The importance of preservation of the ethical principle of equipoise in the design of clinical trials: relative impact of the methodological quality domains on the treatment effect in randomized controlled trials

Previous research has identified methodological problems in the design and conduct of randomized trials that could, if left unaddressed, lead to biased results. In this report we discuss one such problem, inadequate control intervention, and argue that it can be by far the most important design characteristic of randomized trials in overestimating the effect of new treatments. Current guidelines for the design and reporting of randomized trials, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, do not address the choice of the comparator intervention. We argue that an adequate control intervention can be selected if people designing a trial explicitly take into consideration the ethical principle of equipoise, also known as "the uncertainty principle."     

Defining the Research Category in Pediatric Phase I Oncology Trials

Clinical research studies in children are classified by risk into three major categories. These are as follows: a) minimal risk studies, b) more than minimal risk studies but with benefit, and c) studies with minor increase over minimal risk but with no benefit.

Pediatric Phase I oncology trials, which are conducted in a highly vulnerable population of severely ill children with cancer, are designed to establish safety and to determine the maximum tolerated dose (MTD), as well as establish dose limiting toxicity (DLT). These types of studies can be associated with significant risk. The research design of such high- risk studies, which comprise short-term treatments with varying doses, is generally not associated with any clinical benefit. Classification of the research category in these pediatric studies poses a special problem for the Institutional Review Board (IRB) with major implications for the consenting process. The challenges associated with the classification of such studies are discussed in this article.     

Clinical Home Visitation for Children With Externalizing Disorders: A Randomized Study

ABSTRACT

Clinical home visitation (CHV) was empirically tested in a randomized study to determine if it could reduce a child's externalizing behaviors while alleviating parental stress. Clinic-referred waitlisted young children (n = 33) with symptoms suggesting an externalizing disorder were randomly offered a CHV intervention composed of a developmentally guided dyadic-centered syllabus. Families were recruited to participate in an experimental (n = 21) or control group (n = 12). Mothers completed the Parenting Stress Index (PSI) and the Child Behavior Checklist. Results of paired-samples t-tests indicated that postintervention aggression scores were significantly different from the pretest scores for the entire sample. The Difficult Child domain was the only significant PSI subscale. The results did not support definitive conclusions about CHV as an effective intervention to reduce an externalizing disorder or to alleviate parenting stress. Future research should include larger numbers of children with externalizing disorders pooled from the clinic-referred and community samples. To address the complexities involved in treating externalizing disorders, CHV could be offered as part of a multimodal intervention (e.g., CHV combined with parent and family education).     

Integrative Body-Mind-Spirit (I-BMS) Interventions for Posttraumatic Stress Disorder (PTSD): A Review of the Outcome Literature

ABSTRACT

Background: A growing interest in integrative body-mind-spirit (I-BMS) approaches to treatment of PTSD has resulted in a significant increase in related research. Method: This study conducted a synthesized review of randomized controlled trials of I-BMS treatments for PTSD, yielding thirteen studies that included: mindfulness/meditation (7), yoga (3), acupuncture (1), spiritually-based intervention (1), and relaxation (1) from 2004–2015. The study used a modified Delphi List (mDL) and the California Evidence-Based Clearinghouse (CEBC) to evaluate study rigor and level of research support for each practice. Results: Overall, I-BMS interventions demonstrated positive outcomes. Based on an mDL range between 0 and 7, scores were: 6 for meditation/mindfulness, 5.67 for yoga, 7 for acupuncture, 3 for spiritually-based intervention, and 4.5 for relaxation training. All interventions were recommended as practices with Promising Research Evidence (Level 3). Effect sizes (d) ranged from .51 to 1.88 for relaxation, .38 to 1.02 for spiritual, .31 to 1.4 for acupuncture, .1 to 1.54 for yoga and .2 to 1.53 for mindfulness meditation. Discussion: This study identified acupuncture, meditation, and yoga as high-quality alternative therapeutic practices for PTSD with promising evidence as effective and safe approaches. Future studies should assess long-term effects to further elevate the level of research support.     

Overcoming Liability Concerns in Vaccine Trials Involving Pregnant Women

Without the protection of vaccines, the health of pregnant women may be compromised. But assessing the safety and efficacy of vaccines in pregnancy requires research in pregnancy. Furthermore, vaccinating women while they are pregnant may convey immunity to the fetus in utero, but assessing this possible benefit of maternal immunization also requires research. This article argues that one factor inhibiting vaccine research involving pregnant women is that vaccine manufacturers fear incurring liability if they fund such research. We argue that vaccine research in pregnancy can be ethical, and we explore some methods for overcoming vaccine manufacturers' fear of liability.     

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.     

Is the trend to publish reviews and clinical trials related to the journal impact factor? Analysis in dentistry field

ABSTRACT

It is generally accepted that the Journal Impact Factor is a quality criterion. The objective was to determine the evolution along the period 2010–2016 of number of different types of papers, reviews and clinical trials, published by dental journals, as well as if they are related with the quartile occupied in the Journal Impact Factor 2017 ranking. To this end, ten journals per quartile belonging to the field Dentistry, Oral Surgery and Medicine in the 2017 Journal Citation Reports were randomly selected. For each journal and year, the total number of narrative reviews, systematic reviews (with and without meta-analysis), meta-analysis, clinical trials and randomized controlled trials were obtained from Pubmed. To achieve our goal, the slope of these variables over time was estimated using the least squares method, after which one-way analysis of variance of mean values was performed. In Dentistry, the journals of the top quartiles show a trend to publish increasing amounts of systematic reviews and meta-analysis, than the ones of the third and fourth quartile. On the other hand, globally, there was virtually no increase in narrative reviews, clinical trials and randomized controlled trial. Possible causes of this behavior are also discussed in this article.     

Are antidepressant and antipsychotic drug trials registered? A cross-sectional analysis of registration and reporting of methodologic characteristics

Introduction: In 2005, the International Committee of Medical Journal Editors (ICMJE) proposed that all submitted trials in all 11 member journals must be prospectively registered in order to be considered for publication. Registering drug trials was meant to reduce the likelihood of selective reporting. The aim was to determine the proportion of antipsychotic and antidepressant trials that were registered.

Methods: We searched in Pubmed for all randomized controlled trials of any antidepressant or antipsychotic published between July and December 2014. The primary objective was to determine the proportion of trials that were registered. Secondary objectives included comparing the reporting of methodological details and positive study findings between registered and unregistered trials.

Results: Of the 67 studies identified, 58% were registered. 75% of the antipsychotic trials and 51% of the antidepressant trials were registered, respectively. Registered trials were more likely to report important methodological details associated with risk of bias in RCTs. There was no significant difference in trials reporting positive outcomes for the study intervention between registered and unregistered trials.

Conclusion: Approximately 60% of published antidepressant and antipsychotic drug trials during July to December 2014 were registered. Unregistered trials were less likely to report important methodological details.     

The Inclusion of Minority Groups in Clinical Trials: Problems of Under Representation and Under Reporting of Data

Objective: To evaluate the representation of minority groups in randomized control trials (RCTs), and the frequency with which this information is reported.

Study Design: Reviewers collected data on the racial/ethnic composition of study samples from all RCTs published in six leading medical journals in 1999.

Results: Of the 280 RCTs, most (204, 71.3%) provided no information on the race/ethnicity of participants. Of the 89 U.S.-based RCTs, 50 (56.1%) reported their minority distribution. Relative to other trials, those funded by the National Institute of Health (NIH) (n = 52) were more likely to report race/ethnicity data (55.8% vs. 23.7%; χ² = 20.9, p ≤ 0.001) and to include nonwhite participants (13.5% vs. 12.5%; χ² = 22.7, p ≤ 0.001).

Conclusion: Minority groups are currently under-represented in clinical trials. Information on the race and ethnicity of clinical trial participants is currently underreported in six leading medical journals. Reporting of minority group information was significantly better only in NIH funded trials, which also were more likely to include nonwhite participants. This suggests that mandatory reporting policies may have a positive effect on both reporting and representation.     

On the coase theorem and coalitional stability: the principle of equal relative concession

The Coase theorem is argued to be incompatible with bargaining set stability due to a tension between the grand coalition and sub-coalitions. We provide a counter-intuitive argument to demonstrate that the Coase theorem may be in complete consonance with bargaining set stability. We establish that an uncertainty concerning the formation of sub-coalitions will explain such compatibility: each agent fears that others may `gang up' against him and this fear forces the agents to negotiate. The grand coalition emerges from the negotiations if each agent uses the principle of equal relative sacrifice to determine the actual allocation. We also establish the rational basis for the choice of the principle of equal relative concession by the negotiating agents. Hence we argue that the Coase theorem will be valid even if there are stable sub-coalitions.     

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.     

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     

Resonant Texts: Sounds of the American Public Library

ABSTRACT

Public libraries have long been associated with silence and order. Historians have argued that the architecture of library buildings has served in disciplining patrons into silent reading subjects. I argue that, in light of evolving, subjective definitions of and responses to noise, changing philosophies of librarianship and library design and the proliferation of media formats and the sounds they emit, we need to consider new ways of thinking about sound in the library, not as something to be eliminated or controlled, but as something to be orchestrated, and even designed for. In order to do so, I propose that we consider first what sounds people, buildings and media make, and then use architectural design to promote their cooperative interaction.     

Evaluation of a Preventive Intervention for Bereaved Children

Abstract

One hundred eighty four families completed a twelve month parent-guidance (experimental) or a parent telephone-monitoring (comparison) intervention initiated during one parent'S terminal cancer illness and continued until six months after the death. Children in the parent-guidance intervention reported greater reduction in trait anxiety and greater improvement in their perceptions of the surviving parent'S competence and communication, a primary goal of the intervention. Identified problems in implementing evaluations of experimental interventions with bereaved children include the following: (1) Available and commonly used standardized psychopathology measures do not adequately capture changes in non-psychopathological but bereaved distressed, grieving children and adolescents. (2) Experimental and control samples usually have very few children with psychopathology (scores). Relatively small changes in scores within the normal range may be insufficient to allow measurement of meaningful differences between interventions. (3) Both experimental and control interventions must provide sufficient help to retain families for later evaluation. The level of general support and referral for other treatments, if adequately done, may be sufficient to blur differences in standardized psychopathology measure scores between any two interventions. It may only be in the specifically targeted intervention area that differences can be expected to be significant in adequately resourced families.     

Traits predictive of the successful outcome of unmarried mothers’ plans to keep their children 1

Abstract

After reviewing some of the major themes and trends in research on lesbians, lesbian couples, and lesbian families, I argue for a cultural perspective and an ethnographic stance in clinical work with this population. “Story” and “ritual” are suggested as examples of the many possible cultural lenses that can be useful in such practice, and illustration of how these cultural lenses can be worn in the therapeutic conversation are offered. A cultural perspective makes easy alliance with post‐modern thinking and notions of the de‐privileging of “expert” knowledge.     

Development,Feasibility, and Piloting of a Novel Natural Mentoring Intervention for Older Youth in Foster Care

Aging out of foster care is associated with deleterious emerging adulthood outcomes. The enduring presence of a caring adult, such as a natural mentor, can improve outcomes for emancipating foster youth. Caring Adults ‘R’ Everywhere (C.A.R.E.) is a novel, child welfare-based intervention designed to facilitate natural mentor relationships among aging-out youth. Our aims were to test the feasibility of implementing C.A.R.E. and the feasibility of conducting a randomized controlled study with older foster youth. Twenty-four foster youth aged 18–20.5 years were recruited and randomly assigned to the intervention (n = 12) or control groups (n = 12). Ten natural mentors were identified and contacted for participation in the intervention and study. Process-oriented qualitative data and quantitative pre- and postintervention outcome data were collected and analyzed. Utilizing a controlled rigorous design, the findings highlight the positive experience of both the intervention youth and their natural mentors with C.A.R.E. Overall, results support the continued refinement, delivery, and rigorous testing of C.A.R.E. with great promise for programmatically supporting natural mentor relationships among youth aging out of foster care.     

The Flesh and the World: Intercorporeal Body-selves,Ageing and Dancing

ABSTRACT

In this paper I address the role that embodiment, embodied consciousness and what can be termed “extradiscursive” experiences such as body memory and ekstasis as a form of ecstatic experience assume in understanding the body-self of mature dancers. I argue that the body-self of the dancer becomes increasingly intersubjective in maturity through her/his bodily practice, and that this can be understood in terms of the notions of intercorporeity, and of the “flesh” derived from the phenomenology of Merleau-Ponty. I argue that ways of manifestation of intercorporeity in bodily experience are discursively elusive, drawing on two forms of bodily experience—body memory and ekstasis—and examining experiences narrated by mature dancers who were interviewed in my Ph. D. study on ageing, gender and dancers' bodies. I contend that the experience of ekstasis is the “glue” of a corporeal subjectivity that transforms itself through momentary identification with the world, that calls on the invisible as well as the visible. Body memory also challenges Western dualist conceptions of consciousness and bodily experience, and is more easily aligned with Eastern understandings of consciousness as embodied. Finally, I suggest that the concept of body memory is useful for imbuing the body-subject with a cohesion and authenticity through the body's capacity for nonconscious remembrance of movement through a proprioceptively stored “body history,” which enables the constitution of a coherent body-self in older age.     

Effects of a Solution-Focused Program on the Reduction of Aggressiveness and the Improvement of Social Readjustment for Korean Youth Probationers

ABSTRACT

The purpose of this investigation was to explore appropriate intervention methods for helping Korean youth probationers reduce their aggressiveness and increase their social adjustment. This study examined the effectiveness of solution-focused group treatment with Korean youth probationers using a pre- and post-test control group design. The researcher randomly assigned the consented 40 participants either to an experimental group that received the solution-focused session or to a control group that took individual supportive sessions on a needed basis. The pre- and post-test scores of each group were compared using the Aggressiveness and Social Readjustment Questionnaire to confirm the levels of statistical significance between the two groups. Results indicate that solution-focused group treatment was followed by positive changes with the participants' aggressiveness and social adjustment problems. This study also suggests that a solution-focused program is an appropriate short-term intervention for Korean probation youth.     

From Emplaced Knowing to Interdisciplinary Knowledge

ABSTRACT

In this article, we discuss how experiential and unspoken ways of knowing produced through a video-based approach to sensory ethnography can be made meaningful and relevant to the applied practice of design and engineering scholars. We advance discussions of sensory ethnography by interrogating and making explicit the analytical processes that turn the sensory knowing of the ethnographic encounter into convincing accounts of everyday realities whilst engaging new sensitivities and ways of seeing that in themselves contribute to cross-disciplinary knowledge. We argue that through a more self-conscious appreciation of how and where experiential categories become applied knowledge the value of a sensory ethnography approach in design-centered energy research can be realized.     

Chastity value as a risk factor for prostituted adolescents in Indonesia: a qualitative exploration

ABSTRACT

Previous studies suggest that the practice of female child and adolescent prostitution can be attributed to various personal and social risk factors. However, cultural beliefs shared in specific societies may also determine prostitution involvement. We qualitatively explored the risk factors associated with prostitution in a rarely investigated Indonesian society. We interviewed eight female participants who were involved in adolescent prostitution. The findings suggest that prostitution involvement is not only attributed to the common personal and social risk factors, but also to cultural beliefs of chastity preservation. We argue that such beliefs may be rooted in gender inequality.