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.     

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.     

Resolving Beecher's Paradox: Getting beyond IRB reform

Protection of persons participating as research subjects is an essential element of ethical research conduct. There is growing concern that the existing system of institutional review boards (IRBs) and informed consent may not be adequate and is in need of reform. When science and medicine are “merged”; in clinical research, confusion of roles and conflicts of interests arise in relationships between patient‐subjects and physician‐investigators. IRBs have always had a primary role in protection of research participants. Their efforts to protect research subjects may make it more difficult for investigators to conduct research. This tension has lead to the development of an adversarial relationship between IRBs and investigators. Investigators and IRBs are also subject to external pressures that could impact efforts to protect research subjects. Efforts are underway to address these concerns. IRB reform, while needed, is not likely to be sufficient. Adoption of a new paradigm in which IRBs, investigators and research sponsors collectively accept protection of research subjects as their primary and shared responsibility may provide a more effective and efficient model that will be better able to deal with difficult ethical and social issues in clinical research.     

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.     

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.     

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.     

The protection of unrepresented patients in emergency care research

In emergency care research, it may be the case that neither informed consent nor surrogate consent is possible. In order to nonetheless allow for such research, codes and regulations of research ethics have increasingly incorporated provisions regarding this specific situation. The protection that those provisions offer need to be better understood. This article addresses in what ways they protect individuals, and especially the extent to which the suggested protection compensates for the loss of surrogate consent. The Declaration of Helsinki, the Additional Protocol to the Convention on Human Rights and Biomedicine, and the EU Clinical Trials Regulation serve as the main illustrations.     

Informed Consent and Investigational New Drug Abuses in the U.S. Military

Objective: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND). Design: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, consent forms, legal pleadings, and protocols for specific investigational drugs. Results: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs. However, the waiver approval was conditional, and the FDA insisted on several safeguards. Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War. The FDA cited the military for significant deviations from the originally approved protocols. Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical. In addition, there was a gross lack of documentation and no monitoring of adverse reactions. The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy. The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations. There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine. In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules. There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered experimental. Conclusions: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections. The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner. In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent.     

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.     

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.     

Physicians' understanding of consent requirements for phase I clinical trials in cognitively impaired or highly vulnerable populations

We investigated physicians' attitudes about entering patients who cannot give informed consent or who are of a vulnerable population into clinical trials. A survey instrument asked a nationwide sample of practicing physicians about whether ten hypothetical patients could be enrolled in a phase I clinical trials. The impact of demographic variables on the number of scenarios viewed as completely or somewhat acceptable was analyzed via student's T tests or analysis of variance (ANOVA) as applicable. All significant (p<0.01) variables were entered into a multiple logistic regression model. Eighty-four percent of respondents indicated that at least one case scenario was acceptable. A majority of those who conduct clinical trials (62%), who had training in the ethics of clinical research (78%), and who sit on institutional review boards (IRBs) (83%) approved of at least one case scenario. Physicians approved of the entry of some patients who cannot give informed consent or who are of a vulnerable population into clinical trials. More effective education on the guidelines involving clinical research should be available to practicing physicians, residents, and medical students. There should also be assurance that physicians who conduct clinical trials or who sit on IRBs have the requisite knowledge about the ethics of clinical research.     

Physicians' Understanding of Consent Requirements for Phase I Clinical Trials in Cognitively Impaired or Highly Vulnerable Patients

We investigated physicians' attitudes about entering patients who cannot give informed consent or who are of a vulnerable population into clinical trials. A survey instrument asked a nationwide sample of practicing physicians about whether ten hypothetical patients could be enrolled in a phase I clinical trials. The impact of demographic variables on the number of scenarios viewed as completely or somewhat acceptable was analyzed via student's T tests or analysis of variance (ANOVA) as applicable. All significant (p < 0.01) variables were entered into a multiple logistic regression model. Eighty-four percent of respondents indicated that at least one case scenario was acceptable. A majority of those who conduct clinical trials (62%), who had training in the ethics of clinical research (78%), and who sit on institutional review boards (IRBs) (83%) approved of at least one case scenario. Physicians approved of the entry of some patients who cannot give informed consent or who are of a vulnerable population into clinical trials. More effective education on the guidelines involving clinical research should be available to practicing physicians, residents, and medical students. There should also be assurance that physicians who conduct clinical trials or who sit on IRBs have the requisite knowledge about the ethics of clinical 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.     

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.