摘要:

We present a methodology for combining trials some of which report continuous outcome measures and others binary outcomes created by a dichotomy of the continuous measurement. This was motivated by a series of controlled clinical trials investigating the effect of prophylactic use of oxytocics on postpartum blood loss during labor. Data were available in the form of summary statistics from published papers. The log-odds ratio is used as a common measure of treatment difference across all trials. We discuss the general applicability of this approach.

ISSN:1054-3406    

DOI:10.1081/BIP-100100997

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

We discuss an extension of the continual reassessment method (CRM) for use in phase I dose-finding studies. The extension enables the method to be applied to two groups of patients to determine the appropriate dose levels for each group. The method takes the specification of a simple relationship between the dose-toxicity curves for the two groups and runs the CRM on the bivariate model using maximum likelihood. We prove consistency of the method under fairly weak conditions and provide several simulations to give an idea how the method works in practice. We also undertake an evaluation of its performance by considering three possible situations: The first is the two-sample CRM, which directly uses a working model for the relationship between the two groups, carrying out a single trial using this method; the second situation carries out single trials for each of the two groups separately using the original (one-sample) CRM. The third situation is the case where such heterogeneity is ignored and the two groups are pooled into a single group, again using the original (one-sample) CRM. Simulations are carried out under a large class of model misspecifications, both of the dose-toxicity relationships and of the functional form linking the groups, and are backed up by asymptotic results. Our conclusions match intuition: The first scheme gives the most favorable results when the two groups are different but share some features. When the groups are very different, the second scheme performs similarly to the first for finite sample sizes while having some advantages in terms of asymptotic efficiency. The third, as expected, gives the best results in the absence of patient heterogeneity. The two-sample method appears particularly advantageous when there may not be enough subjects in one of the subgroups for it to be feasible to carry out two trials.

ISSN:1054-3406    

DOI:10.1081/BIP-100100998

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

In the randomized clinical trial setting, controlling for covariates is expected to produce variance reduction for the treatment parameter estimate and to adjust for random imbalances of covariates between the treatment groups. However, for the logistic regression model, variance reduction is not obviously obtained. This can lead to concerns about the assumptions of the logistic model.

ISSN:1054-3406    

DOI:10.1081/BIP-100100999

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

Predictive probability is particularly useful in aiding a decision-making process related to drug development. This is especially true for decisions occurring as the result of interim analyses of clinical trials. Examples of clinical trial applications of Bayesian predictive probability and the use of the beta-binomial distribution are described.

ISSN:1054-3406    

DOI:10.1081/BIP-100101000

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

When two medical screening tests for a disease exist, it may be appealing to combine them to increase screening accuracy. Combination of two valid screening tests, where each independently has screening performance, can increase the overall disease screening performance. Some results are obtained when two binary screening tests are combined according to the Boolean Any+ strategy, as defined by Maguire [1]. These results are useful and provide investigators of two screening tests a sense of what to expect of the performance of the two tests when combined. This then may be followed by a clinical trial that directly demonstrates the benefit of the combined test.

ISSN:1054-3406    

DOI:10.1081/BIP-100101001

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

We consider the development of the concentration of a drug in the blood after single oral or intravenous administration. We introduce a new nonlinear model capable of describing concentration-time curves following intravenous administration. A similar model is proposed for oral data. Both models have four parameters, of which two regulate the shape of the curve and two determine the scale of the time and concentration axes. All the parameters are closely related to geometric properties of the curve. The scale parameters determine a point in the curve, and the shape parameters can be calculated by using numerical integration. The models can be used when the object of the analysis is to quantify the shape of a concentration-time curve. We discuss the usefulness of the models in bioequivalency trials, in clinical safety and efficacy trials, and in population pharmacokinetics. The models are applied to two previously presented data sets. To reduce the number of parameters, the shape parameters are assumed common for all individuals. Encouraging results are obtained. We also present a new four-parameter Michaelis-Menten model.

ISSN:1054-3406    

DOI:10.1081/BIP-100101002

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

To assess the efficacy of potential new drugs in the initial phase of clinical research, one must use an efficient design that satisfies conditions to guarantee the safety of the subjects. For a parallel design, a two-period crossover design, two three-period crossover designs, and a Latin square design with three periods, we compared variances of estimators based on a mixed analysis of variance model. The proposed three-period crossover designs turned out to be only slightly less efficient than the Latin square design, which is not capable of satisfying the necessary safety conditions.

ISSN:1054-3406    

DOI:10.1081/BIP-100101003

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

Multifactor ANOVA procedures are commonly used by practitioners. A hierarchical process for testing the interaction effect(s) first, followed by tests for the main effects, is usually employed. Generally, no consideration is given to the overall type I error rate for these dependent (or conditional) tests. In this article, we formulate a method to evaluate the true overall significance levels for two-factor fixed-effect ANOVA models. Methods for evaluating conditionalp-values are discussed. We present the overall significance levels for several specific two-factor designs. We discuss upper bounds on the overall significance level and extensions of the computational methods to higher-order designs as well as applications to random-effect models and mixed models.

ISSN:1054-3406    

DOI:10.1081/BIP-100101004

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

The effects of certain chemical additives at maintaining a high level of activity in protein constructs during storage is investigated. We use a semiparametric regression technique to model the effects of the additives on protein activity. The model is extended to handle categorical explanatory variables. On the basis of the available data, the important factors are estimated to be buffer, detergent, protein concentration, and storage temperature. The relationships among protein activity and these factors appear to be moderately nonlinear with strong interaction effects. These features are revealed in a data-adaptive way by the semiparametric model, without explicit modeling of the nonlinearities or interactions. We use cross-validation to assess the fit of our model. The protein activity response appears to be extremely erratic. We recommend several sets of storage conditions and that further design points be chosen in regions around these estimated optima.

ISSN:1054-3406    

DOI:10.1081/BIP-100101005

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

Longitudinal data present statistical problems of interest in clinical trials and epidemiologic studies. In this article, we consider a dental clinical trial in which the outcome measurements are taken on each subject at two follow-up times, and the primary interest is in the dependence of the outcome variable on covariates. The common data structure of these studies is the presence of an intraclass or serial correlation within primary sampling units or subjects. Recently generalized linear models have had extensions to methods for generalized estimating equations that take correlations within primary sampling units into account. We review and apply the Liang-Zeger methodology to a dental clinical trial. In this study, 109 adult male and female volunteers with preexisting dental plaque were randomized to two mouth rinses (A and B) or a control mouth rinse with double blinding. The major research question in this analysis was: Are the two experimental mouth rinses more effective than the control mouth rinse in inhibiting the development of dental plaque? And if so, what is the effect of baseline plaque measurement?

ISSN:1054-3406    

DOI:10.1081/BIP-100101006

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor