ArticlePharmaceutical research2020
Dose-Response Mixed Models for Repeated Measures - a New Method for Assessment of Dose-Response.
Article in Pharmaceutical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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.
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Who cites it
2 citing papers in PubMed.
- Bayesian Integrated Learning of Longitudinal Dose-Response Relationships via Decentralized Clinical Trials.Statistics in medicine · 2025Article
- Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn this paper we investigated a new method for dose-response analysis of longitudinal data in terms of precision and accuracy using simulations.
methodsThe new method, called Dose-Response Mixed Models for Repeated Measures (DR-MMRM), combines conventional Mixed Models for Repeated Measures (MMRM) and dose-response modeling. Conventional MMRM can be applied for highly variable repeated measure data and is a way to estimate the drug effect at each visit and dose, however without any assumptions regarding the dose-response shape. Dose-response modeling, on the other hand, utilizes information across dose arms and describes the drug effect as a function of dose. Drug development in chronic kidney disease (CKD) is complicated by many factors, primarily by the slow progression of the disease and lack of predictive biomarkers. Recently, new approaches and biomarkers are being explored to improve efficiency in CKD drug development. Proteinuria, i.e. urinary albumin-to-creatinine ratio (UACR) is increasingly used in dose finding trials in patients with CKD. We use proteinuria to illustrate the benefits of DR-MMRM.
resultsThe DR-MMRM had higher precision than conventional MMRM and less bias than a dose-response model on UACR change from baseline to end-of-study (DR-EOS).
conclusionsDR-MMRM is a promising method for dose-response analysis.
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