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.     

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.     

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.     

Research with Older Adult Methadone Clients: The Importance of Monitoring Suicide Ideation

ABSTRACT

This study reports on the importance of monitoring suicide ideation among older adult research participants. A recently completed randomized controlled trial of older adults who are current clients in methadone maintenance treatment (MMT) served as a case study to elucidate a suicide protocol that was designed to account for the potential instances of suicide ideation within the research project structure. As the numbers of older adult heroin users increases, this study’s findings seek to influence research protocols that involve older adults with addictions who may be particularly vulnerable to suicide risk due to comorbid psychiatric conditions and psychosocial adversities.     

Evaluating U.S. Medical Schools' Efforts to Educate Faculty Researchers on Research Integrity and Research Misconduct Policies and Procedures

This paper examines how well U.S. medical school institutions are doing to promote research integrity. It is an important question to ask in order to determine whether there are sufficient and adequate protections in place to protect the U.S. Public Health Service's (PHS) resources devoted to medical research. This paper focuses on 5,100 medical school researchers' knowledge of what constitutes research misconduct as well as their willingness to report it to the research integrity officer (RIO) and educate their Ph.D. trainees. We learned that 5.6% of researchers could correctly distinguish seven or more of the nine scenarios that depicted likely research misconduct, as defined by the PHS regulations, from scenarios describing other ethical issues. Instead, researchers had expansive definitions and often inappropriately identified infractions such as conflicts of interest, Institutional Review Board (IRB) violations, and other breaches in ethical standards to be research misconduct. In addition, researchers who correctly identified four instances of likely research misconduct in the test items were highly unlikely to report their observations to a RIO. Researchers also provided insight on the factors they believe influence their decision making process of whether to report research misconduct. In addition, this paper also reports on the guidance that faculty said they provided their trainees on research misconduct issues. We conclude with a discussion and recommendations on what institutional leaders might consider doing in order to enhance their research integrity efforts and protect their institution's reputation.     

Sensing the Natural in the Caribbean's Nature Island

ABSTRACT

This article uses research carried out in the Caribbean island of Dominica to consider how sensory experiences shape and influence people's perceptions of and relationships to nature. People's ideas of nature are not purely abstract; they are embodied and emplaced in geographical and social contexts. That is, people acquire understandings of nature through their experiences of the natural world, their engagements with flowers and birds, rivers and mountains, forests and vegetable gardens. On this basis, this article explores how sensory perception, in addition to being a way to apprehend the material reality of the natural environment, also plays a role in how people relate to and think about nature and the natural, based on their bodily experiences in a particular place.     

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.     

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.     

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.     

Toward increased public representation on bioethics committees: Lessons from Judging the cold war human radiation experiments∗

The process of judging the Cold War Human Radiation Experiments illuminates a need to develop a model for an appropriate public role on bioethics committees. A citizen representative was appointed to the President's Advisory Committee on Human Radiation Experiments, and the Committee solicited broad public participation in their investigation. However, many members of the affected and interested public desired further representation on the Committee, as they tended towards stronger ethical condemnations of the experiments than the Committee expressed. I offer an account of a testimony before the Committee by a radiation experiment subject's survivor to illustrate this contrast in moral perspective. I consider some the contributions that “non‐expert”; public members can add to committee deliberations, and suggest that concerns about public representatives may be overcome with the guidance of clearer principles for selecting public members. Further efforts to increase membership by the general and affected public on bioethics committees will enhance deliberations and help realize the democratic ideals of bioethics.     

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.     

Planning for future research participation: Ethical and practical considerations

This paper addresses the concept of advance planning for future research participation during episodic or permanent decisional incapacity. First, the concept and its historical origins are described. Second, the concept's ethical justifications are presented. Third, commentary raising ethical and practical concerns about advance research planning is discussed. The paper concludes with the author's views on advance research planning and on the relevant recommendations of the National Bioethics Advisory Commission.     

Self-experimentation

Except in certain cases of unusual risk, self-experimentation should not be encouraged. It is usually scientifically inadequate for lack of proper controls and sufficient subjects to generate meaningful results. It is also inadequate as an ethical test because even if lay persons are also enrolled, self-experimentation is neither necessary nor sufficient to establish that they may participate. It is not necessary to establish that lay persons may participate because institutional ethics review and informed consent are better ways to determine this. It is not sufficient because the investigator may be more risk accepting or not medically typical. Moreover, because scientific research is now done in teams, self-experimentation may involve undue influence when junior investigators participate as research subjects.     

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.     

Love and money: payment, motivation and the fostering task

Although the payment of foster carers has attracted greater attention in recent writing and research, coverage of the issues has been limited. In this study, based on interviews with 20 female carers, the place of payment within foster care is explored in greater depth. The focus is on charting how carers perceive their task as ‘parenting’ or ‘job’, whether and how they experience payment as compensation or as an appropriate reward for their skills. Also examined are the ways in which payment may impact upon the practice of foster care, for example in decision making over the taking or ending of placements and the provision of aftercare support for care leavers. The study highlights the distinctive nature of foster care as an institution that straddles the public and private domains, and examines the resulting complexities. It concludes by suggesting that while payment issues provide important threads that run throughout foster care, their influence is ultimately limited by the latter's base within the family.     

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.     

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.     

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.