Published in Journal of biopharmaceutical statistics
In typical clinical development programs, a new drug is first developed for the adult use. Drugs are often approved for adult use or in the process of obtaining approval in adults in the target indication before pediatric development is initiated. In designing the first pediatric clinical trial, one of the challenges is to select the initial dose t...
Published in Journal of biopharmaceutical statistics
There are various multiple comparison procedures used in confirmatory clinical studies and exploratory research for multiplicity adjustment. Among them are the Hochberg and Benjamini-Hochberg procedures. A common misconception is that these procedures control the type I error rate properly if the test statistics are independent or positively correl...
Published in Journal of biopharmaceutical statistics
A limitation of the common measures of diagnostic test performance, such as sensitivity and specificity, is that they do not consider the relative importance of false negative and false positive test results, which are likely to have different clinical consequences. Therefore, the use of classification or prediction measures alone to compare diagno...
Published in Journal of biopharmaceutical statistics
Phase 1 oncology studies focus on safety of novel treatments and identifying a dose associated with acceptable toxicity level. Various model-based designs have been proposed for guiding dose escalation and estimating maximum tolerated dose in dose-finding studies. However, these methods are either excessively conservative or imprudent by allowing o...
Published in Journal of biopharmaceutical statistics
Response adaptive randomization has the potential to treat more participants in better treatments in a trial to benefit participants. We propose optimal response adaptive randomization designs for a two-stage study with binary response, having the smallest expected sample size or the fewest expected number of failures. Equal randomization is used i...
Published in Journal of biopharmaceutical statistics
Methods to extend the strong internal validity of randomized controlled trials to reliably estimate treatment effects in target populations are gaining attention. This paper enumerates steps recommended for undertaking such extended inference, discusses currently viable choices for each one, and provides recommendations. We demonstrate a complete e...
Published in Journal of biopharmaceutical statistics
Clinical studies sometimes provide clustered data with censored failure times. A crucial factor of the randomized design that lessens selection bias is the random allocation rule. Given this, the weighted rank tests' p-values for stratified survival clustered sampling based on the random allocation rule are approximated using the double saddle-poin...
Published in Journal of biopharmaceutical statistics
Individuals can vary drastically in their response to the same treatment, and this heterogeneity has driven the push for more personalized medicine. Accurate and interpretable methods to identify subgroups that respond to the treatment differently from the population average are necessary to achieving this goal. The Virtual Twins (VT) method is a h...
Published in Journal of biopharmaceutical statistics
In phase I trials of a novel anticancer drug, one of the most important objectives is to identify the maximum tolerated dose (MTD). To this end, a number of methods have been proposed and evaluated under various scenarios. However, the percentages of correct selection (PCS) of MTDs using previous methods are insufficient to determine the dose for l...
Published in Journal of biopharmaceutical statistics
The main purpose of this paper is to survey the statistical inference for covariate-specific time-dependent receiver operating characteristic (ROC) curves with nonignorable missing continuous biomarker values. To construct time-dependent ROC curves, we consider a joint model which assumes that the failure time depends on the continuous biomarker an...
