The oversight system should include several interrelated but distinct functions and responsibilities. It should estab-lish clear and effective policies in the form of regulations or guidance; provide education and assistance to all parties; require review of research to determine whether it is ethically acceptable; monitor ongoing research and the operation and behavior of institutions, IRBs, and investigators; enforce requirements; and maintain public accountability.
Policy: Regulation and Guidance
Establishing policy by providing regulations or guid-ance provides a necessary framework for the entire over-sight system. It also provides leadership by setting the direction, approach, and tone. Policies must be established by the federal government in order to ensure uniform protection of research participants regardless of the source of the research funding. In addition, whether issued as regulations or nonbinding guidance, policies must be presented in an understandable form.
Regulations alone are unlikely to be sufficient to address all types of research (e.g., clinical trials, surveys, records review studies, studies using stored human bio-logical materials, behavioral experiments, or oral history studies). Therefore, guidance, because it establishes stan-dards of acceptable practice while allowing for reasoned deviations, can be used to supplement regulations by indicating how substantive ethical principles can be implemented in particular circumstances.5 Moreover, guidance can be particularly helpful in areas of emerging research where the ethical standards and associated pro-cedures are not entirely clear or well developed. In such situations, thoughtful discussion within the framework of existing guidance may be sufficient to allow innovative research to move forward, and if not, new guidance can be developed promptly.
No matter how well regulations and guidance are written, situations will arise in which it is unclear how ethical princi-ples should be applied or regulations should be interpreted.
Policy interpretation and consultation, provided by a federal oversight office, would be particularly helpful to IRBs struggling with especially complex or difficult research studies.
Education
Understanding basic ethical principles and how they apply in various research situations is the best way to avoid inadvertent harm to the rights and welfare of participants. Education can also prepare individuals to understand and resolve ethical issues, especially novel ethical problems, as they arise in specific research studies.
(Educational programs are discussed in more detail in Chapter 3.)
An effective oversight system helps make education available to all relevant parties. Investigators, IRB staff and members, contract research organizations (CROs), institutional officials, and sponsors (public and private) are the primary audiences for education. Educational activities, however, should be tailored to the particular role of each party in the research enterprise and be relevant to different types of research.
It is also important to educate prospective partici-pants and the general public. Education directed at these audiences should strive to increase the public’s awareness of the system’s functions and operations, which can encourage informed decisionmaking by prospective participants, increase public input regarding policies for the protection of research participants, and increase and sustain the willingness of the public to participate in and support the research enterprise.
Review of Research
In the United States, independent review of proposed research to determine whether it is ethically acceptable is largely performed by local IRBs and is one of the primary means by which the current system provides protection to research participants.6Such review should be respon-sive to the nature of risk and commensurate with the level of risk involved. For example, the risks and poten-tial benefits arising in a clinical trial are generally different from those arising in a study using existing data.
Likewise, social science and humanities research raises risks and potential benefits that differ from those raised by clinical research. Harms may vary from physical to psychological, social, or legal. Within each of these domains, the risk of harm may range from low to high.
Review criteria and mechanisms should be matched to the ethical issues arising from the research. IRBs, as full
committees, should review research involving more than minimal risk; however, IRBs should be able to develop procedures other than full board review for research involving no more than minimal risk.
Research involving difficult ethical considerations, such as highly innovative interventions or technologies, should be reviewed by a body with particular expertise and experience in these special issues, in addition to the local IRB, unless the local IRB is especially qualified to review such research. Several options should be available for providing such heightened review, including specially trained and accredited local IRBs or specially created regional or national review bodies. Often, these special bodies would be reviewing classes of research rather than individual research protocols in order to assist in the development of guidance to local IRBs regarding the criteria for approval. For example, NBAC previously recommended the use of a special standing panel to review research studies involving persons with mental disorders that may affect their decisionmaking capacity and a national-level review for certain types of stem cell research (NBAC 1998; NBAC 1999a). However, because national or special review panels could increase delays or even prevent some research from being conducted, steps must be taken to ensure that the system does not impose undue delays on the approval of ethically sound research.
IRB Review of Research Involving No More Than Minimal Risk
IRBs should be allowed to use procedures that are more expeditious than full board review for research that involves no more than minimal risk. Such procedures should also be permitted for handling other research-related matters, such as determining whether an activity is research and subject to oversight, reviewing minor proposed changes to an approved protocol, conducting some types of continuing review, and reviewing some reports of unanticipated problems. Under the current system, the expedited review process is akin to the pro-cedures proposed here, which are intended to replace the expedited review process and to expand the activities that could be handled by the IRB more expeditiously than through a full board meeting. Generally, IRBs should be able to use more efficient procedures to handle most, if not all, research-related issues, with the exception of protocols involving more than minimal risk.
Such procedures would differ from the current expe-dited review in several ways:
■ All research involving no more than minimal risk would be eligible for review under these more expe-ditious processes (see Chapter 4).
■ The IRB chair or a designee would not need to carry out these more expeditious processes. Instead, NBAC proposes that a minimum requirement of review be carried out by a certified IRB professional who may be a member of the IRB or an IRB administrator. The individual(s) conducting the review might act alone, ask for advice from an IRB member or from a con-sultant, or refer the protocol for full IRB review. IRBs may also choose an individual or a small group of IRB members to conduct such reviews. However, those responsible for reviews must be certified. (Chapter 3 discusses certification in more detail.)
■ The full IRB would not need to be informed of approvals granted through this process.
■ These procedures would be used to review research involving human participants that is currently exempt from the Common Rule, but that is deemed to be covered by the oversight system. One of the advantages of including research that is now exempt is that it would allow institutions to track their human research portfolios.
■ IRBs would use more discretion in reviewing research involving little or no risk so that they can move such research quickly through the IRB process. Using these proposed procedures, IRBs would review minimal risk research in accordance with all regulatory requirements; however, they would have discretion with respect to applying the requirements so that the required levels of scrutiny and protections are com-mensurate with the risks associated with the research.
The use of such procedures should take less time than full IRB review and would reduce the workload of the full board and expedite the review process.
Monitoring
The monitoring of activities is an important component of an effective oversight system. One type of monitoring should occur at the federal level, with the federal over-sight office (see discussion later in this chapter) monitoring the implementation of oversight activities by federal agencies. Such monitoring should include, for example,
National Bioethics Advisory Commission
ensuring that all federal agencies sponsoring or conduct-ing research follow appropriate policies, regulations, and guidance and report violations, noncompliance, and other unanticipated problems. The federal oversight office should also ensure that accrediting or certifying bodies apply standards applicable to assessing a core set of competencies that has been approved by the federal oversight office and should also play a role in monitoring sponsors and institutions from the private sector when these entities are not monitored either by another federal agency (for example, the Food and Drug Administration [FDA], which oversees research involving investigational new drugs) or by an accrediting body. The goal is to ensure that all parties involved in the various aspects of research protect research participants, both at the time studies are initially approved and throughout the research process. The efforts of the federal oversight office should complement but not duplicate the activities of the accrediting and certifying bodies.
A second type of monitoring involves establishing mechanisms to ensure that institutions, IRBs, and investigators are following regulations and guidance.
This type of monitoring is described further in Chapter 3 as verification of compliance. Responsibility for verifying compliance should be shared by different parties. For example, accrediting bodies should be responsible for monitoring accredited institutions and independent IRBs. However, institutions should also establish proce-dures to monitor their IRBs. They could, for example, have an internal audit process for reviewing, on a sample basis, whether IRB decisions are consistent with regulatory requirements. Institutions also should implement such procedures to determine whether investigators are complying with regulatory requirements and conducting research according to IRB-approved protocols.
The third type of monitoring assesses the progress of research through conducting continuing review of ongoing research and monitoring the safety of research participants and whether unanticipated problems or events occur. Investigators, IRBs, sponsors, or those acting on behalf of sponsors, such as CROs or Data and Safety Monitoring Boards, generally carry out these activ-ities. Monitoring should provide the information needed to evaluate whether the oversight system is achieving its
purpose. If gaps exist between purpose and performance, monitoring should help to identify their nature, magni-tude, and location and should ensure the development of measures to close them. The results of monitoring might also show a need for changes in policy, additional or enhanced education, or enforcement measures.
Enforcement
The provision of enforcement measures makes all parties aware that the system must be taken seriously and ensures the public’s continuing trust. Monitoring is used as an additional mechanism to prevent harm to partici-pants, to promote improved practices, and to assess whether any violations are inadvertent or intentional.
When investigators are unwilling or unable to provide appropriate protection to participants, enforcement should stop individuals and possibly their institutions from conducting human research. Enforcement should complement policy, education, and monitoring of com-pliance to ensure that research participants are protected;
however, it should not be the primary focus of an over-sight system.
Sanctions are necessary in serious cases of noncom-pliance or in the case of repeat offenses. Most sanctions involve administrative action by a government agency against an individual or organization for failure to comply with regulatory requirements. The oversight system should include a range of sanctions, including halting research at an institution; de-accrediting an IRB or institution;
requiring special training and probation accompanied by mentoring; disqualifying or debarring an investigator from conducting research involving human participants;
removing the investigator from a particular research study; issuing letters of reprimand to investigators, IRBs, or institutions; conducting special monitoring of investi-gators or IRBs; refusing to publish the research results that do not meet all the ethical obligations to human participants (NBAC 1999b); and levying civil monetary penalties. However, enforcement also might include judicial action. Regulatory agencies have the authority to initiate and conduct such actions, but in a broader sense, enforcement includes all the ways in which the oversight system induces actions that support the purposes of the system. Thus, many parties carry responsibility for
enforcement, including regulators, sponsors, institutions, IRBs, professional societies, editors of scientific publica-tions, and accrediting and certifying bodies.
Accountability
The proposed oversight system is strengthened when its policies, interventions, and outcomes are open to pub-lic view and input. In addition, dissemination of results of research studies and of research protection creates a public record that can form the basis for trust. Easily accessed systems for registering concerns and complaints help to bring problems to the attention of those who can resolve them and offer necessary safeguards to those who believe they have been harmed in the course of research participation.7 See Exhibit 2.1 for a description of the responsibilities of those involved in the oversight system.