دورية أكاديمية
أعرض في EDS

Model-Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial.

التفاصيل البيبلوغرافية
العنوان: Model-Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial.
المؤلفون: Janssen Daalen JM; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Doesburg D; Amsterdam Data Collective, Amsterdam, The Netherlands., Hunik L; Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands., Kessel R; Amsterdam Data Collective, Amsterdam, The Netherlands., Herngreen T; Amsterdam Data Collective, Amsterdam, The Netherlands., Knol D; Amsterdam Data Collective, Amsterdam, The Netherlands., Ruys T; Amsterdam Data Collective, Amsterdam, The Netherlands., van den Bemt BJF; Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands.; Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands., Schers HJ; Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.
المصدر: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Sep; Vol. 116 (3), pp. 824-833. Date of Electronic Publication: 2024 May 06.
نوع المنشور: Journal Article; Validation Study
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Hoboken, NJ : Wiley
Original Publication: St. Louis : C.V. Mosby
مواضيع طبية MeSH: Thyroxine*/administration & dosage , Thyroxine*/therapeutic use , Thyroxine*/pharmacokinetics , Machine Learning* , Hypothyroidism*/drug therapy , General Practice*, Humans ; Middle Aged ; Male ; Female ; Adult ; Aged ; Computer Simulation ; Precision Medicine/methods ; Dose-Response Relationship, Drug ; Models, Biological ; Primary Health Care
مستخلص: Levothyroxine is one of the most prescribed drugs in the western world. Dosing is challenging due to high-interindividual differences in effective dosage and the narrow therapeutic window. Model-informed precision dosing (MIPD) using machine learning could assist general practitioners (GPs), but no such models exist for primary care. Furthermore, introduction of decision-support algorithms in healthcare is limited due to the substantial gap between developers and clinicians' perspectives. We report the development, validation, and a clinical simulation trial of the first MIPD application for primary care. Stable maintenance dosage of levothyroxine was the model target. The multiclass model generates predictions for individual patients, for different dosing classes. Random forest was trained and tested on a national primary care database (n = 19,004) with a final weighted AUC across dosing options of 0.71, even in subclinical hypothyroidism. TSH, fT4, weight, and age were most predictive. To assess the safety, feasibility, and clinical impact of MIPD for levothyroxine, we performed clinical simulation studies in GPs and compared MIPD to traditional prescription. Fifty-one GPs selected starting dosages for 20 primary hypothyroidism cases without and then with MIPD 2 weeks later. Overdosage and underdosage were defined as higher and lower than 12.5 μg relative to stable maintenance dosage. MIPD decreased overdosage in number (30.5 to 23.9%, P < 0.01) and magnitude (median 50 to 37.5 μg, P < 0.01) and increased optimal starting dosages (18.3 to 30.2%, P < 0.01). GPs considered lab results more often with MIPD and most would use the model frequently. This study demonstrates the clinical relevance, safety, and effectiveness of MIPD for levothyroxine in primary care.
(© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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المشرفين على المادة: Q51BO43MG4 (Thyroxine)
تواريخ الأحداث: Date Created: 20240507 Date Completed: 20240821 Latest Revision: 20240821
رمز التحديث: 20240821
DOI: 10.1002/cpt.3293
PMID: 38711388
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-6535
DOI:10.1002/cpt.3293