The expanding purview: institutional review boards and the review of human subjects research

The implications of the institutional review board (IRB) system's growing purview are examined. Among the issues discussed are whether IRBs are censoring research and whether the IRB review process fundamentally alters the research that is being conducted. The intersection between IRB review and free speech is also explored. In general, it is argued that the review system for human subjects research (HSR) should be modified in order to limit the scope of IRB review.     

Too Many Rationales,Not Enough Reason: A Call to Examine the Goals of Including Lay Members on Institutional Review Boards

Every major U.S. commission appointed to review Institutional Review Boards (IRBs) as well as numerous reports and scholarly articles have recommended increasing the number of lay (nonscientist and unaffiliated) members on IRBs. Meanwhile, qualitative studies have shown that lay IRB members experience confusion about their roles, including ambiguity whether their roles are different from other members of the board. Without articulating the unique reasons why unaffiliated and nonscientist members are needed, IRBs have little guidance on how to recruit and train these members, and how many should be at the table. By looking back through the history of IRB regulations, policies, and commentaries we can articulate unique contributions these members can make. Only with these contributions in mind can we make arguments for how to best achieve them and make the case that increasing their numbers is necessary.     

How U.S. research institutions are responding to the single Institutional Review Board mandate

One of the most significant changes to the Common Rule is the requirement that institutions use a single Institutional Review Board (IRB) for cooperative research in the United States, unless more than one IRB is required by state, local, or tribal law, or a signatory federal agency decides an exception is warranted. We surveyed Human Research Protection Program (HRPP) officials at the top U.S. research institutions to understand their knowledge and opinion of the mandate, what steps their institutions are taking, and difficulties their institutions are facing. One-hundred seven institutions (56.9%) responded to the survey. While support for the single-IRB mandate was positive overall, most respondents acknowledged that their institution is likely to face some difficulties complying with it. Regulatory agencies can help institutions to comply with the mandate by providing guidance concerning such issues as exceptions to the mandate, local context review, oversight, and implementation of reliance agreements, and development of policies, procedures, and best practices.     

A Qualitative Study of Non-Affiliated,Non-Scientist Institutional Review Board Members

In addition to outlining criteria for the approval of human subjects research, federal regulations provide guidance regarding local institutional review board (IRB) membership. IRBs are mandated to include “at least one member whose primary concerns are in nonscientific areas” and “at least one member who is not otherwise affiliated with the institution.” Often a single individual serves both of these roles simultaneously. Although there have been calls for increased representation of lay community members on IRBs, little is known regarding their experiences or their perceptions of human subject protections and the IRB process. Using an ethnographic interview approach, this study seeks to gain a perspective from non-affiliated, non-scientist (NA/NS) IRB members about the process in which they participate. Findings suggest a need for clarification regarding whom NA/NS IRB members represent. They also suggest that NA/NS IRB members’ experiences could be improved by an increased show of respect from the IRB chair, other members, and staff; efforts to make participation more convenient for these volunteer members; and training tailored specifically to NA/NS members. Further research on this important and understudied topic is needed to determine best practice and policy recommendations.     

Reforming the Oversight of Multi-Site Clinical Research: A Review of Two Possible Solutions

The current system for the ethical oversight of clinical research suffers from structural, procedural, and performance assessment problems. Initially conceived primarily to handle local investigator-initiated single-site studies, the system of institutionally-based committee review has become progressively more inefficient given the increased prevalence of commercially or federally sponsored multi-center trials. To date, proposed solutions do not adequately address these problems.

Beginning with a review of these structural, procedural, and performance assessment problems, this article will then consider two proposals for addressing these deficiencies: (a) regional ethics organizations; and (b) IRBNet?, a newly developed web-based program for cooperative IRB review. The strengths and weaknesses of these two approaches will be evaluated in light of recent experience with centralized review. The proposal to establish a system of regional ethics organizations presents a comprehensive approach to many of the problems faced by the current system. However, IRBNet? offers an immediate and feasible solution to many of the problems faced by the review of multi-site clinical studies.     

The Role of Intuition in Risk/Benefit Decision-Making in Human Subjects Research

One of the key principles of ethical research involving human subjects is that the risks of research to should be acceptable in relation to expected benefits. Institutional review board (IRB) members often rely on intuition to make risk/benefit decisions concerning proposed human studies. Some have objected to using intuition to make these decisions because intuition is unreliable and biased and lacks transparency. In this article, I examine the role of intuition in IRB risk/benefit decision-making and argue that there are practical and philosophical limits to our ability to reduce our reliance on intuition in this process. The fact that IRB risk/benefit decision-making involves intuition need not imply that it is hopelessly subjective or biased, however, since there are strategies that IRBs can employ to improve their decisions, such as using empirical data to estimate the probability of potential harms and benefits, developing classification systems to guide the evaluation of harms and benefits, and engaging in moral reasoning concerning the acceptability of risks.     

Informed consent for research on stored blood and tissue samples: a survey of institutional review board practices

Numerous position papers have outlined informed consent recommendations for the collection, storage, and future use of biological samples; however, there currently is no consensus regarding what kinds of information should be included in consent forms. This study aimed to determine whether institutional review boards (IRBs) vary in their informed consent requirements for research on stored biological samples, and whether any variation observed could be correlated to factors such as volume of work, IRB members' familiarity with ethical issues in genetic research, and IRBs' use of either of two policy guidelines as resources. A brief survey was mailed to all IRB chairpersons on a mailing list obtained from the Office for Human Research Protections. Survey questions included whether consent forms for the collection of biological samples for future use address each of six provisions recommended in current guidelines and position statements, and whether IRBs used the Office for Protection from Research Risks' 1993 Protecting Human Research Subjects: Institutional Review Board Guidebook, chapter 5 (hereinafter IRB Guidebook) or the National Bioethics Advisory Commission's 1999 Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, Volume I (hereinafter Report) in their deliberations. Despite a low response rate (22%, 427 respondents), results indicate that IRB practices vary substantially. The degree to which the provisions were included in consent forms was found to correlate positively with IRBs that review a greater volume of protocols annually, those that use the National Bioethics Advisory Commission Report in their deliberations, and those that draw on both the Report and the IRB Guidebook.     

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.     

Human Embryonic Stem Cell Research: An Argument for National Research Review

The US National Academy of Sciences (NAS) recently published voluntary guidelines for human embryonic stem (hES) cell research. The NAS guidelines propose two levels of oversight. At the local level, research institutions are to create Embryonic Stem Cell Research Oversight (ESCRO) committees with a mandate to assess the scientific merit and ethical acceptability of hES cell research. At the national level, a new committee is to be created, not to review specific research proposals, but rather to periodically assess, and as needed revise, the NAS guidelines. In this article, we critically assess this proposal. In particular, we review the benefits and limitations of local research review. On this basis, we argue that local review is insufficient for hES cell research and that while there are obvious pragmatic and political reasons for the NAS to favor local research review, there are more compelling reasons for the NAS to have recommended national review of hES cell research proposals.     

Research Subjects with Limited English Proficiency: Ethical and Legal Issues

In this article, we examine Institutional Review Board (IRB) policies, international guidelines, and federal regulations and guidance for dealing with Limited English Proficiency (LEP) research subjects. We show that federal and international guidance concerning this topic is insufficient, and there is considerable variation in IRB policies. While some IRBs have thorough and useful policies, others do not. Many IRBs do not provide researchers and IRB members with answers to several important questions relating to language barriers in research. We recommend that federal agencies, international organizations, IRBs, and researchers take steps to fill in the gaps in guidance and policy to help insure that LEP populations will receive equitable and ethical treatment in research.     

A qualitative study of non-affiliated, non-scientist institutional review board members

In addition to outlining criteria for the approval of human subjects research, federal regulations provide guidance regarding local institutional review boards (IRB) membership. IRBs are mandated to include "at least one member whose primary concerns are in nonscientific areas" and "at least one member who is not otherwise affiliated with the institution." Often a single individual serves both of these roles simultaneously. Although there have been calls for increased representation of lay community members in IRBs, little is known regarding their experiences or their perceptions of human subject protections and the IRB process. Using an ethnographic interview approach, this study seeks to gain a perspective from non-affiliated, non-scientist (NA/NS) IRB members about the process in which they participated. Findings suggest a need for clarification regarding whom NA/NS IRB members represent. They also suggest that NA/NS IRB members' experiences could be improved by an increased show of respect from the IRB chair, other members, and staff; efforts to make participation more convenient for these volunteer members; and training tailored specifically to NA/NS members. Further research on this important and understudied topic is needed to determine best practice and policy recommendations.     

Evaluating U.S. Medical Schools' Efforts to Educate Faculty Researchers on Research Integrity and Research Misconduct Policies and Procedures

This paper examines how well U.S. medical school institutions are doing to promote research integrity. It is an important question to ask in order to determine whether there are sufficient and adequate protections in place to protect the U.S. Public Health Service's (PHS) resources devoted to medical research. This paper focuses on 5,100 medical school researchers' knowledge of what constitutes research misconduct as well as their willingness to report it to the research integrity officer (RIO) and educate their Ph.D. trainees. We learned that 5.6% of researchers could correctly distinguish seven or more of the nine scenarios that depicted likely research misconduct, as defined by the PHS regulations, from scenarios describing other ethical issues. Instead, researchers had expansive definitions and often inappropriately identified infractions such as conflicts of interest, Institutional Review Board (IRB) violations, and other breaches in ethical standards to be research misconduct. In addition, researchers who correctly identified four instances of likely research misconduct in the test items were highly unlikely to report their observations to a RIO. Researchers also provided insight on the factors they believe influence their decision making process of whether to report research misconduct. In addition, this paper also reports on the guidance that faculty said they provided their trainees on research misconduct issues. We conclude with a discussion and recommendations on what institutional leaders might consider doing in order to enhance their research integrity efforts and protect their institution's reputation.     

The market for (Ir)reproducible econometrics

Context: As the volume and complexity of research have increased, the amount of time spent on Institutional Review Board (IRB) review has decreased. The complexity of research has expanded, requiring increasingly specialized knowledge to review it. Dilemma: Under the current system, increasing numbers of research studies requiring expertise in ethics, new technologies or diverse study designs place a substantial burden upon local IRBs and often result in substantial variability among their reviews. This lack of uniformity in the review process creates uneven human subjects’ protection thus undermining the intent of the Common Rule. Objectives: To outline a scenario for expert centralized IRB review via implementation of a national virtual IRB review system overseen by the Office for Human Research Protections (OHRP). Conclusions: The complicated ethical issues and science involved in much of current research warrant an expert review panel. Centralized review would enable expert review specific to the research at hand, ensure consistency in human subjects protection, reduce the burden on local IRBs, and may reduce time spent obtaining approval. A centralized virtual system would allow IRB members to remain at their institutions while providing unprecedented expert review through currently available technology, and make information regarding monitoring and adverse event reporting available online in real-time.     

Public Service Quality Improvements: A Case for Exemption from IRB Review of Public Administration Research

Should the exemption from Institutional Review Board (IRB) evaluations currently in place for quality improvements research be extended to public administration research that addresses questions of improving the quality of public service delivery? As a means to both reduce the level of disdain held by a group of social science researchers for IRBs and to reduce the cost of review for minimal risk studies, I argue here that much of the current public administration research should also be exempted from normal processes of review by IRBs on the basis of their similarity to Quality Improvements (QI) research, a category of studies already granted exemption. This argument dovetails provisions currently in place for studies of public service and public benefit, but reframes these exemptions in the language of “quality improvements,” which may be a more comfortable language for IRBs concerned to demonstrate compliance for review of all fields. To expedite this argument into the practices of IRBs, I included a checklist that researchers could use to self-identify their studies as QI, not research as such.     

Testing drugs in pediatric populations: The FDA mandate

On November 27, 1998 the Food and Drug Administration (FDA) issued a new rule requiring that drugs and biological products be tested in pediatric populations. Since voluntary testing in pediatric populations had not resulted in a significant increase in pediatric labeling of drugs, stronger measures were needed to ensure that infants and children would receive the benefits of properly tested drugs and biologies. The mandate for pediatric testing raises a core ethical question: How should the need for validated treatments that benefit children as a group be weighed against the obligation to protect individual child subjects of research? The preamble to the new rule claims that adherence to Department of Health and Human Services (DHHS) and American Academy of Pediatrics (AAP) guidelines will provide adequate protection to individual subjects. Yet the special protections provided to children in these guidelines are not required by the new FDA rule, and have never been obligatory for research that is regulated by the FDA. While the new rule does not necessitate or encourage violation of these standards, the rule does not pay adequate attention to them nor clarify what role they should play in IRB review of protocols under FDA regulation.     

Reflexive Research Ethics in Fetal Tissue Xenotransplantation Research

For biomedical research in which the only involvement of the human subject is the provision of tissue or organ samples, a blanket consent, i.e., consent to use the tissue for anything researchers wish to do, is considered by many to be adequate for legal and Institutional Review Board (IRB) requirements. Alternatively, a detailed informed consent provides patients or study participants with more thorough information about the research topic. We document here the beliefs and opinions of the research staff on informed consent and the discussion-based reflexive research ethics process that we employed in our fetal tissue xenotransplantion research on the impact of environmental exposures on fetal development. Reflexive research ethics entails the continued adjustment of research practice according to relational and reflexive understandings of what might be beneficent or harmful. Such reflexivity is not solely an individual endeavor, but rather a collective relationship between all actors in the research process.     

'Text-work' in Research Ethics Review: The significance of documents in and beyond committee meetings

ABSTRACT

This article analyzes how a formal text (the Ethics Review Form) available at National Health Service Research Ethics Committees (NHSRECs) in the United Kingdom was used in meetings. Derived from the work of Dorothy Smith on incorporating texts into institutional ethnography (IE), it proposes the concept of “text work” as a way into understanding more about decision-making in ethics review and describes the extent to which this formal text shaped and influenced review work. The research study used observations of committee meetings, field-notes and interviews to produce an ethnographic mapping of Research Ethics Committees’ (RECs) work. This article draws on one aspect of the research which was the process of isolating a particular, ubiquitous text and analyzing how it worked and was worked on in the meetings. The analysis contributes to contemporary discussion offering an alternative to ongoing debates about idealized ways of conducting ethics review. Finally, some tentative suggestions are made about improving training, based on and starting from the work which reviewers undertake.     

Research subjects with limited English proficiency: ethical and legal issues

In this article, we examine Institutional Review Board (IRB) policies, international guidelines, and federal regulations and guidance for dealing with Limited English Proficiency (LEP) research subjects. We show that federal and international guidance concerning this topic is insufficient, and there is considerable variation in IRB policies. While some IRBs have thorough and useful policies, others do not. Many IRBs do not provide researchers and IRB member with answers to several important questions relating to language barriers in research. We recommend that federal agencies, international organizations, IRBs, and researchers take steps to fill in the gaps in guidance and policy to help insure that LEP populations will receive equitable and ethical treatment in research.     

Defining the Research Category in Pediatric Phase I Oncology Trials

Clinical research studies in children are classified by risk into three major categories. These are as follows: a) minimal risk studies, b) more than minimal risk studies but with benefit, and c) studies with minor increase over minimal risk but with no benefit.

Pediatric Phase I oncology trials, which are conducted in a highly vulnerable population of severely ill children with cancer, are designed to establish safety and to determine the maximum tolerated dose (MTD), as well as establish dose limiting toxicity (DLT). These types of studies can be associated with significant risk. The research design of such high- risk studies, which comprise short-term treatments with varying doses, is generally not associated with any clinical benefit. Classification of the research category in these pediatric studies poses a special problem for the Institutional Review Board (IRB) with major implications for the consenting process. The challenges associated with the classification of such studies are discussed in this article.     

Research ethics review for the use of anonymized samples and data: A systematic review of normative documents

While the anonymization of biological samples and data may help protect participant privacy, there is still debate over whether this alone is a sufficient safeguard to ensure the ethical conduct of research. The purpose of this systematic review is to examine whether the review of an ethics committee is necessary in the context of anonymized research, and what the considerations in said ethics review would be. The review of normative documents issued by both national and international level organizations reveals a growing concern over the ability of anonymization procedures to prevent against reidentification. This is particularly true in the context of genomic research where genetic material’s uniquely identifying nature along with advances in technology have complicated previous standards of identifiability. Even where individual identities may not be identifiable, there is the risk of group harm that may not be protected by anonymization alone. We conclude that the majority of normative documents support that the review of an ethics committee is necessary to address the concerns associated with the use of anonymized samples and data for research.