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J C Pinheiro

Publications and source records attributed to J C Pinheiro.

6 recordsLinked to original sources
PubMed2005

Combining multiple comparisons and modeling techniques in dose-response studies.

The analysis of data from dose-response studies has long been divided according to two major strategies: multiple comparison procedures and model-based approaches. Model-based approaches assume a functional relationship between the response and the dose, taken as a quantitative factor, according to a prespecified parametric model. The fitted model is then used to estimate an adequate dose to achieve a desired response but the validity of its conclusions will highly depend on the correct choice of the a priori unknown dose-response model. Multiple comparison procedures regard the dose as a qualitative factor and make very few, if any, assumptions about the underlying dose-response model. The primary goal is often to identify the minimum effective dose that is statistically significant and produces a relevant biological effect. One approach is to evaluate the significance of contrasts between different dose levels, while preserving the family-wise error rate. Such procedures are relatively robust but inference is confined to the selection of the target dose among the dose levels under investigation. We describe a unified strategy to the analysis of data from dose-response studies which combines multiple comparison and modeling techniques. We assume the existence of several candidate parametric models and use multiple comparison techniques to choose the one most likely to represent the true underlying dose-response curve, while preserving the family-wise error rate. The selected model is then used to provide inference on adequate doses.

Clinical Trials, Phase II as Topic↗
PubMed2004

On a hybrid method in dose finding studies.

OBJECTIVES: Combination of multiple testing and modeling techniques in dose-response studies. Use of hypotheses tests to assess the significance of the dose-response signal associated with a given candidate dose-response model. Estimation of target dose(s) following the previous model selection step. Illustration of the method with a real data example. METHODS: We assume a set of candidate models potentially reflecting the data generating process. The appropriateness of each individual model is evaluated in terms of contrast tests, where each set of contrast weights describes a specific dose-response shape. Optimum contrast weights are computed, which maximize the non-centrality parameters associated with the contrast tests. A reference set of appropriate candidate models is obtained while controlling the familywise error rate. A single model is then selected from this reference set using standard model selection criteria. The final step is devoted to dose finding by applying inverse regression techniques. This is illustrated for estimating the minimum effective dose. RESULTS: The method is as powerful as competing standard dose-response tests to detect an overall dose-related trend. In addition, the possibility is given to estimate one or more target doses of interest. The analysis of a real data example confirms the advantages of the proposed hybrid method. CONCLUSIONS: Combining multiple testing and modeling techniques leads to a powerful tool, which uses the advantages of both approaches: Rigid error control at the significance testing step and flexibility at the dose estimation step. The method can be extended to handle more general linear models including covariates and factorial treatment structures.

Clinical Trials as Topic↗
PubMed2000

Estimating significance level and power comparisons for testing multiple endpoints in clinical trials.

Clinical trials generally include several outcome measures of interest for assessing treatment efficacy and harm. Traditionally a single measure, the primary outcome, is selected and used as the basis for the design, including sample size and power. Secondary outcomes are then generally ordered with respect to their clinical relevance and importance. While this has become the traditional paradigm, recent trials have suggested the need for additional approaches. In this setting, two outcomes are viewed as key, either one being sufficient for proof of efficacy, but with an ordering of preference. The basic question, in such cases, is how to control the overall significance level for the trial. We describe and compare two methods for testing primary and secondary endpoints, accounting for their hierarchical nature-the ordering preference. Both methods are sequential, in the sense that the secondary endpoint is only tested when the primary outcome fails to reach significance. The first method uses a global test for the combination of the primary and secondary endpoints, while the second uses a partial Bonferroni correction. Simulation results indicate that the Bonferroni adjustment method performs as well as the global test method in most cases, and even better in some cases.

Clinical Trials as Topic↗
PubMed1995

Prediction of the developmental potential of hamster embryos in vitro by precise timing of the third cell cycle.

Time-lapse videomicrography was used to determine the timing of early developmental events in hamster embryos in vitro. The time intervals from pronuclear envelope breakdown to the completion of the first cleavage (Dt2), second cleavage (Dt4 = 2-4 cells), third cleavage (Dt8 = 4-8 cells), blastocyst formation, and zona escape were precisely measured to determine whether the variable 'time' (t) can be used to predict the developmental potential of preimplantation embryos. The range of the developmental time interval (Dt) from the second to the third cleavage divisions (Dt8) provided the best indicator for predicting the probabilities of blastocyst formation and zona escape (P = 0.015 and 0.041, respectively). Dt8 was subdivided into consecutive time cutoff points of < or = 750, < or = 800, < or = 850 and < or = 900 min. Of the embryos that took < or = 750 min to complete the third cleavage division, 92% developed into blastocysts and 69% escaped from their zonae pellucidae. When the completion of Dt8 extended to < or = 900 min, the percentages decreased to 75% and 49% for blastocyst formation and zona escape, respectively. This study identifies a specific developmental time interval and a model whereby time can be used as a noninvasive parameter to predict embryo developmental potential in vitro.

Animals↗
PubMedDate not supplied

[A measure to evaluate estimates from the population census].

"A measure of efficiency loss for the precision of estimates implied by sampling fractions reduction is described here....A study of the sampling fractions needed to guarantee a given precision level to estimate characteristics...is also performed. An application of the methodology suggested is included. The example is based on household characteristics investigated in [Brazil's]... Census of 1980, with estimates published at a county level and for the set of alternative sampling fractions for the 1990... Census." (SUMMARY IN ENG)

Americas↗