Ratio data and the quantification of drug effects

Anderson, Dwane E.; Lydic, Ralph

doi:10.1016/0147-7552(77)90041-9

Cited by 17 publications

(9 citation statements)

References 5 publications

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“…Traditionally, cotinine and other urinary biomarkers have been studied as a ratio to CR in correlation or regression analysis. However, dependent biological variables standardized by a denominator have unusual statistical properties which have decreased precision and sensitivity when compared to models where the denominator is treated as an independent variable (Anderson & Lydic 1997). …”

Section: Methodsmentioning

confidence: 99%

A comparison of creatinine vs. specific gravity to correct for urinary dilution of cotinine

2011

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Context The validity of urinary correction standards has not been established for most analytes. Methods We compared urinary creatinine and specific gravity as dilution correction standards for cotinine in a community-based study of smokers. Results Models of blood cotinine regressed against CR or SG (measured by total soluble solids) significantly improved the fit compared to a model without a dilution measure (P<0.01). There were no differences in model fit between CR- and SG-corrected values. Both CR and SG were significant predictors of urinary cotinine regressed against cigarettes smoked per day (P<0.01). Conclusion CR and SG are valid and interchangeable correction standards.

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Section: Methodsmentioning

confidence: 99%

A comparison of creatinine vs. specific gravity to correct for urinary dilution of cotinine

2011

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“…A covariance procedure (univariate analysis of covariance; Wildt and Ahtola 1978) was used to assess significance of groups, controlling for basal differences in level of responding to vehicle. Analysis of covariance has been suggested as an alternative to more traditional analysis of variance of percentage transformed data, is more defensible upon statistical grounds (Anderson and Lydic 1977), and is considered a more sensitive indicator of main effects. It should be noted that all assumptions for analysis of variance models are also required for covariance analysis.…”

Section: Methodsmentioning

confidence: 99%

Effects of an ACTH 4-9 related peptide upon intracranial self stimulation and general activity in the rat

Katz

1980

Psychopharmacology

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Adult male Sprague-Dawley rats were stereotactically implanted with electrodes within the anterior medial forebrain bundle. The rats were trained to respond for intracranial self-stimulation (ICS) and treated with control solution or varying doses of an ACTH 4--9 related synthetic peptide (Org 2766; H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH). The drug affected ICS as measured in overnight response records, with the highest dose reliably increasing the amount of responding. In a second experiment rats were similarly treated and general activity was assessed. No remarkable changes in activity were present at any tested dose. The findings corroborate previous reports suggesting ACTH-related peptides may be active in a variety of motivated tasks, but less active with respect to general activity.

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“…3 Dependent biological variables standardized by a denominator (here, uCR) generally tend to present unusual statistical properties, potentially impairing the sensitivity and precision of a marker. 11,16 Figure 1a/b: Relationship between uCR and TWuAs in linear and power functional regression analysis (PFRA). Subset of all samples < 40 µg/L TWuAs (n=4854) for uncorrected (1a) and conventionally CR corrected (1b) TWuAs.…”

Section: Pitfalls In Conventional Creatinine Correction (Ccrc)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variable Power Functional Dilution Adjustment of Spot Urine

Carmine¹

2023

Preprint

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Background Dilution adjustment of spot-urinary biomarkers by conventional creatinine correction (CCRC) remains controversial. Apart from unaccounted confounders like age, sex, muscle mass, or diet, the misperception of constant mass ratios between analyte and creatinine (uCR) over a wide hydration range entails deceptive creatinine correction errors (CRCE), foremost at both ends of the uCR-spectrum. Mitigating CRCE by restricting uCR-ranges to 0.3(0.4)-3 g/L generates high numbers of sample rejects and allows for misleading fluctuations within presumably tolerable uCR-ranges. Methods The CRCE for exemplary total weight Arsenic (TWuAs) was analyzed in a large set of n= 5,599 unselected spot urine samples. After confining data to 14 - 80 years, uncorrected arsenic (uAsUC) < 500 mcg/l, and uCR < 4.5g/L, the remaining 5,400 samples were partitioned, and a calculation method to standardize uAsUC to 1 g/L uCR developed based on uAsUC-stratified power functional regression analysis (PFRA). Findings The obtained standardizing method of variable power-functional creatinine correction (V-PFCRC) represents a progression of reportedly proven simple power-functional modifications of CCRC (S-PFCRC). In contrast to CCRC and S-PFCRC, standardization to 1g/L uCR by V-PFCRC yielded constant uAsN-values over the entire uCR-range in all sextiles. Residual bias was largely neutralized in all sextiles of uAsN (R2 9E-06 - 0.04), compared to uAsUC (R2 0.93 - 0.99) and CCRC (R2 0.42 - 0.89). The efficacy of CRCE compensation was confirmed by simple PFRA in both sexes and seven age bands. The strongest %CRCEs were found in samples at low concentrations of uCR (SBC -0.96) and/or uAsUC (SBC -0.11). Interpretation Standardization to 1g/L uCR by V-PFRA allows for more reliable dilution adjustment of spot urinary results than CCRC and S-PFCRC. As an easily adoptable, novel approach, the calculation method developed in this study can minimize residual dilution bias in urinary biomarkers adjusted by uCR, SG, and osmolality. While minimizing sample rejects, V-PFCRC will improve the reliability and comparability, particularly of lower concentrated urinary biomarkers in both conventional results and multiple linear regression models. Funding Self-funded.

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Ratio data and the quantification of drug effects

Cited by 17 publications

References 5 publications

A comparison of creatinine vs. specific gravity to correct for urinary dilution of cotinine

A comparison of creatinine vs. specific gravity to correct for urinary dilution of cotinine

Effects of an ACTH 4-9 related peptide upon intracranial self stimulation and general activity in the rat

Variable Power Functional Dilution Adjustment of Spot Urine

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