Sequential Allocation and Balancing Prognostic Factors in a Psychiatric Clinical Trial

In controlled clinical trials, each of several prognostic factors should be balanced across the trial arms. Traditional restricted randomization may be proved inadequate especially with small sample sizes. In psychiatric disorders such as obsessive compulsive disorder (OCD), small trials prevail. Therefore, procedures to minimize the chance of imbalance between treatment arms are advisable. This paper describes a minimization procedure specifically designed for a clinical trial that evaluates treatment efficacy for OCD patients. Aitchison's compositional distance was used to calculate vectors for each possibility of allocation in a covariate adaptive method. Two different procedures were designed to allocate patients in small blocks or sequentially one-by-one. Partial results of this allocation procedure as well as simulated ones are shown. In the clinical trial for which this procedure was developed, the balancing between treatment arms was achieved successfully. Simulations of results considering different arrival order of patients showed that most of the patients are allocated in a different treatment arm if arrival order is modified. Results show that a random factor is maintained with the random arrival order of patients. This specific procedure allows the use of a large number of prognostic factors for the allocation decision and was proved adequate for a psychiatric trial design

Testing allele homogeneity: the problem of nested hypotheses

Background: The evaluation of associations between genotypes and diseases in a case-control framework plays an important role in genetic epidemiology. This paper focuses on the evaluation of the homogeneity of both genotypic and allelic frequencies. The traditional test that is used to check allelic homogeneity is known to be valid only under Hardy-Weinberg equilibrium, a property that may not hold in practice. Results: We first describe the flaws of the traditional (chi-squared) tests for both allelic and genotypic homogeneity. Besides the known problem of the allelic procedure, we show that whenever these tests are used, an incoherence may arise: sometimes the genotypic homogeneity hypothesis is not rejected, but the allelic hypothesis is. As we argue, this is logically impossible. Some methods that were recently proposed implicitly rely on the idea that this does not happen. In an attempt to correct this incoherence, we describe an alternative frequentist approach that is appropriate even when Hardy-Weinberg equilibrium does not hold. It is then shown that the problem remains and is intrinsic of frequentist procedures. Finally, we introduce the Full Bayesian Significance Test to test both hypotheses and prove that the incoherence cannot happen with these new tests. To illustrate this, all five tests are applied to real and simulated datasets. Using the celebrated power analysis, we show that the Bayesian method is comparable to the frequentist one and has the advantage of being coherent. Conclusions: Contrary to more traditional approaches, the Full Bayesian Significance Test for association studies provides a simple, coherent and powerful tool for detecting associations

Sequential Allocation to Balance Prognostic Factors in a Psychiatric Clinical Trial

OBJECTIVE: This paper aims to describe and discuss a minimization procedure specifically designed for a clinical trial that evaluates treatment efficacy for OCD patients. METHOD: Aitchison's compositional distance was used to calculate vectors for each possibility of allocation in a covariate adaptive method. Two different procedures were designed to allocate patients in small blocks or sequentially one-by-one. RESULTS: We present partial results of this allocation procedure as well as simulated data. In the clinical trial for which this procedure was developed, successful balancing between treatment arms was achieved. Separately, in an exploratory analysis, we found that if the arrival order of patients was altered, most patients were allocated to a different treatment arm than their original assignment. CONCLUSION: Our results show that the random arrival order of patients determine different assignments and therefore maintains the unpredictability of the allocation method. We conclude that our proposed procedure allows for the use of a large number of prognostic factors in a given allocation decision. Our method seems adequate for the design of the psychiatric trials used as models. Trial registrations are available at clinicaltrials.gov NCT00466609 and NCT00680602

La calidad de vida de las madres de niños trabajadores en las calles de São Paulo, Brasil

The present study evaluated the perceived quality of life of the mothers of street children and investigated the association with their history of childhood violence, the occurrence of current domestic violence, their current mental states and that of their children, and family functioning. the applied instruments were as follows: Strengths and Difficulties Questionnaire, WorldSAFECore Questionnaire, Instrument for the Assessment of Quality of Life of the WHO, Global Assessment of Relational Functioning Scale, Childhood Trauma Questionnaire and a socio-demographic questionnaire. the sample of convenience consisted of 79 low-income mothers who raised their children alone, and most of whom had a positive screening for mental illness. the multiple regression analysis showed that the perception of quality of life of these women was associated with the presence of psychopathology either in themselves or their children and family dysfunction. Thus any program aimed at improving the quality of life of such mothers should consider addressing their mental problems as well as those of their children, besides offering educational and psychotherapeutic approaches to these families to improve the social environment.Universidade Federal de São Paulo, Dept Psiquiatria, BR-04038020 São Paulo, SP, BrazilUniv São Paulo, Inst Matemat & Estat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psiquiatria, BR-04038020 São Paulo, SP, BrazilWeb of Scienc

Risk factors for early treatment discontinuation in patients with obsessive-compulsive disorder

INTRODUCTION: In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments. OBJECTIVE: This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients. METHODS: A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs) or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs) were compared with a paired sample of compliant patients (n = 41). Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chisquare and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable. RESULTS: Agoraphobia was only present in one (2.4%) patient who completed the twelve-week therapy, whereas it was present in six (15.0%) patients who dropped out (p = 0.044). Social phobia was present in eight (19.5%) patients who completed the twelve-week therapy and eighteen (45%) patients who dropped out (p = 0.014). Generalized anxiety disorder was present in eight (19.5%) patients who completed the twelve-week therapy and twenty (50%) dropouts (p = 0.004), and somatization disorder was not present in any of the patients who completed the twelveweek therapy; however, it was present in six (15%) dropouts (p = 0.010). According to the logistic regression model, treatment modality (p = 0.05), agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03) and the Beck Anxiety Inventory (p = 0.02) scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables. DISCUSSION AND CONCLUSION: Early treatment discontinuation is a common phenomenon in obsessive-compulsive disorder patients from our therapeutic setting. Psychiatric comorbidities were associated with discontinuation rates of specific treatments. Future studies might use this information to improve management for increased compliance and treatment effectiveness.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Impact of Healthy Parenting As a Protective Factor for Posttraumatic Stress Disorder in Adulthood: A Case-Control Study

Background: Early life social adversity can influence stress response mechanisms and is associated with anxious behaviour and reductions in callosal area later in life.Objective: To evaluate the association between perceptions of parental bonding in childhood/adolescence, hypothalamic-pituitary-adrenal (HPA) axis response, and callosal structural integrity in adult victims of severe urban violence with and without PTSD.Methods: Seventy-one individuals with PTSD and 62 without the disorder were assessed with the Parental Bonding Instrument (PBI). the prednisolone suppression test was administered to assess cortisol levels, and magnetic resonance imaging was used to assess the total area of the corpus callosum (CC), as well as the areas of callosal subregions.Results: the PBI items related to the perception of 'not having a controlling mother' (OR 4.84; 95% CI [2.26-10.3]; p = 0.01), 'having a caring father' (OR 2.46; 95'% CI [1.18-5.12]; p = 0.02), and 'not having controlling parents' (OR 2.70; 95% CI [1.10-6.63]; p = 0.04) were associated with a lower risk of PTSD. the PTSD group showed a blunted response to the prednisolone suppression test, with lower salivary cortisol levels upon waking up (p = 0.03). Individuals with PTSD had smaller total CC area than those without the disorder, but these differences were not statistically significant (e-value = 0.34).Conclusions: Healthy parental bonding, characterized by the perception of low parental control and high affection, were associated with a lower risk of PTSD in adulthood, suggesting that emotional enrichment and the encouragement of autonomy are protective against PTSD in adulthood.National Research Council (CNP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ São Paulo UNIFESP, São Paulo Sch Med, Dept Psychiat, São Paulo, BrazilUniv São Paulo, Dept Math & Stat, BR-09500900 São Paulo, BrazilFed Univ São Paulo UNIFESP, Interdisciplinary Lab Clin Neurosci LiNC, São Paulo, BrazilFed Univ São Paulo UNIFESP, São Paulo Sch Med, Dept Psychiat, São Paulo, BrazilFed Univ São Paulo UNIFESP, Interdisciplinary Lab Clin Neurosci LiNC, São Paulo, BrazilNational Research Council (CNP): 420122/2005-2FAPESP: 2004/15039-0Web of Scienc