Initiation of Pediatric Clinical Trials for Coagulation Factors: Application of Pharmacokinetics and Allometry to First‐in‐Pediatric Dose Selection

2019 ◽  
Vol 59 (6) ◽  
pp. 829-834 ◽  
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Clinical Trials ◽  
Coagulation Factors ◽  
Dose Selection ◽  
Pediatric Dose

scholarly journals Neonatal and Pediatric Dose Selection: Quo Vadis?

2021 ◽  
Vol 61 (S1) ◽  
Author(s):  
Gilbert J. Burckart ◽  
John N. den Anker
Keyword(s):  
Dose Selection ◽  
Pediatric Dose ◽  
Quo Vadis

scholarly journals Progress in Drug Development–Pediatric Dose Selection: Workshop Summary

2021 ◽  
Vol 61 (S1) ◽  
Author(s):  
Jian Wang ◽  
John N. den Anker ◽  
Gilbert J. Burckart
Keyword(s):  
Drug Development ◽  
Dose Selection ◽  
Pediatric Dose ◽  
Workshop Summary

scholarly journals A Call for Objective Dose Selection to Increase Success in Pediatric Clinical Trials: A Perspective From NICHD and NIMH Program Staff

2021 ◽  
Vol 61 (S1) ◽  
Author(s):  
George Giacoia ◽  
Margaret C. Grabb ◽  
Aaron C. Pawlyk ◽  
Zhaoxia Ren ◽  
Lesly Samedy‐Bates ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Dose Selection ◽  
Program Staff

scholarly journals Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling

Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 40
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Prediction Error ◽  
Allometric Scaling ◽  
Polyclonal Antibodies ◽  
Therapeutic Proteins ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Pediatric Dose ◽  
Age Dependent

Allometric scaling can be used for the extrapolation of pharmacokinetic parameters from adults to children. The objective of this study was to predict clearance of therapeutic proteins (monoclonal and polyclonal antibodies and non-antibody proteins) allometrically in preterm neonates to adolescents. There were 13 monoclonal antibodies, seven polyclonal antibodies, and nine therapeutic proteins (non-antibodies) in the study. The clearance of therapeutic proteins was predicted using the age dependent exponents (ADE) model and then compared with the observed clearance values. There were in total 29 therapeutic proteins in this study with 75 observations. The number of observations with ≤30%, ≤50%, and >50% prediction error was 60 (80%), 72 (96%), and 3 (4%), respectively. Overall, the predicted clearance values of therapeutic proteins in children was good. The allometric method proposed in this manuscript can be used to select first-in-pediatric dose of therapeutic proteins in pediatric clinical trials.

A comprehensive evaluation of exposure–response relationships in clinical trials: application to support guselkumab dose selection for patients with psoriasis

2018 ◽  
Vol 45 (4) ◽  
pp. 523-535 ◽  
Author(s):  
Chuanpu Hu ◽  
Zhenling Yao ◽  
Yang Chen ◽  
Bruce Randazzo ◽  
Liping Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Comprehensive Evaluation ◽  
Dose Selection ◽  
Exposure Response ◽  
Selection For

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

2021 ◽  
Author(s):  
Paul P. Dobesh ◽  
Molly M. Kernan ◽  
Jenni J. Lueshen
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Special Populations ◽  
Dose Selection ◽  
Phase 3 ◽  
Optimal Drug

AbstractThere are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.

scholarly journals CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence

2019 ◽  
Vol 25 (2) ◽  
pp. 95-105
Author(s):  
Agata Blasiak ◽  
Jeffrey Khong ◽  
Theodore Kee
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Standard Of Care ◽  
Small Data ◽  
Current Standard ◽  
Dose Selection ◽  
Support Tool ◽  
Combination Treatments ◽  
Multiple Challenges ◽  
Over Time

The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials’ results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual’s response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team’s experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach—phenotypic personalized medicine (PPM)—finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals’ lives.

An Adaptive Design for Phase II Non-Oncology Dose Selection Clinical Trials

2010 ◽  
Vol 30 (6) ◽  
pp. 397-403 ◽  
Author(s):  
Zheng Su
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Adaptive Design ◽  
Dose Selection

Pediatric Dose Selection and Utility of PBPK in Determining Dose

2018 ◽  
Vol 20 (2) ◽  
Author(s):  
Ian E. Templeton ◽  
Nicholas S. Jones ◽  
Luna Musib
Keyword(s):  
Dose Selection ◽  
Pediatric Dose
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