‘Likelihood-ratio’ and ‘odds’ applied to monitoring of patients as a supplement to ‘reference change value’ (RCV)
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Per Hyltoft Petersen
Abstract
Background: Interpretation of serial data in monitoring of patients is usually performed by use of the ‘reference change value’ (RCV). While this tool for interpretation of measured differences is simple and clear, there are a number of drawbacks attached to the uncritical use of this concept. It is a dichotomised interpretation of continuous data using a fixed probability without any counter hypothesis. Therefore, a tool for better understanding and interpretation of measured differences in monitoring is needed.
Theory: The concept of sensitivity, specificity, likelihood ratios and odds used for diagnostic test evaluations is applied to monitoring by substituting measured concentrations with measured differences. Thus, two frequency distributions of differences are assumed, one for a stable, steady-state, situation and one for a certain change. Values exceeding a measured difference will thus represent ‘false change’ for the stable and ‘true change’ for the change and the ratio between these will define the likelihood. By making the hypothesis of change variable and equal to the actual difference, the distribution corresponding to the true changes for the measured difference varies with this. Consequently, the likelihood ratio for change increases with growing measured difference and when used together with the pre-test odds or pre-test probability, the post-test odds and post-test probability, related to the clinical situation, can be calculated.
Results: One example is acute intermittent porphyria, where increasing excretion of porphobilinogen is characteristic for an attack. The within-subject biological variation is estimated to 25%, which for two measurements gives a variation of 35% for measured differences. Three pre-test probabilities are assumed and illustrate that post-test odds and probability depends on both the pre-test probability and the measured difference. A second example is monitoring women in a follow-up after treatment of breast cancer, using the tumour marker CA 15-3. The within-subject biological variation is estimated to 14.9% and for differences 21% (2½×14.9 due to two measurements). Here, the monitoring is totally scheduled and the frequency of progression depends on the time after treatment. Thus, the pre-test probability varies with time so that a certain measured difference with a given likelihood ratio will result in varying post-test odds depending on time.
Conclusions: The concept presented here expands the earlier concept of RCVs by making it possible to have an estimate of the post-test odds for a certain difference to occur based on likelihood ratios and pre-test odds.
Clin Chem Lab Med 2008;46:157–64.
©2008 by Walter de Gruyter Berlin New York
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- A family with multiple mutations and sequence variations in the α- and β-globin gene clusters
- CTLA-4 polymorphism 49A–G is associated with placental abruption and preeclampsia in Finnish women
- Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects
- Association of high sensitive C-reactive protein with apolipoprotein E polymorphism in children and young adults: The Cardiovascular Risk in Young Finns Study
- Relationship between thiolactonase activity and hyperhomocysteinemia according to MTHFR gene polymorphism in Tunisian Behçet's disease patients
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- Probing the redox activity of T-lymphocytes deposited at electrode surfaces with voltammetric methods
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- Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate
- Reference Values
- Age-related changes of plasma glycosaminoglycans
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- Comparison of creatinine-based estimations of glomerular filtration rate in endurance athletes at rest
- Assay-dependent variability of serum insulin levels during oral glucose tolerance test: influence on reference intervals for insulin and on cut-off values for insulin sensitivity indices
- N-Terminal proB-type natriuretic peptide (NT-proBNP) concentrations in elite rugby players at rest and after active and passive recovery following strenuous training sessions
- Strenuous exercise activates growth factors and chemokines over-expression in human serum of top-level triathlon athletes during a competitive season
- Validation and Outcome Studies
- Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C
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- Different biological matrices (serum and plasma) utilization in consolidation processes: evaluation of seven Access® immunoassays
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- Homocysteine measurement by Vitros® Microtip homocysteine assay
- Evaluation of a novel standardized system for collection and quantification of oral fluid
- Letters to the Editor
- Tumor necrosis factor-α G(–308)A promoter polymorphism, matrix metalloproteinase (MMP)-3 5A/6A gene variation, MMP-9 C(–1562)T promoter polymorphism and risk and extent of ischemic heart disease
- Polyethylene glycol interference in the Immulite prolactin assay: treatment of the calibrators with polyethylene glycol does not improve diagnostic accuracy
Articles in the same Issue
- Opinion Papers
- The double whammy of endogenous insulin antibodies in non-diabetic subjects
- ‘Likelihood-ratio’ and ‘odds’ applied to monitoring of patients as a supplement to ‘reference change value’ (RCV)
- Genetics and Molecular Diagnostics
- A family with multiple mutations and sequence variations in the α- and β-globin gene clusters
- CTLA-4 polymorphism 49A–G is associated with placental abruption and preeclampsia in Finnish women
- Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects
- Association of high sensitive C-reactive protein with apolipoprotein E polymorphism in children and young adults: The Cardiovascular Risk in Young Finns Study
- Relationship between thiolactonase activity and hyperhomocysteinemia according to MTHFR gene polymorphism in Tunisian Behçet's disease patients
- A rapid and sensitive method to detect specific human lymphocyte antigen (HLA) class II alleles associated with celiac disease
- General Clinical Chemistry and Laboratory Medicine
- Probing the redox activity of T-lymphocytes deposited at electrode surfaces with voltammetric methods
- Long-term prognostic value of midregional pro-adrenomedullin and C-terminal pro-endothelin-1 in patients with acute myocardial infarction
- Changes in serum fetuin-A and inflammatory markers levels in end-stage renal disease (ESRD): effect of a single session haemodialysis
- Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate
- Reference Values
- Age-related changes of plasma glycosaminoglycans
- Stability of heparin blood samples during transport based on defined pre-analytical quality goals
- Comparison of creatinine-based estimations of glomerular filtration rate in endurance athletes at rest
- Assay-dependent variability of serum insulin levels during oral glucose tolerance test: influence on reference intervals for insulin and on cut-off values for insulin sensitivity indices
- N-Terminal proB-type natriuretic peptide (NT-proBNP) concentrations in elite rugby players at rest and after active and passive recovery following strenuous training sessions
- Strenuous exercise activates growth factors and chemokines over-expression in human serum of top-level triathlon athletes during a competitive season
- Validation and Outcome Studies
- Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C
- Evaluation of a new Sebia isoelectrofocusing kit for α1-antitrypsin phenotyping with the Hydrasys® System
- Different biological matrices (serum and plasma) utilization in consolidation processes: evaluation of seven Access® immunoassays
- Evaluation of the GEM® Premier™ 4000: a compact blood gas CO-Oximeter and electrolyte analyzer for point-of-care and laboratory testing
- Impact of storage conditions on genetic analysis or viral load determination in clinical specimens
- Homocysteine measurement by Vitros® Microtip homocysteine assay
- Evaluation of a novel standardized system for collection and quantification of oral fluid
- Letters to the Editor
- Tumor necrosis factor-α G(–308)A promoter polymorphism, matrix metalloproteinase (MMP)-3 5A/6A gene variation, MMP-9 C(–1562)T promoter polymorphism and risk and extent of ischemic heart disease
- Polyethylene glycol interference in the Immulite prolactin assay: treatment of the calibrators with polyethylene glycol does not improve diagnostic accuracy
