%0 Journal Article %J J Alzheimers Dis %D 2016 %T Transferring cut-off values between assays for cerebrospinal fluid Alzheimer's disease biomarkers. %A García Barrado, Leandro %A Coart, Els %A Vanderstichele, Hugo M J %A Burzykowski, Tomasz %K Alzheimer Disease %K Amyloid beta-Peptides %K Bayes Theorem %K Biomarkers %K Cognitive Dysfunction %K Datasets as Topic %K Humans %K Linear Models %K Multivariate Analysis %K Peptide Fragments %K tau Proteins %X

Current technologies quantifying cerebrospinal fluid biomarkers to identify subjects with Alzheimer's disease pathology report different concentrations in function of technology and suffer from between-laboratory variability. Hence, lab- and technology-specific cut-off values are required. It is common practice to establish cut-off values on small datasets and, in the absence of well-characterized samples, to transfer the cut-offs to another assay format using 'side-by-side' testing of samples with both assays. We evaluated the uncertainty in cut-off estimation and the performance of two methods of cut-off transfer by using two clinical datasets and simulated data. The cut-off for the new assay was transferred by applying the commonly-used linear regression approach and a new Bayesian method, which consists of using prior information about the current assay for estimation of the biomarker's distributions for the new assay. Simulations show that cut-offs established with current sample sizes are insufficiently precise and also show the effect of increasing sample sizes on the cut-offs' precision. The Bayesian method results in unbiased and less variable cut-offs with substantially narrower 95% confidence intervals compared to the linear-regression transfer. For the BIODEM datasets, the transferred cut-offs for INNO-BIA Aβ1-42 are 167.5 pg/mL (95% credible interval [156.1, 178.0] and 172.8 pg/mL (95% CI [147.6, 179.6]) with Bayesian and linear regression methods, respectively. For the EUROIMMUN assay, the estimated cut-offs are 402.8 pg/mL (95% credible interval [348.0, 473.9]) and 364.4 pg/mL (95% CI [269.7, 426.8]). Sample sizes and statistical methods used to establish and transfer cut-off values have to be carefully considered to guarantee optimal diagnostic performance of biomarkers.

%B J Alzheimers Dis %V 49 %P 187-99 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26484919?dopt=Abstract %R 10.3233/JAD-150511