CPT: Pharmacometrics and Systems Pharmacology 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Item Response Theory in Early Phase Clinical Trials: Utilization of a Reference Model to Analyse the Montgomery ‐Åsberg Depression Rating Scale (MADRS)
AbstractAbstract:In clinical trials, Montgomery- Åsberg Depression Rating Scale (MADRS) questionnaire data is added up to total scores before analysis, assuming equal contribution of each separate question. Item Response Theory (IRT)-based analysis avoids this by using individual question responses to determine the latent variable (ψ), which rep resents a measure of depression severity. However, utilization of IRT in early phase trials remains difficult, because large datasets are needed to develop IRT models. Therefore, we aimed to evaluate the application and assumptions of a reference IRT model for analysis of an earl...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 9, 2023 Category: Drugs & Pharmacology Authors: Marije E. Otto,
Kirsten R. Bergmann,
Marieke L. de Kam,
Kasper Recourt,
Gabri ël E. Jacobs,
Michiel J. van Esdonk Tags: ARTICLE Source Type: research
Can a propensity score matching method be applied to assessing efficacy from single ‐arm proof‐of‐concept trials in oncology?
In this study, we demonstrated the feasibility of using the propensity score matching (PSM) method to improve decision making by matching relevant baseline features between current and historical cohorts. According to our findings, utilizing the PSM method may provide a less biased means of comparing outcomes between current and historical cohorts relative to a na ïve approach, which relies solely on differences in average outcomes between the cohorts. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - August 4, 2023 Category: Drugs & Pharmacology Authors: Shu ‐Wen Teng,
Yu‐Cheng Su,
Ravikumar Pallantla,
Madhav Channavazzala,
Rukmini Kumar,
Yucheng Sheng,
Hao Wang,
Crystal Wang,
Archie Tse Tags: ARTICLE Source Type: research
SARS ‐CoV‐2 viral dynamic modelling to inform model selection and timing and efficacy of antiviral therapy
In this study, eight published viral dynamic models were assessed, and model selection was performed. Viral load data were collected from a community surveillance study, including 2155 measurements from 162 patients (124 household and 38 non-household contacts). An extended version of the target-cell limited model that includes an eclipse phase and an immune response component that enhances viral clearance described best the data. In general, the parameter estimates showed good precision (relative standard error<10), apart from the death rate of infected cells. The parameter estimates were used to simulate the outcomes ...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 3, 2023 Category: Drugs & Pharmacology Authors: Shengyuan Zhang,
Akosua A. Agyeman,
Christoforos Hadjichrysanthou,
Joseph F. Standing Tags: ARTICLE Source Type: research
Multivariate modeling of magnetic resonance biomarkers and clinical outcome measures for Duchenne muscular dystrophy clinical trials
This study aims to identify the optimal use of muscle fat fraction biomarkers in DMD clinical trials through a quantitative disease-drug-trial modeling and simulation approach. We simultaneously developed two multivariate models quantifying the longitudinal associations between six-minute walk distance (6MWD) and fat fraction measures from vastus lateralis and soleus muscles. We leveraged the longitudinal individual-level data collected over 10 years through theImagingDMD study. Age of the individuals at assessment was chosen as the time metric. After the longitudinal dynamic of each measure was modeled separately, the ...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 3, 2023 Category: Drugs & Pharmacology Authors: Sarah Kim,
Rebecca J. Willcocks,
Michael J. Daniels,
Juan Francisco Morales,
Deok Yong Yoon,
William T. Triplett,
Alison M. Barnard,
Daniela J. Conrado,
Varun Aggarwal,
Ramona Belfiore ‐Oshan,
Terina N. Martinez,
Glenn A. Walter,
William D. Tags: ARTICLE Source Type: research
Can a Propensity Score Matching Method be Applied to Assessing Efficacy from Single ‐Arm Proof‐of‐Concept Trials in Oncology?
In this study, we demonstrated the feasibility of using the propensity score matching (PSM) method to improve decision-making by matching relevant baseline features between current and historical cohorts. According to our findings, utilizing the PSM method may provide a less biased means of comparing outcomes between current and historical cohorts relative to a na ïve approach, which relies solely on differences in average outcomes between the cohorts. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - August 2, 2023 Category: Drugs & Pharmacology Authors: Shu ‐Wen Teng,
Yu‐Cheng Su,
Ravikumar Pallantla,
Madhav Channavazzala,
Rukmini Kumar,
Yucheng Sheng,
Hao Wang,
Crystal Wang,
Archie Tse Tags: ARTICLE Source Type: research
Prediction of relative change in free nerve growth factor following subcutaneous administration of tanezumab, a novel monoclonal antibody to nerve growth factor
AbstractTanezumab is a monoclonal antibody against nerve growth factor (NGF). We investigated tanezumab pharmacokinetic (PK)-NGF relationships and predicted the extent of systemic free NGF suppression with target-mediated drug disposition (TMDD) modeling using data from three pivotal phase III interventional studies (NCT02697773, NCT02709486, and NCT02528188) in patients with osteoarthritis. Patients received tanezumab 2.5 mg or 5 mg every 8 weeks (q8w) subcutaneously. A TMDD model using a previously established population PK model was used to describe plasma tanezumab and serum total NGF concentration data, and sim...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 1, 2023 Category: Drugs & Pharmacology Authors: Satoshi Shoji,
Akiyuki Suzuki,
Parya Nouri,
Chun ‐Hua Cai,
Puneet Gaitonde,
Scott Marshall Tags: ARTICLE Source Type: research
Clinical decision support for chemotherapy ‐induced neutropenia using a hybrid pharmacodynamic/machine learning model
AbstractConsensus guidelines recommend use of granulocyte colony stimulating factor (G-CSF) in patients deemed at-risk of chemotherapy-induced neutropenia, however these risk models are limited in the factors they consider and miss some cases of neutropenia. Clinical decision-making could be supported using models that better tailor their predictions to the individual patient using the wealth of data available in electronic health records (EHR). Here, we present a hybrid pharmacokinetic-pharmacodynamic (PKPD)/machine learning (ML) approach that uses predictions and individual Bayesian parameter estimates from a PKPD model ...
Source: CPT: Pharmacometrics and Systems Pharmacology - July 28, 2023 Category: Drugs & Pharmacology Authors: Jasmine H. Hughes,
Dominic M. H. Tong,
Vanessa Burns,
Bobby Daly,
Pedram Razavi,
Jaap J. Boelens,
Srijib Goswami,
Ron J. Keizer Tags: ARTICLE Source Type: research
Exposure ‐safety and exposure‐efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors
AbstractThe antibody-drug conjugate (ADC) tisotumab vedotin (TV) received accelerated approval from the US Food and Drug Administration for treatment of adults with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. A population pharmacokinetic (PK) model, developed using dosing data from four clinical TV studies, was used to estimate individual exposure and explore safety and efficacy exposure-response (ER) relationships. Because PK analysis showed no appreciable accumulation of TV and monomethyl auristatin E (MMAE) with repeated dosing, cycle 1 exposure metrics and predicte...
Source: CPT: Pharmacometrics and Systems Pharmacology - July 27, 2023 Category: Drugs & Pharmacology Authors: Chaitali Passey,
Jenna Voellinger,
Leonid Gibiansky,
Rudy Gunawan,
Leonardo Nicacio,
Ibrahima Soumaoro,
William D. Hanley,
Helen Winter,
Manish Gupta Tags: ARTICLE Source Type: research
Saliva as a noninvasive sampling matrix for therapeutic drug monitoring of intravenous busulfan in Chinese patients undergoing hematopoietic stem cell transplantation: A prospective population pharmacokinetic and simulation study
This study aimed to develop a PopPK model that can describe the relationship between plasma and saliva kinetics in patients receiving intravenous BU. The performance of the model in predicting the area under the concentration-time curve at steady state (AUCss) based on saliva samples is evaluated. Sixty-six patients with HSCT were recruited and administered 0.8 mg/kg BU intravenously. A PopPK model for saliva and plasma was developed using the nonlinear mixed effects model. Bayesian maximum a posteriori (MAP) optimization was used to estimate the model's predictive performance. Plasma and saliva PKs were adequately desc...
Source: CPT: Pharmacometrics and Systems Pharmacology - July 26, 2023 Category: Drugs & Pharmacology Authors: Baohua Xu,
Ting Yang,
Jianxing Zhou,
You Zheng,
Jingting Wang,
Qingxia Liu,
Dandan Li,
Yifan Zhang,
Maobai Liu,
Xuemei Wu Tags: ARTICLE Source Type: research
Knowledge graph aids comprehensive explanation of drug and chemical toxicity
AbstractIn computational toxicology, prediction of complex endpoints has always been challenging, as they often involve multiple distinct mechanisms. State-of-the-art models are either limited by low accuracy, or lack of interpretability due to their black-box nature. Here, we introduce AIDTox, an interpretable deep learning model which incorporates curated knowledge of chemical-gene connections, gene-pathway annotations, and pathway hierarchy. AIDTox accurately predicts cytotoxicity outcomes in HepG2 and HEK293 cells. It also provides comprehensive explanations of cytotoxicity covering multiple aspects of drug activity, i...
Source: CPT: Pharmacometrics and Systems Pharmacology - July 23, 2023 Category: Drugs & Pharmacology Authors: Yun Hao,
Joseph D. Romano,
Jason H. Moore Tags: ARTICLE Source Type: research
