Strategies to minimize risks and exploitation in phase one trials on healthy subjects

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors.     

Enrolling decisionally incapacitated subjects in neuropsychiatric research

This paper discusses the National Bioethics Advisory Commission's (NBAC's) report on research involving persons with mental disorders that may affect decisionmaking capacity. After placing the NBAC recommendations into their historic context, the authors propose a strategy to enroll decisionally incapacitated subjects into neuropsychiatric research. The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.     

Research ethics and the principle of Justice as Fairness – A restatement

In my recent article, I addressed the question of whether a potential categorical exclusion of decisionally impaired patients from non-therapeutic medical research would be inaccordance with the Principle of Justice as Fairness. I came to the conclusion that a categorical exclusion of decisionally impaired persons from relevant research projects may collide with Rawls’s understanding of Justice as Fairness. Derek Bell has criticized my paper by denying that it is legitimate to apply Rawls to this bioethical problem. In my restatement I try to show that an extrapolation of John Rawls’s thought to such bioethical cases is possible, because Rawls himself has written that his orientation towards decisionally non-impaired persons is an idealized situation that allows extrapolations. In a second part I try to show that Bell hasroughly misunderstood my concept of “presumed consent” which I make a prerequisite for the legitimisation of research on decisionally impaired persons. In using advance consent as a proposal for resolving the problem, Bell has indirectly confirmed my approach because he is using a similar construct of consent, which operates with similar hypotheses and probabilities of error. I see here no categorical difference between Bell’s conclusion and my discussion. Thus, Bell’s reply does not represent a refutation of my thoughts, but rather it is a para phrased confirmation of my central theses. I conclude by showing the relevance of Rawls, pointing out that the discussion between Bell and me illustrates how Rawls’s concept of reflective equilibrium is an appropriate approach to finding a solution to this bioethical problem. This revised version was published online in June 2006 with corrections to the Cover Date.     

A virtue ethical approach to decisional capacity and mental health

It is a common assumption that lack of autonomy is incompatible with decisional capacity and mental health. However, there are two general conceptions of autonomy, one value-neutral and the other value-laden, which imply different notions of mental health. I argue that the value-neutral notion of autonomy is independently inadequate and that it also provides an inadequate foundation for judging whether someone is decisionally incapable or mentally disordered. I propose an alternative, value-laden account which posits ten capabilities required for basic human functioning. I then defend this account against objections and highlight its practical utility in designing optimal treatment.     

Surrogate consent to non-beneficial research: erring on the right side when substituted judgments may be inaccurate

Part of the standard protection of decisionally incapacitated research subjects is a prohibition against enrolling them unless surrogate decision makers authorize it. A common view is that surrogates primarily ought to make their decisions based on what the decisionally incapacitated subject would have wanted regarding research participation. However, empirical studies indicate that surrogate predictions about such preferences are not very accurate. The focus of this article is the significance of surrogate accuracy in the context of research that is not expected to benefit the research subject. We identify three morally relevant asymmetries between being enrolled and not being enrolled in such non-beneficial research, and conclude that when there is a non-negligible probability that surrogates’ predictions are wrong, it will generally be better to err on the side of not authorizing enrollment.     

Recommendations for standardized human pedigree nomenclature

The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant inconsistencies in the usage of common pedigree symbols representing situations such as pregnancy, termination of pregnancy, miscarriage, and adoption, as well as less common scenarios such as pregnancies conceived through assisted reproductive technologies. The Pedigree Standardization Task Force (PSTF) was organized through the Professional Issues Committee of the National Society of Genetic Counselors, to establish recommendations for universal standards in human pedigree nomenclature. Nomenclature was chosen based on current usage, consistency among symbols, computer compatibility, and the adaptability of symbols to reflect the rapid technical advances in human genetics. Preliminary recommendations were presented for review at three national meetings of human genetic professionals and sent to >100 human genetic professionals for review. On the basis of this review process, the recommendations of the PSTF for standardized human pedigree nomenclature are presented here. By incorporating these recommendations into medical genetics professional training programs, board examinations, genetic publications, and pedigree software, the adoption of uniform pedigree nomenclature can begin. Usage of standardized pedigree nomenclature will reduce the chances for incorrect interpretation of patient and family medical and genetic information. It may also improve the quality of patient care provided by genetic professionals and facilitate communication between researchers involved with genetic family studies.Reprinted with permission from theAmerican Journal of Human Genetics 56:745–752, 1995, The University of Chicago Press. © 1995 by The American Society of Human Genetics. All rights reserved.     

Psychosocial Interventions for Children with Early-Onset Bipolar Spectrum Disorder

Once considered virtually nonexistent, bipolar disorder in children has recently received a great deal of attention from mental health professionals and the general public. This paper provides a current review of literature pertaining to the psychosocial treatment of children with early-onset bipolar spectrum disorder (EOBPSD). Commencing with evidence of the emerging interest in this topic, we then focus on terminology, the rationale for studying EOBPSD in children, current research and clinical progress, possible explanations for the recent increase in recognition, and essential issues that form the foundation of effective psychosocial treatment. Next we explore areas of research with direct implications for psychosocial treatment. These include biological and psychosocial risk factors associated with bipolar disorder; and the psychosocial treatment of adult-onset bipolar disorder, childhood-onset unipolar disorder, and anger management in children. Following this, we discuss treatments being developed and tested for children with EOBPSD. Finally, we conclude with recommendations for future studies needed to move the field forward.     

Acceptance and Commitment Therapy With Older Adults: Rationale and Considerations

Older adults are the fastest growing segment of the population. With these changing demographics, mental health professionals will be seeing more older clients. Additionally, older adults are an underserved population in that most older adults in need of mental health services do not receive treatment. Thus, it is essential that treatments for mental and behavioral health problems are empirically supported with older adults and that mental health professionals are aware of the special needs of older adult populations. Acceptance and Commitment Therapy (ACT) is an emerging approach to the treatment of distress. The purpose of this article is to provide a rationale for using ACT with older adults based on gerontological theory and research. We also review research on ACT-related processes in later life. We present a case example of an older man with depression and anxiety whom we treated with ACT. Finally, we describe treatment recommendations and important adaptations that need to be considered when using ACT with older adults and discuss important areas for future research.     

Genetic Counseling for Fragile X Syndrome: Recommendations of the National Society of Genetic Counselors

The National Society of Genetic Counselors' (NSGC) recommendations for fragile X syndrome (FXS) genetic counseling are intended to assist health care professionals who provide genetic counseling for individuals and families in whom the diagnosis of FXS is strongly suspected or has been made. The recommendations are the opinions of genetic counselors with expertise in FXS counseling and are based on clinical experience, a review of pertinent English language medical articles, and reports of expert committees. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a particular client.     

Applying “Place” to Research Ethics and Cultural Competence/Humility Training

Research ethics principles and regulations typically have been applied to the protection of individual human subjects. Yet, new paradigms of research that include the place-based community and cultural groups as partners or participants of environmental research interventions, in particular, require attention to place-based identities and geographical contexts. This paper argues the importance of respecting “place” within human subjects protections applied to communities and cultural groups as part of a critical need for research ethics and cultural competence training for graduate research students. These protections and benefits are extensions of the Belmont Principles and have been included in recent recommendations from research regulatory committees.     

Confining Choices: Should Inmates' Participation in Research be Limited?

Historically, prisoners in the United Stateshave served as an inexpensive and readilyavailable source of human subjects forresearch. Coinciding with the civil rightsmovement, however, was an emerging conceptionof prisoners' rights that led to the NationalCommission for the Protection of Human Subjectsof Biomedical and Behavioral Research beingcharged with investigating the use of prisonersas research subjects. The recommendations thatevolved and the subsequent guidelines that havebeen implemented by the Department of Healthand Human Services significantly curtail theuse of prisoners as research subjects. Whilethese measures are designed to protect inmatesfrom the abuses of the past, of particularconcern to many health care officials isexclusion of inmates from experimental HIV/AIDSand hepatitis treatments. This paper addresseswhether the vulnerability of prisoners in theUnited States due to their incarceration issufficient to prohibit them from participationin clinical trials that offer the possibilityof life-saving treatment. It first outlinesthe evolution in moral thinking that has led tolaws broadly prohibiting prisoners frombiomedical research studies and then analyzescases in the law to develop ethical argumentsin support of the view that prisoners should beallowed to participate in clinical trials. Theconclusion is that prisoners should be allowedto participate in such trials.     

Tuning Clinical Recruitment around Cultural Taboos in a Human Microbiome Study

ABSTRACT

Human microbial communities are bodies of microorganisms that reside in or on different body parts. Importantly, they have been found to affect human health. However, scientific research on human microbial communities has created new challenges for human subject recruitment. First, individuals are asked to collect samples of bodily substances that can be seen as repulsive (e.g. feces and urine). Second, because scientists want to understand how human microbial communities evolve over time, individuals are asked to commit to a regular sample collection for extended periods of time. A longitudinal qualitative study of the work of scientists, physicians, research staff, and study coordinators involved in a human microbiome research project has found that these actors can bypass some aspects of these recruitment and retention challenges through ‘tuning work’. Tuning work is a collaborative process where professionals agree to adjust their practices towards shared goals. Such professionals reconfigure their work practices, personal routines, and the study protocol in an effort to obviate cultural taboos against handling bodily substances. The burden of long-term participation provides fewer opportunities for tuning work for these professionals, however. As such, long-term commitment by human subjects remains a recruitment and retention obstacle.     

Are research subjects adequately protected? A review and discussion of studies conducted by the Advisory Committee on Human Radiation Experiments

In light of information uncovered about human radiation experiments conducted during the Cold War, an important charge for the Advisory Committee on Human Radiation Experiments was to assess the current state of protections for human research subjects. This assessment was designed to enhance the Committee's ability to make informed recommendations for the improvement of future policies and practices for the protection of research subjects. The Committee's examination of current protections revealed great improvement over those from the past, yet some problems remain. Although the data collected by the Committee highlight specific areas in need of attention, the Committee's work should be viewed in part as the beginning of a series of ongoing assessments of the adequacy and effectiveness of the protections afforded to human subjects.     

Liability of professional and volunteer mental health practitioners in the wake of disasters: a framework for further considerations

Qualified immunity from civil liability exists for acts of disaster mental health (DMH) practitioners responding to disasters or acts of terrorism. This article reviews current legal regimens dictating civil liability for potentially wrongful acts of DMH professionals and volunteers responding to disasters. Criteria are proposed to inform determinations of civil liability for DMH workers in disaster response, given current legal parameters and established tort law in relevant areas. Specific considerations are examined that potentially implicate direct liability of DMH professionals and volunteers, and vicarious liability of DMH supervisors for actions of volunteer subordinates. The relevance of pre-event DMH planning and operationalization of the plan post-event is linked to considerations of liability. This article concludes with recommendations to minimize liability exposure for DMH workers in response efforts.     

Digital Mental Health Services: Moving From Promise to Results

The papers in this special series make a compelling case for the value of digital mental health services (DMHS; including technology-based interventions, assessments, and prevention programs) to help address some of the currently unmet needs in mental health care. At the same time, the papers highlight the work that needs to be accomplished for DMHS to fulfill their promise. We review the papers’ contributions in terms of (a) the imperative to increase access to evidence-informed, high-quality care, especially for underserved populations, both in the United States and globally; (b) ways to use DMHS to improve the ways that clinical care is provided to make treatment provision more effective and efficient; and (c) the current state of the research on DMHS for emotional disorders. We then consider lessons learned and recommendations to move the field forward, such as increasing (and making transparent) the research base on DMHS, adopting regulatory standards for DMHS, attending carefully to training issues for DMHS and best practices for dissemination and implementation, designing specifically for digital platforms, and being intentional about efforts to reduce disparities regarding who benefits from DMHS.     

Gay and Lesbian Speaker Panels: Implementation and Research

Speaker panels are educational interventions in which lesbian women and gay men share their personal stories and respond to questions and comments. The panels are frequently used with college and community groups to reduce homophobic attitudes. Counselors, student development professionals, and other human services professionals are given practical information on effective panel presentations. Then the empirical findings concerning panels are discussed, and recommendations are made to human development professionals for research to expand empirical knowledge about this intervention.     

Future Directions for Advancing Issues in Children’s Mental Health: A Delphic Poll

The current study utilized a Delphic poll to identify significant problems regarding children and families in which psychologists can assist. The Delphic poll methodology combines both qualitative and quantitative methodologies to obtain information and predictions about the future from a panel of knowledgeable experts. Thirty-one professionals participated in the first round of the survey, and 26 participants (83.9 % of the round 1 participants) chose to complete the second-round survey. Several themes emerged consistently across questions as important issues to be addressed in the future of childhood mental health. For example, participants frequently identified access, advocacy, research and research dissemination, prevention/early intervention, and integration of services as important issues. Implications and recommendations are drawn for organizations and individual psychologists as advocates for improving children’s mental health in the United States.     

An examination of tax professionals' judgments: The role of experience,client condition and reciprocal obligation

In spite of the expanding role of tax preparers in the tax reporting process, very little research has been directed at how tax preparers make tax-related decisions. This study extends prior research by using tax preparers as opposed to taxpayers as subjects. The judgment of tax preparers presumably can be influenced by three categories of factors: 1) factors relating to the law and regulatory environment, 2) individual differences between professionals, and 3) differences across clients and client conditions. This research has focused on the second and third categories of influence. Individual differences examined were experience, ethical disposition and fear of reprisals related to tax preparer penalties. Client related influences examined were reciprocity demands of an aggressive client and year-end client overpayment/underpayment tax position.The subjects in our study indicated significant reticence to recommend an aggressive (yet supportable) position to a client noted to want to follow an aggressive strategy. Further, experienced tax professionals indicated resistance to client condition pressures—underpayment tax status and reciprocity pressure.     

A Survey of Ethical and Professional Challenges Experienced by Spanish Health-Care Professionals that Provide Genetic Counseling Services

Genetic testing is increasingly applied for diagnosis and clinical treatment. In some countries, genetic counseling services are provided by professionals with specific training in this discipline, whereas other countries have no teaching programs and counseling is offered by physicians, nurses, pharmacists or biochemists. This counseling raises more and more ethical dilemmas for health professionals at their clinics. The purpose of this study was to analyze the characteristics of Spanish professionals devoted to providing genetic counseling services and to investigate the frequency of the ethical dilemmas they face. Results from 72 survey respondents revealed this counseling is provided by an almost even number of male and female professionals, mostly physicians with many years of professional experience. The overall frequency of the ethical dilemmas encountered was not high. The most frequent dilemmas corresponded to emotional responses by patients, informed consent, uncertainty about test results, and limitations on health-care resources. The frequency of dilemmas involving discrimination and provider directiveness was very low. Additional findings, practice implications, and research recommendations are presented.