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.

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

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

Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia: Children’s Oncology Group trial AALL15P1

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children’s Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358

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

Bolus Volume And Viscosity Effects On Pharyngeal Swallowing Power—How Physiological Bolus Accommodation Affects Bolus Dynamics

Background: Pharyngeal swallowing power (PSP) is a novel measure of pharyngeal bolus-driving function derived from fluid dynamics principles. This study examined the impact of bolus volume and viscosity on PSP to determine bolus effects on pharyngeal bolus dynamics. The impact of bolus accommodation and physical characteristics of boluses were also explored. Methods: Thirty-four healthy subjects swallowed materials consisting of two bolus volumes (10 and 20 mL) and four bolus viscosities (thin liquid, nectar-thick liquid, honey-thick liquid and pudding). High-resolution impedance manometry was used for data collection. The pharyngeal swallowing mechanism was conceptualized as a hydraulic power system with the UES as a conduit, and PSP was calculated as the product of bolus pressure and flow across the UES. The impact of bolus characteristics on PSP was evaluated using a mixed model approach. Key Results: Both bolus volume (F1,32.8 = 412.73, P \u3c 0.0001) and viscosity (F3,84.7 = 28.94, P \u3c 0.0001) were significant predictors of PSP. PSP for 20 mL bolus volume was greater than for 10 mL bolus volume. PSP was lowest in the thin liquid bolus condition and highest in the pudding bolus. All pairwise comparisons among bolus viscosities were significant except between thin liquid and nectar-thick liquid bolus viscosities. Test of linear trend across bolus viscosities was significant (F1,97.2 = 77.25, P \u3c 0.0001). Conclusions & Inferences: Pharyngeal swallowing power variation across bolus conditions illustrates bolus-related changes in bolus dynamics. Bolus effects on PSP likely result from physiological bolus accommodation combined with physical characteristics of boluses