model evaluation

模型评估
  • 文章类型: Journal Article
    土壤的表观热导率(λ)作为土壤含水量(θ)的函数,即,需要λ(θ)来确定土壤中的热流。为了简单起见,可以在热和水流模型中使用λ(θ)的函数。这项研究的目的是建立一个基于逻辑方程的S型模型,用于整个土壤含水量范围和各种土壤质地,可用于模拟受尊重模式的热量和水流。Further,评估了开发的S形模型以及文献中的其他两个模型的性能。在提出的S形模型中,该模型的常数是基于经验多变量方程,通过使用土壤沙粒含量和容重来估计的。S形模型在广泛的土壤质地下具有良好的准确性。由于测量和预测的λ之间的关系显示斜率和截距值分别接近1.0和0.0。通过S形模型获得的结果与Johansen和Lu等人获得的结果的比较。模型表明,对于各种土壤质地和土壤含水量,S型模型在预测λ方面优于其他两种模型。此外,与熊等人最近提出的模型进行比较。表明我们的S形模型是优越的。因此,我们开发的sigmoidal模型可用于热和水流模型来预测土壤温度和热流。
    Apparent thermal conductivity of soil (λ) as a function of soil water content (θ), i.e., λ(θ) is needed to determine the heat flow in soil. The function of λ(θ) can be used in heat and water flow models for simplicity. The objective of this study was to develop a sigmoidal model based on logistic equation for entire range of soil water contents and a wide range of soil textures that can be used in simulation of heat and water flow in respected modes. Further, performance of the developed sigmoidal model along with two other models in literature was evaluated. In the proposed sigmoidal model, the constants of this model are estimated based on empirical multivariate equations by using soil sand content and bulk density. The sigmoidal model was validated with good accuracy for a wide range of soil textures, as the relationship between the measured and predicted λ showed slope and intercept values of nearly 1.0 and 0.0, respectively. Comparison of the results obtained by sigmoidal model with those obtained from Johansen and Lu et al. models indicated that, the sigmoidal model was superior to the other two models in prediction of λ for a wide range of soil textures and soil water contents. Furthermore, comparison with a recently proposed model by Xiong et al. indicated that our sigmoidal model is superior. Therefore, our developed sigmoidal model can be used in heat and water flow models to predict the soil temperature and heat flow.
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  • 文章类型: Journal Article
    背景:男性和女性身体之间存在固有的差异,女性在临床试验中的历史代表性不足扩大了现有医疗保健数据中的这一差距.基于有偏见的数据开发时,临床决策支持工具的公平性存在风险。本文旨在定量评估风险预测模型中的性别偏见。我们的目标是通过对不同医院的多个用例进行调查来概括我们的发现。
    方法:首先,我们对源数据进行了彻底的分析,以发现基于性别的差异。其次,我们评估了模型在不同医院和不同用例的不同性别组的性能.使用接受者操作特征曲线下面积(AUROC)量化性能评价。最后,我们通过分析漏诊和过度诊断率来研究这些偏见的临床意义,和决策曲线分析(DCA)。我们还研究了模型校准对减轻决策过程中与性别相关的差异的影响。
    结果:我们的数据分析揭示了发病率的显著差异,AUROC,以及不同性别的过度诊断率,医院和临床用例。然而,还观察到女性人群的低诊断率始终较高。总的来说,女性人群的发病率较低,模型应用于该组时表现较差。此外,决策曲线分析显示,在感兴趣的阈值范围内,不同性别组之间的模型临床效用差异无统计学意义.
    结论:风险预测模型中性别偏见的存在因不同的临床用例和医疗机构而异。尽管在数据源级别观察到男性和女性人群之间存在固有差异,这种差异不影响临床效用的均等性。总之,本研究中进行的评估突出了在临床风险预测模型的不同视角下持续监测基于性别的差异的重要性.
    BACKGROUND: An inherent difference exists between male and female bodies, the historical under-representation of females in clinical trials widened this gap in existing healthcare data. The fairness of clinical decision-support tools is at risk when developed based on biased data. This paper aims to quantitatively assess the gender bias in risk prediction models. We aim to generalize our findings by performing this investigation on multiple use cases at different hospitals.
    METHODS: First, we conduct a thorough analysis of the source data to find gender-based disparities. Secondly, we assess the model performance on different gender groups at different hospitals and on different use cases. Performance evaluation is quantified using the area under the receiver-operating characteristic curve (AUROC). Lastly, we investigate the clinical implications of these biases by analyzing the underdiagnosis and overdiagnosis rate, and the decision curve analysis (DCA). We also investigate the influence of model calibration on mitigating gender-related disparities in decision-making processes.
    RESULTS: Our data analysis reveals notable variations in incidence rates, AUROC, and over-diagnosis rates across different genders, hospitals and clinical use cases. However, it is also observed the underdiagnosis rate is consistently higher in the female population. In general, the female population exhibits lower incidence rates and the models perform worse when applied to this group. Furthermore, the decision curve analysis demonstrates there is no statistically significant difference between the model\'s clinical utility across gender groups within the interested range of thresholds.
    CONCLUSIONS: The presence of gender bias within risk prediction models varies across different clinical use cases and healthcare institutions. Although inherent difference is observed between male and female populations at the data source level, this variance does not affect the parity of clinical utility. In conclusion, the evaluations conducted in this study highlight the significance of continuous monitoring of gender-based disparities in various perspectives for clinical risk prediction models.
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  • 文章类型: Journal Article
    随着个人经济水平的提高,对羊肉的需求也是如此。增强肉羊的品种不仅提高了生产效率和经济效益,而且促进了肉羊养殖业的可持续增长。因此,本研究考察了天目赛诺羊的早期生长和繁殖性状,分析这些性状之间的遗传相互作用,为完善育种策略和加快该品种的遗传发展提供理论基础。调查收集了29,966个数据条目,涉及111个父亲的出生体重(BWT)和113个其他指标。数据包含来自1633个水坝的10415个BWT记录,来自1,570个水坝的12,753个断奶重量(WWT)记录,1,597个水坝的12,793个平均日收益(ADG)记录,和1499个水坝的13594个产仔数(LS)记录。利用SAS9.2软件中的GLM程序,该研究分析了羔羊BWT的非遗传影响,WWT,ADG,和LS。同时,DMU软件针对每种性状估计了各种动物模型的方差分量。采用Akaike信息准则(AIC)和似然比检验(LRT),测试了六个模型,纳入或排除母亲继承和环境影响,确定推导遗传参数的最优模型。研究结果表明,出生年份(BY),出生季度(BQ),出生类型(BT),母亲年龄(AM),出生性别(BS)对BWT产生了重大影响,WWT,和ADG(p<0.01)。此外,BQ和AM显著影响LS(p<0.01)。最准确的遗传评价模型确定了BWT的遗传力,WWT,ADG,和LS分别为0.0695、0.0849、0.0777和0.1252。
    As the economic level of individuals rises, so too does the demand for mutton. Enhancing the breeds of mutton sheep not only boosts production efficiency and economic benefits but also fosters the sustainable growth of the mutton sheep breeding industry. Thus, this study examines the early growth and reproductive traits of Tianmu Sainuo sheep, analyzing the genetic interactions among these traits to furnish a theoretical foundation for refining breeding strategies and expediting the genetic advancement of this breed. The investigation compiled 29,966 data entries, involving 111 sires for birth weight (BWT) and 113 for other metrics. The data encompassed 10,415 BWT records from 1,633 dams, 12,753 weaning weight (WWT) records from 1,570 dams, 12,793 average daily gain (ADG) records from 1,597 dams, and 13,594 litter size (LS) records from 1,499 dams. Utilizing the GLM procedure in SAS 9.2 software, the study analyzed the non-genetic influences on lamb BWT, WWT, ADG, and LS. Concurrently, DMU software estimated the variance components across various animal models for each trait. Employing the Akaike Information Criterion (AIC) and likelihood ratio test (LRT), six models were tested, incorporating or excluding maternal inheritance and environmental impacts, to identify the optimal model for deriving genetic parameters. The findings reveal that birth year (BY), birth quarter (BQ), birth type (BT), age of mother (AM), and birth sex (BS) exerted significant impacts on BWT, WWT, and ADG (p < 0.01). Additionally, BQ and AM significantly influenced LS (p < 0.01). The most accurate genetic evaluation model determined the heritability of BWT, WWT, ADG, and LS to be 0.0695, 0.0849, 0.0777, and 0.1252, respectively.
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  • 文章类型: Journal Article
    在过去的40年里,治疗性抗体的发现和开发取得了相当大的进展,机器学习(ML)提供了一种有前途的方法,通过降低成本和所需的实验数量来加快这一过程。数据集和评估方法的多样性阻碍了ML指导抗体设计和开发(D&D)的最新进展,这使得很难进行比较和评估效用。建立标准和准则对于更广泛地采用ML和该领域的发展至关重要。这个观点批判性地回顾了当前的实践,突出了常见的陷阱,并提出了治疗性抗体D&D中各种基于ML的技术的方法开发和评估指南。解决机器学习过程中的挑战,建议每个阶段采用最佳做法,以提高可重复性和进展性。
    In the past 40 years, therapeutic antibody discovery and development have advanced considerably, with machine learning (ML) offering a promising way to speed up the process by reducing costs and the number of experiments required. Recent progress in ML-guided antibody design and development (D&D) has been hindered by the diversity of data sets and evaluation methods, which makes it difficult to conduct comparisons and assess utility. Establishing standards and guidelines will be crucial for the wider adoption of ML and the advancement of the field. This perspective critically reviews current practices, highlights common pitfalls and proposes method development and evaluation guidelines for various ML-based techniques in therapeutic antibody D&D. Addressing challenges across the ML process, best practices are recommended for each stage to enhance reproducibility and progress.
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  • 文章类型: Journal Article
    自动测量甲烷和二氧化碳的浓度比,[CH4]:[CO2],在单个动物的呼吸中(所谓的“嗅探器技术”)和估计的二氧化碳产量可用于估计CH4产量,前提是可以可靠地计算CO2产量。这将允许在大型奶牛队列中估计个体奶牛的CH4产量,由此,根据它们的CH4产量对奶牛进行排序可能成为可能,并且它们的值可用于低CH4排放动物的育种。二氧化碳产量的估计通常基于产热预测,可以根据体重(BW)计算,能量校正牛奶产量,和怀孕的日子。本研究的目的是直接从牛奶生产中预测二氧化碳的产生,饮食,和动物变量,并进一步开发用于不同场景的不同模型,取决于可用的数据。国际数据集包含2,244条来自个体泌乳奶牛的记录,包括二氧化碳产量和相关性状,作为干物质摄入量(MDI),饮食组成,BW,牛奶生产和成分,牛奶和怀孕的日子,被编译以构成训练数据集。研究地点和嵌套在研究地点内的实验被包括为随机截距。CO2产生的测量方法(呼吸室(RC)或GreenFeed(GF))与研究地点混淆,因此被排除在模型之外。总的来说,基于当前训练数据集开发了3个模型:模型1(“最佳模型”),其中包括所有重要的特征,模型2(“农场模型”),在那里,MI被排除在外,和模型3(“简化农场模型”),其中DMI和BW均被排除在外。用RC数据(n=103)对测试数据集进行评估,没有添加剂的GF数据(n=478)或仅包括硝酸盐、3-硝基氧基丙醇(3-NOP),或硝酸盐和3-NOP的组合饲喂奶牛(GF+:n=295),显示了3个模型的良好精度,通过绝对值(-0.22至0.097)和均方误差(MSE)的百分比(0.049至4.89)的低斜率偏差来说明。然而,平均偏差(MB)表明,当在GF和RC测试数据集上评估模型时,系统的CO2产量过度预测和预测不足,分别。为了解决这种偏见,这3个模型是在修改后的测试数据集上进行评估的,通过从RC上的特定模型的评估中减去(测量值通过RC获得)或添加绝对MB(测量值通过GF获得)来调整CO2产量(g/d),GF,和GF+测试数据集。通过这种修改,MB的绝对值和MB占MSE的百分比变得可以忽略不计。总之,这3个模型在预测泌乳奶牛的二氧化碳产量方面是精确的。
    Automated measurements of the ratio of concentrations of methane and carbon dioxide, [CH4]:[CO2], in breath from individual animals (the so-called \"sniffer technique\") and estimated CO2 production can be used to estimate CH4 production, provided that CO2 production can be reliably calculated. This would allow CH4 production from individual cows to be estimated in large cohorts of cows, whereby ranking of cows according to their CH4 production might become possible and their values could be used for breeding of low CH4-emitting animals. Estimates of CO2 production are typically based on predictions of heat production, which can be calculated from body weight (BW), energy-corrected milk yield, and days of pregnancy. The objectives of the present study were to develop predictions of CO2 production directly from milk production, dietary, and animal variables, and furthermore to develop different models to be used for different scenarios, depending on available data. An international dataset with 2,244 records from individual lactating cows including CO2 production and associated traits, as dry matter intake (DMI), diet composition, BW, milk production and composition, days in milk, and days pregnant, was compiled to constitute the training dataset. Research location and experiment nested within research location were included as random intercepts. The method of CO2 production measurement (respiration chamber [RC] or GreenFeed [GF]) was confounded with research location, and therefore excluded from the model. In total, 3 models were developed based on the current training dataset: model 1 (\"best model\"), where all significant traits were included; model 2 (\"on-farm model\"), where DMI was excluded; and model 3 (\"reduced on-farm model\"), where both DMI and BW were excluded. Evaluation on test dat sets with either RC data (n = 103), GF data without additives (n = 478), or GF data only including observations where nitrate, 3-nitrooxypropanol (3-NOP), or a combination of nitrate and 3-NOP were fed to the cows (GF+: n = 295), showed good precision of the 3 models, illustrated by low slope bias both in absolute values (-0.22 to 0.097) and in percentage (0.049 to 4.89) of mean square error (MSE). However, the mean bias (MB) indicated systematic overprediction and underprediction of CO2 production when the models were evaluated on the GF and the RC test datasets, respectively. To address this bias, the 3 models were evaluated on a modified test dataset, where the CO2 production (g/d) was adjusted by subtracting (where measurements were obtained by RC) or adding absolute MB (where measurements were obtained by GF) from evaluation of the specific model on RC, GF, and GF+ test datasets. With this modification, the absolute values of MB and MB as percentage of MSE became negligible. In conclusion, the 3 models were precise in predicting CO2 production from lactating dairy cows.
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  • 文章类型: Journal Article
    关于评估模型和理论的标准的共识是每门科学的组成部分。尽管如此,在心理学中,相对较少关注定义可靠的公共指标来评估模型性能。评估实践通常是特殊的,并且受到许多缺点的影响(例如,未能评估模型\'泛化到看不见的数据的能力),这使得很难区分好的和坏的模型。从机器学习和统计遗传学等领域汲取灵感,我们主张引入共同的基准,作为克服目前在心理学中观察到的缺乏可靠的模型评估标准的一种手段。我们讨论了基准应该满足的一些原则,以实现最大效用,确定社区可以采取的具体步骤来促进这些基准的发展,并解决在实施过程中可能出现的一些潜在陷阱和问题。我们认为,就共同评估基准达成共识将促进心理学的累积进步,并鼓励研究人员更加重视科学模型的实际应用。
    Consensus on standards for evaluating models and theories is an integral part of every science. Nonetheless, in psychology, relatively little focus has been placed on defining reliable communal metrics to assess model performance. Evaluation practices are often idiosyncratic and are affected by a number of shortcomings (e.g., failure to assess models\' ability to generalize to unseen data) that make it difficult to discriminate between good and bad models. Drawing inspiration from fields such as machine learning and statistical genetics, we argue in favor of introducing common benchmarks as a means of overcoming the lack of reliable model evaluation criteria currently observed in psychology. We discuss a number of principles benchmarks should satisfy to achieve maximal utility, identify concrete steps the community could take to promote the development of such benchmarks, and address a number of potential pitfalls and concerns that may arise in the course of implementation. We argue that reaching consensus on common evaluation benchmarks will foster cumulative progress in psychology and encourage researchers to place heavier emphasis on the practical utility of scientific models.
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  • 文章类型: Journal Article
    由于经济全球化的快速发展和经贸往来的加剧,跨国际和区域的碳排放日益严峻。世界各国政府制定法律和法规来保护本国对环境的影响。因此,选择稳健性评价模型和指标是一个迫切的研究课题。本文通过文献耦合评价,证明了评价数据的可靠性和科学性,多学科耦合数学模型与国际工程案例分析。本项目研究的创新之处在于综合分析了各种离散数据和不确定性指标对跨国际项目研究模型的复杂耦合效应,以及如何对交互效应进行准确建模和评估。本文为世界各国政府制定碳关税和碳排放政策提供了科学的计量标准和数据支持。案例分析数据显示,出口国和进口国的碳排放比为0.577:100;碳交易配额比为32.50:100。
    Due to the rapid economic development of globalization and the intensification of economic and trade exchanges, cross-international and regional carbon emissions have become increasingly severe. Governments worldwide establish laws and regulations to protect their countries\' environmental impact. Therefore, selecting robustness evaluation models and metrics is an urgent research topic. This article proves the reliability and scientific of the assessment data through literature coupling evaluation, multidisciplinary coupling mathematical model and international engineering case analysis. The innovation of this project\'s research lies in the comprehensive analysis of the complex coupling effects of various discrete data and uncertainty indicators on the research model across international projects and how to model and evaluate interactive effects accurately. This article provides scientific measurement standards and data support for governments worldwide to formulate carbon tariffs and carbon emission policies. Case analysis data shows that the carbon emission ratio of exporting and importing countries is 0.577:100; the carbon trading quota ratio is 32.50:100.
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  • 文章类型: Review
    估算蚯蚓对有机化学物质的生物积累的建模方法对于提高化学品风险评估的现实性非常重要。然而,现有模型的适用性是不确定的,部分原因是缺乏独立的数据集来测试它们。因此,本研究对现有的经验和动力学模型进行了全面的文献综述,这些模型估计有机化学物质在蚯蚓中的生物积累,并从已发表的文献中收集了两个独立的数据集来评估这些模型的预测性能。Belfuid等人。(1995a)模型是表现最好的经验模型,91.2%的蚯蚓身体残留物模拟在一个数量级的观察范围内。然而,该模型仅限于疏水性更强的农药和蚯蚓物种。Jager等人提出的动力学模型。(2003b)优于Armitage和Gobas(2007),预测蚯蚓E.andrei中PCB153的吸收在10倍以内。然而,Jager等人的适用性。由于评估数据集有限,因此对其他有机化合物和其他蚯蚓物种的模型未知。该模型需要针对不同的化学物质进行参数化,土壤,和使用前的物种类型,这限制了其在广泛范围内的风险评估的适用性。经验模型和动力学模型在可靠预测蚯蚓生物累积的能力方面都有改进的余地。它们是否适合环境风险评估,需要逐案仔细考虑。
    Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.\'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.
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  • 文章类型: Journal Article
    与复杂性状相关的非编码变体可以改变转录因子(TF)-脱氧核糖核酸结合的基序。尽管已经开发了许多计算模型来预测非编码变体对TF结合的影响,它们的预测能力缺乏系统的评估。在这里,我们评估了基于位置权重矩阵(PWM)的14种不同模型,支持向量机,普通最小二乘和深度神经网络(DNN),使用大规模的体外(即SNP-SELEX)和体内(即等位基因特异性结合,ASB)TF绑定数据。我们的结果表明,每个模型在体外预测SNP效应的准确性显着超过体内实现的准确性。对于体外变异影响预测,基于kmer/gkm的机器学习方法(deltaSVM_HT-SELEX,在体外数据集上训练的QBiC-Pred)表现出最佳性能。对于体内ASB变异预测,基于DNN的多任务模型(DeepSEA,Sei,在ChIP-seq数据集上训练的Enformer)表现出相对优异的性能。在基于PWM的方法中,tRap在体外和体内评价中显示出更好的性能。此外,我们发现可以更准确地预测TF类,如碱性亮氨酸拉链因子,而诸如C2H2锌指因子的预测精度较低,与这些TF类的进化保守性保持一致。我们还强调了非序列因子的重要性,如顺式调控元件类型,TF表达式,影响TFs体内预测性能的相互作用和翻译后修饰。我们的研究为选择非编码变体的优先级方法和进一步优化此类模型提供了有价值的见解。
    Non-coding variants associated with complex traits can alter the motifs of transcription factor (TF)-deoxyribonucleic acid binding. Although many computational models have been developed to predict the effects of non-coding variants on TF binding, their predictive power lacks systematic evaluation. Here we have evaluated 14 different models built on position weight matrices (PWMs), support vector machines, ordinary least squares and deep neural networks (DNNs), using large-scale in vitro (i.e. SNP-SELEX) and in vivo (i.e. allele-specific binding, ASB) TF binding data. Our results show that the accuracy of each model in predicting SNP effects in vitro significantly exceeds that achieved in vivo. For in vitro variant impact prediction, kmer/gkm-based machine learning methods (deltaSVM_HT-SELEX, QBiC-Pred) trained on in vitro datasets exhibit the best performance. For in vivo ASB variant prediction, DNN-based multitask models (DeepSEA, Sei, Enformer) trained on the ChIP-seq dataset exhibit relatively superior performance. Among the PWM-based methods, tRap demonstrates better performance in both in vitro and in vivo evaluations. In addition, we find that TF classes such as basic leucine zipper factors could be predicted more accurately, whereas those such as C2H2 zinc finger factors are predicted less accurately, aligning with the evolutionary conservation of these TF classes. We also underscore the significance of non-sequence factors such as cis-regulatory element type, TF expression, interactions and post-translational modifications in influencing the in vivo predictive performance of TFs. Our research provides valuable insights into selecting prioritization methods for non-coding variants and further optimizing such models.
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  • 文章类型: Journal Article
    背景:ORIN1001是一类口服IRE1-α核糖核酸内切酶抑制剂,可阻断XBP1的激活,目前正在临床开发中,用于抑制肿瘤生长并增强化学或靶向治疗的效果。早期建立群体药代动力学(PopPK)模型可以表征ORIN1001的药代动力学(PK),并评估个体特异性因素对PK的影响。这将促进该研究药物的未来发展。方法:采用PhoenixNLME软件构建非线性混合效应模型,在I期临床试验中利用中国晚期实体瘤患者的信息(注册编号:NCT05154201).通过逐步过程筛选出具有统计学意义的PK协变量。最终的模型,在通过拟合优度图验证后,非参数引导,归一化预测分布误差的视觉预测检查和检验,进一步应用于模拟和评估协变量对ORIN1001暴露的影响,稳态时高达900毫克/天作为单一药剂。结果:选择具有一阶吸收(具有滞后时间)/消除的两室模型作为最佳结构模型。总胆红素(TBIL)和瘦体重(LBW)被认为是ORIN1001清除率(CL/F)的统计学上显着的协变量。在模型模拟后,它们还被证实对ORIN1001稳态暴露产生临床显着影响。基于这两个协变量的剂量调整的必要性仍有待在更大的群体中验证。结论:成功构建了ORIN1001的第一个PopPK模型,为今后的研究提供一些重要的参考。
    Background: ORIN1001, a first-in-class oral IRE1-α endoribonuclease inhibitor to block the activation of XBP1, is currently in clinical development for inhibiting tumor growth and enhancing the effect of chemical or targeted therapy. Early establishment of a population pharmacokinetic (PopPK) model could characterize the pharmacokinetics (PK) of ORIN1001 and evaluate the effects of individual-specific factors on PK, which will facilitate the future development of this investigational drug. Methods: Non-linear mixed effect model was constructed by Phoenix NLME software, utilizing the information from Chinese patients with advanced solid tumors in a phase I clinical trial (Register No. NCT05154201). Statistically significant PK covariates were screened out by a stepwise process. The final model, after validating by the goodness-of-fit plots, non-parametric bootstrap, visual predictive check and test of normalized prediction distribution errors, was further applied to simulate and evaluate the impact of covariates on ORIN1001 exposure at steady state up to 900 mg per day as a single agent. Results: A two-compartment model with first-order absorption (with lag-time)/elimination was selected as the best structural model. Total bilirubin (TBIL) and lean body weight (LBW) were considered as the statistically significant covariates on clearance (CL/F) of ORIN1001. They were also confirmed to exert clinically significant effects on ORIN1001 steady-state exposure after model simulation. The necessity of dose adjustments based on these two covariates remains to be validated in a larger population. Conclusion: The first PopPK model of ORIN1001 was successfully constructed, which may provide some important references for future research.
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