Physician duties in the conduct of human subject research

In this article, I examine a skeptical argument against the possibility of ethically justifying risky human subject research (rHSR). That argument asserts that such research is unethical because it holds the possibility of wronging subjects who are harmed and whose consent to participate was less than fully voluntary. I conclude that the skeptical argument is not in the end sufficient to undermine the ethical foundation of rHSR because it fails to take account of the special positive duty researchers owe their clients and future patients. Although the skeptical argument is defeated, it exacts certain novel concessions from the pro-research position. Of particular importance are the admissions (a) that researchers presumptively owe a fiduciary duty to research subjects, (b) that because the most important risks of rHSR are unknown and unquantifiable that duty must be explicitly waived by all subjects before they participate in any protocol, and (c) that such waivers must be made by individuals who satisfy objective criteria of competence for giving fully voluntary consent. The implementation of procedures responsive to these concerns might have a dampening effect on the conduct of research. However, the article concludes with a consideration of the likely benefits to researchers and society of a more cautious ethical regime.     

Person-oriented research ethics: integrating relational and everyday ethics in research

Research ethics is often understood by researchers primarily through the regulatory framework reflected in the research ethics review process. This regulatory understanding does not encompass the range of ethical considerations in research, notably those associated with the relational and everyday aspects of human subject research. In order to support researchers in their effort to adopt a broader lens, this article presents a “person-oriented research ethics” approach. Five practical guideposts of person-oriented research ethics are identified, as follows: (1) respect for holistic personhood; (2) acknowledgement of lived world; (3) individualization; (4) focus on researcher-participant relationships; and (5) empowerment in decision-making. These guideposts are defined and illustrated with respect to different aspects of the research process (e.g., research design, recruitment, data collection). The person-oriented research ethics approach provides a toolkit to individual researchers, research groups, and research institutions in both biomedical and social science research wishing to expand their commitment to ethics in research.     

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.     

Guinea Pigs on the payroll: The ethics of paying research subjects

Regulatory bodies and scholars have traditionally conceptualized biomedical research on healthy subjects in the same way as research on patients. Guidelines and regulations have portrayed payment to a healthy subject as a potential constraint, or “undue influence,”; on the subject's free consent. In this essay we suggest an alternative way of conceptualizing research on healthy subjects, which sees the basic issue not as one of undue influence but as one of justice. Healthy subjects generally enroll in research protocols not for humanitarian reasons but for the money they will receive. Many of these protocols are conducted by profit‐driven corporations. Yet current guidelines and regulations prohibit subjects from negotiating for fair payment for the risks, discomforts and inconveniences they undergo, and IRBs are not staffed adequately to monitor the subject's safety. We propose to remedy the situation by regulating payment to healthy subjects as a labor relation.     

The Issue of Consent in Research that Administers Drugs of Addiction to Addicted Persons

In addiction, impaired control over drug use raises questions about the capacity of addicted persons to consent to participate in research studies in which they are given their drug of addiction. We review the case for doing such research, and the arguments that addiction does, and does not, prevent addicted persons from consenting to such research. We argue for a more nuanced view that acknowledges that while in some situations addiction impairs decision-making capacity, it does not eliminate such capacity. We conclude with some suggestions for recruiting addicted subjects and designing experiments in ways to obtain free and informed consent.     

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.     

Protecting the Nation's Military May Include the Use of Investigational New Drugs

Clinician researchers have a number of roles, each of which carries specific obligations. There are times when these obligations may be in competition (up to and including conflict) with each other. Using a narrative case study that describes a group of colleagues discussing their clinical department's participation in an industry-sponsored research protocol, we illustrate a number of the obligations faced by clinician researchers, and discuss how competing interests and obligations can lead to ethical problems. The case study is followed by a discussion of the effect of university–industry relations on competing interests and obligations in both clinical research and the role of the university, and a suggested framework that could be used to determine when university involvement in commercial research is ethically acceptable.     

A choice of one's own research advance directives: Anticipatory planning for research subjects with fluctuating or prospective decisionmaking impairments

Mental disorders that may affect decisionmaking capacity, like schizophrenia, have a deleterious effect not only on persons who are afflicted with the disorders but also on their families, their friends, and their communities. Realizing research to develop generalizable knowledge that may benefit this heterogeneous population is crucial. The moral challenge is to fashion processes that both respect research subjects’ autonomy and protect their wellbeing. Research advance directives may provide a mechanism that authorizes potential research subjects to make choices of their own regarding whether they wish to participate in a research protocol, to choose and appoint a surrogate decision maker, and to secure an array of protections for themselves should they lose their decisionmaking capacity during the period of the research protocol. Such research advance directives may be used by persons with fluctuating, limited or prospective decisionmaking impairments.     

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.     

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.     

Implementation of a responsible conduct of research education program at Duke University School of Medicine

Academic medical centers rarely require all of their research faculty and staff to participate in educational programs on the responsible conduct of research (RCR). There is also little published evidence of RCR programs addressing high-profile, internal cases of misconduct as a way of promoting deliberation and learning. In the wake of major research misconduct, Duke University School of Medicine (DUSoM) expanded its RCR education activities to include all DUSoM faculty and staff engaged in research. The program included formal deliberation of the Translational Omics misconduct case, which occurred at Duke. Over 5,000 DUSoM faculty and staff participated in the first phase of this new program, with a 100% completion rate. The article reports on the program’s development, challenges and successes, and future directions. This experience at Duke University illustrates that, although challenging and resource intensive, engagement with RCR activities can be integrated into programs for all research faculty and staff. Formal, participatory deliberation of recent cases of internal misconduct can add a novel dimension of reflection and openness to RCR educational activities.     

Mapping responsible conduct in the uncharted field of research-creation: A scoping review

This scoping review addresses the issues of responsible conduct of research (RCR) that can arise in the practice of research-creation (RC), an emergent, interdisciplinary, and heterogeneous field at the interface of academic research and creative activities. Little is yet known about the nature and scope of RCR issues in RC, so our study examined three questions: (1) What are the specific issues in RC in relation to RCR? (2) How does the specificity of RC influence the understanding and practice of RCR? (3) What recommendations could help address the issues highlighted in the literature? To answer these questions, we conducted a scoping review of the academic literature (n = 181 texts) dealing with RCR in RC. We found that researcher-creators faced some very different RCR challenges in comparison with their colleagues in the rest of academia. Addressing these issues is important for both the RCR and RC communities in order to ensure that the rapid development of this field occurs in line with the norms of RCR which, nonetheless, should be adapted to respect the particularities of RC and allow its contributions to the academic world.     

Disclosure Issues in Neuroscience Research

Issues of disclosure arise in neuroscientific research during the informed consent process, whenever incidental findings are identified, and when study results are generated. The possibility of disclosure of incidental findings and/or research results may raise informational expectations on the part of subjects and may alter a study's risk:benefit ratio. We recommend that the informed consent process address this potential consequence of research participation, and specify the conditions under which particular types of information will be offered, the conditions under which information may not be disclosed, and any provisions for helping subjects make sense of the information to be disclosed.     

The Cycle of Bias in Health Research: A Framework and Toolbox for Critical Appraisal Training

Recognizing bias in health research is crucial for evidence-based decision making. We worked with eight community groups to develop materials for nine modular, individualized critical appraisal workshops we conducted with 102 consumers (four workshops), 43 healthcare providers (three workshops), and 33 journalists (two workshops) in California. We presented workshops using a “cycle of bias” framework, and developed a toolbox of presentations, problem-based small group sessions, and skill-building materials to improve participants' ability to evaluate research for financial and other conflicts of interest, bias, validity, and applicability. Participant feedback indicated that the adaptability of the toolbox and our focus on bias were critical elements in the success of our workshops.     

Current issues in clinical research and the development of new pharmaceuticals

As a normal part of the drug development process, U.S. pharmaceutical companies conduct many thousands of clinical trials each year. Only after a reasonable assurance of safety is made can the drug be given to patients who have the underlying medical condition that the drug is designed to treat. Patient welfare is assured by adhering to the Food and Drug Administration's interpretation of the “common rule”; if the data will be used to support a licensing application. 21 CFR Part 50 sets forth the regulations along with the principles of informed consent and the use of institutional review boards (IRBs) that assure patients’ rights are protected. Any potential conflict of interest on the part of a clinical investigator must be reported to the FDA. Pharmaceutical companies extensively monitor ongoing clinical trials for compliance with appropriate regulations. The recent revision of the Declaration of Helsinki governing placebo‐controlled clinical trials may adversely impact drug development     

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.     

Institutional Pathology and the Death of Dan Markingson

In the spring of 2015, 11 years after a mentally ill young man named Dan Markingson stabbed himself to death in an industry-sponsored drug study, officials at the University of Minnesota suspended recruitment of subjects into drug trials in its Department of Psychiatry. University officials agreed to act only after a scathing investigation by Minnesota Office of the Legislative Auditor found damning evidence of coerced recruitment, inadequate clinical care, superficial research oversight, a web of serious, disturbing conflicts of interest, and a pattern of misleading public statements by university officials aimed at deflecting scrutiny. In this article, I examine the larger institutional factors leading up to Markingson’s suicide and prevented corrective action for so long.     

Informed consent comprehension among vulnerable populations in Ecuador: video-delivered vs. in-person standard method

The informed consent comprehension process is key to engaging potential research subject participation. The aim of this study is to compare informed consent comprehension between two methods: standard and video-delivered. We compared the in-person and video-delivered informed consent process in the Familias Unidas intervention. We evaluated comprehension using a 7-item true/false questionnaire. There were a total of 152 participants in the control group and 87 in the experimental. General characteristics were similar between both groups (p > 0.05). First-attempt informed consent comprehension was higher in the intervention group but was not statistically significant (80% and 78% respectively p = 0.44). A video-delivered informed consent process did not differ from the standard method of informed consent in a low educational and socioeconomic environment.     

Federal agencies can do more to ensure correction of the literature when research misconduct is found

Federal agencies can do more to ensure the integrity of the peer-reviewed literature including providing timely notice of misconduct findings or admissions regarding published articles, requiring the individual found guilty of misconduct to provide notice to affected journals, and to work with the journals and co-authors on making appropriate correction. The case of Andrew Cullinane underscores weakness in the current U.S. government administrative processes and the negative impact on journals.