The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnera...The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.展开更多
Many covariate-adaptive randomization procedures have been proposed and implemented to balance important covariates in clinical trials. These methods are usually based on fully observed covariates. In practice,the cov...Many covariate-adaptive randomization procedures have been proposed and implemented to balance important covariates in clinical trials. These methods are usually based on fully observed covariates. In practice,the covariates of a patient are often partially missing. We propose a novel covariate-adaptive design to deal with missing covariates and study its properties. For the proposed design, we show that as the number of patients increases, the overall imbalance, observed margin imbalance and fully observed stratum imbalance are bounded in probability. Under certain covariate-dependent missing mechanism, the proposed design can balance missing covariates as if the covariates are observed. Finally, we explore our methods and theoretical findings through simulations.展开更多
文摘The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.
基金supported by National Natural Science Foundation of China(Grant Nos.11371366 and 11201479)Research Fund for the Doctoral Program of Higher Education of China(Grant No.20120004120007)the Basic Research Funds in Renmin University of China from the central government(Grant Nos.13XNLJ03 and 12XNQ049)
文摘Many covariate-adaptive randomization procedures have been proposed and implemented to balance important covariates in clinical trials. These methods are usually based on fully observed covariates. In practice,the covariates of a patient are often partially missing. We propose a novel covariate-adaptive design to deal with missing covariates and study its properties. For the proposed design, we show that as the number of patients increases, the overall imbalance, observed margin imbalance and fully observed stratum imbalance are bounded in probability. Under certain covariate-dependent missing mechanism, the proposed design can balance missing covariates as if the covariates are observed. Finally, we explore our methods and theoretical findings through simulations.
