|Request for Information No.:||NHLBI-98-02|
|Issue Date:||September 25, 1998|
|Issued By:||Ms. Lisa O'Neill
Contracts Operations Branch
II Rockledge Centre
6701 Rockledge Drive, Room 6132, MSC 7902
Bethesda, Maryland 20892-7902
|Response Due Date:
||October 16, 1998
The National Heart, Lung, and Blood Institute (NHLBI) is soliciting information on the feasibility of a possible study on Iron Overload and Hereditary Hemochromatosis. Respondents are asked to study the below draft Statements of Work for the Field Center, the Coordinating Center, and the Central Laboratory, and provide information on the feasibility and design of the proposed study.
Below is a general description of the study:
The Iron Overload and Hereditary Hemochromatosis Study will study 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 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 screen will be used to identify potential 'case' participants with sustained elevated transferrin saturation levels and matched random 'control' participants with non-elevated transferrin saturation levels. Data on the prevalence of genetic factors in a primary care population will also be collected via candidate gene assays on a 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 sustained elevated transferrin saturation potential 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.
The final component of the study is a family study using comprehensive clinical examinees as probands 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. Identification of new genetic variants, particularly in minorities, is also of 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.
The study will involve five to seven Field Centers, a Coordinating Center, and a Central Laboratory. 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.
A more detailed description of the study and background material, as well as specific objectives, are provided with the draft Statements of Work. The respondent should address any potential problems or concerns with the proposed design and feasibility of the study.
This Request For Information (RFI) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the Government to issue a Request for Proposal or award a contract. The Government does not intend to award a contract on the basis of responses nor otherwise pay for the preparation of any information submitted or the Government's use of such information. Acknowledgment of receipt of responses will not be made, nor will respondents be notified of the Government's evaluation of the information received. However, should such a requirement materialize, no basis for claims against the Government shall arise as a result of a response to this Request For Information or the Government's use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement. Responses should be identified with RFI-NHLBI-98-02, and are due by October 16, 1998. Please submit three copies of your response to: Ms. Lisa O'Neill, Contracts Operations Branch, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive MSC 7902, Sixth Floor, Room 6132, Bethesda, MD 20892-7902. Phone: (301) 435-0353, E-mail: Lisa O'Neill.