Pharmaceutical Statistics最新文献_第5页

PKBOIN-12: A Bayesian Optimal Interval Phase I/II Design Incorporating Pharmacokinetics Outcomes to Find the Optimal Biological Dose. PKBOIN-12：贝叶斯最优间隔 I/II 期设计，纳入药代动力学结果以找到最佳生物剂量。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-10-24 DOI: 10.1002/pst.2444

Hao Sun, Jieqi Tu

{"title":"PKBOIN-12: A Bayesian Optimal Interval Phase I/II Design Incorporating Pharmacokinetics Outcomes to Find the Optimal Biological Dose.","authors":"Hao Sun, Jieqi Tu","doi":"10.1002/pst.2444","DOIUrl":"https://doi.org/10.1002/pst.2444","url":null,"abstract":"Immunotherapies and targeted therapies have gained popularity due to their promising therapeutic effects across multiple treatment areas. The focus of early phase dose-finding clinical trials has shifted from finding the maximum tolerated dose (MTD) to identifying the optimal biological dose (OBD), which aims to balance the toxicity and efficacy outcomes, thus optimizing the risk-benefit trade-off. These trials often collect multiple pharmacokinetics (PK) outcomes to assess drug exposure, which has shown correlations with toxicity and efficacy outcomes but has not been utilized in the current dose-finding designs for OBD selection. Moreover, PK outcomes are usually available within days after initial treatment, much faster than toxicity and efficacy outcomes. To bridge this gap, we introduce the innovative model-assisted PKBOIN-12 design, which enhances BOIN12 by integrating PK information into both the dose-finding algorithm and the final OBD determination process. We further extend PKBOIN-12 to TITE-PKBOIN-12 to address the challenges of late-onset toxicity and efficacy outcomes. Simulation results demonstrate that PKBOIN-12 more effectively identifies the OBD and allocates a greater number of patients to it than BOIN12. Additionally, PKBOIN-12 decreases the probability of selecting inefficacious doses as the OBD by excluding those with low drug exposure. Comprehensive simulation studies and sensitivity analysis confirm the robustness of both PKBOIN-12 and TITE-PKBOIN-12 in various scenarios.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of Prior Distributions for the Heterogeneity Parameter in a Rare Events Meta-Analysis of a Few Studies. 少数研究的罕见事件 Meta 分析中异质性参数的先验分布比较。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-10-23 DOI: 10.1002/pst.2448

Minghong Yao, Fan Mei, Kang Zou, Ling Li, Xin Sun

{"title":"Comparison of Prior Distributions for the Heterogeneity Parameter in a Rare Events Meta-Analysis of a Few Studies.","authors":"Minghong Yao, Fan Mei, Kang Zou, Ling Li, Xin Sun","doi":"10.1002/pst.2448","DOIUrl":"https://doi.org/10.1002/pst.2448","url":null,"abstract":"Bayesian meta-analysis is a promising approach for rare events meta-analysis. However, the inference of the overall effect in rare events meta-analysis is sensitive to the choice of prior distribution for the heterogeneity parameter. Therefore, it is crucial to assign a convincing prior specification and ensure that it is both plausible and transparent. Various priors for the heterogeneity parameter have been proposed; however, the comparative performance of alternative prior specifications in rare events meta-analysis is poorly understood. Based on a binomial-normal hierarchical model, we conducted a comprehensive simulation study to compare seven heterogeneity prior specifications for binary outcomes, using the odds ratio as the metric. We compared their performance in terms of coverage, median percentage bias, width of the 95% credible interval, and root mean square error (RMSE). We illustrate the results with two recently published rare events meta-analyses of a few studies. The results show that the half-normal prior (with a scale of 0.5), the prior proposed by Turner et al. for the general healthcare setting (without restriction to a specific type of outcome) and for the adverse event setting perform well when the degree of heterogeneity is not relatively high, yielding smaller bias and shorter interval widths with similar coverage and RMSE in most cases compared to other prior specifications. None of the priors performed better when the heterogeneity between-studies were significantly extreme.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Number of Repetitions in Re-Randomization Tests. 再随机测试中的重复次数。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-10-16 DOI: 10.1002/pst.2438

Yilong Zhang, Yujie Zhao, Bingjun Wang, Yiwen Luo

引用次数: 0

Balance Index to Determine the Follow-Up Duration of Oncology Trials. 确定肿瘤学试验随访时间的平衡指数。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-10-11 DOI: 10.1002/pst.2442

Lei Yang, Feinan Lu

{"title":"Balance Index to Determine the Follow-Up Duration of Oncology Trials.","authors":"Lei Yang, Feinan Lu","doi":"10.1002/pst.2442","DOIUrl":"https://doi.org/10.1002/pst.2442","url":null,"abstract":"Several indices were suggested to determine the follow up duration in oncology trials from either maturity or stability perspective, by maximizing time <math> <semantics><mrow><mi>t</mi></mrow> <annotation>$$ t $$</annotation></semantics> </math> such that the index was either greater or less than a pre-defined cutoff value. However, the selection of cutoff value was subjective and usually no commonly agreed cutoff value existed; sometimes one had to resort to simulations. To solve this problem, a new balance index was proposed, which integrated both data stability and data maturity. Its theoretical properties and relationships with other indices were investigated; then its performance was demonstrated through a case study. The highlights of the index are: (1) easy to calculate; (2) free of cutoff value selection; (3) generally consistent with the other indices while sometimes able to shorten the follow-up duration thus more flexible. For the cases where the new balance index cannot be calculated, a modified balance index was also proposed and discussed. For either single arm trial or randomized clinical trial, the two new balance indices can be implemented to widespread situations such as designing a new trial from scratch, or using aggregated trial information to inform the decision-making in the middle of trial conduct.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Adaptive Three-Arm Comparative Clinical Endpoint Bioequivalence Study Design With Unblinded Sample Size Re-Estimation and Optimized Allocation Ratio. 采用非盲样本量再估计和优化分配比例的自适应三臂临床终点生物等效性比较研究设计

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-10-08 DOI: 10.1002/pst.2439

David Hinds, Wanjie Sun

{"title":"An Adaptive Three-Arm Comparative Clinical Endpoint Bioequivalence Study Design With Unblinded Sample Size Re-Estimation and Optimized Allocation Ratio.","authors":"David Hinds, Wanjie Sun","doi":"10.1002/pst.2439","DOIUrl":"https://doi.org/10.1002/pst.2439","url":null,"abstract":"A three-arm comparative clinical endpoint bioequivalence (BE) study is often used to establish bioequivalence (BE) between a locally acting generic drug (T) and reference drug (R), where superiority needs to be established for T and R over Placebo (P) and equivalence needs to be established for T vs. R. Sometimes, when study design parameters are uncertain, a fixed design study may be under- or over-powered and result in study failure or unnecessary cost. In this paper, we propose a two-stage adaptive clinical endpoint BE study with unblinded sample size re-estimation, standard or maximum combination method, optimized allocation ratio, optional re-estimation of the effect size based on likelihood estimation, and optional re-estimation of the R and P treatment means at interim analysis, which have not been done previously. Our proposed method guarantees control of Type 1 error rate analytically. It helps to reduce the average sample size when the original fixed design is overpowered and increases the sample size and power when the original study and group sequential design are under-powered. Our proposed adaptive design can help generic drug sponsors cut cost and improve success rate, making clinical study endpoint BE studies more affordable and more generic drugs accessible to the public.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the Operational Characteristics of the Individual Causal Association as a Metric of Surrogacy in the Binary Continuous Setting. 在二元连续环境中评估作为代孕指标的个体因果关联的操作特征。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-09-29 DOI: 10.1002/pst.2437

Fenny Ong, Geert Molenberghs, Andrea Callegaro, Wim Van der Elst, Florian Stijven, Geert Verbeke, Ingrid Van Keilegom, Ariel Alonso

{"title":"Assessing the Operational Characteristics of the Individual Causal Association as a Metric of Surrogacy in the Binary Continuous Setting.","authors":"Fenny Ong, Geert Molenberghs, Andrea Callegaro, Wim Van der Elst, Florian Stijven, Geert Verbeke, Ingrid Van Keilegom, Ariel Alonso","doi":"10.1002/pst.2437","DOIUrl":"https://doi.org/10.1002/pst.2437","url":null,"abstract":"In a causal inference framework, a new metric has been proposed to quantify surrogacy for a continuous putative surrogate and a binary true endpoint, based on information theory. The proposed metric, termed the individual causal association (ICA), was quantified using a joint causal inference model for the corresponding potential outcomes. Due to the non-identifiability inherent in this type of models, a sensitivity analysis was introduced to study the behavior of the ICA as a function of the non-identifiable parameters characterizing the aforementioned model. In this scenario, to reduce uncertainty, several plausible yet untestable assumptions like monotonicity, independence, conditional independence or homogeneous variance-covariance, are often incorporated into the analysis. We assess the robustness of the methodology regarding these simplifying assumptions via simulation. The practical implications of the findings are demonstrated in the analysis of a randomized clinical trial evaluating an inactivated quadrivalent influenza vaccine.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quality by Design for Preclinical In Vitro Assay Development. 临床前体外检测开发的设计质量。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-09-24 DOI: 10.1002/pst.2430

Jonathan Jones, Bairu Zhang, Xiang Zhang, Peter Konings, Pia Hansson, Anna Backmark, Alessia Serrano, Ulrike Künzel, Steven Novick

引用次数: 0

On Some Modeling Issues in Estimating Vaccine Efficacy 关于估算疫苗疗效的一些模型问题

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-09-10 DOI: 10.1002/pst.2440

Mauro Gasparini

引用次数: 0

Propensity Score Analysis With Baseline and Follow-Up Measurements of the Outcome Variable. 对结果变量进行基线和随访测量的倾向得分分析。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-09-05 DOI: 10.1002/pst.2436

Peter C Austin

{"title":"Propensity Score Analysis With Baseline and Follow-Up Measurements of the Outcome Variable.","authors":"Peter C Austin","doi":"10.1002/pst.2436","DOIUrl":"https://doi.org/10.1002/pst.2436","url":null,"abstract":"A common feature in cohort studies is when there is a baseline measurement of the continuous follow-up or outcome variable. Common examples include baseline measurements of physiological characteristics such as blood pressure or heart rate in studies where the outcome is post-baseline measurement of the same variable. Methods incorporating the propensity score are increasingly being used to estimate the effects of treatments using observational studies. We examined six methods for incorporating the baseline value of the follow-up variable when using propensity score matching or weighting. These methods differed according to whether the baseline value of the follow-up variable was included or excluded from the propensity score model, whether subsequent regression adjustment was conducted in the matched or weighted sample to adjust for the baseline value of the follow-up variable, and whether the analysis estimated the effect of treatment on the follow-up variable or on the change from baseline. We used Monte Carlo simulations with 750 scenarios. While no analytic method had uniformly superior performance, we provide the following recommendations: first, when using weighting and the ATE is the target estimand, use an augmented inverse probability weighted estimator or include the baseline value of the follow-up variable in the propensity score model and subsequently adjust for the baseline value of the follow-up variable in a regression model. Second, when the ATT is the target estimand, regardless of whether using weighting or matching, analyze change from baseline using a propensity score that excludes the baseline value of the follow-up variable.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generalizing Treatment Effect to a Target Population Without Individual Patient Data in a Real-World Setting. 在真实世界环境中，在没有个体患者数据的情况下，将治疗效果推广到目标人群。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-09-03 DOI: 10.1002/pst.2435

Hui Quan, Tong Li, Xun Chen, Gang Li

{"title":"Generalizing Treatment Effect to a Target Population Without Individual Patient Data in a Real-World Setting.","authors":"Hui Quan, Tong Li, Xun Chen, Gang Li","doi":"10.1002/pst.2435","DOIUrl":"https://doi.org/10.1002/pst.2435","url":null,"abstract":"The innovative use of real-world data (RWD) can answer questions that cannot be addressed using data from randomized clinical trials (RCTs). While the sponsors of RCTs have a central database containing all individual patient data (IPD) collected from trials, analysts of RWD face a challenge: regulations on patient privacy make access to IPD from all regions logistically prohibitive. In this research, we propose a double inverse probability weighting (DIPW) approach for the analysis sponsor to estimate the population average treatment effect (PATE) for a target population without the need to access IPD. One probability weighting is for achieving comparable distributions in confounders across treatment groups; another probability weighting is for generalizing the result from a subpopulation of patients who have data on the endpoint to the whole target population. The likelihood expressions for propensity scores and the DIPW estimator of the PATE can be written to only rely on regional summary statistics that do not require IPD. Our approach hinges upon the positivity and conditional independency assumptions, prerequisites to most RWD analysis approaches. Simulations are conducted to compare the performances of the proposed method against a modified meta-analysis and a regular meta-analysis.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0