A Practical Response Adaptive Block Randomization Design with Analytic Type I Error Protection

Response adaptive randomization is appealing in confirmatory adaptive clinical trials from statistical, ethical, and pragmatic perspectives, in the sense that subjects are more likely to be randomized to better performing treatment groups based on accumulating data. The Doubly Adaptive Biased Coin Design (DBCD) is a popular solution due to its asymptotic normal property of final allocations, which further justifies its asymptotic type I error rate control. As an alternative, we propose a Response Adaptive Block Randomization (RABR) design with pre-specified randomization ratios for the control and high-performing groups to robustly achieve desired final sample size per group under different underlying responses, which is usually required in industry-sponsored clinical studies. We show that the usual test statistic has a controlled type I error rate. Our simulations further highlight the advantages of the proposed design over the DBCD in terms of consistently achieving final sample allocations and of power performance. We further apply this design to a Phase III study evaluating the efficacy of two dosing regimens of adjunctive everolimus in treating tuberous sclerosis complex but with no previous dose-finding studies in this indication

Deep Historical Borrowing Framework to Prospectively and Simultaneously Synthesize Control Information in Confirmatory Clinical Trials with Multiple Endpoints

In current clinical trial development, historical information is receiving more attention as providing value beyond sample size calculation. Meta-analytic-predictive (MAP) priors and robust MAP priors have been proposed for prospectively borrowing historical data on a single endpoint. To simultaneously synthesize control information from multiple endpoints in confirmatory clinical trials, we propose to approximate posterior probabilities from a Bayesian hierarchical model and estimate critical values by deep learning to construct pre-specified decision functions before the trial conduct. Simulation studies and a case study demonstrate that our method additionally preserves power, and has a satisfactory performance under prior-data conflict

Workplace learning in China: transferring training into practice to improve performance

Purpose: The present study seeks to examine the efficacy of different training modalities on increasing workplace learning, representatives\u27 intent to transfer what they learned into their work, and importantly how training impacts actual work performance. These relationships are tested in the context of a Chinese division of a multinational pharmaceutical company, where pharmaceutical representatives are tasked with relaying relevant efficacy and safety information on pharmaceutical products to health care professionals who prescribe them to patients. Methods: The present study employed a three-group between-subjects experimental design. Representatives received varying forms of training (instruction only, instruction plus reflection, and instruction, reflection, plus direct feedback) based on experimental conditions. After three training sessions over the course of six weeks, representatives were assessed on how much they learned in the training and their actual work performance through observer assessment of meetings with health care professionals, facilitated by the representatives. Findings: In this study, it was found that the process of actively reflecting on what was learned in training led to increased learning, as well as increased performance, compared to simply studying the material. However, receiving direct feedback on training performance, combined with active reflection training, did not provide any further benefits in terms of learning or work performance. Notably, there were no differences in intent to transfer learned material to work, as all conditions reported high levels of transfer intention. Conclusion: The finding provides insightful evidence to support the benefits of fostering trainees\u27 active reflections for work-based learning in the Chinese industry training scenario. In contrast, receiving direct comments on how students performed from a manager or trainer, as well as advise on how do better in the future, had no effect on increasing learning or performance. Although the effect of direct feedback is not statistically significant in this context, further research should be done in understanding individuals\u27 thoughts and behaviors when received direct feedbacks received in workplace training. Relatively little workplace research has assessed both workplace learning and performance in the same study,specifically in the Chinese context. While training efficacy likely varies across cultures to begin with, compensation structures in China do not provide the same monetary incentives for workplace learning (i.e. chance to increase income) as Western culture. This means that any way to increase workplace learning should be of extra value, as employees otherwise may not engage in it at all. (DIPF/Orig.

Workplace Learning in China: Transferring Training Into Practice to Improve Performance

Purpose: The present study seeks to examine the efficacy of different training modalities on increasing workplace learning, representatives' intent to transfer what they learned into their work, and importantly how training impacts actual work performance. These relationships are tested in the context of a Chinese division of a multinational pharmaceutical company, where pharmaceutical representatives are tasked with relaying relevant efficacy and safety information on pharmaceutical products to health care professionals who prescribe them to patients. Methods: The present study employed a three-group between-subjects experimental design. Representatives received varying forms of training (instruction only, instruction plus reflection, and instruction, reflection, plus direct feedback) based on experimental conditions. After three training sessions over the course of six weeks, representatives were assessed on how much they learned in the training and their actual work performance through observer assessment of meetings with health care professionals, facilitated by the representatives. Findings: In this study, it was found that the process of actively reflecting on what was learned in training led to increased learning, as well as increased performance, compared to simply studying the material. However, receiving direct feedback on training performance, combined with active reflection training, did not provide any further benefits in terms of learning or work performance. Notably, there were no differences in intent to transfer learned material to work, as all conditions reported high levels of transfer intention. Conclusion: The finding provides insightful evidence to support the benefits of fostering trainees' active reflections for work-based learning in the Chinese industry training scenario. In contrast, receiving direct comments on how students performed from a manager or trainer, as well as advise on how do better in the future, had no effect on increasing learning or performance. Although the effect of direct feedback is not statistically significant in this context, further research should be done in understanding individuals' thoughts and behaviors when received direct feedbacks received in workplace training. Relatively little workplace research has assessed both workplace learning and performance in the same study, specifically in the Chinese context. While training efficacy likely varies across cultures to begin with, compensation structures in China do not provide the same monetary incentives for workplace learning (i.e. chance to increase income) as Western culture. This means that any way to increase workplace learning should be of extra value, as employees otherwise may not engage in it at all.

The Effects of Intelectin-1 on Antioxidant and Angiogenesis in HUVECs Exposed to Oxygen Glucose Deprivation

Objective: Ischemic stroke leads to cellular death and tissue damage by depriving the areas of glucose and oxygen supplies. The effective treatment of stroke remains a challenge for modern medicine. This study used an oxygen-glucose deprivation (OGD) model of human umbilical vein endothelial cells (HUVECs) to mimic ischemic injuries and explored the role and mechanism of intelectin-1.Methods: Intelectin-1 was transduced into the HUVECs using a lentiviral vector. The PI3K/Akt signaling was examined in intelectin-induced eNOS phosphorylation. The PI3K inhibitor LY294002 was dealed in HUVECs.Results: Our results demonstrated an increase in capillary density, decrease in apoptotic cells, and increase in HIF-1α protein expression following intelectin-1 treatment. Real-time PCR and Western blotting revealed the increased intelectin-1 expression alongside eNOS and Akt phosphorylation with enhanced bcl-2 expression under OGD. Capillary density decreased significantly after LY294002 treatment.Conclusion: These results suggest intelectin-1 promotes angiogenesis, inhibits oxidative stress and reduces apoptosis by stimulating the Akt-eNOS signaling pathway in response to ischemia in vitro