Towards the development of ethical practices in paediatric clinical trials: the special position of the terminally ill child

This article examines the emotive and vexing issue of the involvement of terminally children in paediatric clinical trials. Particular emphasis is placed on the participation of such children in Phase I clinical studies, as such studies do not yield any benefit to the individual child. It provides an historical overview of medical research involving children and examines the moral arguments surrounding the participation of children in clinical trials. The article examines the conflict between doctor-as-researcher and doctor-as-treater as well as the problems presented by proxy consent providers. The role played by the human research ethics committee in this area is examined, as is the regulatory framework established by the National Health and Medical Research Council. The article argues that the participation of terminally ill children in Phase I clinical trials is not morally repugnant provided that there is a total commitment to the protection of the child participant's well-being during the dying process. It is argued that the moral justification for such position derives from the utilitarian notion that participation in such studies aims to benefit future generations of ill children.     

TRICARE; coverage of National Cancer Institute (NCI) sponsored Phase I studies. Final rule

This final rule adds coverage of National Cancer Institute (NCI) sponsored Phase I studies for certain beneficiaries. The NCI sponsored clinical treatment trials are conducted in a series of steps called phases. Phase I trials are the first studies conducted in people. They evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle), how often, and what dose is safe.     

First-in-Human Trial Participants: Not a Vulnerable Population, but Vulnerable Nonetheless

The 21st-century translational science campaign could lead to an increase in first-in-human (FIH) trials. As tests of investigational interventions move from the laboratory to human research, scientists, officials, and review committees should address ongoing concerns about the ethics of FIH trials. In this article, I describe three ethical considerations relevant to all FIH trials: (1) the requirement for adequate preclinical research; (2) study design safeguards; and (3) choice of subject population. I also examine specific ethical considerations relevant to the three subject populations (healthy volunteers, seriously ill patients lacking standard treatment options, and stable patients) involved in FIH research. I recommend a variety of actions that could increase subject protection and the value of the information generated in FIH trials.     

A Leap of Faith? Sanctioning Xenotransplant Clinical Trials

Introducing a new medical technique, procedure or drug to the public via clinical trials is risky at the best of times. When the trial involves a biotechnology which holds out the promise of prolonging, if not saving, life the push to move from the laboratory to clinical trials may be hard to resist. In this article I explore whether the regulatory scheme for clinical trials in the UK is able to accommodate developing technologies by considering how the current legal and ethical frameworks determine when a procedure such as xenotransplantation should proceed to trials. In particular, I discuss whether basing our regulatory schemes on the principles espoused in the Declaration of Helsinki offer sufficient protection to those who may be affected by xenotransplant trials – the recipient, their health-care workers, close contacts and, unusually, the wider public. I question whether it is possible for a technology to be approved for clinical trials when allowing such trials may benefit the individual but ultimately negatively impact on society as a whole.     

The “process” of field research in the courtoom

This article is meant to contribute to understanding the process of “live” courtroom research by describing and reflecting upon the choices my colleagues and I made in a recently completed study of judicial behavior. In light of the tremendous need for such research and in recognition of the perils attendant to conducting it, social scientists must begin to articulate in detail their philosophy, strategies, and methods of study in the actual courtroom setting. The present article discusses the methodological and ethical issues that we faced in the context of the research project on trial judges' verbal volved in our courtroom research included: (1) developing the theory and purpose of study, (2) organizing entry and logistics in the field, (3) assessing ethical costs and benefits, (4) gathering field data and developing methods that accommodate the field setting, and (5) understanding follow-up and ethical concerns after the research is over.     

European Union. Ethical considerations for clinical trials on medicinal products conducted with the paediatric population

This document has been developed by the ad hoc group for the development of implementing guidelines for Directive 2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human use, chaired by the European Commission. The document provides recommendations on various ethical aspects of clinical trials performed in children from birth up to the legal age of adulthood. This will contribute to the protection of all children who are the subject of clinical trials. As the approval of clinical trials, including ethical approval, is performed by the Member States, any recommendations on ethical aspects of clinical trials in children will also facilitate a harmonised approach to the application of the clinical trials directive across the EU, thereby facilitating the conduct of clinical trials in the EU and in whichever country the paediatric trial occurs. The protection against the risks of research in such a vulnerable population is paramount whilst this should not lead to denying them the benefits of research. Children are not small adults and there is a need to carry out specific trials that cannot be performed in adults. In general, children (minors) are unable to consent (in the legal sense) but their assent should be sought using age appropriate information. Ethics Committees need paediatric expertise to balance the benefits and risks of research in children. The lack of legal ability to consent has implications on the design, analysis and the choice of comparators used in trials, which should only be performed by trained investigators with paediatric experience. Pain, fear, distress and parental separation should be prevented and minimised when unavoidable. The neonate represents the most vulnerable of all paediatric age groups and requires even more careful review. Finally, various other aspects relating to the performance of trials in children are discussed.     

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/ TRICARE; coverage of phase II and phase III clinical trials sponsored by the National Institutes of Health National Cancer Institute. Final rule

The final rule allows the Department of Defense to waive normal requirements so that covered beneficiaries can participate in Phase II and Phase III clinical trials sponsored or approved by the National Institutes of Health National Cancer Institute (NIH NCI). This waiver authority is expected to promote beneficiary access to promising new treatments and contribute to the development of such treatments.     

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); methodology for coverage of phase II and phase III clinical trials sponsored by the National Institutes of Health. Office of the Secretary; DoD. Final rule

This final rule allows the Department of Defense to waive normal requirements so that covered beneficiaries can participate in Phase II and Phase III clinical trials sponsored or approved by the National Institutes of Health National Cancer Institute (NIH NCI). This waiver authority is expected to promote beneficiary access to promising new treatments and contribute to the development of such treatments.     

Hazardous waste management programs; Florida: authorization for interim authorization phase I--Environmental Protection Agency. Notice of final determination

The State of Florida has applied for interim Authorization Phase I. EPA has reviewed Florida's application for Phase I and has determined that Florida's hazardous waste program is substantially equivalent to the Federal program covered by Phase I. The State of Florida is, hereby, granted Interim Authorization for Phase I to operate the State 's hazardous waste program, in lieu of the Federal program.     

Ethical standards for clinical trials conducted in third countries: the new strategy of the European Medicines Agency

Clinical trials increasingly occur on a global scale as industry and government sponsors in wealthy countries move trials to low- and middle-income countries. The globalization of clinical research raises important questions about the economical and ethical aspects of clinical research and the translation of trial results to clinical practice: which ethical standards are applied? Are trials results accurate and valid, and can they be extrapolated to other settings? This article provides an overview of the strategy approved by the European Medicines Agency (EMA) to clarify ethical standards for clinical research conducted outside the European Economic Area (EEA) and included in Marketing Authorization Applications. Reference to the EMA Reflection paper is made.     

Narrative,Rhetorical Argument,and Ethical Authority

The great challenge of rhetorical argument is to make discourse ethical without making it less logical. This challenge is of central importance throughout the full range of practical argument, and understanding the relation of the ethical to the logical is one of the principal contributions the humanities, in this case the study of rhetoric, can make to legal scholarship. Aristotle’s Rhetoric shows how arguments can be ethical and can create ethical relations between speaker and hearer. I intend to apply Aristotle’s analysis to a phenomenon that did not yet exist for him, that of authority, by asking how the acts of asserting and accepting authority can be ethical acts. I take as a test case a peculiarly unfortunate and inept appeal to authority, that offered by the counsel for the District of Columbia in arguing Bolling v Sharp who cited Taney’s opinion in Dred Scott to clinch his point. By seeing just what goes wrong in such a maladroit appeal, I explore the rational, voluntary and ethical dimensions of a decision to accept a given commitment to authority. I use Joseph Raz’s analysis of authority and the relation of reason to authority, yet think I go beyond Raz by exploring the deliberate and voluntary nature of submission to authority. Choosing to be bound by an authority is an ethical act. As such it is always rational and yet never purely rational. The Supreme Court’s choice of authorities is part of its making itself into an authority, and is a paradigm of the ethical act of choosing to be obligated. Choosing to be committed or obligated is a central paradox of political theory and considerations of authority and obligation, at least since early social contract theorists. However, its importance for judicial reasoning, which at the same time chooses to submit to authority and itself becomes an authority, has not been noted. Consideration of the relations between the ethical and the logical can help us better to articulate the constitution of ethical authority. This revised version was published online in July 2006 with corrections to the Cover Date.     

Multilevel public funding for small business innovation: a review of US state SBIR match programs

US State governments invest in early-stage innovative activity as an economic development strategy. Nevertheless, attention directed at the public sector’s role in this capacity has been placed on federal policy actions overlooking the growing role of states. The primary aims of this paper are two-fold: (1) to articulate the motivations for multilevel public support for small business innovative activity, placing emphasis on state level incentives directed towards entrepreneurial activity; and (2) to empirically evaluate the State Match Phase I (SMP-I) program. The SMP-I program is a diffuse state level policy designed to complement the federal Small Business Innovation Research (SBIR) program by offering noncompetitive matching funds to the state’s successful SBIR Phase I recipients. This offers an opportunity to examine the marginal impact of public R&D given the state intervention. This paper employs a state and year fixed effects model and considers two outcome variables—SBIR Phase II success rates and SBIR Phase I application activity. To account for industrial heterogeneity, the data are stratified by the federal mission agencies. Results from the empirical analysis indicate that the state match increases the Phase II success rates for firms participating in the National Science Foundation SBIR program.     

Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme

Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.     

Levinasian Ethics and Legal Obligation*

Abstract. This paper discusses the implications of the ethical theory of Emmanuel Levinas for theoretical debates about legal obligation. I begin by examining the structure of moral reasoning in light of Levinas's account of ethics, looking particularly at the role of the “third party” (le tiers) in modifying Levinas's primary ethical structure of the “face to face” relation. I then argue that the primordial role of ethical experience in social discourse, as emphasised by Levinas, undermines theories, such as that of H. L. A. Hart, that propose a systematic distinction between legal and moral species of obligation.     

The ethics of promulgating principles of research ethics: the problem of diversion effects

There is an important distinction between ethical standards for the conduct of research with human subjects and the ethics of promulgating principles of research ethics. Those who promulgate ethical standards for the conduct of research have an ethical responsibility to consider the consequences to which those promulgations give rise. In particular, they must consider whether their promulgations will give researchers incentives not to conduct research or not to conduct research in locales in which participants would benefit from participation. I first show how such ‘diversion effects’ are possible and then examine four principles of research ethics in that light. I then consider several objections to the argument that those who promulgate principles of research ethics should consider diversion effects.     

Can an employer-based health insurance system be just?

It is America's distinctive practice to tie private health insurance to employment, and recent proposals have tried to retain this link through mandating that all employers provide health insurance to their employees. My primary approach to these issues is neither economic, nor historical, nor political but ethical. After a brief historical overview, I outline a general approach to evaluating the ethical significance of linking the distributions of distinct goods. I examine whether an unjust distribution of jobs spoils justice in the distribution of health insurance, taking as a central example gender inequities in employment and exploring their impact on job-based health insurance. Second, I explore the possibility that justly awarding jobs guarantees justice in employment-sponsored insurance. However, linking the distributions of different goods remains problematic, because such links inevitably undermine equality by enabling the same individuals to enjoy advantages in many different distributive areas. Finally, I examine recent proposals to reform America's health care system by requiring all employers to provide health insurance to their employees. I argue that such proposals lend themselves to the same ethical problems that the current system does and urge greater attention to alternative reform options.     

Enter Ghost: Haunted Courts and Haunting Judgments in Transitional Justice

How can we account for trials in which the judgment speaks not only to and about the defendants and their deeds, but also about injustices from a more distant past? Building on approaches to ghosts and haunting by Jacques Derrida and Avery Gordon, I propose to examine a set of the German post-1990 trials for human rights violations committed in the former East Germany as instances of haunted justice. Here, the courts not only adjudicated the present cases, but also tried to ‘go back and make whole what has been smashed’ (Benjamin 1969) by their own lack of judgment in the failed trials of the Nazi perpetrators. In this instance, the ‘time is out of joint’, and we see the ghosts of the failed trials of Nazi perpetrators standing next to the inheritance of impunity fostered in West German courts, and next to the now present East German perpetrators. What can justice mean in such a complex constellation of injustices? I argue that the ghostly dimension of these cases point to a need for a kind of justice and engagement that can ultimately not be found in courts—yet the courts’ engagement with this ghostly matter is nevertheless important.     

An abolitionist theory on crime: ending the abusive relationship with Racist-Imperialist-Patriarchy [R.I.P.]

In this article I re-assess the parameters of what we seek to abolish as we pursue penal abolition. I apply Black Feminist Hauntology to exorcize the barriers of traditional and ineffective deconstructions of crime and criminalization. To illustrate these weaknesses I discuss police killings and related vigilante white supremacist violence. I present the aftermath of the deaths and trials (when there were trials) to bring to light the large disconnects that exist between abolitionism and the world in which crime lives. To begin to address this disconnect I present an abolitionist theory on crime founded upon five pillars of assessment: abolition’s perceived minimization of violence; the abusive R.I.P. relationship between crime and justice; a cultural phenomenon of achieving significance through proximity or by association; abusive naturalizations of violence that have been unaddressed in penal abolition; locating the struggles to exit abusive relationships within the core of our studies of criminal justice and penal abolition. I conclude that when penal abolitionists conceive of crime as a social construction tied to criminal justice institutions alone, as opposed to part of a structurally Racist-Imperialist-Patriarchal [R-I-P] abusive relationship, they stunt the possibilities of abolition in manners akin to pushing against a 500 year old tree from its trunk and expecting it to topple over without any account for the roots that hold it firmly in the ground.     

Ensuring safety, implementation and scientific integrity of clinical trials: lessons from the Criminal Justice–Drug Abuse Treatment Studies Data and Safety Monitoring Board

Data and safety monitoring boards (DSMBs) provide independent oversight to bio-medical clinical trials, ensuring safe and ethical treatment of research participants, data quality, and credibility of study findings. Recently, the type of research monitored by DSMBs has been expanded to include randomized clinical trials of behavioral and psychosocial interventions in community and justice based settings. This paper focuses on the development and role of a DSMB created by the National Institute on Drug Abuse (NIDA) to monitor six multi-site clinical trials conducted within the Criminal Justice–Drug Abuse Treatment Studies (CJ-DATS). We believe this is one of the first such applications of formal DSMBs in justice settings. Special attention is given to developing processes for measuring and monitoring a range of implementation issues for research conducted within criminal justice settings. Lessons learned and recommendations to enhance future DSMB work within this area are discussed.