1.2 Ethical Principles: The Belmont Report
The preamble to Harvard University’s “Statement of Policies and Procedures Governing the Use of Human Subjects in Research” (voted by the President and Fellows of Harvard College on September 22, 2003) informs the oversight of all research covered by these policies and procedures:
Harvard University is guided by the ethical principles regarding research involving human subjects set forth in the report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (Ethical Principles and Guidelines for the Protection of Human Subjects of Research [the “Belmont Report”]). The minimum standard is set by the Department of Health and Human Services [DHHS] regulations at 45 CFR 46 (the “Common Rule”). Harvard University has additional provisions beyond that standard, which help to establish the highest expectations for performance and oversight by investigators, Institutional Review Boards (IRBs), and the University.
The actions of Harvard University regarding research involving human subjects also must conform to all other applicable federal, state, and local laws and regulations.
To oversee and regulate research involving human subjects most effectively, the University maintains three Institutional Review Boards under the direction of the Office of the Provost, with three separate Federal Wide Assurances: one for the “University Area” (described more fully below); one for the Harvard Medical School and Harvard School of Dental Medicine; and one for the Harvard School of Public Health. Each of these three IRBs reviews research protocols involving human subjects and evaluates risk to subjects, protection against risks, and potential benefits likely to result from proposed research. It is the function of each IRB to 1) determine and certify that all projects reviewed by the IRB conform to policies and procedures set forth by the University’s “Statement of Policies And Procedures Governing the Use of Human Subjects in Research,” and, as appropriate, applicable regulations of the DHHS and the Food and Drug Administration (FDA) regarding the health, welfare, safety, rights, and privileges of human subjects; and 2) assist the investigator in complying with relevant federal, state, and local laws and regulations, and University policy. While the three IRBs operate independently, all participate in a University-wide Human Subjects Research Committee, established and run by the Office of the Provost.
This document, Policies and Procedures for Human Research Protection – University Area, Committee on the Use of Human Subjects in Research, Harvard University, describes the Human Research Protection Plan (HRPP), including the policies, procedures, and regulations governing research with human subjects and the requirements for submitting research proposals for the:
Faculty of Arts and Sciences; Harvard Graduate School of Education; John F. Kennedy School of Government; Harvard Divinity School; Harvard Business School; Harvard Law School; Harvard Graduate School of Design; and the Radcliffe Institute for Advanced Study (the “University-Area institutions”). This IRB will be referred to as the Committee on the Use of Human Subjects (CUHS), and is the IRB of record for the University Area. These policies and procedures apply to all research involving human subjects, regardless of sponsorship and performance site, conducted under the auspices of one or more University-Area institutions. A University-Area institution becomes "engaged" in human subjects research when its employees or agents (i) intervene or interact with living individuals for research purposes; or (ii) obtain individually identifiable private information for research purposes. For the purpose of determining engagement in human subjects research, “agents” include all individuals performing institutionally designated activities or exercising institutionally delegated authority or responsibility. The policies and procedures that follow are an implementation of the University-wide “Statement of Policies And Procedures Governing the Use of Human Subjects in Research” as voted by the President and Fellows of Harvard College, September 22, 2003 (“the Vote”), the preamble of which appears above.
All sites, domestic or foreign, engaged in research that is conducted by or in collaboration with any of the University Area institutions, will be obligated to conform to ethical principles that are at least equivalent to those cited in the previous paragraph or, when appropriate, as may be determined by the DHHS Secretary.
1.2 Ethical Principles: The Belmont Report
It is the duty of the CUHS to review and make decisions on all protocols for research involving human subjects. The primary responsibility of the CUHS is the protection of research subjects from undue risk and from deprivation of personal rights and dignity. This protection is best assured by consideration of three principles, which are the touchstones of ethical research involving human subjects:
(1) that voluntary participation by the subjects, indicated by free and informed consent, is assured;
(2) that an appropriate balance exists between the potential benefits of the research to the subject or to society and the risks assumed by the subject; and
(3) that there are fair procedures and outcomes in the selection of research subjects and the potential distribution of likely benefits.
These principles are summarized as respect for persons, beneficence, and justice.
Respect for Persons: Voluntary Participation and Informed Consent
One of the most important elements in any research involving human research subjects is the assurance of voluntary informed consent. Any person who is to be a research subject, whether the research is designed for his/her own direct benefit or for the advancement of scientific knowledge in general, must understand as completely as possible what is to be done and what the potential risks and benefits are. The person must give his/her consent freely, without pressure or inappropriate inducement. The CUHS strives to ensure voluntary informed consent of research subjects through careful review of the recruitment and consent process, including the consent form, information sheet, and/or oral consent script to be used with subjects.
The capacity for truly informed and voluntary participation in research varies widely among study populations. At one extreme, there may be ample understanding and manifest freedom from coercion; at the other, there may be degrees of understanding and freedom that affect the consent of potential subjects. The concept of informed consent extends to those studies in which the subjects are not able to give personal consent for themselves. In such cases the consent process and any documentation are addressed to those who have been designated responsible for the research subject’s well being (e.g., parents of children). The CUHS’s concern is to verify that the consent process and any consent documentation are likely to assist these persons in making an informed decision that is in the best interest of the research subject. The CUHS must exercise special care when considering subjects whose ability to give free and informed consent may be compromised in any way.
Beneficence: The Risk-Benefit Balance
The CUHS is charged with deciding, for any proposed activity that falls under its jurisdiction, whether “the risks to the subject are so outweighed by the sum of the benefit to the subject and the importance of the knowledge to be gained as to warrant a decision to allow the subject to accept (those) risks” (Federal Register, May 30, 1974).
Assessment of the risk/benefit balance is a complex task. Risks of injury or discomfort to the individual may be physical, psychological, and/or social. Potential benefits may accrue to the individual, to a group to which the individual belongs, and/or to society. In reviewing applications, the CUHS must carefully assess not only the types and degrees of risks and benefits for the proposed subject population, but also the investigator’s communication of these risks and benefits in the consent process and, where appropriate, the written consent form.
While the CUHS is not explicitly charged with reviewing scientific design, it must sometimes do so in order to weigh risk against benefit. If a study design seems unlikely to attain the stated aim of the investigation, then no benefit could be anticipated from conducting the study, and there is no justification for placing any research subject at risk. The design of the study must be sound, and the nature and likelihood of all risks and benefits must be made clear in any application to the CUHS.
Justice: The Fair Selection of Research Subjects
Both the risks and the potential benefits of research should be spread fairly among potential individual research subjects and research subject groups. Study design and selection of subjects should avoid bias against particular groups on the basis of race or national origin, ethnicity, gender, age, or social or socio-economic status.
Sharing Research Risks. The guiding principle in the ethical selection of research subject groups is that any risks of the research should fall upon the groups who might benefit from the research. If the results of a risky protocol might benefit the general population, it would be unethical to focus subject recruitment on vulnerable or disadvantaged groups (e.g., institutionalized people or prisoners; patients at free clinics primarily patronized by people unable to afford other medical care) simply because they are easily accessible or can be persuaded to participate. Nor should an undue share of research risks burden groups already burdened by other factors. Rather, attempts should be made to include a fair sampling of the populations who might benefit from the study. When research involves persons whose autonomy is compromised, it is expected that the research will relate to the conditions or circumstances of the research subject population. Whenever possible, groups fully able to consider research risks and informed consent should be asked to face research risks before more vulnerable populations. For example, investigational drugs are usually tested in adults before they are tested in children; some investigational drugs and procedures may be tested in healthy volunteers before being tested in patients.
Sharing Research Benefits. In recent years, increasing attention has been paid to the rights of various groups to be included in research. As individuals and through advocacy groups, many patients seek access to experimental treatments, believing that these experimental treatments may potentially provide the best medical care available. In addition, researchers, ethicists, and public officials have recognized that because many clinical trials focus primarily on white middle-class male research subject groups, the results of some trials may have been of questionable value for members of other social, racial, sexual, and ethnic groups. As a result, both the National Institutes of Health and the Food and Drug Administration now require that study design include as broad a range of research subjects as feasible and the data be analyzed to uncover responses that differ between groups. For example, where women of child-bearing potential and pregnant and nursing women previously were routinely excluded from new drug trials, it is now required that whenever possible these women be asked to make their own choices after being fully informed of the risks of the research.
While most social and behavioral research does not, in general, directly benefit subjects in the same manner that clinical drug trials may, the principle of inclusion pertains.