Cluster randomized trials with treatment noncompliance

Cluster randomized trials (CRTs) have been widely used in field experiments treating a cluster of individuals as the unit of randomization. This study focused particularly on situations where CRTs are accompanied by a common complication, namely, treatment noncompliance or, more generally, intervention nonadherence. In CRTs, compliance may be related not only to individual characteristics but also to the environment of clusters individuals belong to. Therefore, analyses ignoring the connection between compliance and clustering may not provide valid results. Although randomized field experiments often suffer from both noncompliance and clustering of the data, these features have been studied as separate rather than concurrent problems. On the basis of Monte Carlo simulations, this study demonstrated how clustering and noncompliance may affect statistical inferences and how these two complications can be accounted for simultaneously. In particular, the effect of the intervention on individuals who not only were assigned to active intervention but also abided by this intervention assignment (complier average causal effect) was the focus. For estimation of intervention effects considering noncompliance and data clustering, an ML-EM estimation method was employed.     

The legal consensus about foregoing life-sustaining treatment: its status and its prospects

The legal consensus that has evolved through adjudication and legislation since the Karen Quinlan case in 1976 is founded on the premise that there is a bright line between passive euthanasia and active euthanasia. Indeed, the term passive euthanasia is often eschewed in favor of less emotionally-laden terminology such as "forgoing life-sustaining treatment" or "terminating life support" so as to further sever any possible connection with active euthanasia. Legal approval has been bestowed upon passive euthanasia under certain circumstances while active euthanasia is routinely condemned. This consensus was put to a test in 1990 when the United States Supreme Court ruled on the Cruzan case. However, the Court's narrow decision did not upset the consensus, and in the most significant appellate decisions handed down by state courts since Cruzan, there has been a reaffirmation--and possibly even an extension--of the consensus. Two other threats to the legal consensus about forgoing life-sustaining treatment have begun to manifest themselves: the increasing pressure for mercy killing and "futility" cases. Both of these challenge the fundamental premises on which the consensus is grounded.     

Being a therapist in eating disorder treatment trials: constraints and creativity

This paper gives a brief overview of the sequence and content of the eating disorder treatment trials at the Maudsley Hospital in London, and describes the experience of the author working as a research therapist on these trials. It considers the different ways research constraints affected the therapist, how she learnt to make creative use of what appeared to be therapeutic restrictions, and how having her clinical freedom curtailed taught her to be more flexible and showed her new ways of understanding her patients.     

Review of controlled psychotherapy treatment trials for binge eating disorder

This paper reviews investigations of psychotherapy outcome studies for binge eating disorder, which has recently been intensively studied as several researchers have undertaken the task of delineating which treatment options are the most effective. Several randomized, controlled clinical trials have provided important findings. A current debate concerns what the initial course of treatment should be, reducing binge eating patterns or reducing weight. Several limitations to this literature are mentioned, including the dearth of studies investigating treatment for men and boys with binge eating disorder.     

Autism clinical trials: biological and medical issues in patient selection and treatment response

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.     

Clinical trials for rapid changes in suicidal ideation: Lessons from ketamine

Rapid‐acting treatments for suicidal thoughts are critically needed. Consequently, there is a burgeoning literature exploring psychotherapeutic, pharmacologic, or device‐based brief interventions for suicidal thoughts characterized by a rapid onset of action. Not only do these innovative treatments have potentially important clinical benefits to patient populations, they also highlight a number of methodological considerations for suicide research. First, while most clinical trials related to suicide risk focus on suicide attempts, new clinical trials that use suicidal thoughts as the primary outcome require a number of slight modifications to their clinical trial design. Second, the rapid onset of these new interventions permits an experimental therapeutics approach to suicide research, in which psychological and neurobiological markers are embedded into clinical trials to better understand the underlying pathophysiology of suicidal thoughts. The following review discusses these methodological innovations in light of recent research using the N‐methyl‐D‐aspartate (NMDA) receptor antagonist ketamine, which has been associated with rapid effects on suicidal thoughts. We hope that “lessons learned” from the ketamine literature will provide a blueprint for all researchers evaluating rapid‐acting treatments for suicidal thoughts, whether pharmacologic or psychotherapeutic.     

Family-based treatment for adolescent substance abuse: controlled trials and new horizons in services research

This article provides an overview of controlled trials research on treatment processes and outcomes in family-based approaches for adolescent substance abuse. Outcome research on engagement and retention in therapy, clinical impacts in multiple domains of adolescent and family functioning, and durability and moderators of treatment effects is reviewed. Treatment process research on therapeutic alliance, treatment fidelity and core family therapy techniques, and change in family processes is described. Several important research issues are presented for the next generation of family-based treatment studies focusing on delivery of evidence-based treatments in routine practice settings.     

Global ethics: dimensions and prospects

Global ethics is an emerging discipline which has not yet reached maturity. The main tasks before it to gain maturity are: first, to achieve a greater integration of various domains of enquiry all of which are concerned with global normative issues. At a general level this includes integrating global ethics with cosmopolitanism, global justice and human right discourse. At the level of areas of concern, there needs to be greater integration of various areas such as development, trade, environment and climate change. And it must grapple with the question of diversity within universality: how far can diversity of practices be accommodated within a culturally sensitive universal framework? Second, there is the question of finding a shared normative framework with respect to the diverse worldviews that may lie behind this: what degree and kind of convergence/consensus are worth working for? Third, there is the task of creating the conditions for its own wider acceptance, which should include taking the idea of global citizenship seriously.     

Moral antitheodicy: prospects and problems

Proponents of the view which I call ‘moral antitheodicy’ call for the theistic discourse of theodicy to be abandoned, because, they claim, all theodicies involve some form of moral impropriety. Three arguments in support of this view are examined: the argument from insensitivity, the argument from detachment, and the argument from harmful consequences. After discussing the merits of each argument individually, I attempt to show that they all must presuppose what they are intended to establish, namely, that the set of premises advanced in any given theodicy will be untenable. I conclude by discussing what uses there might be for the moral critique of theodicy, if it cannot be used to ground a global rejection of theodical practice.     

Parity,prospects, and predominance

Philosophical Studies - Let’s say that you regard two things as on a par when you don’t prefer one to other and aren’t indifferent between them. What does rationality require of...     

Design of randomized controlled trials: Principles and methods applied to a treatment for early stuttering

The “gold standard” methodology for treatment efficacy research is the randomized controlled trial (RCT), which is used extensively in medical research and in other areas such as psychology. Results from a well designed and conducted RCT, which show a new treatment to be clinically and statistically superior to current standard practice, can lead to a change in clinical practice. This paper presents a tutorial on RCTs, presenting and discussing the following principles and methods: the trial protocol, choice of control treatment, eligibility criteria, random allocation, outcomes and hypotheses, sample size, subject recruitment, analysis by intention to treat, interim analysis, stopping rules, safety data monitoring/trial management, and study documentation. RCTs are a complicated and logistically involved methodology. Hence, prior to the commitment of resources to such a trial in the development of a new treatment, the safety and clinical promise of the new treatment needs to be demonstrated with preliminary studies. Such preliminary studies have been completed for the Lidcombe Program (LP) of early stuttering intervention, and an RCT of that treatment is being conducted at the time of writing. The principles and methods of RCTs are illustrated with reference to that study.

Educational objectives: The reader will understand the design principles and methods of RCTs. The reader will understand the logistics of conducting a RCT of a treatment for early stuttering.