|
|
Studies of the Ethical, Legal and Social Implications of Research Into Human Genetic VariationRelease Date: April 29, 1999 RFA: HG-99-002 P.T. National Human Genome Research Institute Letter of Intent Receipt Date: June 15, 1999 PURPOSEThis Request for Applications (RFA) solicits projects that examine the ethical, legal and social implications of the study of human DNA sequence variation. Of particular interest are studies that explore:
The study of sequence variation and the exploration of related ethical, legal and social issues have been identified as two of the new five year goals of the United States Human Genome Project and will be of continuing interest to the National Human Genome Research Institute (NHGRI) Ethical, Legal and Social Implications (ELSI) Research Program over the next several years. HEALTHY PEOPLE 2000The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Studies of The Ethical, Legal and Social Implications of Research Into Human Genetic Variation, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2000" at www.crisny.org/health/us/health7.html [crisny.org]. ELIGIBILITY REQUIREMENTSApplications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORTThis RFA will use the National Institutes of Health (NIH) individual research grant (R01), small research grant (R03) and education grant (R25) award mechanisms. NHGRI and the National Institute of Environmental Health Sciences (NIEHS) will accept applications using the R01, R03 or R25 mechanism. The National Institutes of Deafness and Other Communications Disorders (NIDCD) will accept applications using R01 and R03 mechanisms only. The National Institute of General Medical Sciences (NIGMS) will accept only those applications using the R01 mechanism. Responsibility for the planning and direction of the proposed project will be that of the applicant. However, research teams supported under this RFA will be asked to collaborate and share information in order to reduce duplication of research efforts and assure that a variety of the research questions are addressed. Awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement. This RFA is a one-time solicitation, although it may be re-released in FY 2000. The purpose of the RFA is to stimulate research on these issues and build a foundation for future explorations in this area. Future unsolicited competing applications proposing research in this area are encouraged and will be reviewed along side and compete with all other unsolicited investigator-initiated applications. Annual TOTAL costs for R01s and R25s should not exceed $400,000 and $250,000 respectively, for a maximum of three years. Annual DIRECT costs for R03s should not exceed $50,000 per year, for a maximum of two years. The anticipated award date is March 2000. FUNDS AVAILABLEIt is expected that approximately $2 million per year for up to three years will be available from the above named Institutes beginning in fiscal year 2000, to fund approximately eight to ten projects. This level of support is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the identified institutes, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. The level of support for these projects may be increased if a large number of highly meritorious applications are received and if funds are available. RESEARCH OBJECTIVESBackground and SignificanceThe NIH, along with several other federal and private, national and international organizations, is currently engaged in a research effort known as the Human Genome Project (HGP). This project is designed to characterize the human genome and the genomes of selected model organisms. The HGP has several interrelated goals: the determination of the complete nucleotide sequence of human DNA and the DNA of several model organisms; the development of new technologies to make sustained high throughput DNA sequencing efficient, accurate and cost effective; the exploration of human genome sequence variation; the development of technologies for interpreting the function of DNA sequence; the identification and analysis of related ethical, legal, and social issues; and research training. The knowledge and technologies that will become available as a result of accomplishing these goals will: serve as a resource for studies of gene structure and function; promote research into the genetic aspects of human growth, development, and variability; increase the understanding of genetic contributions to human diseases and disorders; and inform clinical and health policies related to genetics. This understanding will lead to insights into new ways of dealing with health and disease, including new prevention, diagnostic and treatment options. It will also help to elucidate more clearly the interaction between genes and the environment in the development of disease. Knowing the entire sequence of the human genome and understanding more about genetic variation among individuals and groups will, however, raise questions about how this information will be interpreted and used by individuals, families and society. As the Human Genome Project draws closer to the completion of the first human DNA sequence, researchers are focusing increasing attention on the discovery of variations found in the DNA sequences of individuals. The identification, classification, quantification and analysis of these sequence variations is expected to constitute one of the most powerful, and direct, approaches to the study of a wide range of important biological questions. It will allow researchers to identify genetic contributions to many common diseases and disorders, such as diabetes, depression, heart disease, deafness and hearing impairment, and some forms of cancer, and will provide the basis for studying how sequence variation influences gene function in human growth and development and in the development of disease. To stimulate research in this area, in January 1998, NHGRI and seventeen other NIH Institutes and Centers released an RFA, Methods for Discovering and Scoring Single Nucleotide Polymorphisms (SNPs). To facilitate discovery of DNA sequence variation, the NHGRI has coordinated the assembly of a DNA Polymorphism Discovery Resource of anonymous samples from 450 U.S. residents with ancestry from all the major regions of the world. This initial resource was set up solely for the purpose of the initial discovery of human variation. Therefore, no medical, phenotypic, or demographic information was linked to individual samples. A second activity, the Environmental Genome Project, was also begun in 1998. A program of the National Institute of Environmental Health Sciences, its overarching goal is to understand the impact and interaction of environmental exposures on human disease, which will allow more precise identification of the environmental agents that cause disease and the true risks of exposure. A third related activity was the 1999 release of RFA GM-99-004 [grants.nih.gov], "Pharmacogenetic Research Network and Database," sponsored by the NIGMS and a number of other NIH Institutes. This RFA was designed to solicit applications to study functional variation in genes and proteins that play essential roles in individual drug responses and to make predictions about phenotypic responses based on genotypic make-up. In addition to these and other federally-sponsored activities, broad and vigorous efforts to discover human variation are also proceeding in the private sector. The research into sequence variation that will result from these and other similar initiatives, will raise a number of ethical, legal, and social issues. These include: how to design and conduct this research, not only in a scientifically sound, but also an ethical manner; how to interpret and use this information; whether and how to integrate this information into clinical settings; and what impact this information will have in non-clinical and research settings. Many of these issues may be of special concern to individuals from diverse communities, including those who traditionally have not been involved in genetic research, as researchers, research participants, or policy makers. Questions have already been raised concerning the inclusion of members of these populations in early genetic studies and whether the under-representation or, in some cases, the over-representation of these populations have led to an increase in stigmatization and discrimination in employment, health care, insurance or in society more broadly. These issues may become even more acute if research into human genetic variation reveals data on the interactions between genotype, disease, and traditional, socially-constructed concepts of race, ethnicity and culture. This RFA is designed to solicit applications that will begin to address the ethical, legal and social issues being raised as this research moves forward. Research ScopeThe goal of this RFA is to solicit applications for studies that will identify, explore and begin to address the ethical, legal and social issues that may arise in the course of research on human DNA sequence variation and in the use of the information that may result from this research. The ways in which this new information will interact with cultural and socioeconomic factors and concepts of race, ethnicity and culture are of particular interest. Research topics that may be appropriately addressed in applications responding to this RFA could include, but are not limited to the following broad areas. Examples of possible research questions are provided, but are designed only to help clarify the areas of research, and are not, in any sense, exhaustive or exclusive.
SPECIAL REQUIREMENTSIn order to increase the scope and pace of the research, the NIH will organize a consortium of studies. Such an arrangement will allow researchers to compare findings on issues common to all the projects, to reduce duplication of effort and to promote sharing of information. To facilitate such coordination, grantee workshops will be arranged on an annual basis in the Bethesda area. The initial meeting of the consortium will take place shortly after the grants are funded. Funds for travel to these meetings for up to two investigators (the PI and one other) per year should be included in the requested budget. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTSIt is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. 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," [grants.nih.gov] which was published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTSIt is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the Inclusion of Children as Participants in Research Involving Human Subjects [nih.gov] that was published in the NIH Guide for Grants and Contracts, March 6, 1998. Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENTProspective applicants are asked to submit, by June 15, 1999, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Elizabeth Thomson, R.N., M.S., C.G.C. APPLICATION PROCEDURESThe research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: GrantsInfo@nih.gov. The RFA label available in the PHS 398 (rev. 4/98) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three, signed photocopies, in one package to: Center for Scientific Review To expedite the review process, at the time of submission, two additional copies of the application must be sent to: Rudy Pozzatti, Ph.D. Applications must be received by August 31, 1999. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. CSR will also not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of previously reviewed applications with substantial revisions. Such applications must include an "Introduction to the Revised Application" in which the response to the previous summary statement is made. REVIEW CONSIDERATIONSUpon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the participating institutes. Incomplete applications will be returned to the applicant by CSR without further consideration. If the application is not responsive to the RFA, NHGRI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with other unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI, in accordance with the review criteria stated below. As part of the initial merit review, a process will be used by the initial review group in which only those applications deemed to have the highest scientific merit (generally the top half of the applications under review) will be discussed, assigned a priority score, and receive a written critique of their application. The second level of review will be by the National Advisory Council for Human Genome Research and other National Advisory Councils as assigned. Review CriteriaThe goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Innovation: Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers (if any)? Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following:
The initial review group will also examine the provisions for the protection of human subjects and the safety of the research environment. Other review criteria will include:
Schedule Letter of Intent Receipt Date: June 15, 1999 AWARD CRITERIAAward criteria that will be used to make award decisions include:
INQUIRIESInquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Elizabeth Thomson, R.N., M.S., C.G.C. Amy M. Donahue, Ph.D. Michael E. McClure, Ph.D. Rochelle M. Long, Ph.D. Direct inquiries regarding fiscal matters to: Ms. Jean Cahill Ms. Sherry Dennison Mr. David Mineo Ms. Antoinette Holland AUTHORITY AND REGULATIONSThis program is described in the Catalog of Federal Domestic Assistance No. 93.172, (NHGRI); No. 93.173 (NIDCD); Nos. 93.113, 93.854 and 93.242 (NIEHS); and Nos. 93.859 and 93.862 (NIGMS). Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. REFERENCESDepartment of Health and Human Services. Healthy People DHHS Publication No. PHS 91-50212, 1991. Collins, F.S., A. Patrinos, E. Jordan et al. "New Goals for the U.S. Human Genome Project: 1998-2003." SCIENCE. October 1998; 282: 682-689. Collins, F.S., L.D. Brooks, and A. Chakravarti. "A DNA Polymorphism Discovery Resource for Research on Human Genetic Variation." Genome Research. December 1998; 8:1229-1231 Collins, F.S., M.S. Guyer and A. Chakravarti. "Variations on a Theme: Cataloging Human DNA Sequence Variation." SCIENCE. November 1997; 278: 1580-1581. Foster, M.S., A.J. Eisenbraun and T.H. Carter. "Communal discourse as a supplement to informed consent for genetic research." Nature Genetics. November 1997; 17: 277-279. Foster, M.S., D. Bernsten and T.H. Carter. "A Model Agreement for Genetic Research in Socially Identifiable Populations." Am. J. Hum. Genetics. 1998; 63: 696-702. Freeman, H.P. "The Meaning of Race in Science--Considerations for Cancer Research." CANCER. January 1998; 82(1): 219-225. Jackson, F. "Concerns and Priorities in Genetic Studies: Insights from Recent African American Biohistory." Seton Hall Law Review. 1997; 27(3): 951-970. Juengst, E.T. "Human Genetics ?98: Ethical Issues in Genetics. Group Identity and Human Diversity: Keeping Biology Straight from Culture." Am. J. Hum. Genetics. 1998; 63: 673-677. RFA: HG-98-001 "Methods for Discovering and Scoring Single Nucleotide Polymorphisms" NIH GUIDE, January 9, 1998. Schafer, A.J. and J.R. Hawkins. "DNA Variation and the Future of Human Genetics." Nature Biotechnology. January 1998; 16: 33-39.
Last Reviewed: October 15, 2008 |
PrivacyCopyrightContactAccessibilitySite MapStaff DirectoryFOIAHome | |