National Institutes of Health, National Heart, Lung, and Blood Institute, Contracts Operations Branch, 6701 Rockledge Drive, Room 6100, MSC 7902, Bethesda, MD 20892

A -- IRON OVERLOAD AND HEREDITARY HEMOCHROMATOSIS DUE 113098 POC Ms. Lisa O'Neill, (301) 435-0345 E-MAIL: o7l@cu.nih.gov, o7l@cu.nih.gov. The National Heart, Lung, and Blood Institute (NHLBI) is conducting a market survey to determine the availability and potential technical capability of small business firms (SIC Code 8731 -- 500 employees) to perform as a Coordinating Center. The purpose of the study is to ascertain the prevalence and 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 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. One hundred thousand (100,000) participants undergoing routine screening or testing involving a blood draw will be recruited from five to seven Field Centers and screened for transferrin saturation levels. A repeat fasting transferrin saturation/serum ferritin screen 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. Data on the prevalence of genetic factors will also be collected via candidate gene assays on a large random subgroup of the main study. Additional subgroups and substudies will be used to determine participants' knowledge and attitudes about, interest in, and support for genotype- and phenotype-based screening programs. Following these screens, a comprehensive clinical examination will be conducted in the confirmed iron overload case participants, the genotype-positive non-elevated participants, and the 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. The examination will also include an extended and follow-up ELSI assessment of issues related to genetic screening and testing and diagnosis of disease. In addition, a family study using comprehensive clinical examinees as probands will be conducted to seek to identify modifier genetic variants related to the expression of iron overload and hereditary hemochromatosis disorders via genome scanning and assessment of linkage. 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. Necessary functions of the Coordinating Center will include active participation in the development of the study protocol and pilot testing procedures; leadership in organizing and conducting the centralized training and certification of study personnel; development of procedures to identify random subgroups of the participants during the initial screen and for the control group; design, implementation and maintenance of quality control procedures including assessment of reproducibility, validity, bias and drift in laboratory measurements, invasive and non-invasive testing, and genotyping data in large multicenter studies; design of forms (including informed consent documents), Manuals of Operation, data entry and recruitment tracking computer programs, data bases and web sites for use by all Centers participating in the study; generation and enhancement of applications of appropriate statistical methods of analysis (including genetic association and linkage analyses) and presentation of data collected during the study; and leadership in manuscript writing and publication. Information provided should establish: 1) professional qualifications of scientific, managerial and technical personnel including genetic, statistical and computer specialists; 2) evidence of leadership in first-authoring and publishing scientific papers in a collaborative study; 3) experience and expertise in design, implementation and maintenance of quality control procedures including assessment of reproducibility, validity, bias and drift in laboratory measurements, invasive and non-invasive testing, and genotyping data in large multicenter studies; 4) substantial experience pertinent to the development of protocols and management of a wide variety of large-scale multicenter clinical/genetic epidemiology studies; 5) experience and expertise in the epidemiology of iron overload and hemochromatosis and related hepatic, endocrinologic, hematologic, and cardiovascular disease, and the ethical, legal, and social implications of genetic screening and testing; 6) experience in generation and enhancement of applications of appropriate statistical methods of analysis and interpretation of medical data including genetic association and linkage studies; 7) access to a large capacity computer facility and networking to remote terminals, and experience in installing and maintaining such networks; and 8) the firm's status as a small business under SIC 8731, Commercial, Physical and Biological Research. This is not an RFP. No RFP is available. Three copies of the information requested above should be submitted to Ms. Lisa O'Neill, NHLBI Contracting Officer, by November 30, 1998, 5:00 PM (E.S.T.). Posted 11/13/98 (W-SN271117). (0317)

Loren Data Corp. http://www.ld.com (SYN# 0004 19981117\A-0004.SOL)