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Report on Ethical and Policy Issues in Research Involving Human Participants Volume I - Report and Recommendations



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Summary of Recommendations (Research Involving Human Participants V1)


The charter of the National Bioethics Advisory Commission (NBAC), a presidential commission created in 1995, states that "[a]s a first priority, NBAC shall direct its attention to consideration of protection of the rights and welfare of human research subjects." During NBAC's first five years, the Commission focused on several special issues surrounding research involving human participants, issuing five reports and numerous recommendations that, when viewed as a whole, reflect an evolving appreciation of the various and complex challenges facing the implementation and oversight of the system that protects those who volunteer to participate in research.

In May 1997, NBAC unanimously resolved that "[n]o person in the United States should be enrolled in research without the twin protections of informed consent by an authorized person and independent review of the risks and benefits of the research." In 1999, NBAC indicated to the White House the following areas of concern regarding the oversight of human research in the United States:

  1. not all research participants are protected by the federal oversight system;
  2. a number of federal departments and agencies that sponsor primarily nonbiomedical research or modest amounts of research have failed to implement fully the federal protections available;
  3. the federal protections do not always include specific provisions for those individuals who are especially vulnerable; and
  4. the federal protections are difficult to enforce and improve effectively across the government, in part, because no single authority or office oversees research protections across all agencies and departments.

Based on these findings and in response to a special request from the White House Office of Science and Technology Policy to further develop recommendations for improving the system for protecting research participants, NBAC undertook a comprehensive examination of the various aspects of the oversight system, including its purpose; its structure, including its local configuration composed of investigators, institutions, and Institutional Review Boards (IRBs); and the ethical issues relevant to review of research. The recommendations contained in this report reflect a dual commitment to ensuring the protection of those who volunteer for research while supporting the continued advancement of science. The recommendations are based on a view of the oversight system as a whole and provide both a rationale for change and an interrelated set of proposals to improve the protection of human participants and enable the oversight system to operate more efficiently.

Readers should note that three general themes are found in the recommendations. First, they suggest that there should be fewer federal regulations and more guidance. Second, they generally focus attention on research for which participants need the most protection and strive to make the level of protection commensurate with the level of risk involved in the research. This theme is strongest in recommendations regarding continuing review, verification of compliance, adverse event reporting, informed consent, and the review of minimal risk research. Third, the recommendations both increase the scope of regulated research and streamline the process of regulatory compliance.

The most significant proposed change is that of consolidation. In place of the current multiple sets of overlapping regulations, a unified comprehensive policy is proposed in the form of a single set of regulations with a single source of guidance and interpretation. Six distinct functions or responsibilities of a consolidated oversight system are recommended: policy development through regulations and guidance; educational programs aimed at the responsibilities of all parties; ethical review of proposed research; monitoring of ongoing research; enforcement of the requirements; and accountability for all those involved in the review and conduct of research. By focusing attention and resources on these functions, the system will provide the necessary infrastructure for protecting research participants and promoting ethical research. To ignore any one of them is to have a system that functions less than optimally.

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Scope and Structure of the Oversight System

The entitlements due to all research participants of a prior independent review of risks and potential benefits and the opportunity to exercise voluntary informed consent are the most basic and essential protections for all research participants. However, not all research participants receive these entitlements and not all are protected by the existing oversight system. The commitment to protect participants should not be voluntary, nor should requirements be in place for only some human research. Extending current protections to all research, whether publicly or privately funded, and making uniform all federal regulations and guidance cannot be accomplished within the current oversight system, in which no entity has the authority to act on behalf of all research participants. Thus, to facilitate the extension of the same protections to all humans participating in research, a unified, comprehensive federal policy promulgated and interpreted by a single office is needed.

Recommendation 2.1:

The federal oversight system should protect the rights and welfare of human research participants by requiring 1) independent review of risks and potential benefits and 2) voluntary informed consent. Protection should be available to participants in both publicly and privately sponsored research. Federal legislation should be enacted to provide such protection.

Recommendation 2.2:

To ensure the protection of the rights and welfare of all research participants, federal legislation should be enacted to create a single, independent federal office, the National Office for Human Research Oversight (NOHRO), to lead and coordinate the oversight system. This office should be responsible for policy development, regulatory reform (see Recommendation 2.3), research review and monitoring, research ethics education, and enforcement.

Recommendation 2.3:

A unified, comprehensive federal policy embodied in a single set of regulations and guidance should be created that would apply to all types of research involving human participants (see Recommendation 2.2).

Determining whether particular research activities involving human participants should be subject to a federal oversight system has been a source of confusion for some time. No regulatory definition of covered research can be provided that has the sensitivity and specificity required to ensure that all research activities that include human participants that should be subject to oversight are always included and all activities that should be excluded from oversight protections are always excluded. Clarification and interpretation of the definition of what constitutes research involving human participants will invariably be required if the oversight system is to work effectively and efficiently. Moreover, there will always be cases over which experts disagree about the research status of a particular activity. One of the important leadership roles the proposed oversight office should fulfill is that of providing guidance on determining whether an activity is research involving human participants and is therefore subject to oversight.

Recommendation 2.4:

Federal policy should cover research involving human participants that entails systematic collection or analysis of data with the intent to generate new knowledge. Research should be considered to involve human participants when individuals

  1. are exposed to manipulations, interventions, observations, or other types of interactions with investigators or
  2. are identifiable through research using biological materials, medical and other records, or databases. Federal policy also should identify those research activities that are not subject to federal oversight and outline a procedure for determining whether a particular study is or is not covered by the oversight system.

The proposed federal office should initiate a process in which representatives from various disciplines and professions (e.g., social science, humanities, business, public health, and health services) contribute to the development of the definition and the list of research activities subject to the oversight system.

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Level of Review

Although the definition of research involving human participants should be applied to all disciplines, the risks differ both qualitatively and quantitatively across the spectrum of research. Therefore, the oversight system should ensure that all covered research is subject to basic protections — such as a process of informed consent — with the exceptions of the specified conditions for which these protections can be waived, including protection of privacy and confidentiality and minimization of risks. Because the proposed oversight system may include more research activities, it is more critical than ever that review mechanisms and criteria for various types of research are suited to the nature of the research and the likely risks involved. More specific guidance is needed for review of different types of research, including appropriate review criteria and IRB composition. For example, procedures other than full board review could be used for minimal risk research, and national level reviews could supplement local IRB review of research involving novel or controversial ethical issues.

Recommendation 2.5:

Federal policy should require research ethics review that is commensurate with the nature and level of risk involved. Standards and procedures for review should distinguish between research that poses minimal risk and research that poses more than minimal risk. Minimal risk should be defined as the probability and magnitude of harms that are normally encountered in the daily lives of the general population (see Recommendation 4.2). In addition, the federal government should facilitate the creation of special, supplementary review bodies for research that involves novel or controversial ethical issues.

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Education, Certification, and Accreditation

Protecting the rights and welfare of research participants is the major ethical obligation of all parties involved in the oversight system, and to provide these protections, all parties must be able to demonstrate competence in research ethics — that is, conducting, reviewing, or overseeing research involving human participants in an ethically sound manner. Such competence entails not only being knowledgeable about relevant research ethics issues and federal policies, but also being able to identify, disclose, and manage conflicting interests for institutions, investigators, or IRBs. Finally, the oversight system must include a sufficiently robust monitoring process to provide remedies for lapses by institutions, IRBs, and investigators.

Recommendation 3.1:

All institutions and sponsors engaged in research involving human participants should provide educational programs in research ethics to appropriate institutional officials, investigators, Institutional Review Board members, and Institutional Review Board staff. Among other issues, these programs should emphasize the obligations of institutions, sponsors, Institutional Review Boards, and investigators to protect the rights and welfare of participants. Colleges and universities should include research ethics in curricula related to research methods, and professional societies should include research ethics in their continuing education programs.

Recommendation 3.2:

The federal government, in partnership with academic and professional societies, should enhance research ethics education related to protecting human research participants and stimulate the development of innovative educational programs. Professional societies should be consulted so that educational programs are designed to meet the needs of all who conduct and review research.

Educating all parties in research ethics and human participant protections is effective only when it results in the necessary competence for designing and conducting ethically sound research, including analyzing, interpreting, and disseminating results in an ethically sound manner. Such competence, however, cannot be assumed to follow from exposure to an educational course or program. As the complexion of research continues to change and as technology advances, new and challenging ethical dilemmas will emerge. And, as more people become involved in research as investigators or in roles that are specifically related to oversight, it becomes increasingly important for all parties to be able to demonstrate competence in the ethics of research involving human participants.

Although accreditation and certification do not always guarantee the desired outcomes, these programs, which generally involve experts and peers developing a set of standards that represents a consensus of best practices, can be helpful in improving performance. Therefore, the choice of standards for these programs and the criteria for evaluating whether an institution has met them are critically important. Accreditation and certification programs should emphasize providing education and assuring that appropriate protections are in place, while avoiding excessively bureaucratic procedures.

Recommendation 3.3:

All investigators, Institutional Review Board members, and Institutional Review Board staff should be certified prior to conducting or reviewing research involving human participants. Certification requirements should be appropriate to their roles and to the area of research. The federal government should encourage organizations, sponsors, and institutions to develop certification programs and mechanisms to evaluate their effectiveness. Federal policy should set standards for determining whether institutions and sponsors have an effective process of certification in place.

Recommendation 3.4:

Sponsors, institutions, and independent Institutional Review Boards should be accredited in order to conduct or review research involving human participants. Accreditation should be premised upon demonstrated competency in core areas through accreditation programs that are approved by the federal government.

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Assessing and Monitoring Compliance

Assessing institutional, IRB, and investigator compliance can help to ensure that standards are being followed consistently. Current mechanisms for assessment include assurances of compliance issued by the Department of Health and Human Services and several other federal departments, site inspections of IRBs conducted by the Food and Drug Administration, other types of site inspections for participant protection, and institutional audits. In addition, some institutions have established ongoing mechanisms for assessing investigator compliance with regulations. However, institutions vary considerably in their efforts and abilities to monitor investigator compliance, from those that have no monitoring programs to those that conduct random audits. Assessing the behavior of investigators is an important part of protecting research participants and should be taken seriously as a responsibility of each institution. Investigators, IRBs, and institutions should discuss the many practical issues involved in monitoring investigators as they conduct their research studies and provide input into the regulatory process.

Recommendation 3.5:

The process for assuring compliance with federal policy should be modified to reduce any unnecessary burden on institutions conducting research and to register institutions and Institutional Review Boards with the federal government. The assurance process should not be duplicative of accreditation programs for institutions (see Recommendation 3.4).

Recommendation 3.6:

Institutions should develop internal mechanisms to ensure Institutional Review Board compliance and investigator compliance with regulations, guidance, and institutional procedures. Mechanisms should be put in place for reporting noncompliance to all relevant parties.

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Managing Conflicts of Interest

A research setting that involves human participants necessarily creates a conflict of interest for investigators who seek to develop or revise knowledge by enrolling individuals in research protocols to obtain that knowledge. Overzealous pursuit of scientific results could lead to harm if, for example, investigators design research studies that pose unacceptable risks to participants, enroll participants who should not be enrolled, or continue studies even when results suggest they should have been modified or halted. Conflicts of interest can also exist for IRB members or the institutions in which the research will be conducted. Thus, it is important to address prospectively the potentially harmful effects on participants that conflicts of interest might cause.

Organizations, particularly academic institutions, should become more actively involved in managing investigators' and IRB members' conflicts of interest and increase their efforts for self-regulation in this arena. IRB review of research studies is one method for identifying and dealing with conflicts of interest that might face investigators. By having IRBs review research studies prospectively and follow an IRB-approved protocol, investigators and IRBs together can manage conflict between the investigators' desire to advance scientific knowledge and to protect the rights and welfare of research participants. Financial and other obvious conflicts for IRB members, such as collaboration in a research study, are often less difficult to identify and manage than some of the more subtle and pervasive conflicts. Guidance should be developed to assist IRBs in identifying various types of conflict.

Recommendation 3.7:

Federal policy should define institutional, Institutional Review Board, and investigator conflicts of interest, and guidance should be issued to ensure that the rights and welfare of research participants are protected.

Recommendation 3.8:

Sponsors and institutions should develop policies and mechanisms to identify and manage all types of institutional, Institutional Review Board, and investigator conflicts of interest. In particular, all relevant conflicts of interest should be disclosed to participants. Policies also should describe specific types of prohibited relationships.

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IRB Membership

Appropriate composition of IRB membership ensures that research studies are reviewed with the utmost regard for protecting the rights and welfare of research participants. Current federal regulations require that each IRB have "at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution" (45 CFR 46.107(d); 21 CFR 56.107(d)). The regulations also require that each IRB include eat least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in non-scientific areas." Some have raised the concern of whether only 1 unaffiliated member on an IRB is sufficient to avoid institutional influence, especially when IRBs have 15 to 21 members on average. In addition, unaffiliated members do not have to be present for an IRB to conduct review and approve research studies. Thus, IRBs can approve research with only institutional representation present as long as a nonscientist and a quorum are also present. IRBs should strive to complement their membership by having clearly recognizable members who are unaffiliated with the institutions, members who are nonscientists, and members who represent the perspectives of participants. However, it is difficult to require that IRBs increase the presence and participation of more unaffiliated members to reduce the influence of institutional interests on IRB decisionmaking, because finding them can be difficult. Currently, there are no rules or guidance that describe criteria for meeting the definition of an unaffiliated member, that specify how long such members should serve, or that provide guidance regarding under what circumstances they may be removed or what payment should be provided. Institutions should be careful to select unaffiliated members who are truly separated from the institution, except for their role on the IRB. Procedures for the selection and removal of unaffiliated members should be established in a way that empowers the independent voices of those members. In addition, providing reasonable payment to IRB members who are otherwise unaffiliated with the institution can be a valuable way to strengthen these members' role.

Recommendation 3.9:

Federal policy should establish standards and criteria for the selection of Institutional Review Board members. The distribution of Institutional Review Board members with relevant expertise and experience should be commensurate with the types of research reviewed by the Institutional Review Board (see Recommendation 3.10).

Recommendation 3.10:

Institutional Review Boards should include members who represent the perspectives of participants, members who are unaffiliated with the institution, and members whose primary concerns are in nonscientific areas. An individual can fulfill one, two, or all three of these categories. For the purposes of both overall membership and quorum determinations 1) these persons should collectively represent at least 25 percent of the Institutional Review Board membership and 2) members from all of these categories should be represented each time an Institutional Review Board meets (see Recommendation 3.9).

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Guidance for Assessing Risks and Potential Benefits

In addition to protecting the rights and welfare of research participants, it is equally important to protect them from avoidable harm. Thus, an IRB's assessment of the risks and potential benefits of research is central to determining whether a research study is ethically acceptable. Yet, this assessment can be a difficult one to make, as there are no clear criteria for IRBs to use in judging whether the risks of research are reasonable in terms of what might be gained by the individual or society.

IRBs should be able to identify whether a clear and direct benefit to society or the research participants might result from participating in the study. However, IRBs should be cautious in classifying procedures as offering the prospect of direct benefit. In fact, if it is not clear that a procedure also offers the prospect of direct benefit, IRBs should treat the procedure as one solely designed to answer the research question(s). A major advantage of this approach is that it avoids justifying the risks of procedures that are designed solely to answer the research question(s) based on the likelihood that another procedure in the protocol would provide a benefit.

Recommendation 4.1:

An analysis of the risks and potential benefits of study components should be applied to all types of covered research (see Recommendation 2.4). In general, each component of a study should be evaluated separately, and its risks should be both reasonable in themselves as well as justified by the potential benefits to society or the participants. Potential benefits from one component of a study should not be used to justify risks posed by a separate component of a study.

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Minimal Risk

Determining whether a study poses more than minimal risk is a central ethical and procedural function of the IRB. The definition of minimal risk in federal regulations (45 CFR 46.102(i); 21 CFR 56.102(i)) provides an ambiguous standard by which risks involved in a research study are compared to those encountered in daily life. However, it is unclear whether this applies to those risks found in the daily lives of healthy individuals or those of individuals who belong to the group targeted by the research. If it refers to the individuals to be involved in the research, then the same intervention could be classified as minimal risk or greater than minimal risk, depending on the health status of those participants and their particular experiences. According to this understanding, the standard for minimal risk is a relative one.

This report recommends that IRBs use a standard related to the risks of daily life that are familiar to the general population for determining whether the level of risk is minimal or more than minimal, rather than using a standard that refers to the risks encountered by particular persons or groups. These common risks would include, for example, driving to work, crossing the street, getting a blood test, or answering questions over the telephone. Thus, research would involve no more than minimal risk when it is judged that the level of risk is no greater than that encountered in the daily lives of the general population.

Recommendation 4.2:

Federal policy should distinguish between research studies that pose minimal risk and those that pose more than minimal risk (see Recommendation 2.5). Minimal risk should be defined as the probability and magnitude of harms that are normally encountered in the daily lives of the general population. If a study that would normally be considered minimal risk for the general population nonetheless poses higher risk for any prospective participants, then the Institutional Review Board should approve the study only if it has determined that appropriate protections are in place for all prospective participants.

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Evaluating Vulnerability

All segments of society should have the opportunity to participate in research, if they wish to do so and if they are considered to be appropriate participants for a given protocol. However, some individuals may need additional protections before they can fully participate in the research study; otherwise they might be more susceptible to coercion or exploitation. Individuals might be considered vulnerable within the research context because of intrinsic characteristics (e.g., they are children or have mental illness or retardation) or because of the situation in which they find themselves (e.g., they are impoverished, unemployed, or incarcerated). Recognizing various types of vulnerability and providing adequate safeguards can prove challenging for IRBs.

Appropriate and specific safeguards should be established to protect persons who are categorized as vulnerable. Once safeguards are established, investigators should not exclude persons categorized as vulnerable from research involving greater than minimal risk because this would deprive them of whatever potential direct benefits they might receive from the research and deprive their communities and society from the benefit of the knowledge such research might generate.

Recommendation 4.3:

Federal policy should promote the inclusion of all segments of society in research. Guidance should be developed on how to identify and avoid situations that render some participants or groups vulnerable to harm or coercion. Sponsors and investigators should design research that incorporates appropriate safeguards to protect all prospective participants.

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Emphasizing the Informed Consent Process

Rather than focusing on the ethical standard of informed consent and what is entailed in the process of obtaining informed consent, IRBs and investigators have followed the lead of the federal regulations and have tended to focus on the disclosures found in the consent form. However, from an ethics perspective, the informed consent process, not the form of its documentation, is the critical communication link between the prospective participant and the investigator throughout a study, beginning when the investigator initially approaches the participant. Informed consent should be an active process through which both parties share information and during which the participant at any time can freely decide whether to withdraw from or continue to participate in the research. It is time to place the emphasis on the process of informed consent to ensure that information is fully disclosed, that competent participants fully understand the research in order to make informed choices, and that decisions to participate or not are always made voluntarily.

Recommendation 5.1:

Federal policy should emphasize the process of informed consent rather than the form of its documentation and should ensure that competent participants have given their voluntary informed consent. Guidance should be issued about how to provide appropriate information to prospective research participants, how to promote prospective participants' comprehension of such information, and how to ensure that participants continue to make informed and voluntary decisions throughout their involvement in the research.

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Waiver of Informed Consent

Obtaining voluntary informed consent should not be a requirement for every research study. In fact, waiving the informed consent process is justifiable in research studies that include no interaction between investigators and participants, such as in studies using existing identifiable data (e.g., studies of records) and in studies in which risks generally are not physical. In these kinds of research, risks are likely to arise from the acquisition, use, or dissemination of information resulting from the study and are likely to involve threats to privacy and breaches in confidentiality. The criteria for waiving informed consent in such instances should be revised, so that if such studies have protections in place for both privacy and confidentiality, IRBs may waive the requirement for informed consent.

Recommendation 5.2:

Federal policy should permit Institutional Review Boards in certain, limited situations (e.g., some studies using existing identifiable data or some observational studies) to waive informed consent requirements if all of the following criteria are met:

  1. all components of the study involve minimal risk or any component involving more than minimal risk must also offer the prospect of direct benefit to participants;
  2. the waiver is not otherwise prohibited by state, federal, or international law;
  3. there is an adequate plan to protect the confidentiality of the data;
  4. there is an adequate plan for contacting participants with information derived from the research, should the need arise; and
  5. in analyzing risks and potential benefits, the Institutional Review Board specifically determines that the benefits from the knowledge to be gained from the research study outweigh any dignitary harm associated with not seeking informed consent.

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Documentation of Informed Consent

Although the federal regulations may have been intended to reflect a legal standard for documentation of informed consent, NBAC is aware of no case law in which a signed, written consent form is required. To fulfill the substantive ethical standard of informed consent, depending on the type of research proposed, it may be more appropriate to use other forms of documentation, such as audiotape, videotape, witnesses, or telephone calls to participants verifying informed consent and participation in the research study.

Recommendation 5.3:

Federal policy should require investigators to document that they have obtained voluntary informed consent, but should be flexible with respect to the form of such documentation. Especially when individuals can easily refuse or discontinue participation, or when signed forms might threaten confidentiality, Institutional Review Boards should permit investigators to use other means of verifying that informed consent has been obtained.

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Protecting Privacy and Confidentiality

Privacy and confidentiality are complex and poorly understood concepts in the context of some research. Privacy refers to the ways and circumstances under which investigators access information from participants. Because privacy concerns vary by type and context of research and the culture and individual circumstances of participants, investigators should be well informed and mindful of the cultural norms of the participants. In addition, investigators should be aware of the various research procedures and methods that can be used to respect privacy. Needed is a clear, comprehensive regulatory definition of privacy along with guidance for protecting privacy in various types of research.

Like privacy concerns, concerns about confidentiality vary by the type and context of the research. No one set of procedures can be developed to protect confidentiality in all research contexts. Thus, IRBs and investigators must tailor confidentiality protections to the specific circumstances and methods used in each specific research study. Further, IRBs and investigators are encouraged to consider the use of strong confidentiality protections, which can also reduce some of the violations associated with privacy. A clear, comprehensive definition of confidentiality is needed, along with guidance for protecting confidentiality in various types of research.

Recommendation 5.4:

Federal policy should be developed and mechanisms should be provided to enable investigators and institutions to reduce threats to privacy and breaches of confidentiality. The feasibility of additional mechanisms should be examined to strengthen confidentiality protections in research studies.

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Monitoring of Ongoing Research

Continual review and monitoring of research that is in progress is a critical element of the oversight system. Such review is necessary to ensure that emerging data or evidence have not altered the risks/potential benefits assessment so that risks are no longer reasonable. In addition, mechanisms are needed to monitor adverse events, unanticipated problems, and changes to the protocol. IRBs can do a better job in this area with the appropriate guidance and some restructuring of the review and monitoring process.

Currently, the requirement of continuing review is overly broad. The frequency and need for continuing review vary depending on the nature of research, with some protocols not requiring continuing review. In research involving high or unknown risks, the first few trials of a new intervention may substantially affect what is known about the risks and potential benefits of that intervention. Even if the knowledge does not warrant changes in study design, it may warrant changes in the information presented to prospective and enrolled participants.

On the other hand, the ethics issues and participant protections necessary in minimal risk research are unlikely to be affected by developments from within or outside the research — for example, research involving the use of existing data or research that will no longer involve contact with participants because it is in the data analysis phase. Continuing review of such research should not be required because it is unlikely to provide any additional protection to research participants and merely increases the burden of IRBs. However, because minimal risk research does involve some risk, IRBs may choose to require continuing review. In these cases, other types of monitoring may be more appropriate, such as assessing investigator compliance with the approved protocol or reporting of protocol changes and unanticipated problems. Clarifying the nature of the continuing review requirements would allow IRBs to better focus their efforts on reviewing riskier research and would increase protections for participants where they are most needed.

Recommendation 6.1:

Federal policy should describe how sponsors, institutions, and investigators should monitor ongoing research.

Recommendation 6.2:

Federal policy should describe clearly the requirements for continuing Institutional Review Board review of ongoing research. Continuing review should not be required for research studies involving minimal risk, research involving the use of existing data, or research that is in the data analysis phase when there is no additional contact with participants. When continuing review is not required, other mechanisms should be in place for ensuring compliance of investigators and for reporting protocol changes or unanticipated problems encountered in the research.

Recommendation 6.3:

Federal policy should clarify when changes in research design or context require review and new approval by an Institutional Review Board.

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Adverse Event Reporting

Assessing adverse events reports can be a major burden for IRBs and investigators because of the high volume and ambiguous nature of such events and the complexity of the pertinent regulatory requirements. Investigators have reported frustration in attempting to understand what constitutes an adverse event, the required reporting times, and to whom adverse events should be reported. The regulations need to be simplified, and one set of regulations should be available for safety monitoring. Regulations and guidance should be written so that investigators and sponsors understand what constitutes an adverse event, what type of event must be reported within what time period, and to whom it should be reported. In addition, regulations and guidance should be clear regarding whose responsibility it is to analyze and evaluate adverse event reports and should describe the required communication and coordination channels for these reports among IRBs and safety monitoring entities, such as Data Safety Monitoring Boards, investigators, sponsors, and federal agencies.

Recommendation 6.4:

The federal government should create a uniform system for reporting and evaluating adverse events occurring in research, especially in multi-site research. The reporting and evaluation responsibilities of investigators, sponsors, Institutional Review Boards, Data Safety Monitoring Boards, and federal agencies should be clear and efficient. The primary concern of the reporting system should be to protect current and prospective research participants.

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Review of Cooperative or Multi-Site Research Studies

One of the greatest burdens on IRBs and investigators is the review of multi-site studies. Requiring multiple institutions to review the same protocol is unnecessarily taxing and provides no additional protection to participants. In addition, such review poses problems in the initial stages of review as well as in the continual review and monitoring stages and is especially problematic in the evaluation of adverse events in clinical research.

Innovative and creative alternative mechanisms and processes for reviewing protocols in multi-site research are needed. To allow for such projects and to support a change in the current system toward a more flexible review system, federal policy should be clear about the functions that must be performed, but be less restrictive about who performs each function.

Recommendation 6.5: For multi-site research, federal policy should permit central or lead Institutional Review Board review, provided that participants' rights and welfare are rigorously protected.

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Compensation for Research-Related Injuries

Participants who volunteer to be in a research study and are harmed as a direct result of that study should be cared for and compensated. However, no adequate database exists that describes the number of injuries or illnesses that are suffered by research participants, the proportion of these illnesses or injuries that are caused by the research, and the medical treatment and rehabilitation expenses that are subsequently borne by the participants. It may be argued that regardless of the magnitude of the problem, the costs of research injuries should never be borne by participants. If individuals are injured by research participation, those who benefit from the research (e.g., institutions and sponsors) bear some obligation to compensate those who risked and suffered injury on their behalf. At this time, injured research participants alone bear both the cost of lost health and the expense of medical care, unless they have adequate health insurance or successfully pursue legal action to gain compensation from the specific individuals or organizations that were involved in conducting the research.

A comprehensive system of oversight of human research should include a mechanism to compensate participants for medical and rehabilitative costs resulting from research-related injuries.

Recommendation 6.6:

The federal government should study the issue of research-related injuries to determine if there is a need for a compensation program. If needed, the federal government should implement the recommendation of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1982) to conduct a pilot study to evaluate possible program mechanisms.

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The Need for Resources

Adopting the recommendations made in this report will generate additional costs for institutions, sponsors, and the federal government (through the establishment of a new federal oversight office). Sponsors of research, whether public or private, should work together with institutions carrying out the research to make the necessary funds available.

Recommendation 7.1:

The proposed oversight system should have adequate resources to ensure its effectiveness and ultimate success in protecting research participants and promoting research:

  1. Funds should be appropriated to carry out the functions of the proposed federal oversight office as outlined in this report.
  2. Federal appropriations for research programs should include a separate allocation for oversight activities related to the protection of human participants.
  3. Institutions should be permitted to request funding for Institutional Review Boards and other oversight activities.
  4. Federal agencies, other sponsors, and institutions should make additional funds available for oversight activities.

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Future Research

This report raises many questions about ethical issues that cannot be answered because of insufficient or nonexistent empirical evidence. Current thinking about ethical issues in research such as analysis of risks and potential benefits, informed consent, privacy and confidentiality, and vulnerability would greatly benefit from additional research. Deserving of more study, for example, are questions regarding the development of effective approaches for assessing cognitive capacity, for evaluating what participants want to know about research, and for determining how to ascertain best practices for seeking informed consent. Clearer and more effective guidance could be developed from a stronger knowledge base. In general, understanding the ethical conduct of research would be advanced by increased interdisciplinary discussion that would include biomedical and social scientists, lawyers, and historians.

Recommendation 7.2:

The federal government, in partnership with academic institutions and professional societies, should facilitate discussion about emerging human research protection issues and develop a research agenda that addresses issues related to research ethics.

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This report proposes 30 recommendations for changing the oversight system at the national and local levels to ensure that all research participants receive the appropriate protections. The adoption of these recommendations, which are directed at all who are involved in the research enterprise, will not only lead to better protection for the participants of research, but will also serve to promote ethically sound research while reducing unnecessary bureaucratic burdens. Achieving these goals will, in turn, restore the respect of investigators for the system used to oversee research, support the public's trust in the research enterprise, and enhance public enthusiasm for all research involving human beings.

Cite this page: "Summary of Recommendations (Research Involving Human Participants V1)" Online Ethics Center for Engineering 6/15/2006 OEC Accessed: Friday, May 25, 2018 <>