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.     

Central Ethical Dilemmas in Research Involving Children

We are obligated to protect individual child subjects of research, yet it is also necessary to investigate the safety and efficacy of medical treatments that benefit children as a class. The federal regulations on research with children have provided ethical guidance since 1983, but divergent interpretations persist. Since varying interpretations can lead to confusion and abuses, efforts are underway to clarify the criteria. Clarity is needed to protect individual child subjects from harm while enabling ethical research to proceed. The "pediatric rule" and the "pediatric exclusivity" incentive are important policy initiatives for promoting sound research on the medical treatment of children.     

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.     

Empirically supported ethical research practice: The costs and benefits of research from the participants’ view

Researchers and institutional review boards are routinely called upon to evaluate the cost‐benefit status of proposed research protocols that involve human participants. Often these assessments are based on subjective judgments in the absence of empirical data. This reliance on subjective judgments is of particular concern for studies involving clinical samples where unfounded assumptions may adversely affect research progress or clinical outcomes. The Reactions to Research Participation Questionnaire (RRPQ) was designed to address this shortcoming and to help promote ethical decision making about research practice. The present study describes development of the RRPQ and presents a series of exploratory and confirmatory analyses investigating its structure. Based on these findings, a revised version of the instrument and suggestions for future research are presented. This approach provides a foundation for scientifically informed protection of human subjects.     

Noncompliance with Human Subjects’ Protection Requirements as a Reason for Retracting Papers: Survey of Retraction Notices on Medical Papers Published from 1981 to 2011

Though protection of human research subjects is universally recognized as a critical requirement for the ethical conduct of research, few studies have examined retractions of medical articles through apparent noncompliance with that requirement. From our survey of 99 retracted papers published from 1981 to 2011, we found that the basis for those decisions was poorly explained in retraction notices and that most of the articles continued to be cited. In retraction notices, the current manner of explaining failure to protect human subjects is misleading and confusing.     

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.     

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.     

Ethical Beliefs of Social Work Researchers

Abstract

The purpose of this study is to examine the beliefs of social work researchers about ethical practices. Surveys were mailed to a random sample of 240 members of the Society for Social Work and Research (SSWR) to elicit their views about ethical practices in social work research. Responses from 160 members (67% response rate) yielded information regarding the appropriateness of dual relationships, authorship practices, informed consent procedures, and other conduct in social work research. Age, gender, educational level, years of social work research experience, and current teaching of social work research were related to respondents' ethical views about practices with students and sexual relationships with research subjects. The need for additional resources on ethics in social work research is highlighted.     

Evaluation of Research Ethics Committees: Criteria for the Ethical Quality of the Review Process

Repeatedly, adequacy, performance and quality of Ethics Committees that oversee medical research trials are being discussed. Although they play a crucial role in reviewing medical research and protecting human subjects, it is far from clear to what degree they fulfill the task they have been assigned to. This eventuates in the call for an evaluation of their activity and, in some places, led to the establishment of accreditation schemes. At the same time, IRBs have become subject of detailed legislation in the process of the ongoing global juridification of medical research. Unsurprisingly, there is a tendency to understand the evaluation of RECs as a question of controlling their legal compliance. This paper discusses the need for a quality evaluation of IRBs from an ethical point of view and, by systematically reviewing the major ethical guidelines for IRBs, proposes a system of criteria that should orientate any evaluation of IRBs.     

Ethics of research design

Discussions of ethical issues in research involving human subjects most usually provoke concerns about valid informed consent procedures. However, considering the recognized limitations of informed consent, arguably the way a study is designed is a more consequential concern for subject well‐being. This paper summarizes ethical issues in the design of clinical research, with reference to historic and current guidelines. Special attention is given to randomized clinical trials (RCTs) and psychiatric research.     

Competence and consent to research: A critique of the recommendations of the national bioethics advisory commission*

Concern about the participation of incompetent subjects in psychiatric research has grown in the last several years. In response, the National Bioethics Advisory Commission (NBAC) recommended in its recent report that all investigations involving persons with mental disorders that may be associated with cognitive impairment that may pose greater than minimal risk to subjects utilize independent assessors to verify the capacities of subjects prior to entry into the study. This recommendation poses several problems for the conduct of research and the protection of research subjects. First, it fails to target that group of subjects most likely to be at risk for incapacity. Second, it focuses on too broad a range of research projects, many of which pose little risk to participants. The substantial costs of this approach are therefore not likely to be outweighed by concomitant benefits. In place of the NBAC recommendation, the author proposes a more flexible system of capacity assessment, designed to balance the costs with a greater likelihood of achieving meaningful protection for research subjects with mental disorders.     

Medical school guidelines for investigating misconduct and fraud in science

Institutional review boards (IRBs) are legally required to determine whether the balance between the risks and benefits (the risk-benefit ratio or RBR) of a proposed study is “reasonable” or “proportional”. This obligation flows from their duty to protect the interests of research subjects. It has been argued that it is difficult, perhaps even impossible for IRBs to determine the RBR of studies, because the risks and benefits are not only heterogeneous, but also incommensurable. After arguing that the relevant meaning of incommensurability is incomparability, we discuss whether the risks of participating in a trial and the benefits are comparable. We conclude that at least the risks and the benefits to participants are comparable. In the last section we show that the main problem of RBR analyses is that of interpersonal incompensability. IRBs have to assume that risks to research subjects be compensated by benefits to others. The question is: To what extent? When does it become unreasonable to ask that patients accept the risks of participating in a trial for the benefit of science and/or future patients?     

Are risks and benefits of oncological research protocols both incommensurable and incompensable?

Institutional review boards (IRBs) are legally required to determine whether the balance between the risks and benefits (the risk-benefit ratio or RBR) of a proposed study is "reasonable" or "proportional". This obligation flows from their duty to protect the interests of research subjects. It has been argued that it is difficult, perhaps even impossible for IRBs to determine the RBR of studies, because the risks and benefits are not only heterogeneous, but also incommensurable. After arguing that the relevant meaning of incommensurability is incomparability, we discuss whether the risks of participating in a trial and the benefits are comparable. We conclude that at least the risks and the benefits to participants are comparable. In the last section we show that the main problem of RBR analyses is that of interpersonal incompensability. IRBs have to assume that risks to research subjects be compensated by benefits to others. The question is: To what extent? When does it become unreasonable to ask that patients accept the risks of participating in a trial for the benefit of science and/or future patients?     

Ethical guidelines for research with children: A review of current research ethics documentation in New Zealand

Abstract

Children's rights to participate in matters affecting them, including research, have gained increasing recognition over recent decades. This recognition, and the growth in research with children as participants, has given rise to greater attention from researchers to ethical issues related to child research. This article reviews the current ethics documentation in New Zealand. The findings indicate that considerable variation exists between ethical codes and guidelines in relation to research with children. The dominant focus is on attending to issues of consent and protection from harm, at the outset of the research, rather than recognition of the ongoing nature of ethical issues throughout the research process. Although the findings indicate an increase in the consideration of ethical issues, the existing documentation is inconsistent and inadequate in attending to specific child‐related issues. Suggestions are made to enhance children's participation in research and demonstrate a respect for their participation rights.     

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.     

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.     

International research: Ethical imperialism or ethical pluralism? 1

Conflicts have arisen in international research when countries in which research is being carried out lack the ethical rules or mechanisms for review employed in the United States and Europe. It is objected that a requirement to adhere to regulations promulgated by the US government constitutes “ethical imperialism.”; But if researchers in some countries need not be bound by ethical standards widely accepted in the conduct of research, it could open the door to an ethical relativism allowing virtually any standard a country desires to accept. One example is the variations in informed consent, especially in countries that accord lesser importance to the individual than do the US and Europe. A recent controversy centered on a series of placebo‐controlled, HIV/AIDS trials sponsored by the United States and conducted in several developing countries. These trials could not ethically be carried out in the United States because a proven effective treatment exists. Attempts to avoid similar controversies in forthcoming HIV/AIDS vaccine trials have been initiated by the joint United Nations AIDS program, with a process of regional consultations in the countries where the research will be conducted.     

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.