Estimates of subgroup treatment effects in overall nonsignificant trials: To what extent should we believe in them?

In drug development, it sometimes occurs that a new drug does not demonstrate effectiveness for the full study population but appears to be beneficial in a relevant subgroup. In case the subgroup of interest was not part of a confirmatory testing strategy, the inflation of the overall type I error is substantial and therefore such a subgroup analysis finding can only be seen as exploratory at best. To support such exploratory findings, an appropriate replication of the subgroup finding should be undertaken in a new trial. We should, however, be reasonably confident in the observed treatment effect size to be able to use this estimate in a replication trial in the subpopulation of interest. We were therefore interested in evaluating the bias of the estimate of the subgroup treatment effect, after selection based on significance for the subgroup in an overall “failed” trial. Different scenarios, involving continuous as well as dichotomous outcomes, were investigated via simulation studies. It is shown that the bias associated with subgroup findings in overall nonsignificant clinical trials is on average large and varies substantially across plausible scenarios. This renders the subgroup treatment estimate from the original trial of limited value to design the replication trial. An empirical Bayesian shrinkage method is suggested to minimize this overestimation. The proposed estimator appears to offer either a good or a conservative correction to the observed subgroup treatment effect hence provides a more reliable subgroup treatment effect estimate for adequate planning of future studies.     

Cognitive-Behavioral Therapy for Bipolar Disorder: Implications for Clinical Social Workers

ABSTRACT

The purposes of this review article are to orient clinical social workers to cognitive-behavioral theory, intervention, and research on bipolar disorder (BD); identify pros and cons of applying cognitive-behavioral therapy (CBT) to social work clients with BD; and identify specific implications for clinical social work practice. Of the 545 articles that were obtained via the systematic review, 18 studies were identified as being potentially eligible for inclusion, and 9 of those studies ultimately satisfied the inclusion criteria. The results of each study were summarized via identifying statistically significant (p< .05) differences that existed between experimental cohorts who received CBT (plus pharmacotherapy) and control cohorts who received treatment as usual. Outcomes showed CBT cohorts as having significant improvement over their respective control groups. The review's implications for clinical social workers and the need for future research are discussed.     

Randomization tests in recursive response-adaptive randomization procedures

In a randomized clinical trial, response-adaptive randomization procedures use the information gathered, including the previous patients' responses, to allocate the next patient. In this setting, we consider randomization-based inference. We provide an algorithm to obtain exact p-values for statistical tests that compare two treatments with dichotomous responses. This algorithm can be applied to a family of response adaptive randomization procedures which share the following property: the distribution of the allocation rule depends only on the imbalance between treatments and on the imbalance between successes for treatments 1 and 2 in the previous step. This family includes some outstanding response adaptive randomization procedures. We study a randomization test to contrast the null hypothesis of equivalence of treatments and we show that this test has a similar performance to that of its parametric counterpart. Besides, we study the effect of a covariate in the inferential process. First, we obtain a parametric test, constructed assuming a logit model which relates responses to treatments and covariate levels, and we give conditions that guarantee its asymptotic normality. Finally, we show that the randomization test, which is free of model specification, performs as well as the parametric test that takes the covariate into account.     

Back to basics: explaining sample size in outcome trials,are statisticians doing a thorough job?

Time to event outcome trials in clinical research are typically large, expensive and high‐profile affairs. Such trials are commonplace in oncology and cardiovascular therapeutic areas but are also seen in other areas such as respiratory in indications like chronic obstructive pulmonary disease. Their progress is closely monitored and results are often eagerly awaited. Once available, the top line result is often big news, at least within the therapeutic area in which it was conducted, and the data are subsequently fully scrutinized in a series of high‐profile publications. In such circumstances, the statistician has a vital role to play in the design, conduct, analysis and reporting of the trial. In particular, in drug development it is incumbent on the statistician to ensure at the outset that the sizing of the trial is fully appreciated by their medical, and other non‐statistical, drug development team colleagues and that the risk of delivering a statistically significant but clinically unpersuasive result is minimized. The statistician also has a key role in advising the team when, early in the life of an outcomes trial, a lower than anticipated event rate appears to be emerging. This paper highlights some of the important features relating to outcome trial sample sizing and makes a number of simple recommendations aimed at ensuring a better, common understanding of the interplay between sample size and power and the final result required to provide a statistically positive and clinically persuasive outcome. Copyright © 2009 John Wiley & Sons, Ltd.     

The Effects of a Computer Network on Pediatric Pain and Anxiety

SUMMARY

The objective of this study was to test the impact of an enhanced version of STARBRIGHT World (SBW2)-a private computer network for hospitalized children. The impact of SBW2 was assessed with a series of 44 replicated single system designs. Utilizing an ecological momentary assessment approach, self-reports were obtained regarding children's perceptions of their pain intensity, pain aversive-ness and anxiety. The results from the single system designs were aggregated using meta-analysis. Children experienced significantly less pain intensity, pain aversiveness, and anxiety in the SBW2 condition. These findings provide evidence regarding the effectiveness of SBW2 and demonstrate the utility of employing meta-analysis with single system designs.     

Colorful Disclosures: Identifying Identity-Based Differences and Enhancing Critical Consciousness in Supervision

ABSTRACT

Managing microaggressions and marginalizing experiences while negotiating the ongoing oppression that occurs in micro, mezzo, and macro settings can be particularly challenging for clinicians of color. Thus, supervision with clinicians of color must include affirmation, empowerment, and exploration of the intracultural/intercultural dynamics inherent in the treatment-providing process and clinical supervision. Through case studies, autoethnographic studies of our supervision experiences, and interviews with supervisors and supervisees, we reflect on how axes of identity, including race, power, and privilege, inform practitioners’ clinical lenses and affect their vulnerability in treatment and the clinical supervision dyad. Special attention is placed on the clinical supervisor–clinician–client triad (the triple process) and the interpersonal dynamics of cultural sensitivity, cultural humility, and authentic responsiveness that supervisors aim to model and cultivate in the supervisory relationship. In addition to sustaining clinical growth for clinicians of color, adding this level of complexity to supervision supports equity in direct clinical practice, enhancing efficacy outcomes for clients and communities. Recommendations and pedagogical strategies are offered to support supervisors in initiating difficult dialogues and shifting the paradigm to promote this transformational perspective.     

Unifying CRM and EWOC designs for phase I cancer clinical trials

The main goal of phase I cancer clinical trials is to determine the highest dose of a new therapy associated with an acceptable level of toxicity for the use in a subsequent phase II trial. The continual reassessment method (CRM) [O’Quigley, J., Pepe, M., Fisher, L., 1990. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 46, 33–48] and escalation with overdose control (EWOC) [Babb, J., Rogatko, A., Zacks, S., 1998. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statist. Med. 17 (10), 1103–1120] are two model-based designs used for phase I cancer clinical trials. A few modifications of the (original) CRM and EWOC have been made by many authors. In this paper, we show how CRM and EWOC can be unified and present a hybrid design. We study the characteristics of the approach of the hybrid design. The comparisons of the three designs (CRM, EWOC, and the hybrid design) are presented by convergence rates and overdose proportions. The simulation results show that the hybrid design generally has faster convergence rates than EWOC and smaller overdose proportions than CRM, especially when the true maximum tolerated dose (MTD) is above the mid-level of the dose range considered. The performance of these three designs is also evaluated in terms of sensitivity to outliers.     

Counselor Trainees' Assessment and Diagnosis of Lesbian Clients with Dysthymic Disorder

SUMMARY

Graduate-level counselor trainees completed an Assessment and Diagnostic Inventory consisting of clinical vignettes and a series of questions pertaining to conceptualization of client problem, diagnosis, and assessment of overall level of psychopathology.We hypothesized that participants would assign different diagnoses to clients with lesbian versus heterosexual sexual orientation. Participants responded to vignettes in which clients were identified as either a lesbian or a heterosexual female, with all other content identical. Participants were significantly more likely to perceive lesbian clients' problems to be related to sexual orientation for the vignette corresponding to dysthymic disorder. However, they were not more likely to assign personality disorder diagnoses, nor did they attribute a greater degree of psychopathology to lesbian clients with dysthymic disorder.     

When the Learning Disabled Go to College

Abstract

During the last decade, federal laws have provided for remedial education in elementary and secondary schools for students with learning disabilities, preparing large numbers of them for college. Federal law also mandates helping learning-disabled students with their needs once they matriculate. Declining numbers of high school graduates in the aftermath of the baby boom have made more colleges open their doors to these students. The disabilities, and the accommodations they require, arrive in college with the rest of a student's baggage, demanding attention. Colleges and universities have chosen a variety of approaches, from specific remedial programs and individual accomodations according to need to more general programs. Some colleges pretend these disabilities do not exist and seem oblivious to their presence on campus. Learning disabilities can have an impact in every class and lecture hall and can contribute to unhappiness and the college's attrition rate. On the other hand, responsive and responsible programs provide students with the resources for the same education, honors, and opportunities as their nondisabled peers.