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.     

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.     

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.     

National,independent oversight: Reinforcing the safety net for human subjects research*

National, independent oversight is vital to resolve the problems and inconsistencies in oversight of human subjects research. Three key functions that must be considered in any proposal for such a mechanism are (1) issue spotting, (2) guidance on identified issues, and (3) sampling and follow‐up. The 1998 report and recommendations of the National Bioethics Advisory Commission concerning research involving persons with mental disorders that may affect decisionmaking capacity address these functions in part, but application is limited to a small segment of the research population. Incorporation of these three key functions in a formal, national, independent oversight process is necessary in order to ensure accountability and maintain public trust in research.     

Attitudes towards using animals in research and teaching: opinions from a selected group of female secondary school students

Abstract

This research provides details about a group of young New Zealand women's awareness of, interest in and attitudes towards the use of animals in scientific research and teaching. These findings were compared to a similar survey of the New Zealand public. An adapted, anonymous questionnaire was used to gather data from 90 young women (14–15 years) from an urban secondary school. While nearly half expressed concern about animal use in research (43%), their awareness was not consistent with the reality of animal research in New Zealand, either in terms of its impact on animals or animal species used. They were unconcerned about the use of animals in teaching and associated such use with enhanced learning. Justification for the use of animals in research and teaching was shown to be complex and contextualized, with an instrumental qualifier being used to justify their opinions. Even though many students were unaware of the regulations surrounding animal use in research and teaching, they were mistrustful that these regulations were being followed by scientists. Instead, their trust was placed in the SPCA and in veterinarians.     

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.     

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.     

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.     

Research ethics and clinical trials: Fostering collaboration with research participants

Accountability in research is a concept that applies to researchers and study participants alike. Human subjects play an active part in the success or failure of a clinical trial by virtue of their understanding of a study's goals expectations of personal gain, and adherence to study design. Trials must be designed to address patient concerns, offer an improved consent process, and move beyond our narrow conception of “patient rights.”; Problems with protocol adherence may be reduced by conceptualizing clinical research as an endeavor with mutual accountability within a relational ethic.     

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.     

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     

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.     

Patients’ competence to consent to neurobiological research

Progress has been made defining the standards for determining subjects’ competence to consent to research: abilities to communicate a choice, understand relevant information, appreciate the nature of the situation and its consequences, and manipulate information rationally. Available data show clearly that persons with mental illness display a spectrum of decisionmaking abilities, with many performing well, but some doing quite poorly. More attention now is required to identifying the degree of capacity required for competent consent to projects with varying risk/benefit characteristics. Practical means are also required for screening for subjects with impaired capacities, attempting to improve their performance, and providing substituted consent when their deficiencies are intractable.     

The therapeutic misconception,beneficence, and respect

In order to provide benefits to society, human medical trials must place subjects at risk of harm. This activity is thought to be justified in part by the consent of the subjects involved. But, studies have shown that most such consents are based on a therapeutic misconception (TM); the false belief of subjects that their researchers will act as their personal physicians (seeking their benefit and protecting them from harm), rather than placing them at risk of harm for the good of others. Toleration by researchers of the TM in their subjects is a form of “informational manipulation”; that renders consent procedures disrespectful to subject autonomy. Consent obtained from subjects who labor under a TM is neither voluntary nor informed; as long as they have not been disabused of the TM, the action they take in enrolling in a trial is not the one they intend nor is it autonomously chosen. Changes in consent procedures should be adopted to ensure that all subjects are aware inter alia that (a) the health interests of future patients (as well as the researchers’ and their sponsors’ financial interests) may be more important to researchers than the interest of a subject in his or her health, and (b) normal subjects neither understand nor believe this when told. Close attention to the response of prospective subjects to this information should allow for the exclusion of all but the truly altruistic. However, the result of conscientious implementation of such policies would likely be that human medical research could no longer be conducted on more than a minimal level.     

Research Subject Advocate: A New Protector of Research Participants

In 2001, the National Center for Research Resources (NCRR) directed the 78 General Clinical Research Centers (GCRC) to develop a Research Subject Advocate (RSA) position. The RSA would report directly to the Principal Investigator (PI) of each GCRC and assure compliance of studies conducted on the GCRC with federal regulations and policies. Seven RSAs agreed to be interviewed about their new role. Website documents, electronic correspondence, and presentations at the first annual national meeting of RSAs were scrutinized using discursive analysis to shed light on this new organizational form and its potential for increased protection of human research participants. The RSA role actualizes the ethical principles of respect for persons, justice, and beneficence that are the foundation of the protection of research participants. The results also reveal the regulatory, institutional, collegial, and personal resources and barriers that assist the RSA in the successful implementation of the RSA role. In addition, issues important to the RSAs are described.     

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 use of social science research to inform policy development: case studies from recent immigration policy

Abstract

This paper explores how social science research has informed recent immigration policy development in Aotearoa/New Zealand. Examples of research use, drawn from in-depth interviews with policy advisors and social science researchers working in the immigration area, are discussed using the stages model of policy development. Intersections between the stages and multiple-streams models of policy development, and Weiss's typologies of research use, are used to examine research use at various stages in the policy development process. The findings suggest that at any point in time there may be any number of policy development stages in action, with research exerting different types of influence, and being used in different ways, within each of these. A two-way conversation between researchers and policy-makers, building mutual understanding and enabling reciprocated influence over research and policy decisions, is shown as critical in bridging the research to policy gap.     

EXCLUDING PARTICULAR INFORMATION FROM CONSENT FORMS

Although the informed consent process is crucial to protecting human research subjects, there are cases when particular information within the consent form may present risks to those subjects. In this paper, we examine a case in which including the sponsor’s name on the consent form may allow the form to serve as a surrogate for subjects’ HIV status.

There is no literature addressing the ethical acceptability of excluding particular information from consent forms, and there exists little regulatory guidance on this issue. We argue that excluding information from the consent form is, in fact, obligatory when that information is disclosed orally during the consent process but its presence on the form poses risks to the subjects the consent process is designed to protect. Further, we argue that the regulations ought to be amended to reflect this obligation.