-
Clinical Chemistry 08/2012; 58(8):1187-90. · 7.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Interference in immunoassays may cause both false-negative and false-positive results. It may be detected using a number of affirmative tests such as reanalysis of certain samples using different assay platforms with known bias, after the addition of blocker antibodies, or assessment of linearity and parallelism following serial doubling dilutions. One should look for interference where it is likely and has high medical impact. Probabilistic Bayesian reasoning is a statistical tool to identify samples where interference is most likely. But when looking for interference where it is likely, do we find it where it has the largest population health consequences?
We used information theory to quantify the effect of assay interference by calculating the Shannon information content (using logarithms with base 2). We then obtained lower bounds of the population health consequences of a particular test and combined these expressions to get lower bounds of the population health consequences of interference.
We suggest that assays having a low frequency of true positives should be the primary target of retesting because: (i) assays with a low frequency of true positives exhibit a high likelihood of interference and (ii) the population health consequences of false-positive results are generally higher for assays with a low frequency of true positives. Finally, we give a worked example having a realistic frequency of interference and test costs. In some immunoassays (e.g., tumour markers), adding a blocker to all tests can be a more cost-efficient mean than retesting positive samples.
Annals of Clinical Biochemistry 06/2012; 49(Pt 4):381-6. · 2.17 Impact Factor
-
Clinical Chemistry and Laboratory Medicine 02/2012; 50(2):409. · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objectives of this study are to establish reference limits for human epididymis protein 4, HE4, and investigate factors influencing HE4 levels in healthy subjects. HE4 was measured in 1,591 samples from the Nordic Reference Interval Project Bio-bank and Database biobank, using the manual HE4 EIA (Fujirebio) for 802 samples and the Architect HE4 (Abbott) for 792 samples. Reference limits were calculated using the statistical software R. The influence of donor characteristics such as age, sex, body mass index, smoking habits, and creatinine on HE4 levels was investigated using a multivariate model. The study showed that age is the main determinant of HE4 in healthy subjects, corresponding to 2% higher HE4 levels at 30 years (compared to 20 years), 9% at 40 years, 20% at 50 years, 37% at 60 years, 63% at 70 years, and 101% at 80 years. HE4 levels are 29% higher in smokers than in nonsmokers. In conclusion, HE4 levels in healthy subjects are associated with age and smoking status. Age-dependent reference limits are suggested.
Tumor Biology 11/2011; 33(1):141-8. · 1.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Heterophilic antibodies are still an important source of interference in immunoassays. We have conducted a screening study for interference in a panel of commercially available assays using two sera known to contain high titer Fc-reactive heterophilic antibodies.
The sera were distributed to laboratories participating in the Nordic External Quality Assessment cooperation (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33 were also supplied. Discrepancies (>50%) between the results for native and blocked samples were used to classify the tested assays as susceptible to interference. A total of 170 different assay kits covering 91 analytes were tested.
We found that 21 assays, covering 19 different analytes, were susceptible to interference from the heterophilic antibodies in the two sera. Many of these are clinically and commercially important assays. Some of the false results were grossly elevated and could have been detrimental to patient care in a clinical setting.
Heterophilic antibodies with Fc-reactivity remain a threat. A more widespread use of antibody fragments and aggregated immunoglobulin could potentially improve the heterophilic antibody resistance of assays intended for clinical use.
Clinical Chemistry and Laboratory Medicine 09/2011; 49(12):2001-6. · 2.15 Impact Factor
