ArticleThe AAPS journal2012
Performance of methods for handling missing categorical covariate data in population pharmacokinetic analyses.
Article in The AAPS journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.Antimicrobial agents and chemotherapy · 2025Trial
- High-Dose Isoniazid Lacks EARLY Bactericidal Activity against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized Phase II Clinical Trial.American journal of respiratory and critical care medicine · 2024Trial
- Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.Clinical pharmacology and therapeutics · 2021Trial
- A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.Antimicrobial agents and chemotherapy · 2019Trial
- Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania.PloS one · 2015Trial
- Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi-physiologic population pharmacokinetic approach.Clinical and translational science · 2024Article
- Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.CNS drugs · 2024Article
- Covariate modeling in pharmacometrics: General points for consideration.CPT: pharmacometrics & systems pharmacology · 2024Review
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- Pharmacokinetics of Efavirenz 600mg in Combination with Rifampicin in Chinese HIV/TB Co-Infection Patients.Infection and drug resistance · 2023Article
- Pharmacogenetics of Dolutegravir Plasma Exposure Among Southern Africans With Human Immunodeficiency Virus.The Journal of infectious diseases · 2022Article
- Pharmacokinetics of standard versus high-dose isoniazid for treatment of multidrug-resistant tuberculosis.The Journal of antimicrobial chemotherapy · 2022Observational
- Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Effect of efavirenz-based ART on the pharmacokinetics of rifampicin and its primary metabolite in patients coinfected with TB and HIV.The Journal of antimicrobial chemotherapy · 2021Article
- Investigating the influence of relevant pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of orally administered docetaxel combined with ritonavir.The pharmacogenomics journal · 2021Article
- Approaches to handling missing or "problematic" pharmacology data: Pharmacokinetics.CPT: pharmacometrics & systems pharmacology · 2021Article
- Item Response Theory Modeling of the International Prostate Symptom Score in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.The AAPS journal · 2020Article
- Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV.Antimicrobial agents and chemotherapy · 2020Article
- Pharmacokinetics of Capecitabine and Four Metabolites in a Heterogeneous Population of Cancer Patients: A Comprehensive Analysis.CPT: pharmacometrics & systems pharmacology · 2019Article
- A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women.Clinical pharmacokinetics · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
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Abstract
In population pharmacokinetic analyses, missing categorical data are often encountered. We evaluated several methods of performing covariate analyses with partially missing categorical covariate data. Missing data methods consisted of discarding data (DROP), additional effect parameter for the group with missing data (EXTRA), and mixture methods in which the mixing probability was fixed to the observed fraction of categories (MIX(obs)), based on the likelihood of the concentration data (MIX(conc)), or combined likelihood of observed covariate data and concentration data (MIX(joint)). Simulations were implemented to study bias and imprecision of the methods in datasets with equal-sized and unbalanced category ratios for a binary covariate as well as datasets with non-random missingness (MNAR). Additionally, the performance and feasibility of implementation was assessed in two real datasets. At either low (10%) or high (50%) levels of missingness, all methods performed similarly well. Performance was similar for situations with unbalanced datasets (3:1 covariate distribution) and balanced datasets. In the MNAR scenario, the MIX methods showed a higher bias in the estimation of CL and covariate effect than EXTRA. All methods could be applied to real datasets, except DROP. All methods perform similarly at the studied levels of missingness, but the DROP and EXTRA methods provided less bias than the mixture methods in the case of MNAR. However, EXTRA was associated with inflated type I error rates of covariate selection, while DROP handled data inefficiently.
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