Pharmaceutical Statistics最新文献_第10页

Effects of duration of follow-up and lag in data collection on the performance of adaptive clinical trials. 随访持续时间和数据收集滞后对适应性临床试验表现的影响。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-03-01 Epub Date: 2023-10-14 DOI: 10.1002/pst.2342

Anders Granholm, Theis Lange, Michael O Harhay, Aksel Karl Georg Jensen, Anders Perner, Morten Hylander Møller, Benjamin Skov Kaas-Hansen

{"title":"Effects of duration of follow-up and lag in data collection on the performance of adaptive clinical trials.","authors":"Anders Granholm, Theis Lange, Michael O Harhay, Aksel Karl Georg Jensen, Anders Perner, Morten Hylander Møller, Benjamin Skov Kaas-Hansen","doi":"10.1002/pst.2342","DOIUrl":"10.1002/pst.2342","url":null,"abstract":"Different combined outcome-data lags (follow-up durations plus data-collection lags) may affect the performance of adaptive clinical trial designs. We assessed the influence of different outcome-data lags (0-105 days) on the performance of various multi-stage, adaptive trial designs (2/4 arms, with/without a common control, fixed/response-adaptive randomisation) with undesirable binary outcomes according to different inclusion rates (3.33/6.67/10 patients/day) under scenarios with no, small, and large differences. Simulations were conducted under a Bayesian framework, with constant stopping thresholds for superiority/inferiority calibrated to keep type-1 error rates at approximately 5%. We assessed multiple performance metrics, including mean sample sizes, event counts/probabilities, probabilities of conclusiveness, root mean squared errors (RMSEs) of the estimated effect in the selected arms, and RMSEs between the analyses at the time of stopping and the final analyses including data from all randomised patients. Performance metrics generally deteriorated when the proportions of randomised patients with available data were smaller due to longer outcome-data lags or faster inclusion, that is, mean sample sizes, event counts/probabilities, and RMSEs were larger, while the probabilities of conclusiveness were lower. Performance metric impairments with outcome-data lags ≤45 days were relatively smaller compared to those occurring with ≥60 days of lag. For most metrics, the effects of different outcome-data lags and lower proportions of randomised patients with available data were larger than those of different design choices, for example, the use of fixed versus response-adaptive randomisation. Increased outcome-data lag substantially affected the performance of adaptive trial designs. Trialists should consider the effects of outcome-data lags when planning adaptive trials.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41208637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conditional power and information fraction calculations at an interim analysis for random coefficient models. 随机系数模型的中期分析中的条件功率和信息分数计算。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-03-01 Epub Date: 2023-11-02 DOI: 10.1002/pst.2345

Sandra A Lewis, Kevin J Carroll, Todd DeVries, Jonathan Barratt

引用次数: 0

An illness-death multistate model to implement delta adjustment and reference-based imputation with time-to-event endpoints. 一个疾病死亡多状态模型，用于实现基于时间到事件终点的德尔塔调整和参考插补。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-03-01 Epub Date: 2023-11-08 DOI: 10.1002/pst.2348

Alberto García-Hernandez, Teresa Pérez, María Del Carmen Pardo, Dimitris Rizopoulos

{"title":"An illness-death multistate model to implement delta adjustment and reference-based imputation with time-to-event endpoints.","authors":"Alberto García-Hernandez, Teresa Pérez, María Del Carmen Pardo, Dimitris Rizopoulos","doi":"10.1002/pst.2348","DOIUrl":"10.1002/pst.2348","url":null,"abstract":"With a treatment policy strategy, therapies are evaluated regardless of the disturbance caused by intercurrent events (ICEs). Implementing this estimand is challenging if subjects are not followed up after the ICE. This circumstance can be dealt with using delta adjustment (DA) or reference-based (RB) imputation. In the survival field, DA and RB imputation have been researched so far using multiple imputation (MI). Here, we present a fully analytical solution. We use the illness-death multistate model with the following transitions: (a) from the initial state to the event of interest, (b) from the initial state to the ICE, and (c) from the ICE to the event. We estimate the intensity function of transitions (a) and (b) using flexible parametric survival models. Transition (c) is assumed unobserved but identifiable using DA or RB imputation assumptions. Various rules have been considered: no ICE effect, DA under proportional hazards (PH) or additive hazards (AH), jump to reference (J2R), and (either PH or AH) copy increment from reference. We obtain the marginal survival curve of interest by calculating, via numerical integration, the probability of transitioning from the initial state to the event of interest regardless of having passed or not by the ICE state. We use the delta method to obtain standard errors (SEs). Finally, we quantify the performance of the proposed estimator through simulations and compare it against MI. Our analytical solution is more efficient than MI and avoids SE misestimation-a known phenomenon associated with Rubin's variance equation.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522338","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

Propensity score-incorporated adaptive design approaches when incorporating real-world data. 倾向得分纳入自适应设计方法时，纳入现实世界的数据。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-03-01 Epub Date: 2023-11-28 DOI: 10.1002/pst.2347

Nelson Lu, Wei-Chen Chen, Heng Li, Changhong Song, Ram Tiwari, Chenguang Wang, Yunling Xu, Lilly Q Yue

{"title":"Propensity score-incorporated adaptive design approaches when incorporating real-world data.","authors":"Nelson Lu, Wei-Chen Chen, Heng Li, Changhong Song, Ram Tiwari, Chenguang Wang, Yunling Xu, Lilly Q Yue","doi":"10.1002/pst.2347","DOIUrl":"10.1002/pst.2347","url":null,"abstract":"The propensity score-integrated composite likelihood (PSCL) method is one method that can be utilized to design and analyze an application when real-world data (RWD) are leveraged to augment a prospectively designed clinical study. In the PSCL, strata are formed based on propensity scores (PS) such that similar subjects in terms of the baseline covariates from both the current study and RWD sources are placed in the same stratum, and then composite likelihood method is applied to down-weight the information from the RWD. While PSCL was originally proposed for a fixed design, it can be extended to be applied under an adaptive design framework with the purpose to either potentially claim an early success or to re-estimate the sample size. In this paper, a general strategy is proposed due to the feature of PSCL. For the possibility of claiming early success, Fisher's combination test is utilized. When the purpose is to re-estimate the sample size, the proposed procedure is based on the test proposed by Cui, Hung, and Wang. The implementation of these two procedures is demonstrated via an example.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445736","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

Enrollment forecast for clinical trials at the portfolio planning phase based on site-level historical data. 基于站点级历史数据的投资组合规划阶段临床试验的入组预测。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-03-01 Epub Date: 2023-10-23 DOI: 10.1002/pst.2343

Sheng Zhong, Yunzhao Xing, Mengjia Yu, Li Wang

{"title":"Enrollment forecast for clinical trials at the portfolio planning phase based on site-level historical data.","authors":"Sheng Zhong, Yunzhao Xing, Mengjia Yu, Li Wang","doi":"10.1002/pst.2343","DOIUrl":"10.1002/pst.2343","url":null,"abstract":"An accurate forecast of a clinical trial enrollment timeline at the planning phase is of great importance to both corporate strategic planning and trial operational excellence. The naive approach often calculates an average enrollment rate from historical data and generates an inaccurate prediction based on a linear trend with the average rate. Under the traditional framework of a Poisson-Gamma model, site activation delays are often modeled with either fixed initiation time or a simple random distribution while incorporating the user-provided site planning information to achieve good forecast accuracy. However, such user-provided information is not available at the early portfolio planning stage. We present a novel statistical approach based on generalized linear mixed-effects models and the use of non-homogeneous Poisson processes through the Bayesian framework to model the country initiation, site activation, and subject enrollment sequentially in a systematic fashion. We validate the performance of our proposed enrollment modeling framework based on a set of 25 preselected studies from four therapeutic areas. Our modeling framework shows a substantial improvement in prediction accuracy in comparison to the traditional statistical approach. Furthermore, we show that our modeling and simulation approach calibrates the data variability appropriately and gives correct coverage rates for prediction intervals of various nominal levels. Finally, we demonstrate the use of our approach to generate the predicted enrollment curves through time with confidence bands overlaid.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691914","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

What they forgot to tell you about machine learning with an application to pharmaceutical manufacturing. 他们忘了告诉你机器学习在制药业中的应用。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-02-28 DOI: 10.1002/pst.2366

Kjell Johnson, Max Kuhn

引用次数: 0

Sample size calculation for comparing two ROC curves 比较两条 ROC 曲线的样本量计算

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-02-28 DOI: 10.1002/pst.2371

Sin‐Ho Jung

引用次数: 0

Introduction to qualification and validation of an immunoassay. 免疫测定的鉴定和验证简介。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-02-13 DOI: 10.1002/pst.2370

Sarah Janssen

引用次数: 0

Evaluating hybrid controls methodology in early-phase oncology trials: A simulation study based on the MORPHEUS-UC trial. 评估早期肿瘤学试验中的混合对照方法：基于MOPHEUS-UC试验的模拟研究。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-01-01 Epub Date: 2023-09-24 DOI: 10.1002/pst.2336

Guanbo Wang, Melanie Poulin-Costello, Herbert Pang, Jiawen Zhu, Hans-Joachim Helms, Irmarie Reyes-Rivera, Robert W Platt, Menglan Pang, Artemis Koukounari

{"title":"Evaluating hybrid controls methodology in early-phase oncology trials: A simulation study based on the MORPHEUS-UC trial.","authors":"Guanbo Wang, Melanie Poulin-Costello, Herbert Pang, Jiawen Zhu, Hans-Joachim Helms, Irmarie Reyes-Rivera, Robert W Platt, Menglan Pang, Artemis Koukounari","doi":"10.1002/pst.2336","DOIUrl":"10.1002/pst.2336","url":null,"abstract":"Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase statistical precision. Here we assess combining two sources of Roche HTD to construct a hybrid control in targeted therapy for decision-making via an extensive simulation study. Our simulations are based on the real data of one of the experimental arms and the control arm of the MORPHEUS-UC Phase Ib/II study and two Roche HTD for atezolizumab monotherapy. We consider potential complications such as model misspecification, unmeasured confounding, different sample sizes of current treatment groups, and heterogeneity among the three trials. We evaluate two frequentist methods (with both Cox and Weibull accelerated failure time [AFT] models) and three different commensurate priors in Bayesian dynamic borrowing (with a Weibull AFT model), and modifications within each of those, when estimating the effect of treatment on survival outcomes and measures of effect such as marginal hazard ratios. We assess the performance of these methods in different settings and the potential of generalizations to supplement decisions in early-phase oncology trials. The results show that the proposed joint frequentist methods and noninformative priors within Bayesian dynamic borrowing with no adjustment on covariates are preferred, especially when treatment effects across the three trials are heterogeneous. For generalization of hybrid control methods in such settings, we recommend more simulation studies.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41146781","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

Simulating and reporting frequentist operating characteristics of clinical trials that borrow external information: Towards a fair comparison in case of one-arm and hybrid control two-arm trials. 模拟和报告借用外部信息的临床试验的频繁操作特征：对单臂试验和混合对照双臂试验进行公平比较。

IF 1.5 4区医学

Pharmaceutical Statistics Pub Date : 2024-01-01 Epub Date: 2023-08-26 DOI: 10.1002/pst.2334

Annette Kopp-Schneider, Manuel Wiesenfarth, Leonhard Held, Silvia Calderazzo

{"title":"Simulating and reporting frequentist operating characteristics of clinical trials that borrow external information: Towards a fair comparison in case of one-arm and hybrid control two-arm trials.","authors":"Annette Kopp-Schneider, Manuel Wiesenfarth, Leonhard Held, Silvia Calderazzo","doi":"10.1002/pst.2334","DOIUrl":"10.1002/pst.2334","url":null,"abstract":"Borrowing information from historical or external data to inform inference in a current trial is an expanding field in the era of precision medicine, where trials are often performed in small patient cohorts for practical or ethical reasons. Even though methods proposed for borrowing from external data are mainly based on Bayesian approaches that incorporate external information into the prior for the current analysis, frequentist operating characteristics of the analysis strategy are often of interest. In particular, type I error rate and power at a prespecified point alternative are the focus. We propose a procedure to investigate and report the frequentist operating characteristics in this context. The approach evaluates type I error rate of the test with borrowing from external data and calibrates the test without borrowing to this type I error rate. On this basis, a fair comparison of power between the test with and without borrowing is achieved. We show that no power gains are possible in one-sided one-arm and two-arm hybrid control trials with normal endpoint, a finding proven in general before. We prove that in one-arm fixed-borrowing situations, unconditional power (i.e., when external data is random) is reduced. The Empirical Bayes power prior approach that dynamically borrows information according to the similarity of current and external data avoids the exorbitant type I error inflation occurring with fixed borrowing. In the hybrid control two-arm trial we observe power reductions as compared to the test calibrated to borrowing that increase when considering unconditional power.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10448800","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