Bayesian sample size for exploratory clinical trials incorporating historical data

This paper presents a simple Bayesian approach to sample size determination in clinical trials. It is required that the trial should be large enough to ensure that the data collected will provide convincing evidence either that an experimental treatment is better than a control or that it fails to improve upon control by some clinically relevant difference. The method resembles standard frequentist formulations of the problem, and indeed in certain circumstances involving 'non-informative' prior information it leads to identical answers. In particular, unlike many Bayesian approaches to sample size determination, use is made of an alternative hypothesis that an experimental treatment is better than a control treatment by some specified magnitude. The approach is introduced in the context of testing whether a single stream of binary observations are consistent with a given success rate p(0). Next the case of comparing two independent streams of normally distributed responses is considered, first under the assumption that their common variance is known and then for unknown variance. Finally, the more general situation in which a large sample is to be collected and analysed according to the asymptotic properties of the score statistic is explored. Copyright (C) 2007 John Wiley & Sons, Ltd.

A combined score test for binary and ordinal endpoints from clinical trials

There is growing interest, especially for trials in stroke, in combining multiple endpoints in a single clinical evaluation of an experimental treatment. The endpoints might be repeated evaluations of the same characteristic or alternative measures of progress on different scales. Often they will be binary or ordinal, and those are the cases studied here. In this paper we take a direct approach to combining the univariate score statistics for comparing treatments with respect to each endpoint. The correlations between the score statistics are derived and used to allow a valid combined score test to be applied. A sample size formula is deduced and application in sequential designs is discussed. The method is compared with an alternative approach based on generalized estimating equations in an illustrative analysis and replicated simulations, and the advantages and disadvantages of the two approaches are discussed.

Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations

A comparison of methods for constructing confidence intervals after phase II/III clinical trials

Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.

Efeitos individuais e interativos da diversidade de detritos, contexto e variabilidade ambiental sobre a magnitude e estabilidade do processo de decomposição

Studies on the effects of changes in biodiversity and ecosystem functioning have been a central theme in ecology over the past two decades. Several studies have showed that the diversity of plant debris differently affects the decomposition process in aquatic and terrestrial environments, but we know very about the effects of detritus diversity on decomposition under fluctuating environmental conditions. We tested whether and how the environmental contexts, as well as the dynamic of their alternation, influence the effects of detritus diversity on the decomposition process. We performed a field experiment where we manipulate the litter diversity of 8 species of terrestrial plants decomposing (litterbags) in single and in mixture containing the eight species together in three different environmental contexts: the terrestrial environment (T), aquatic (A) and interface (I) - experimental treatment that simulates variation in flooding regime. We measured the rate of decomposition through the loss of mass of the community and each individual detritus in monocultures and mixtures. Species richness and environmental variability had no effects on the magnitude and stability of the decomposition process. However, there were significant diversity effects on the decomposition of an individual alien species, F. benjamina. Environmental context had significant effects on the magnitude and variability of decomposition. Detritus decomposition was faster and more variable on aquatic, interface and terrestrial conditions, respectively. Our results demonstrate that the diversity of plant detritus has minor effects to the decomposition across disparate environmental conditions and suggest that it is necessary to consider the potential of other abiotic factors in affect the magnitude and variability of the decomposition processes

Depósitos unitários de calda de pulverização com e sem surfatante em plantas de Salvinia molesta

Uma das opções para o manejo de Salvina molesta é o controle químico; contudo, a presença de grande quantidade de pêlos na epiderme foliar reduz a molhabilidade das folhas, o que pode afetar a eficiência dos herbicidas. O objetivo deste trabalho foi o de avaliar a deposição do corante azul FDC-1, no qual se simulou a aplicação de herbicidas em plantas dessa espécie, com e sem a mistura de um surfatante. Os tratamentos foram as concentrações de 0 e 5% do surfatante Aterbane (espalhante adesionante), utilizado na elaboração da calda de pulverização. O delineamento experimental foi o inteiramente casualizado, com 150 repetições. A aplicação foi realizada com um pulverizador estacionário à pressão de 2,0 bar, com consumo de calda de 180 L ha-1. Foram utilizados bicos de jato plano, tipo XR 110.02. Foram ajustadas curvas de regressão entre os depósitos individuais em cada planta (mL calda/planta) e as freqüências acumuladas. Utilizou-se o modelo de Gompertz, e os valores de R² foram de 0,99 e 0,97 com e sem o espalhante, respectivamente. em termos médios, a adição de Aterbane reduziu em 1,13% os depósitos do FDC-1. No entanto, o espalhante melhorou em 76, 41 e 29% a deposição em 1, 5 e 10% da população com menores depósitos do corante.

Effects of the opiold remifentanil on the arrhythmogenicity of epinephrine in halothane-anesthetized dogs

Opioids may exert a protective effect against ventricular arrhythmias via a vagally mediated mechanism. This study evaluated the effects of the opioid remifentanil on arrhythmogenicity of epinephrine during halothane anesthesia. Eight dogs were assigned to 2 treatments in a randomized crossover design, with 1-week intervals between treatments. Anesthesia was maintained with 1.3% end-tidal halothane in oxygen and mechanical ventilation to maintain eucapnia. A constant rate infusion of remifentanil (0.72 mu g/kg/min) was administered throughout the study in the experimental treatment, while control animals received physiologic saline as placebo. The arrhythmogenic dose of epinephrine (ADE), defined as 4 premature ventricular complexes (PVCs) within 15 s, was determined by administering progressively increasing infusion rates of epinephrine (2.5, 5.0, and 10 mu g/kg/min), allowing 20 min intervals between each infusion rate. In both treatments, epinephrine infusions induced bradyarrhythmias and atrioventricular conduction disturbances, which were followed by escape beats and PVCs. In the remifentanil treatment, mean s ADE values (11.3 +/- 4.9 mu g/kg) did not differ from values observed in control animals (9.9 +/- 6.1 mu g/kg). on the basis of the ADE model for assessing the arrhythmogenity of drugs during halothane anesthesia, the present study did not demonstrate a protective effect of remifentanil (0.72 mu g/kg/min) against ventricular arrhythmias in dogs.

Physiological parameters in sugarcane cultivars submitted to water deficit

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clinical assessment of the efficacy of low-level laser therapy on muscle pain in women with temporomandibular dysfunction, by surface electromyography

The use of low-level laser (LLL) may be an useful tool to promote reduction of muscular pain caused by TMD. Aim: This study evaluated the immediate efficacy of low-level laser therapy on women reporting pain and diagnosed with temporomandibular dysfunction (TMD). Methods: Diode laser (GaAlAs) at 790 nm wavelength (infrared spectrum) was applied as experimental treatment. Irradiations of 1.5 J/cm2 were made at 4 points of the temporomandibular joint (TMJ) and of 3 J/cm2 at 3 points in the temporal muscle. An electromyographic (EMG) evaluation of the masseter and anterior temporal was done at the following intervals: before, immediately after, 5 min and 20 min after laser application. Results: Comparison of the electrical activity at the times of measurement revealed a statistically significant difference in masseter muscles before (P=0.025) and immediately after (P=0.013) LLLT. Conclusions: Both masseter and temporal muscles showed a reduction in the measured EMG activities at all times after LLLT, and the temporal muscle showed higher EMG activity than the masseter muscle at all the evaluation times. LLLT caused significant immediate relaxation of the masseter muscles.

Controle químico e deposição da calda de pulverização em dois estágios de desenvolvimento de plantas de Typha subulata Crespo & Peres-Moreau f

Pós-graduação em Agronomia (Agricultura) - FCA

Observação clínica da aplicação de um produto a base de peróxido de hidrogênio a 35% não fotoativado: efeitos na sensibilidade e na alteração de cor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação de parâmetros fisiológicos em cultivares de cana-de-açúcar submetidas ao déficit hídrico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Suplementação mineral protéica com cromo orgânico sobre o desempenho produtivo e qualidade da carne de bovinos Nelore e F1 Brangus X Nelore terminados em pastagem no Centro-Oeste do Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ação do laser em baixa intensidade no tratamento da doença periodontal induzida em ratos diabéticos e não diabéticos: estudo histológico e histométrico. -

Pós-graduação em Odontologia - FOA

Produção in vitro de metano, dióxido de carbono e oxigênio utilizando líquido ruminal de bovinos alimentados com diferentes rações

Pós-graduação em Zootecnia - FCAV