal should be organized as follows:
PROVIDE NARRATIVE FOR:
[NOTE: For personnel, include a two-page biosketch under APPENDICES below.]
List/describe all facilities, equipment and other resources available for this project.
Complete the Form "Summary of Current and Proposed Activities." All key personnel must be listed on this form. The form is located in the Streamlined RFP References under "FORMS, FORMATS, & ATTACHMENTS."
(Form located in the Streamlined RFP References under "FORMS, FORMATS, & ATTACHMENTS.")
Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor.
HUMAN MATERIALS (It is anticipated that this clause will appear in the contract.)
It is understood that the acquisition and supply of all human specimen material (including fetal material) used under this contract will be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States and that no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.
PUBLICATION AND PUBLICITY (It is anticipated that this article will appear in the contract.)
The contractor shall acknowledge the support of the National Institutes of Health whenever publicizing the work under this contract in any media by including an acknowledgment substantially as follows: "This project has been funded in whole or in part with Federal funds from the National Heart, Lung and Blood Institute, National Institutes of Health, under Contract No. "TBD"."
HHSAR 352.270-6 PUBLICATION AND PUBLICITY (JULY 1991) (It is anticipated that this clause will appear in the contract.)
Unless otherwise specified in this contract, the Contractor is encouraged to publish, and make available through accepted channels, the results of its work under this contract. A copy of each article submitted by the Contractor for publication shall be promptly sent to the Project Officer. The Contractor shall also inform the Project Officer when the article or other publication is published, and furnish a copy of it as finally published.
NHLBI PUBLIC USE DATA CLAUSE--EPIDEMIOLOGY FIELD CENTER
Public use data will be released under this observational epidemiology study. After completion of the closing date of each examination cycle, the coordinating center will prepare the data from the examination component and will deliver it to the NHLBI. The data will be prepared in a format suitable for use by the public. Such release is expected to occur no later than five years after the closing date of each examination cycle. The coordinating center will provide the data to the NHLBI within four years of the closing date of each examination cycle so that the NHLBI can check the data before release. This will provide time for NHLBI review, discussion of the data and opportunity for any changes needed in content or presentation prior to release.
The public use data set will include all of the examination data obtained in the examination cycle, and/or all of the follow up information available up to the cutoff time. Inclusion of raw data that has been processed into summary information shall be discussed with the Project Officer prior to submission. Data prepared for release will not contain personal identifiers. The coordinating center will coordinate preparation of the data with the NHLBI to assure patient confidentiality.
Ancillary study data (not funded under this contract) are not required to be included in the public use data set, though the data may be included if agreed upon by the ancillary study investigator. The study investigators will be expected to answer basic questions regarding data set characteristics, format and content, during the study. Documentation is expected to be of the highest quality so that such questions will be minimized. Data will not be prepared for public use if the investigators and NHLBI believe that they are unreliable or invalid. These exceptions must be justified in writing through the coordinating center to the NHLBI and will be reviewed and, if the NHLBI concurs, approved in writing by the Director of the Division that sponsored the study.
ATTACHMENT E
APPLICABLE RFP REFERENCES
This section identifies the items located in the Streamlined RFP References that are applicable to this Request For Proposal (RFP).
SUBMIT WITH TECHNICAL PROPOSAL (with original and every copy of technical proposal)