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Suejane Wang - One of the best experts on this subject based on the ideXlab platform.
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modified toxicity probability interval design a safer and more reliable method than the 3 3 design for practical phase i trials
Journal of Clinical Oncology, 2013Co-Authors: Yuan Ji, Suejane WangAbstract:The 3!3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3!3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3!3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3!3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3!3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3!3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3!3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3!3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3!3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3!3 design is also considered. We provide free software to allow direct comparisons of the 3!3 design with other model-based designs in simulation studies with matched sample sizes. J Clin Oncol 31:1785-1791. © 2013 by American Society of Clinical Oncology
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modified toxicity probability interval design a safer and more reliable method than the 3 3 design for practical phase i trials
Journal of Clinical Oncology, 2013Co-Authors: Suejane WangAbstract:The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes.
Changwook Nam - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamic profile in east asian patients with acs treated with prasugrel standard dose v de escalation strategy a randomized a match trial
Thrombosis and Haemostasis, 2021Co-Authors: Younghoon Jeong, Hyuckjun Yoon, Yongwhi Park, Jon Suh, Sewhan Lee, Kyounghoon Lee, Jeong Su Kim, Woo Jung Chun, Yong Hwan Park, Changwook NamAbstract:Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACS) treated with prasugrel standard-dose vs. De-Escalation strategy. Before discharge, ACS patients with age <75 year or weight ≥60 kg (n=250) were randomly assigned to the standard-dose (10-mg group) or De-Escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 Reaction Units [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85≤PRU≤208). The percentage of patients within the therapeutic window was significantly lower in the 10-mg group compared to the 5-mg and PFT-guided groups (35.3% vs. 67.5% vs. 65.9%) (Odds ratio [OR], 3.80 and 3.54; 95% confidence interval [CI], 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with De-Escalation strategies (35.3% vs. 24.1% vs. 23.2%) (Hazard ratio [HR], 0.58 and 0.55; 95% CI, 0.30-1.14 and 0.28-1.09, respectively). 'PRU<127' was the optimal cut-off for predicting one-month bleeding events (area under curve, 0.616; 95% CI, 0.543-0.689; p= 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR, 2.00; 95% CI, 1.28-3.03; p= 0.001). In conclusion, compared with the standard-dose prasugrel, prasugrel De-Escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes.
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pharmacodynamic profile and prevalence of bleeding episode in east asian patients with acute coronary syndromes treated with prasugrel standard dose versus de escalation strategy a randomized a match trial
Thrombosis and Haemostasis, 2021Co-Authors: Younghoon Jeong, Hyuckjun Yoon, Yongwhi Park, Jon Suh, Kyounghoon Lee, Jeong Su Kim, Woo Jung Chun, Yong Hwan Park, S G Lee, Changwook NamAbstract:Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a De-Escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or De-Escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with De-Escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel De-Escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.
Jeffrey W Moses - One of the best experts on this subject based on the ideXlab platform.
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de escalation of antianginal medications after successful chronic total occlusion percutaneous coronary intervention frequency and relationship with health status
American Heart Journal, 2019Co-Authors: Mohammed Qintar, James Sapontis, William Lombardi, Dimitri Karmpaliotis, Taishi Hirai, Suzanne V Arnold, Justin P Sheehy, Phil Jones, Yuanyuan Tang, Jeffrey W MosesAbstract:Background Successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can markedly reduce angina symptom burden, but many patients often remain on multiple antianginal medications (AAMs) after the procedure. It is unclear when, or if, AAMs can be de-escalated to prevent adverse effects or limit polypharmacy. We examined the association of De-Escalation of AAMs after CTO PCI with long-term health status. Methods In a 12-center registry of consecutive CTO PCI patients, health status was assessed at 6 months after successful CTO PCI with the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Among patients with technical CTO PCI success, we examined the association of AAM De-Escalation with 6-month health status using multivariable models adjusting for revascularization completeness and predicted risk of post-PCI angina (using a validated risk model). We also examined predictors and variability of AAMs De-Escalation. Results Of 669 patients with technical success of CTO PCI, AAMs were de-escalated in 276 (35.9%) patients at 1 month. Patients with AAM De-Escalation reported similar angina and dyspnea rates at 6 months compared with those whose AAMs were reduced (any angina: 22.5% vs 20%, P = .43; any dyspnea: 51.8% vs 50.1%, P = .40). In a multivariable model adjusting for complete revascularization and predicted risk of post-PCI angina, De-Escalation of AAMs at 1 month was not associated with an increased risk of angina, dyspnea, or worse health status at 6 months. Conclusions Among patients with successful CTO PCI, De-Escalation of AAMs occurred in about one-third of patients at 1 month and was not associated with worse long-term health status.
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patient characteristics associated with antianginal medication escalation and de escalation following chronic total occlusion percutaneous coronary intervention
Circulation-cardiovascular Quality and Outcomes, 2019Co-Authors: Taishi Hirai, James Sapontis, William Lombardi, Dimitri Karmpaliotis, William J Nicholson, Mohammed Qintar, Aaron J Grantham, David J Cohen, Jeffrey W Moses, Karen NugentAbstract:Background: Prior research has shown that providers may infrequently adjust antianginal medications (AAMs) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Patient ...
Nicholas H. Ogden - One of the best experts on this subject based on the ideXlab platform.
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De-Escalation by Reversing the Escalation with a Stronger Synergistic Package of Contact Tracing, Quarantine, Isolation and Personal Protection: Feasibility of Preventing a COVID-19 Rebound in Ontario, Canada, as a Case Study
Biology, 2020Co-Authors: Biao Tang, Nicola Luigi Bragazzi, Zachary Mccarthy, Francesca Scarabel, Michael Glazer, Yanyu Xiao, Jane M. Heffernan, Ali Asgary, Nicholas H. OgdenAbstract:Since the beginning of the COVID-19 pandemic, most Canadian provinces have gone through four distinct phases of social distancing and enhanced testing. A transmission dynamics model fitted to the cumulative case time series data permits us to estimate the effectiveness of interventions implemented in terms of the contact rate, probability of transmission per contact, proportion of isolated contacts, and detection rate. This allows us to calculate the control reproduction number during different phases (which gradually decreased to less than one). From this, we derive the necessary conditions in terms of enhanced social distancing, personal protection, contact tracing, quarantine/isolation strength at each escalation phase for the disease control to avoid a rebound. From this, we quantify the conditions needed to prevent epidemic rebound during De-Escalation by simply reversing the escalation process.
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De-Escalation by Reversing the Escalation with a Stronger Synergistic Package of Contact Tracing, Quarantine, Isolation and Personal Protection: Feasibility of Preventing a COVID-19 Rebound in Ontario, Canada, as a Case Study
2020Co-Authors: Biao Tang, Nicola Luigi Bragazzi, Zachary Mccarthy, Francesca Scarabel, Michael Glazer, Yanyu Xiao, Jane M. Heffernan, Ali Asgary, Nicholas H. OgdenAbstract:Since the beginning of the COVID-19 pandemic, most Canadian provinces have gone through four distinct phases of social distancing and enhanced testing. A transmission dynamics model fitted to the cumulative case time series data permits us to estimate the effectiveness of interventions implemented in terms of the contact rate, probability of transmission per contact, proportion of isolated contacts, and detection rate. This allows us to calculate the control reproduction number during different phases (which is gradually decreasing until it becomes smaller than one). Therefore, we can derive the necessary and sufficient conditions in terms of enhanced social distancing, personal protection, contact tracing, quarantine/isolation strength at each escalation phase for the disease control to avoid a rebound. This research aims to quantify these conditions for De-Escalation by simply reversing the escalation process.
Taishi Hirai - One of the best experts on this subject based on the ideXlab platform.
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de escalation of antianginal medications after successful chronic total occlusion percutaneous coronary intervention frequency and relationship with health status
American Heart Journal, 2019Co-Authors: Mohammed Qintar, James Sapontis, William Lombardi, Dimitri Karmpaliotis, Taishi Hirai, Suzanne V Arnold, Justin P Sheehy, Phil Jones, Yuanyuan Tang, Jeffrey W MosesAbstract:Background Successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can markedly reduce angina symptom burden, but many patients often remain on multiple antianginal medications (AAMs) after the procedure. It is unclear when, or if, AAMs can be de-escalated to prevent adverse effects or limit polypharmacy. We examined the association of De-Escalation of AAMs after CTO PCI with long-term health status. Methods In a 12-center registry of consecutive CTO PCI patients, health status was assessed at 6 months after successful CTO PCI with the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Among patients with technical CTO PCI success, we examined the association of AAM De-Escalation with 6-month health status using multivariable models adjusting for revascularization completeness and predicted risk of post-PCI angina (using a validated risk model). We also examined predictors and variability of AAMs De-Escalation. Results Of 669 patients with technical success of CTO PCI, AAMs were de-escalated in 276 (35.9%) patients at 1 month. Patients with AAM De-Escalation reported similar angina and dyspnea rates at 6 months compared with those whose AAMs were reduced (any angina: 22.5% vs 20%, P = .43; any dyspnea: 51.8% vs 50.1%, P = .40). In a multivariable model adjusting for complete revascularization and predicted risk of post-PCI angina, De-Escalation of AAMs at 1 month was not associated with an increased risk of angina, dyspnea, or worse health status at 6 months. Conclusions Among patients with successful CTO PCI, De-Escalation of AAMs occurred in about one-third of patients at 1 month and was not associated with worse long-term health status.
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patient characteristics associated with antianginal medication escalation and de escalation following chronic total occlusion percutaneous coronary intervention
Circulation-cardiovascular Quality and Outcomes, 2019Co-Authors: Taishi Hirai, James Sapontis, William Lombardi, Dimitri Karmpaliotis, William J Nicholson, Mohammed Qintar, Aaron J Grantham, David J Cohen, Jeffrey W Moses, Karen NugentAbstract:Background: Prior research has shown that providers may infrequently adjust antianginal medications (AAMs) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Patient ...