GLUMIP 2.0: SAS/IML Software for Planning Internal Pilots

Internal pilot designs involve conducting interim power analysis (without interim data analysis) to modify the final sample size. Recently developed techniques have been described to avoid the type~I error rate inflation inherent to unadjusted hypothesis tests, while still providing the advantages of an internal pilot design. We present GLUMIP 2.0, the latest version of our free SAS/IML software for planning internal pilot studies in the general linear univariate model (GLUM) framework. The new analytic forms incorporated into the updated software solve many problems inherent to current internal pilot techniques for linear models with Gaussian errors. Hence, the GLUMIP 2.0 software makes it easy to perform exact power analysis for internal pilots under the GLUM framework with independent Gaussian errors and fixed predictors.

An Internal Pilot Study with Interim Analysis for Gaussian Linear Models

Misspecification of a nuisance parameter can lead to study power far from the desired level. Internal pilots for Gaussian data protect study power by allowing sample size re-estimation based on an interim power analysis using a revised estimate of the variance parameter, but without any data analysis. In order to reduce study time and cost, researchers and sponsors of studies often desire early decision possibilities that the internal pilot design lacks but that group sequential methods allow. Combining early stopping rules with internal pilot methods would increase study flexibility, scope, and efficiency for general linear models. An internal pilot with an interim analysis (IPIA) design for Gaussian linear models is introduced and defined. The design allows for early stopping for efficacy and futility while also re-estimating sample size needs based on an interim variance estimate. In order for accurate study planning in small samples, exact theory is derived for both the one or two group [tau] test setting, as well as more complex multiple degree of freedom hypothesis tests within the general linear univariate model framework. Exact and computable forms of distributions allow accurate calculations of power, type I error rate, and expected sample size. In general, the IPIA design maintains and controls power to the desired level and also provides sample size savings. However, it can also inflate type I error rate, especially in smaller studies. By utilizing the exact theory, planning procedures associated with the design are examined and refined to create a working method for planning sound studies. A bounding method successfully controls the type I error rate while maintaining the benefits of the design. Explicit recommendations are detailed that achieve the combined goals of an internal pilot and a two-stage group sequential design. The results can be used during planning to create an efficient two-stage study with early stopping rules and predictable power properties, even in small samples

GLUMIP 2.0: SAS/IML Software for Planning Internal Pilots

Internal pilot designs involve conducting interim power analysis (without interim data analysis) to modify the final sample size. Recently developed techniques have been described to avoid the type~I error rate inflation inherent to unadjusted hypothesis tests, while still providing the advantages of an internal pilot design. We present GLUMIP 2.0, the latest version of our free SAS/IML software for planning internal pilot studies in the general linear univariate model (GLUM) framework. The new analytic forms incorporated into the updated software solve many problems inherent to current internal pilot techniques for linear models with Gaussian errors. Hence, the GLUMIP 2.0 software makes it easy to perform exact power analysis for internal pilots under the GLUM framework with independent Gaussian errors and fixed predictors

Point and interval estimation in two-stage adaptive designs with time to event data and biomarker-driven subpopulation selection

In personalized medicine, it is often desired to determine if all patients or only a subset of them benefit from a treatment. We consider estimation in two‐stage adaptive designs that in stage 1 recruit patients from the full population. In stage 2, patient recruitment is restricted to the part of the population, which, based on stage 1 data, benefits from the experimental treatment. Existing estimators, which adjust for using stage 1 data for selecting the part of the population from which stage 2 patients are recruited, as well as for the confirmatory analysis after stage 2, do not consider time to event patient outcomes. In this work, for time to event data, we have derived a new asymptotically unbiased estimator for the log hazard ratio and a new interval estimator with good coverage probabilities and probabilities that the upper bounds are below the true values. The estimators are appropriate for several selection rules that are based on a single or multiple biomarkers, which can be categorical or continuous

A randomized controlled trial to improve health among women receiving welfare in the U.S.: The relationship between employment outcomes and the economic recession

The high prevalence of health conditions among U.S. women receiving Temporary Assistance for Needy Families (TANF, or `welfare') impedes the ability of many in this group to move from `welfare-to-work', and the economic recession has likely exacerbated this problem. Despite this, few interventions have been developed to improve employment outcomes by addressing the health needs of women receiving TANF, and little is known about the impact of economic downturns on the employment trajectory of this group. Using data from a recent randomized controlled trial (RCT) that tested the efficacy of a public health nursing (PHN) intervention to address the chronic health condition needs of 432 American women receiving TANF, we examine the effect of the intervention and of recession exposure on employment. We further explore whether intervention effects were modified by select sociodemographic and health characteristics. Both marginal and more robust intervention effects were noted for employment-entry outcomes (any employment, p=0.05 and time-to-employment, p=0.01). There were significant effects for recession exposure on employment-entry (any employment, p=0.002 and time-to-employment, p<0.001). Neither the intervention nor recession exposure influenced longer-term employment outcomes (employment rate or maximum continuous employment). Intervention effects were not modified by age, education, prior TANF receipt, functional status, or recession exposure, suggesting the intervention was equally effective in improving employment-entry across a fairly heterogeneous group both before and after the recession onset. These findings advance our understanding of the health and employment dynamics among this group of disadvantaged women under variable macroeconomic conditions, and have implications for guiding health and TANF-related policy

Public Health Nursing Case Management for Women Receiving Temporary Assistance for Needy Families: A Randomized Controlled Trial Using Community-Based Participatory Research

Objectives. We evaluated the effectiveness of a community-based participatory research–grounded intervention among women receiving Temporary Assistance for Needy Families (TANF) with chronic health conditions in increasing (1) health care visits, (2) Medicaid knowledge and skills, and (3) health and functional status. Methods. We used a randomized controlled trial design to assign 432 women to a public health nurse case management plus Medicaid intervention or a wait control group. We assessed Medicaid outcomes pre- and posttraining; other outcomes were assessed at 3, 6, and 9 months. Results. Medicaid knowledge and skills improved (P<.001 for both). Intervention group participants were more likely to have a new mental health visit (odds ratio [OR]=1.92; P=.007), and this likelihood increased in higher-risk subgroups (OR=2.03 and 2.83; P=.04 and .006, respectively). Depression and functional status improved in the intervention group over time (P=.016 for both). No differences were found in routine or preventive care, or general health. Conclusions. Health outcomes among women receiving TANF can be improved with public health interventions. Additional strategies are needed to further reduce health disparities in this population

Practical Methods for Bounding Type I Error Rate with an Internal Pilot Design

New analytic forms for distributions at the heart of internal pilot theory solve many problems inherent to current techniques for linear models with Gaussian errors. Internal pilot designs use a fraction of the data to re-estimate the error variance and modify the final sample size. Too small or too large a sample size caused by an incorrect planning variance can be avoided. However, the usual hypothesis test may need adjustment to control the Type I error rate. A bounding test achieves control of Type I error rate while providing most of the advantages of the unadjusted test. Unfortunately, the presence of both a doubly truncated and an untruncated chi-square random variable complicates the theory and computations. An expression for the density of the sum of the two chi-squares gives a simple form for the test statistic density. Examples illustrate that the new results make the bounding test practical by providing very stable, convergent, and much more accurate computations. Furthermore, the new computational methods are effectively never slower and usually much faster. All results apply to any univariate linear model with fixed predictors and Gaussian errors, with the t-test a special case

Highlights of the Brazilian Thoracic Association guidelines for interstitial lung diseases

Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.As doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Curso de Pós-Graduação de Doenças Pulmonares IntersticiaisUniversidade Federal de Ciências da Saúde de Porto AlegreSanta Casa de Porto Alegre Ambulatório de Doenças IntersticiaisSES Hospital Regional da Asa Norte Serviço de Doenças TorácicasFundação Jorge Duprat Figueiredo de Segurança e Medicina do Trabalho Serviço de MedicinaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Clínica MédicaUniversidade Federal do Estado do Rio de JaneiroUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaHospital do Servidor Público Estadual de São Paulo Serviço de Anatomia PatológicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Divisão de PneumologiaUniversidade Federal de Santa Catarina Departamento de Clínica MédicaUniversidade Federal de Santa Catarina Hospital UniversitárioHospital de Messejana Ambulatório de Doenças IntersticiaisHospital do Servidor Público Estadual de São Paulo Ambulatório de Doenças IntersticiaisUniversidade de São Paulo Faculdade de Medicina Instituto do CoraçãoUniversidade Federal FluminenseUniversidade de São Paulo Faculdade de MedicinaHospital Sírio Libanês Núcleo Avançado de TóraxUniversidade Federal da BahiaHospital do Servidor Público Estadual de São PauloHospital do Câncer Antônio Cândido CamargoUNIFESP, EPM, Curso de Pós-Graduação de Doenças Pulmonares IntersticiaisUNIFESP, EPM, Depto. de PatologiaUNIFESP, EPMSciEL

In-Home Training for Fathers of Children with Autism: A Follow up Study and Evaluation of Four Individual Training Components

Literature regarding fathers of children with autism remains sparse, and because mothers are the more common intervening parent, few training methods have focused on fathers. Thus, we sought to evaluate effects of in-home training directed at fathers and their ability to train mothers in the same manner in which they were trained. Fathers were taught four skills commonly associated with in-home training interventions for parents of children with autism: following the child’s lead, imitation with animation, commenting on the child, and expectant waiting. Father skills were evaluated twice a week for 12 weeks during videotaped in-home father–child play sessions. Analyses included visual inspection of graphed data and statistical analyses of father skill acquisition, mother skill acquisition, and child behaviors with both parents. A multivariate repeated measures analysis of 18 dyads revealed significant increases in frequencies of fathers’ imitation with animation, expectant waiting, and commenting on the child. Child initiating rates increased significantly as did frequencies of child non-speech vocalizations. Analysis of mothers revealed significant increases in frequencies of imitation with animation, expectant waiting, and following the child’s lead. Child behaviors had similar results for father and mother sessions. Findings are consistent with those from our first study indicating that fathers can effectively implement skills that promote father–child social interactions and that children respond positively to this approach

Highlights of the Brazilian Thoracic Association guidelines for interstitial lung diseases

Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.As doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.28229