Sample size re-estimation without un-blinding for time-to-event outcomes in oncology clinical trials

Sample size re-estimation is essential in oncology studies. However, the use of blinded sample size reassessment for survival data has been rarely reported. Based on the density function of the exponential distribution, an expectation-maximization（EM） algorithm of the hazard ratio was derived, and several simulation studies were used to verify its applications. The method had obvious variation in the hazard ratio estimates and overestimation for the relatively small hazard ratios. Our studies showed that the stability of the EM estimation results directly correlated with the sample size, the convergence of the EM algorithm was impacted by the initial values, and a balanced design produced the best estimates. No reliable blinded sample size re-estimation inference can be made in our studies, but the results provide useful information to steer the practitioners in this field from repeating the same endeavor.

Models for Improving Software System Size Estimates during Development

This paper addresses the challenge of estimating eventual software system size during a development project. The ap-proach is to build a family of estimation models that use information about architectural design characteristics of the evolving software product as leading indicators of system size. Four models were developed to provide an increasingly accurate size estimate throughout the design process. Multivariate regression analyses were conducted using 21 Ada subsystems, totaling 183,000 lines of code. The models explain from 47% of the variation in delivered software size early in the design phase, to 89% late in the design phase.

Utility of Adaptive Sample Size Designs and A Review Example

Sample size can be a key design feature that not only affects the probability of a trial＇s success but also determines the duration and feasibility of a trial. If an investigational drug is expected to be effective and address unmet medical needs of an orphan disease, where the accrual period may require many years with a large sample size to detect a minimal clinically relevant treatment effect, a minimum sample size may be set to maintain nominal power. In limited situations such as this, there may be a need for flexibility in the initial and final sample sizes; thus, it is useful to consider the utility of adaptive sample size designs that use sample size re-estimation or group sequential design. In this paper, we propose a new adaptive performance measure to consider the utility of an adaptive sample size design in a trial simulation. Considering that previously proposed sample size re-estimation methods do not take into account errors in estimation based on interim results, we propose Bayesian sample size re-estimation criteria that take into account prior information on treatment effect, and then, we assess its operating characteristics in a simulation study. We also present a review example of sample size re-estimation mainly based on published paper and review report in Pharmaceuticals and Medical Devices Agency （PMDA）.

Study of M-estimator Variational Retrieval Using Simulated Feng Yun-3A Data

This paper adopts satellite channel brightness temperature simulation to study M-estimator variational retrieval. This approach combines both the advantages of classical variational inversion and robust M-estimators. Classical variational inversion depends on prior quality control to elim- inate outliers, and its errors follow a Gaussian distribution. We coupled the M-estimators to the framework of classical variational inversion to obtain a M-estimator variational inversion. The cost function contains the M-estimator to guarantee the robustness to outliers and improve the retrieval re- sults. The experimental evaluation adopts Feng Yun-3A （FY-3A） simulated data to add to the Gaussian and Non-Gaussian error. The variational in- version is used to obtain the inversion brightness temperature, and temperature and humidity data are used for validation. The preliminary results demonstrate the potential of M-estimator variational retrieval.