Research on ethical issues in human studies. (Fellowships, Grants, & Awards).

NIH invites research grant applications to investigate ethical issues in research using human subjects. The Code of Federal Regulations (45 CFR, Part 46) provides a regulatory framework that all NIH-supported researchers must follow. However, recent developments in biomedical and behavioral research--including the rapid growth of new interventions and technologies (e.g., stem cells, genetics research), increasing involvement of foreign populations in clinical research, and concerns about financial conflicts of interest among researchers--challenge investigators' abilities to interpret and apply the regulations. Other situations (e.g., research with vulnerable populations, the use of data banks or archives, research on stigmatizing diseases or conditions) may present difficulties for identifying strategies, procedures, and/or techniques that will enhance and ensure the ethical involvement of human participants in research.

The purpose of this PA is to support empirical research addressing the ethical challenges of involving human participants in research in order to inform and optimize protections for human participation in research. Examples of the types of topics that would be appropriate for applications submitted under this announcement include, but are not limited to, the following:

Minimizing Risks in Human Research

1) Assess how features of the research and research setting affect evaluations of risks versus potential benefits of different types of research for investigators, institutional review board (IRB) members, and potential participants, groups, and communities. Examples of features of the research or research setting may include characteristics of the participants (e.g., age, health status and stage of disease, ethnic/cultural background, cognitive capacity, social status, gender, incarceration), aspects of the condition/disease (e.g., prevalence, severity, chronicity, degree of disability), and the nation or culture in which the study will take place.

2) Identify potential social, psychological, and/or economic harms (e.g., stigma, discrimination, personal distress, loss of insurance coverage, loss of employment) that may be associated with recruitment, participation; or self-determined or study-determined withdrawal from research. Evaluate strategies or procedures for minimizing these harms in regard to individuals', groups', communities', and populations' willingness to participate in different types of research.

3) Assess the conditions and assumptions under which IRB evaluation of risk versus potential benefits is similar to or different from the evaluation of risks versus potential benefits by individuals, groups, communities, and populations.

4) Assess the impact of obtaining a certificate of confidentiality on perceptions of IRB members and/or participants in terms of evaluation of risks, understanding of the research, and/or understanding of the rights to privacy.

5) Identify and evaluate strategies for protecting and minimizing disclosure of private information when identifiable data are collected via the Internet, preserved for secondary analysis (e.g., in a tissue or gene bank, data archive, warehouse), and/or collected about third parties in research (e.g., network studies).

Issues in Informed Consent

1) Determine how features of the informed consent process affect participants' comprehension and/or willingness to participate in research. Examples of these features include a) variations in the style of presentation (e.g., oral, written, graphic, video); b) readability, complexity, and/or format of the consent document; c) characteristics of the participants (e.g., language preference, age, health status, education, cultural/ethnic background, personal motivations, cognitive capacity); and d) contextual features or circumstances in which informed consent takes place (e.g., characteristics of the research staff, location such as research hospital versus private office versus home, presence/involvement of family members, presence/involvement of patient advocates).

2) Evaluate different methods and identify best-practice strategies for consulting with communities in the United States and/or other countries regarding comprehension, willingness to participate, and/or willingness to continue with research at the individual, group, community, and/or population level.

3) Assess how recontacting participants to obtain informed consent for additional uses of their data affects participant comprehension, willingness to participate, and sense of coercion.

4) Identify and evaluate strategies, procedures, and/or techniques for improving comprehension of research by individuals, groups, communities, and/or populations at the time of initial consent, during, and/or after completion of the study. Also, determine how these strategies may differ depending on age, health status, ethnic/cultural background, cognitive capacity, social status, and/or gender of the target audience.

5) Assess how participants' willingness to participate versus sense of coercion, may be affected by use of different types of incentives, remuneration, and/or provision of medical care; different features of the research setting (e.g., personal physician as recruiter and/or researcher, private funding versus federal funding); and characteristics of the participants (e.g., health status, age, ethnic/cultural background, education, gender).

6) Assess the impact of communicating or not communicating individual test results, study progress, and/or study results on participants' willingness to continue with the protocol and/or participate in research again.

Oversight of Research and Research Data

1) Identify and evaluate strategies to improve the oversight of human participants protection by IRBs, data and safety monitoring boards (DSMB), conflict of interest (COI) committees, etc. Examples may include a) develop and evaluate best-practice outcome measures for decision making about the acceptability of research protocols; b) assess the consistency of protocol review decisions within DSMBs, IRBs, or COI committees; c) assess the impact of conflicts of interest among members of oversight committees on decision making about the acceptability of research protocols, interpretations of adverse events, and/or perceptions of "independence of review" by the research community; and d) assess the impact of disclosing varying degrees of financial conflicts of interest involving the principal investigator, members of oversight committees, sponsor, institution, etc. on research participant willingness to participate and/or continue with research, and/or participant understanding of the research.

2) Compare and evaluate different methods and strategies for identifying, reporting, and handling adverse events based on the perspectives of individual participants, institutions, DSMBs, and/or IRBs.

This PA will use the NIH R01 award mechanism and Just in Time concepts. It will also use the modular as well as the nonmodular budgeting formats (see http://grants.nih.gov/grants/funding/ modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular format. Otherwise follow the instructions for nonmodular research grant applications.

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398. html in an interactive format. Complete information on this PA is available at http://grants1.nih.gov/ grants/guide/pa-files/PA-02-103.html. To assist in identifying which NIH institute/office most closely matches your research topic, the following website provides additional information about institute- and office-specific research interests that will be supported by this PA: http://grants.nih.gov/grants/ funding/ethics_contacts.htm.

Contact: Della M. Hann, Office of Extramural Research, NIH, Building 1, Room 152, Bethesda, MD 20892 USA, 301-402-2725, fax: [phone], e-mail: [e-mail]. Reference: PA No. PA-02-103