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In the field of hyperspectral target detection, algorithms based on collaborative representation have shown excellent performance. However, the pollution of background dictionaries by anomaly has always been a problem, which affects the detection performance of this algorithm partly. This paper proposes an improved collaborative representation algorithm for hyperspectral anomaly detection, and designs a double-layer collaborative representation structure. Firstly, the first layer collaborative representation algorithm is used to detect most of the anomaly. Its neighborhood pixels are used for background purification to eliminate the pollution of the detected anomaly on the background dictionary. Then, the purified background dictionary is used to predict the background, and in the second layer, the collaborative representation is used for anomaly detection. Simulation experiments show that a simple double layer collaborative representation structure can effectively alleviate the background pollution caused by anomaly. The detection performance of this algorithm is significantly improved compared to the basic collaborative representation algorithm, and it also has relatively good detection performance.

Longitudinal studies are often subject to missing data. The recent guidance from regulatory agencies, such as the ICH E9(R1) addendum addresses the importance of defining a treatment effect estimand with the consideration of intercurrent events. Jump-to-reference (J2R) is one classical control-based scenario for the treatment effect evaluation, where the participants in the treatment group after intercurrent events are assumed to have the same disease progress as those with identical covariates in the control group. We establish new estimators to assess the average treatment effect based on a proposed potential outcomes framework under J2R. Various identification formulas are constructed, motivating estimators that rely on different parts of the observed data distribution. Moreover, we obtain a novel estimator inspired by the efficient influence function, with multiple robustness in the sense that it achieves n 1/2-consistency if any pairs of multiple nuisance functions are correctly specified, or if the nuisance functions converge at a rate not slower than n −1/4 when using flexible modeling approaches. The finite-sample performance of the proposed estimators is validated in simulation studies and an antidepressant clinical trial. [ABSTRACT FROM AUTHOR]

Returning to baseline (RTB) has been a practical method for handling missing data. Here we consider longitudinal clinical trials with daily patient reported outcomes (PROs), where efficacy endpoints are often defined as the average daily values in a cycle (such as a month or a week). The conventional method treats data at cycle level and ignores daily values. In this paper, we build a two-level constrained longitudinal data analysis (cLDA) model on daily values and propose two-level RTB method to impute daily values. Standard multiple imputation (MI) approach and likelihood-based approach are proposed and evaluated by simulations. [ABSTRACT FROM AUTHOR]

Censored survival data are common in clinical trial studies. We propose a unified framework for sensitivity analysis to censoring at random in survival data using multiple imputation and martingale, called SMIM. The proposed framework adopts the δ‐adjusted and control‐based models, indexed by the sensitivity parameter, entailing censoring at random and a wide collection of censoring not at random assumptions. Also, it targets a broad class of treatment effect estimands defined as functionals of treatment‐specific survival functions, taking into account missing data due to censoring. Multiple imputation facilitates the use of simple full‐sample estimation; however, the standard Rubin's combining rule may overestimate the variance for inference in the sensitivity analysis framework. We decompose the multiple imputation estimator into a martingale series based on the sequential construction of the estimator and propose the wild bootstrap inference by resampling the martingale series. The new bootstrap inference has a theoretical guarantee for consistency and is computationally efficient compared to the nonparametric bootstrap counterpart. We evaluate the finite‐sample performance of the proposed SMIM through simulation and an application on an HIV clinical trial. [ABSTRACT FROM AUTHOR]

Missing data is inevitable in longitudinal clinical trials. Conventionally, the missing at random assumption is assumed to handle missingness, which however is unverifiable empirically. Thus, sensitivity analyses are critically important to assess the robustness of the study conclusions against untestable assumptions. Toward this end, regulatory agencies and the pharmaceutical industry use sensitivity models such as return-to-baseline, control-based, and washout imputation, following the ICH E9(R1) guidance. Multiple imputation is popular in sensitivity analyses; however, it may be inefficient and result in an unsatisfying interval estimation by Rubin's combining rule. We propose distributional imputation in sensitivity analysis, which imputes each missing value by samples from its target imputation model given the observed data. Drawn on the idea of Monte Carlo integration, the distributional imputation estimator solves the mean estimating equations of the imputed dataset. It is fully efficient with theoretical guarantees. Moreover, we propose weighted bootstrap to obtain a consistent variance estimator, taking into account the variabilities due to model parameter estimation and target parameter estimation. The superiority of the distributional imputation framework is validated in the simulation study and an antidepressant longitudinal clinical trial. [ABSTRACT FROM AUTHOR]

Missing data are commonly encountered in clinical trials due to dropout or nonadherence to study procedures. In trials in which recurrent events are of interest, the observed count can be an undercount of the events if a patient drops out before the end of the study. In many applications, the data are not necessarily missing at random and it is often not possible to test the missing at random assumption. Consequently, it is critical to conduct sensitivity analysis. We develop a control-based multiple imputation method for recurrent events data, where patients who drop out of the study are assumed to have a similar response profile to those in the control group after dropping out. Specifically, we consider the copy reference approach and the jump to reference approach. We model the recurrent event data using a semiparametric proportional intensity frailty model with the baseline hazard function completely unspecified. We develop nonparametric maximum likelihood estimation and inference procedures. We then impute the missing data based on the large sample distribution of the resulting estimators. The variance estimation is corrected by a bootstrap procedure. Simulation studies demonstrate the proposed method performs well in practical settings. We provide applications to two clinical trials. [ABSTRACT FROM AUTHOR]

In longitudinal clinical trials with daily patient-reported outcomes, the analysis endpoints are often defined as the averaged daily diary outcomes in a treatment cycle (such as a month or a week). Conventional methods often deal with missing data at the cycle level by imputing the average, and the cycle average is treated as missing if the number of days with available outcomes in the treatment cycle is less than a certain number. This was the method used for a case study of a phase 3 clinical trial evaluating a treatment for insomnia with daily patient-reported outcomes. Such methods may introduce bias. Motivated by this, we propose methods to impute missing daily outcomes in this paper. Specifically, we define a two-level missing pattern for clinical trials with daily patient-reported outcomes, and propose two-level methods to impute missing data at daily base. Other than the standard methods by multiple imputations, we derive analytic formulas for the proposed two-level methods to reduce computational intensity and improve the estimates of variances. The proposed two-level methods provide more powerful approaches to estimate the treatment difference compared to the conventional cycle-level methods, which are evaluated by theoretical development and simulation studies. In addition, the methods are applied to the motivating phase 3 trial evaluating a treatment for insomnia with daily patient-reported outcomes. [ABSTRACT FROM AUTHOR]