Release Date: September 22, 2000

PA NUMBER: PA-00-133

National Human Genome Research Institute
National Institute on Aging
National Institute of Child Health and Human Development
National Institute on Drug Abuse
National Institute on Deafness and Other Communication Disorders
National Institute of Environmental Health Sciences
National Institute for General Medical Sciences
National Institute of Mental Health
National Institute of Nursing Research
National Institute of Neurological Disorders and Stroke

THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.

This Program Announcement replaces the regular research grant (R01) component of PA-96-042, The Ethical, Legal and Social Implications of Genetics Research, which was published in the NIH Guide for Grants and Contracts, Vol. 25, No. 13, April 26, 1996. It is supplemented by the ELSI Education (R25) and Small Grants (R03) Program Announcements.

PURPOSE

This Program Announcement (PA) is designed to solicit research projects that anticipate, analyze, and address the ethical, legal, and social implications of the discovery of new genetic technologies and the availability and use of genetic information resulting from human genetics and genomic research. Of particular interest are studies that: 1) examine the issues surrounding the completion of the human DNA sequence and the study of human genetic variation; 2) examine the issues raised by the integration of genetic technologies and information into health care and public health activities; 3) examine the issues raised by the integration of knowledge about genomics and gene-environment interactions into non-clinical settings; 4) explore the ways in which new genetic knowledge may interact with a variety of philosophical, theological, and ethical perspectives; and 5) explore how socioeconomic factors, gender, and concepts of race, ethnicity and culture influence the use and interpretation of genetic information, the utilization of genetic services, and the development of policy.

This PA is supplemented by the ELSI Education Grants (R25) Program (http://www.nhgri.nih.gov/Grant_info/Funding/Research/ELSI_R25_PA.html), which is aimed at developing innovative educational approaches that will increase knowledge and understanding of genetics and genomics research and its ethical, legal and social implications.

In addition, a new ELSI Small Grant (R03) Program has been developed and can be accessed online at: http://www.nhgri.nih.gov/Grant_info/Funding/Research/ELSI_R03_PA.html. This Small Grant Program, which is limited to applications requesting up to $50,000 in direct costs per year, makes use of a streamlined application process and is designed to encourage the development of small, focused research projects by legal, historical, ethics and social sciences scholars. It is also designed to support smaller exploratory studies that may provide preliminary findings for larger research proposals in all research areas of interest.

Applicants who are preparing an Education (R25) or Small Grant (R03) application should refer to the announcements referenced above. The ELSI Research Program also will accept conference grant (R13) applications. These applications are limited to $50,000 and to conferences that are highly focused and result in a specific product, such as the publication of conference proceedings or policy recommendations in a journal article or book. For specific application guidelines and instructions for each of the participating Institutes and Centers (ICs), applicants should refer to the "Guidelines for Support of Scientific Meetings by NIH," which are available online at http://grants.nih.gov/grants/guide/notice-files/not98-151.html.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS led national activity for setting priority areas. This PA, "Ethical, Legal, and Social Implications of Human Genetics and Genomic Research", is related to one or more of the priority areas identified in that report. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and non-
profit organizations, either public or 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. Participation in the program by investigators at minority institutions is strongly encouraged. Investigators from foreign institutions should be aware that, in the area of ethical, legal and social issues, the standard NIH criteria for funding foreign applications are applied very strictly (see Award Criteria below). These investigators are strongly encouraged to contact program staff before preparing an application.

To be eligible for this award, the proposed Principal Investigator must be an independent investigator. That is, he or she should be genuinely independent of a mentor. Individuals in the final stages of training may apply, but individuals can not be in a training status at the time the award is made.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) regular research project grant (R01) mechanism. Program contacts at the relevant Institutes and Centers (IC)s are available for consultation prior to submission of an application. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant.

RESEARCH OBJECTIVES

Background and Significance

The 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 currently 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 the ethical, legal, and social implications of this research; 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 risk identification, risk reduction, diagnostic and therapeutic options. It will also help to elucidate more clearly the interaction between genes and the environment in the development of disease.

As the Human Genome Project draws closer to completion of the final "finished" human DNA sequence, researchers are focusing increasing attention on the discovery of variations found in the DNA sequences among individuals. The identification, classification, quantification and analysis of these genetic 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, heart disease, depression and other forms of mental illness, deafness and hearing impairment, and some forms of cancer. It will also provide the basis for studying how genetic variation influences gene function in human growth and development.

Knowing the entire sequence of the human genome and understanding more about genetic variation among individuals and groups will, however, raise a number of ethical, legal, and social issues. These include: how to design and conduct genetic and genomic 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 who traditionally have not been involved in genetics and genomics research, or who may have been adversely affected in the past by certain types of research. On the one hand, the exclusion of certain groups from research studies has contributed to disparities in the diagnostic and treatment options available to members of these groups. On the other hand, the inclusion of members of these populations in some early genetic studies may have led to an increase in stigmatization and to the potential for discrimination in employment, health care, insurance, or society more broadly. These issues may become even more pressing if ongoing research reveals data on the interactions among genotype, diseases or traits, and traditional, socially-constructed concepts of race, ethnicity and culture.

Research Scope and Objectives

This program announcement emphasizes the ongoing commitment of the NIH to support research and educational activities related to these and other ethical, legal, and social implications of human genetics and genomic research. The ultimate mission of the ELSI Research Program is to support research and education activities that: 1) promote genetic privacy and fair use of genetic information; 2) encourage the responsible integration of new genetic information and technologies into clinical and non-clinical settings; 3) ensure that genetic research is conducted in an ethical manner; and 4) improve public and professional understanding about genetics, genome technology and related ethical, legal and social issues.

In July 1997, the ELSI Research Planning and Evaluation Group (ERPEG) was created to evaluate the portfolio of ELSI research grants and develop goals and recommendations to help guide and strengthen the ELSI research program. In February 2000, ERPEG released their final report (http://www.nhgri.nih.gov:80/ELSI/erpegreport.html), which included five goals to help guide ELSI research over the next few years and a series of programmatic recommendations for enhancing the ELSI research program.

The five research goals, which were originally published in the October 1998 issue of Science as part of the five year plan for the HGP (http://www.sciencemag.org/cgi/content/full/282/5389/682), were designed to capture some of the emerging topics in genetics research and to help focus the ELSI research agenda through the year 2003. The goals, described below, should be seen as a guide to areas of particular interest to the ELSI Research Program, but should not be interpreted as an exhaustive listing of all possible research topics. As genetic research evolves and the interpretation and use of genetic information continue to emerge, applicants are encouraged to identify additional research topics and issues.

To demonstrate the breadth and complexity of these goals, examples of possible research questions are provided. These examples are meant only to give a flavor of the possible issues to be addressed, and are not, in any sense, exhaustive or comprehensive.

This program announcement, along with the ELSI Education Grant (R25) and Small Grant (R03) program announcements, is designed to be complementary to several other National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), and other Interagency Program Announcements, including:

1. PA-99-079, "Research on Ethical Issues in Human Studies" which solicits applications to conduct research on ethical issues that arise with research involving human participants (http://www.nih.gov/grants/guide/pa-files/PA-99-079.html);

2. PA-97-028, "Individual National Research Service Award (NRSA)" which solicits applications for post-doctoral, cross-disciplinary training in genetics, genomics and ELSI research (http://www.nih.gov/grants/guide/pa-files/PA-99-122.html);

3. PA-97-039, "Linking Nursing and Genetic Research-Individual Postdoctoral and Senior Fellowships" which solicits applications for fellowships that will enable researchers to investigate the clinical implications of human genetics research (http://www.nih.gov/grants/guide/pa-files/PA-97-039.html);

4. PA-99-059, "Courses in Genomic Analysis and Interpretation and ELSI Related Research" which solicits short courses to enhance the skills of individuals interested in pursuing laboratory or scholarly research relevant to ELSI issues and the Human Genome Project (http://www.nih.gov/grants/guide/pa-files/PAR-99-059.html);

5. PA-99-051, "Short Courses in Research Ethics" which solicits applications for grants to develop, conduct, and evaluate short-term courses on ethical issues in research, particularly those involving human participants. (http://grants.nih.gov/grants/guide/pa-files/PA-99-051.html);

6. PA-99-050, "Mentored Scientist Development Award in Research Ethics" which supports training in research ethics for health professionals working at academic and other health-related institutions in biomedical, behavioral, or public health research, particularly research involving human participants (http://grants.nih.gov/grants/guide/pa-files/PA-99-050.html);

7. "Small Business Innovation Research (SBIR) Program" which includes a solicitation for education projects related to the Ethical, Legal, and Social Implications of human genetics research, technologies, and information (http://grants.nih.gov/grants/funding/sbir.htm).

8. PA-97-047, "Opportunities in Genetics and Nursing Research" which solicits applications from ongoing funded NIH nurse researchers to submit a competitive supplement on various aspects of genetic research to complement their ongoing program of research (http://grants.nih.gov/grants/guide/pa-files/PA-97-047.html).

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating 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 UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It 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" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
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.

URLs IN NIH GRANT APPLICATIONS AND APPENDICES

All applications and proposals for NIH funding must be self-contained within specified page limits. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access the Internet site.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research, or on the Internet at http://grants.nih.gov/grants/funding/phs398/phs398/html and may be obtained 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 title and number of the program announcement must be typed on line 2 of the face page of the application form and the YES box must be marked.

The Center for Scientific Review (CSR) will not accept any application in response to this PA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique.

Applicants planning to submit an investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended/revised version of an application requesting $500,000 or more in direct costs for any year are advised that they must contact the Institute or Center (IC) program staff before submitting the application, i.e., as plans for the study are being developed. Furthermore, the applicant must obtain agreement from the IC staff that the IC will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and IC who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of both any such application and any such subsequent amendment. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 at: http://grants.nih.gov/grants/guide/notice-files/not98-030.html.

Applications requesting more than $250,000 direct costs in any year must use the standard application instructions.

Applications that request $250,000 or less in direct costs in any year must use the modular grant application instructions. Complete instructions and information on Modular Grant applications can be found at http://grants.nih.gov/grants/funding/modular/modular.htm.

The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers and Institute staff. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants, with the modifications noted below.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $250,000 per year. (Applications that request more than $250,000 direct costs in any year must follow the traditional PHS 398 application instructions.) The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below:

PHS 398

For Consortium/Contractual costs, provide an estimate of total costs (direct plus facilities and administrative) for each year, each rounded to the nearest $1,000. List the individuals/ organizations with whom consortium or contractual arrangements have been made, the percent effort of key personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost for a consortium/contractual arrangement is included in the overall requested modular direct cost amount. Include the Letter of Intent to establish a consortium. Provide an additional narrative budget justification for any variation in the number of modules requested.

Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710

BETHESDA, MD 20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be assigned to specific ICs on the basis of established PHS referral guidelines. Applications will be evaluated for scientific and technical merit by an appropriate scientific review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board.

Review Criteria

The 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.

1. 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?

2. 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?

3. Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?

4. 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)?

5. 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 accordance with NIH policy, all applications will also be reviewed with respect to the following:

AWARD CRITERIA

Applications will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: scientific merit of the proposed project as determined by peer review, availability of funds, and program priority. In order for the NIH to fund applications from foreign institutions, the application must meet the following three criteria: (1) The proposed project must have special relevance to the mission and objectives of the awarding organization and have the potential to advance knowledge that will benefit the United States; (2) The project must present special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries which are not readily available in the United States or which provide augmentation of existing U.S. resources; and (3) The foreign grant application must be in the upper half of the research grant priority scores.

INQUIRIES

Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome.

Direct general inquiries regarding programmatic issues to:

The ELSI Research Program
National Human Genome Research Institute
Building 31, Room B2B07
31 Center Drive, MSC 2033
National Institutes of Health
Bethesda, MD 20892-2033
TEL: (301) 402-4997

FAX: (301) 402-1950
E-mail: elsi@nhgri.nih.gov

Specific programmatic contacts at each of the participating NIH Institutes can be found at the following website: http://www.nhgri.nih.gov/ELSI/R01contacts.html

Direct general inquiries regarding fiscal matters to:

Grants Administration Branch
Division of Extramural Research
National Human Genome Research Institute
Building 31, Room B2B34
31 Center Drive, MSC 2031
Bethesda, MD 20892-2031
TEL: (301) 435-7858
FAX: (301) 402-1951
E-mail: jc166o@nih.gov

Specific fiscal contacts at each of the participating NIH Institutes can be found at the following website: http://www.nhgri.nih.gov/ELSI/R01contacts.html

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 93.172, Human Genome Research; No. 93.866, National Institute on Aging; No. 93.865, National Institute of Child Health and Human Development; No. 93.279, National Institute on Drug Abuse; No. 93.173, National Institute on Deafness and Other Communication Disorders; No. 93.121, National Institute of Dental and Craniofacial Research; Nos. 93.113 and 93.115, National Institute of Environmental Health Sciences; Genetics Program 93.862, National Institute of General Medical Sciences; No. 93.242, National Institute of Mental Health; and No. 93.361, National Institute of Nursing Research. Awards are made under authorization of sections 301 and 405 of the Public Health Service Act, Title IV, part A (public Law 78-410, as amended by Public Law 99-158, 43 USC 241 and 285)and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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 and contract 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, and 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.