Risk Assessment as a Paradox: When Actions of an IRB Become Incompatible with Ethical Principles

As anecdotal evidence mounts up of Institutional Review Boards becoming an impediment to research, I share a personal experience in this article to argue how the conduct of an Institutional Review Board was incompatible with a number of ethical principles such as Respect for Persons, Deception, Informed Consent, and Justice. I conclude by promoting Evidence-Based Ethical Problem Solving to facilitate and enhance risk assessments through empirical evidence.     

Giving Voice to Research Participants: Should IRBs Hear From Research Participant Representatives?

The current decision-making model for the review of human research contains inadequate mechanisms to ensure that the interests and perspectives of research participants are considered by Institutional Review Boards, whose decisions may profoundly affect the safety and well-being of participants. As a result, this model is far from being optimized to realize Institutional Review Boards' principal mandate and undermines the credibility of the research review process. This article proposes a procedural mechanism that would ameliorate these systemic deficiencies by allowing “research participant representatives” to give voice to participants during the research review process.     

Giving voice to research participants: should IRBs hear from research participant representatives?

The current decision-making model for the review of human research contains inadequate mechanisms to ensure that the interests and perspectives of research participants are considered by Institutional Review Boards, whose decisions may profoundly affect the safety and well-being of participants. As a result, this model is far from being optimized to realize Institutional Review Boards' principal mandate and undermines the credibility of the research review process. This article proposes a procedural mechanism that would ameliorate these systemic deficiencies by allowing "research participant representatives" to give voice to participants during the research review process.     

Building a More Connected DSMB: Better Integrating Ethics Review and Safety Monitoring

Data and Safety Monitoring Boards (DSMBs) have become an increasingly common feature of clinical trial oversight, yet a paucity of legal or ethical frameworks govern these Boards’ composition or operation, or their relationship with other actors with monitoring responsibilities. This paper argues that prevailing structural gaps are impeding harmonized systems for monitoring the ongoing ethical acceptability of clinical trials. Particular tensions stem from DSMBs’ sweeping discretion in deciding whether and when to recommend that a trial should be terminated or amended based on safety and efficacy information. This discretion becomes especially challenging in light of DSMBs’ monopoly over emerging trial data, which prevents Institutional Review Boards, sponsors, and investigators from participating in certain pivotal and ethically charged decisions. To address these disconnects, I advocate for strengthened pre-trial and post-trial communication in addition to innovative strategies to support DSMB decision making through the life of a trial.     

Unethical Research and the C.I.A. Inspector General Report of 2004: Observations Implicit in Terms of the Common Rule

Declassification of documents has given rise to the allegation that the Central Intelligence Agency may have conducted unethical research targeting detainee subjects. That allegation is examined using document analysis and the development of research goals and roles as defined in the Common Rule. This article sets aside issues as to whether enhanced interrogation techniques described in the declassified documents rise to legal definitions of torture. Instead, it presents a post hoc ethics review raising questions addressed by Institutional Review Boards recommending the filing of a for-cause noncompliance complaint with the Office for Human Research Protection against the Central Intelligence Agency.     

Disclosing conflicts of interest to research subjects: an ethical and legal analysis

In this article, I examine the ethical and legal issues related to disclosure of conflicts of interest to research subjects, and discuss some empirical studies related to the topic. I argue that researchers have an ethical obligation to disclose conflicts of interest to research subjects, provided that they take steps to help subjects understand information about conflicts of interest and how to interpret it. Researchers also may have a legal duty to disclose conflicts of interests to subjects, depending on the facts of the case and the court's interpretation of the law. To reinforce and clarify the legal obligation to disclose conflicts of interest, the federal regulations should be amended to include disclosure of conflicts of interest as one of the informed consent requirements. Institutional review boards play a key role in helping researchers to disclose conflicts of interest to subjects in an appropriate manner. Institutional review boards should approve the disclosure language in informed consent documents, and they should require researchers to disclose financial interests to research subjects, if they have any, as a condition of approval.     

Comparison of conflict of interest policies and reported practices in academic medical centers in the United States

The authors reviewed the conflict of interest policies of 9 academic medical centers in the United States and interviewed members of the Institutional Review Boards (IRBs) and Conflict of Interest Committees (COICs) at those institutions. They found that many institutions used processes for reporting and managing conflicts of interest that were more decentralized than the processes described in their policies. Also, most institutions had no clear and comprehensive policy to guide investigators regarding disclosure of conflicts of interest to potential research participants. Considerable differences in understanding of conflict of interest policies were observed between IRB and COIC officials.     

Comparison of Conflict of Interest Policies and Reported Practices in Academic Medical Centers in the United States

The authors reviewed the conflict of interest policies of 9 academic medical centers in the United States and interviewed members of the Institutional Review Boards (IRBs) and Conflict of Interest Committees (COICs) at those institutions. They found that many institutions used processes for reporting and managing conflicts of interest that were more decentralized than the processes described in their policies. Also, most institutions had no clear and comprehensive policy to guide investigators regarding disclosure of conflicts of interest to potential research participants. Considerable differences in understanding of conflict of interest policies were observed between IRB and COIC officials.     

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.     

Neurobiological research involving human subjects: Perspectives from the office for protection from research risks

Department of Health and Human Services (HHS) regulations at 45 CFR 46 require that all human subjects research supported by HHS be reviewed and approved by a local Institutional Review Board (IRB). Investigators may not involve human subjects in research without their informed consent, and additional safeguards are required when subjects are likely to be vulnerable to coercion or undue influence. Application of the regulations to neurobiological research is discussed.     

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.     

Scientific evidence and the judicial system

Research involving the vulnerable sick raises difficult challenges for investigators and Institutional Review Boards. Exactly who among the ill counts as vulnerable is a matter of judgement, and involves consideration of susceptibility to harm and capacity to provide free and informed consent. A balanced approach is required when protections are considered, and the benefits as well as the risks of research participation must be carefully weighed. A variety of protections for the vulnerable sick in research are available, including enrolling subjects in a study only with a strong justification, ensuring that consent is free and comprehending, and setting limits on the risk to which they may be asked to endure. Discussion of three contemporary controversies, placebo‐controlled trials in the psychiatric setting, phase I clinical trials and oncology patients, and emergency room research involving patients incapable of giving consent, highlights the little recognized prominence of risk‐benefit issues in the clinical studies in the vulnerable sick.     

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.     

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.     

Disclosing Conflicts of Interest to Research Subjects: An Ethical and Legal Analysis

In this article, I examine the ethical and legal issues related to disclosure of conflicts of interest to research subjects, and discuss some empirical studies related to the topic. I argue that researchers have an ethical obligation to disclose conflicts of interest to research subjects, provided that they take steps to help subjects understand information about conflicts of interest and how to interpret it. Researchers also may have a legal duty to disclose conflicts of interests to subjects, depending on the facts of the case and the court's interpretation of the law. To reinforce and clarify the legal obligation to disclose conflicts of interest, the federal regulations should be amended to include disclosure of conflicts of interest as one of the informed consent requirements. Institutional review boards play a key role in helping researchers to disclose conflicts of interests to subjects in an appropriate manner. Institutional review boards should approve the disclosure language in informed consent documents, and they should require researchers to disclose financial interests to research subjects, if they have any, as a condition of approval.     

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.     

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.     

The responsible conduct of bioethics research

The responsible conduct of research in the biomedical and behavioral sciences has received significant attention since the late 1980s. However, very little has been written about the responsible conduct of bioethics research. Bioethics is an interdisciplinary field and brings together divergent ethical standards and practices which may be the source of tension or conflict. This article argues that bioethicists should reflect more on ethical issues in the responsible conduct of bioethics research through examination of authorship practices and peer review. I also outline three possible approaches to promote research integrity in bioethics.