uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Likelihood based approaches to handling data below the quantification limit using NONMEM VI
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
2008 (English)In: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 35, no 4, 401-421 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To evaluate the likelihood-based methods for handling data below the quantification limit (BQL) using new features in NONMEM VI. METHODS: A two-compartment pharmacokinetic model with first-order absorption was chosen for investigation. Methods evaluated were: discarding BQL observations (M1), discarding BQL observations but adjusting the likelihood for the remaining data (M2), maximizing the likelihood for the data above the limit of quantification (LOQ) and treating BQL data as censored (M3), and like M3 but conditioning on the observation being greater than zero (M4). These four methods were compared using data simulated with a proportional error model. M2, M3, and M4 were also compared using data simulated from a positively truncated normal distribution. Successful terminations and bias and precision of parameter estimates were assessed. RESULTS: For the data simulated with a proportional error model, the overall performance was best for M3 followed by M2 and M1. M3 and M4 resulted in similar estimates in analyses without log transformation. For data simulated with the truncated normal distribution, M4 performed better than M3. CONCLUSIONS: Analyses that maximized the likelihood of the data above the LOQ and treated BQL data as censored provided the most accurate and precise parameter estimates.

Place, publisher, year, edition, pages
2008. Vol. 35, no 4, 401-421 p.
Keyword [en]
NONMEM VI, limit-of-quantification, likelihood
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-102607DOI: 10.1007/s10928-008-9094-4ISI: 000259371900002PubMedID: 18686017OAI: oai:DiVA.org:uu-102607DiVA: diva2:216515
Erratum in: Journal of Pharmacokinetics and pharmacodynamics,vol. 37, nr. 3, p. 305-308, doi: 10.1007/s10928-010-9158-0 Available from: 2009-05-09 Created: 2009-05-09 Last updated: 2010-12-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Journal of Pharmacokinetics and Pharmacodynamics
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 257 hits
ReferencesLink to record
Permanent link

Direct link