Analysis and Proposed Actions Regarding the NBAC Report: Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity

Prepared by
HHS Working Group on the NBAC Report

Cover letter

Dr. Harold Shapiro, Chair
National Bioethics Advisory Commission
6705 Rockledge Drive, Suite 700 MSC 7979
Bethesda, Maryland 20892-7979

Dear Dr. Shapiro:

I am pleased to forward to you a copy of the response of the Department of Health and Human Services (DHHS) to the National Bioethics Advisory Commission’s report, Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity. This response is the product of a DHHS working group. consisting of representatives from all the relevant agencies within the Department, that was convened to review and address the specific recommendations of the NBAC report. The decisionmaking capacity report is a valuable document that not only contributes to the public discourse on the protection of vulnerable subjects in research but also provides important insights that will help the Department strengthen its policies and procedures for safeguarding the rights and welfare of such individuals.

With respect to NBAC’s report on Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, another working group within the Department is reviewing the report and formulating a set of responses to its recommendations. We anticipate that a report will be forthcoming within the next few months.

I want to take this opportunity to extend my best wishes to you and the other. Commissioners and express my appreciation for the fine work that all of you have done and will continue to do.

Sincerely,

Donna E. Shalala
Enclosure

Introduction

The National Bioethics Advisory Commission (NBAC) presented its report entitled Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity (the “Report”) to the National Science and Technology Council (NSTC) in January, 1999. The Report makes 2I recommendations, which are variously directed to investigators or institutional review boards (IRBs); the National Institutes of Health (NIH) or other agencies and offices of the Department of Health and Human Services (HHS); other Federal agencies that, along with HHS, have adopted the Common Rule

• COMMENTS AND PROPOSED ACTIONS ON SPECIFIC RECOMMENDATIONS

  This section presents the WG’s comments on each of NBAC’s 21 recommendations using the order and titles from the Report. Most recommendations are addressed singly, but some are grouped together to facilitate discussion. Each section begins with the text of the recommendation, then presents the WG’s analysis, and concludes with the WG’s proposed action.

  1. Recommendations Regarding Review Bodies

     NBAC Recommendation 1: Institutional Review Board (IRB) Membership

     All IRBs that regularly consider proposals involving persons with mental disorders should include at least two members who are familiar with the nature of these disorders and with the concerns of the population being studied. At least one of these IRB members should be a member of the population being studied, a family member of such a person, or a representative of an advocacy organization for this population. These IRB members should be present and voting when such protocols are discussed. IRBs that only occasionally consider such protocols should involve in their discussion two ad hoc consultants who are familiar with the nature of these disorders and with the concerns of the population being studied; at least one of these consultants should be a member of the population being studied, a family member of such a person, or a representative of an advocacy organization for this population.

     Discussion

     The WG agrees with the principle, reflected in this NBAC recommendation, that IRB deliberations should include persons who are familiar with conditions that may affect decisionmaking capacity and with the concerns of the population being studied.

     http://grants.nih.gov/grants/policy/questionablecapacity.htm) under the heading “Use of a Surrogate.” This statement was developed to assist IRBs and clinical investigators in protecting research participants who are, may be, or may become decisionally impaired by NIH in consultation with a broad array of experts on, and participants in, clinical research, bioethics, mental health, substance abuse, and age-related conditions, as well as agencies and groups concerned about clinical research and human subject protections. According to the statement, “where permitted by law, individuals with impaired capacity may have a family member or other legally authorized representative serve as a surrogate for research decisions, with this role documented during the consent process.” The surrogate should make research decisions based on substituted judgment whenever possible. Otherwise, best interest standards are to be used if the values of the individual are not known or cannot be given legal effect. The statement also emphasizes the importance of surrogates receiving some education about their own role and the cognitive and health status of the research participant, as well as about the study in which the participant may be involved.

     http://www.nimh.nih.gov/studies/clinres.htm

  2. Office of Intramural Research/NIH Committee on Scientific Conduct and Ethics. The Committee on Scientific Conduct and Ethics is composed of a broad spectrum of members from the Institutes and Centers. The committee was established in September 1995 and its charge includes: developing and/or refining the existing Guidelines for the Conduct of Research; developing Guidelines for Training and Mentoring; developing effective mechanisms for ethics training for the NIH scientific community, including the ethics column in the NIH Catalyst. The third edition of the Guideline for the Conduct of Research (http://www.nih.gov/news/irnews/guidelines.htm) was published in 1997. The Guidelines for Training and Mentoring are being developed now. Training of facilitators to lead ethics case discussions, developed by NHGRI (http://www.nhgri.nih.gov/about_nhgri/dir/ethics/message.html) are underway.
  3. Trans-NIH - Training in the Responsible Conduct of Research. Every predoctoral and postdoctoral National Research Service Award (NRSA) trainee supported by an institutional training grant must receive training in the responsible conduct of research. Grant applications must include a description of a program to provide formal or informal instruction in scientific integrity on the responsible conduct of research. Programs are encouraged to include topics such as: conflict of interest, responsible authorship, policies for handling misconduct, policies regarding the use of human and animal subjects, and data management. More details are provided in the NIH Guide for Grants and Contracts, Volume 21, Number 43, November 27, 1992.
  4. NIH/CDC/HRSA/AHCPR Program Announcement on Short-Term Courses in Research Ethics. Bioethics Training Initiative. The National Institutes of Health (NIH), Centers for Disease Control (CDC), Health Resources and Services Administration (HRSA), Substance Abuse and Mental Health Services Administration, and the Agency for Health Care Policy and Research (AHCPR) invite applications for grants to develop, conduct, and evaluate short-term courses on ethical issues in research, particularly those involving human participants. Courses should improve the skills of biomedical, behavioral, social science, and public health researchers in identifying and addressing the ethical, legal, and social implications of their research, especially when human participants are involved. Courses developed include Ethics Course on Scientist­Participant Partnerships, Ethical Issues in International Research, and Ethics of Research Participation in Vulnerable and Special Populations.
  5. Office of Intramural Research/NIH Computer-Based Training for NIH Researchers. Protecting Human Subjects in the NIH Intramural Research Program. This computer-based training module was developed to orient NIH research staff to the special requirements associated with research involving human subjects. Completion of this training is required by NIH staff who contemplate involvement with this type of research. The training is also available for download and use by staff in other organizations beyond the NIH. The training can be found at: http://helix.nih.gov:8001/ohsr/newcbt/
  6. NIH Bioethics Interest Group Website. Interest group includes participants from the intramural and extramural communities at NIH. Topics addressed have included: research with the decisionally impaired, bioethics training, and end-of-life issues. Website contains resources on bioethics issues for easy access by NIH staff: http://www.nih.gov/sigs/bioethics/index.html
  7. National Institutes of Environmental Health Sciences Research Ethics Program. The Office of the Scientific Director supports several programs designed to promote responsible conduct in research. Located within the Division of Intramural Research at the National Institute of Environmental Health Sciences (NIEHS), the Office coordinates educational activities, training workshops, and conferences on ethical issues in environmental health research. The Office of the Scientific Director works closely with the NIEHS Institutional Review Board, the Office of Clinical Research, the Office of the Director, and the NIEHS Division of Extramural Research to develop institutional policies that promote research integrity. The Office also conducts interdisciplinary research on ethical, legal, and social issues in environmental health research, spanning such fields as environmental toxicology, cancer research, and environmental genomics.
  8. National Institutes of Health (NIH) And The Food and Drug Administration (FDA) National Human Subject Protections Education Workshop Program. The NIH and the FDA are continuing to sponsor a series of workshop on responsibilities of researchers, Institutional Review Boards (IRBs), and institutional officials for the protection of human subjects in research. The workshops are open to everyone with an interest in research involving human subjects. The meetings should be of special interest to those persons currently serving or about to begin serving as ‘a member of an IRB. Issues discussed at these workshops are relevant to all other Public Health Service agencies. Upcoming workshops include: “Human Subjects Research & IRBs Under Fire” “Cultural Diversity in Clinical Research” “Ethical Research in the New Millennium: What the Belmont Report Didn’t Anticipate” and “Protection of Human Subjects: Involving Special Populations.”
• CDC Training Activities
  1. Office of the Director/CDC Computer-Based Training for CDC Researchers. Scientific Ethics training for CDC researchers involved in intra- and extramural research. Scientific Ethics was launched on February 17, 1999. This computer-based training program, designed in five discrete modules, was developed to familiarize CDC scientists and other public health professionals with basic ethical principles, policies, and procedures for the responsible conduct of science. All scientific staff and managers are required to complete the training within six months of its introduction to their respective Centers/lnstitute/Offices (CIO). New staff members will be required to complete the training before they conduct research at CDC or ATSDR. The program is a self-directed learning opportunity that allows users to exit and re-enter at will, choose areas of greatest personal interest, and select levels of complexity through optional exercises. The five modules: CDCs Mission in Science, Protection of Human Subjects, Scientific Integrity, Science-related Responsibilities, and Case Studies, can be studied in any order. Scientific Ethics may be accessed via the CDC Intranet. A CD-ROM disk is available for staff in remote locations. A passing score on the certifying exam included in Scientific Ethics will trigger the program to print a personalized certificate to which a unique identifier will be assigned. This identifier will also be required on requests for Institutional Review Board-approval of research involving human participants.
  2. CDC Corporate University Science Survival Skills Course. A 40 hour introductory course for CDC scientists engaged in research has been developed by the Office of the Associate Director and the Epidemiology Program Office to enhance scientists’ knowledge of the CDC policies and procedures involved in the conduct of science. Sessions on scientific integrity, misconduct, human subjects research, authorship and manuscript clearances policies and procedures are included. In addition, a mock Institutional Review Board (IRB) meeting is conducted with the students serving as IRB members. CME, CNE, and CEU credits are offered upon successful completion of the course.
  3. Scientific Ethics Seminar Series. During 2000 and 2001, the Office of the Associate Director for Science will host a seminar series designed to stimulate thought on ethical issues CDC researchers encounter while conducting both domestic and international public health research. The goals of the series are to introduce ethical topics of broad concern within CDC, provide updated information on new ethical issues, and to facilitate a networking opportunity for CDC researchers to later share, debate and discuss related experiences. Each seminar will be two hours long, have a public health theme, and be conducted by an experienced researcher, philosopher, ethicist or a combination of these individuals. The format for each seminar will vary, some will involve panel discussions with panelists taking opposing views. All will provide time to question and interact with the speaker/panelists.
  4. “Brown Bag” Seminars on Human Subjects Research. The Office of the Associate Director for Science sponsors a series of “brown bag” seminars throughout the year which are designed to educate CDC scientists on human subjects issues. CDC’s Human Subjects Public Health Educator and CDC’s Human Subjects Manager regularly team up to present various human subjects-related topics at branch and division meetings.
  5. International Ethics Working Group. The Office of the Associate Director for Science and the Office of Global Health have formed a working group of CDC researchers interested in the area of ethical issues related to CDC’s international health activities. The purpose of the working group is to discuss CDC responsibilities and needs in the area of international ethics in relation to its mission and to identify activities that can help CDC effectively accomplish this mission.
  6. International Human Subjects Research Web Page. This page (http://www.cdc.gov/od/ads/ihsr/index.htm) was designed to keep CDC investigators involved in international researcher involving human subjects and collaborators abreast of international ethical codes and guidance documents; organizations involved in international human subjects research; articles of interest in international ethics; and meetings, conferences and training opportunities. In addition to English, many documents may be found in Spanish, French and Russian.
  7. Joint CDC/University International Bioethics Fellowship Program. Discussions are underway with a local university to co-sponsor an international bioethics fellowship program. Such a program could provide an opportunity for CDC collaborators in developing countries to develop leadership skills in bioethics, and for CDC and its partner to facilitate critical dialogue on the topic.
  8. Annual IRB Training. Each January CDC conducts an all-day training session primarily for new IRB members; however, all IRB members are encouraged to attend. In addition, CDC has invited IRB members from Morehouse School of Medicine and Life University to participate. Topics include the Federal regulations for protecting human subjects (45CFR46) and assurances of compliance with 45CFR46. During the afternoon, a mock IRB meeting is held. About two months later, a make-up training day is held for IRB members unable to attend the January session. Interested investigators are invited to attend the make-up session.
     
     CDC’s IRB chairs also have instituted a mentoring program where seasoned IRB members mentor new IRB members. Further, seasoned lRB members are also available to sit with investigators to provide one-on-one training in developing protocols that involve human subjects.
  9. IRB Training for Community Partners. CDC has been invited by a number of state health departments to provide IRB training.
  10. Human Subjects Web Page. The Associate Director for Science hosts a Human Subjects home page (http://www.cdc.gov/od/ads/hsr2.htm) Highlights include:
      1. Guidelines for Developing a Consent Document. Developed by a former CDC IRB Chair, this guide helps the investigator write consent documents at the 8th grade reading level. The guide is also useful to find standard wording for various parts of a consent document.
      2. Protocol Development Checklist. The checklist helps guide the investigator to think about what should go into a research protocol. It is used to prompt the investigator to include all items that may apply to the proposed research. Not all items may apply, however. In addition, a Human Subjects Supplement to the checklist is included as the Protocol Development Checklist does not include items that pertain to research involving human participants. The Human Subjects Supplement checklist helps the investigator think about what should go into the human subjects part of a research protocol, when applicable.
      3. Informed Consent/Assent Checklist This checklist helps guide the IRB and investigator when developing ALL research protocols involving human participants. A separate column is for use when developing assent forms.
      4. Vulnerable Populations Checklists. Three separate checklists help guide the IRB and investigator in addressing issues of added safeguards for research targeting pregnant women, fetuses, and in vitro fertilization or involving prisoners or children.
• CDC Reports on Human Subject Participation in Research
  1. Participation of Women, Minorities and Children in CDC-Conducted Research. A report entitled An Evaluation of the Participation of Women, Minorities and Children in CDC-Conducted Research was recently completed and distributed to all CDC CIOs. The report discusses the status of CDC’s inclusion of women, minorities and children in research in light of federal policies adopted in the 1990s to ensure that under represented populations are included in federally supported research. The CDC report was undertaken to (1) determine how well CDC is implementing its policy to include women and minorities in research and (2) determine whether a need exists to develop a formal policy to include children in research. The report is available on the Internet at http://www.cdc.gov/od/ads/hsr2.htm.
  2. State Statutes Addressing the Inclusion of Children in Research. The Office of the Associate Director for Science and the Office of General Counsel are nearing completion on a comprehensive report all U.S. State statutes on the involvement of children in research. In addition, the report will define the age of majority for each state and provide a point-of-contact. Once complete, the report will be available on the Internet at http://www.cdc.gov/od/ads/hsr2.htm.

Appendix C

APPENDIX C

Interim - Research Involving Individuals with Questionable Capacity to Consent:
Points to Consider

Importance of Research Involving Individuals with Impaired Decisionmaking Capacity.

Research is essential to improve our understanding of and ability to treat human diseases and disorders that place great burdens on individuals and their families. The quest for new knowledge, however, should never take precedence over the welfare of the research participant. Research may at times involve individuals with limited decisionmaking capacity. The NIH is committed to helping researchers and Institutional Review Boards (IRBs) carry out this research in an ethical manner, protecting the rights and welfare of research participants while advancing treatment opportunities and vital knowledge. Critical to this research process are appropriate safeguards that ensure legally effective