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Simple Summary: This paper provides a review of statistical methods for tumor-agnostic clinical trials. In particular, the review focuses on basket trials and provides methodological insights into various Bayesian approaches. The key concept of borrowing information through Bayesian hierarchical models is emphasized, and some novel trial designs are introduced. The review is expected to provide oncology and biostatistics researchers with more exposure to powerful Bayesian methods for the design and analysis of tumor-agnostic clinical trials. Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and power in estimating and detecting the treatment effects in different baskets. We review recent developments in Bayesian methods for the design and analysis of basket trials, focusing on the mechanism of information borrowing. We explain the common components of these methods, such as a prior model for the treatment effects that embodies an assumption of exchangeability. We also discuss the distinct features of these methods that lead to different degrees of borrowing. Through simulation studies, we demonstrate the impact of information borrowing on the operating characteristics of these methods and discuss its broader implications for drug development. Examples of basket trials are presented in both phase I and phase II settings. [ABSTRACT FROM AUTHOR]

Background: Bayesian methods, with the predictive probability (PredP), allow multiple interim analyses with interim posterior probability (PostP) computation, without the need to correct for multiple looks at the data. The objective of this paper was to illustrate the use of PredP by simulating a sequential analysis of a clinical trial.Methods: We used data from the Laryngobloc trial that planned to include 480 patients to demonstrate the equivalence of success between a laryngoscopy performed with the Laryngobloc® device and a control device. A crossover Bayesian design was used. The success rates of the two laryngoscopy devices were compared. Interim analyses, computed from random numbers of subjects, were simulated.Results: The PostP of equivalence rapidly reached the predefined bound of 0.95. The PredP computed with an equivalence margin of 10% reached the efficacy bound between 352 and 409 of the 480 included patients. If a frequentist analysis had been made on the basis of 217 out of 480 subjects, the study would have been prematurely stopped for equivalence. The PredP indicated that this result was nonetheless unstable and that the equivalence was, thus far, not guaranteed.Conclusions: Based on these interim analyses, we can conclude with a sufficiently high probability that the equivalence would have been met on the primary outcome before the predetermined end of this particular trial. If a Bayesian approach using PredP had been used, it would have allowed an early termination of the trial by reducing the calculated sample size by 15-20%. [ABSTRACT FROM AUTHOR]

This paper proposes a new estimation procedure for the survival time distribution with left-truncated and right-censored data, where the distribution of the truncation time is known up to a finite-dimensional parameter vector. The paper expands on the Vardis multiplicative censoring model (Vardi, 1989. Multiplicative censoring, renewal processes, deconvolution and decreasing density: non-parametric estimation. Biometrika 76: , 751-761), establishes the connection between the likelihood under a generalized multiplicative censoring model and that for left-truncated and right-censored survival time data, and derives an Expectation-Maximization algorithm for model estimation. A formal test for checking the truncation time distribution is constructed based on the semiparametric likelihood ratio test statistic. In particular, testing the stationarity assumption that the underlying truncation time is uniformly distributed is performed by embedding the null uniform truncation time distribution in a smooth alternative (Neyman, 1937. Smooth test for goodness of fit. Skandinavisk Aktuarietidskrift 20: , 150-199). Asymptotic properties of the proposed estimator are established. Simulations are performed to evaluate the finite-sample performance of the proposed methods. The methods and theories are illustrated by analyzing the Canadian Study of Health and Aging and the Channing House data, where the stationarity assumption with respect to disease incidence holds for the former but not the latter. [ABSTRACT FROM AUTHOR]

Context: Self-report questionnaires are an important method of evaluating lifespan health, exercise, and health-related quality of life (HRQL) outcomes among elite, competitive athletes. Few instruments, however, have undergone formal characterization of their psychometric properties within this population. Objective: To evaluate the validity and reliability of a novel health and exercise questionnaire, the Trojan Lifetime Champions (TLC) Health Survey. Design: Descriptive laboratory study. Setting: A large National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 63 university alumni (age range, 24 to 84 years), including former varsity collegiate athletes and a control group of nonathletes. Intervention(s): Participants completed the TLC Health Survey twice at a mean interval of 23 days with randomization to the paper or electronic version of the instrument. Main Outcome Measure(s): Content validity, feasibility of administration, test-retest reliability, parallel-form reliability between paper and electronic forms, and estimates of systematic and typical error versus differences of clinical interest were assessed across a broad range of health, exercise, and HRQL measures. Results: Correlation coefficients, including intraclass correlation coefficients (ICCs) for continuous variables and K agreement statistics for ordinal variables, for test-retest reliability averaged 0.86, 0.90, 0.80, and 0.74 for HRQL, lifetime health, recent health, and exercise variables, respectively. Correlation coefficients, again ICCs and K, for parallel-form reliability (ie, equivalence) between paper and electronic versions averaged 0.90, 0.85, 0.85, and 0.81 for HRQL, lifetime health, recent health, and exercise variables, respectively. Typical measurement error was less than the a priori thresholds of clinical interest, and we found minimal evidence of systematic testretest error. We found strong evidence of content validity, convergent construct validity with the Short-Form 12 Version 2 HRQL instrument, and feasibility of administration in an elite, competitive athletic population. Conclusions: These data suggest that the TLC Health Survey is a valid and reliable instrument for assessing lifetime and recent health, exercise, and HRQL, among elite competitive athletes. Generalizability of the instrument may be enhanced by additional, larger-scale studies in diverse populations. [ABSTRACT FROM AUTHOR]