ArticleClinical pharmacology and therapeutics2024
Rationale, Development, and Validation of HdxSim, a Clinical Decision Support Tool for Model-Informed Precision Dosing of Hydroxyurea for Children with Sickle Cell Anemia.
Article in Clinical pharmacology and therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
Who cites it
12 citing papers in PubMed.
- Undetectable Hydroxyurea in an Untimed Blood Sample Does Not Establish Nonadherence.American journal of hematology · 2026Article
- Undetectable Hydroxyurea Levels in the Majority of Sickle Cell Disease Patients, Especially in Young Children.American journal of hematology · 2026Article
- Clinical Model-Informed Precision Dosing Consult Service for Accelerating Personalized Medication in Pediatric Patients.Clinical pharmacology and therapeutics · 2026Review
- Article
- Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations.Blood advances · 2026Article
- The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Integrated Physiologically-based Pharmacokinetic Model with a Quantitative Systems Pharmacology and Toxicology Model for Statins in Disease Population. Part 2: MIDD and MIPD Applications.The AAPS journal · 2025Article
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- The modern use of hydroxyurea for children with sickle cell anemia.Haematologica · 2025Review
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.Acta haematologica · 2025Article
- Model-informed precision dosing of quetiapine in bipolar affective disorder patients: initial dose recommendation.Frontiers in psychiatry · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Hydroxyurea treatment for children with sickle cell anemia (SCA) is effective and life-saving. Stepwise escalation to maximum tolerated dose (MTD) provides optimal benefits, but is logistically challenging and time-consuming, especially in low-income countries where most people with SCA live. Model-informed precision dosing (MIPD) of hydroxyurea expedites MTD determination and improves outcomes compared with trial-and-error dose adjustments. HdxSim, a user-friendly, online, clinical decision support tool was developed to facilitate hydroxyurea MIPD and evaluated using real-world pharmacokinetic (PK) data. First-dose hydroxyurea PK profiles were analyzed from two clinical trial datasets (Hydroxyurea Study of Long-Term Effects (HUSTLE), NCT00305175 and Therapeutic Response Evaluation and Adherence Trial (TREAT), NCT02286154). Areas under the concentration-time curve (AUC) estimated by HdxSim were compared with those determined using traditional trapezoidal methodology and PK software (MWPharm-DOS). The doses predicted by HdxSim and MWPharm-DOS were compared with the observed clinical MTD. For HUSTLE participants, HdxSim accurately estimated hydroxyurea AUC compared with the trapezoidal method, with < 20% variance. The average (mean ± SD) AUC for TREAT participants estimated with HdxSim (68.6 ± 18.0 mg*hour/L) was lower than MWPharm-DOS (78.6 ± 20.7 mg*hour/L, P = 0.012), but the average recommended doses were not different (425 vs. 423 mg/day, P = 0.97). Moreover, HdxSim was non-inferior to MWPharm-DOS at predicting clinical MTD (absolute difference 3.9 ± 5.8 vs. 4.9 ± 8.2 mg/kg/day, P = 0.19). HdxSim accurately estimates hydroxyurea exposure and is noninferior to traditional PK approaches at predicting the clinical hydroxyurea MTD. Hydroxyurea dosing based on target exposure leads to improved outcomes in children with SCA, and has the potential to make PK-guided hydroxyurea dosing more accessible to this neglected population globally.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.