Biomedical subjects
W Greg Miller
Publications and source records attributed to W Greg Miller.
The importance of metrological traceability on the validity of creatinine measurement as an index of renal function.
The glomerular filtration rate (GFR) is currently considered the best overall index of kidney function. The possibility that laboratories might routinely report an estimated GFR has become practically feasible with the development of a formula, the "four-variable" Modification of Diet in Renal Disease study (MDRD) equation that uses age, sex, race, and serum creatinine parameters. However, a limitation of this equation for general implementation in healthcare is related to the use of differently calibrated creatinine measurement procedures among laboratories. The only way to achieve universal implementation of the GFR prediction equation, with the associated clinical benefits for patients, is, therefore, to promote worldwide standardization of methods to determine creatinine, together with the introduction of a revised GFR-estimating equation appropriate for use with standardized creatinine methods.
Data mining and clinical data repositories: Insights from a 667,000 patient data set.
Clinical repositories containing large amounts of biological, clinical, and administrative data are increasingly becoming available as health care systems integrate patient information for research and utilization objectives. To investigate the potential value of searching these databases for novel insights, we applied a new data mining approach, HealthMiner, to a large cohort of 667,000 inpatient and outpatient digital records from an academic medical system. HealthMiner approaches knowledge discovery using three unsupervised methods: CliniMiner, Predictive Analysis, and Pattern Discovery. The initial results from this study suggest that these approaches have the potential to expand research capabilities through identification of potentially novel clinical disease associations.
Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.
BACKGROUND: Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. METHODS: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. RESULTS: The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. CONCLUSIONS: The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 micromol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL.min(-1).(1.73 m2)(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.
Creatinine measurement: state of the art in accuracy and interlaboratory harmonization.
CONTEXT: The National Kidney Disease Education Program recommends calculating glomerular filtration rate from serum creatinine concentration. Accurate creatinine measurements are necessary for this calculation. OBJECTIVE: To evaluate the state of the art in measuring serum creatinine, as well as the ability of a proficiency testing program to measure bias for individual laboratories and method peer groups. DESIGN: A fresh-frozen, off-the-clot pooled serum specimen plus 4 conventional specimens were sent to participants in the College of American Pathologists Chemistry Survey for assay of creatinine. Creatinine concentrations were assigned by isotope dilution mass spectrometry reference measurement procedures. PARTICIPANTS: Clinical laboratories with an acceptable result for all 5 survey specimens (n = 5624). RESULTS: The fresh frozen serum (FFS) specimen had a creatinine concentration of 0.902 mg/dL (79.7 micromol/L). Mean bias for 50 instrument-method peer groups varied from -0.06 to 0.31 mg/dL (-5.3 to 27.4 micromol/L), with 30 (60%) of 50 peer groups having significant bias (P < .001). The bias variability was related to instrument manufacturer (P < or = .001) rather than method type (P = .02) with 24 (63%) of 38 alkaline picric acid methods and with 6 (50%) of 12 enzymatic methods having significant biases. Two conventional specimens had creatinine concentrations of 0.795 and 2.205 mg/dL (70.3 and 194.9 micromol/L) and had apparent survey biases significantly different (P < .001) from that of the FFS specimen for 34 (68%) and 35 (70%) of 50 peer groups, respectively. CONCLUSIONS: Thirty of 50 peer groups had significant bias for creatinine. Bias was primarily associated with instrument manufacturer, not with type of method used. Proficiency testing using a commutable specimen measured participant bias versus a reference measurement procedure and provided trueness surveillance of instrument-method peer groups.
Specimen materials, target values and commutability for external quality assessment (proficiency testing) schemes.
BACKGROUND: The objective of external quality assessment is to evaluate clinical acceptability of laboratory results. It is desirable to evaluate intermethod harmonization and traceability to a reference system. METHODS: Conventional matrix-modified processed materials are used in most programs, because they can be produced in large quantities, can have multiple abnormal analytes in the same vial and have excellent stability. The principal limitation of these materials is non-commutability which makes them unsuitable for traceability or harmonization evaluation. Peer group evaluation is used which allows an individual laboratory to confirm appropriate use of a measurement technology and a manufacturer to monitor uniformity in their calibration transfer process. Authentic clinical specimen pools provide commutability but are limited by the quantity available and number of analytes at pathologic levels in the same vial. Hybrid approaches have used authentic clinical specimen pools in conjunction with non-commutable processed materials to determine method-specific matrix-corrected target values which have enabled evaluation of traceability to reference methods. CONCLUSIONS: Conventional processed materials are limited by non-commutability. Pooled clinical specimens are limited by availability. When used together, external quality assessment can evaluate traceability to reference systems and harmonization between test procedures.
Performance of four homogeneous direct methods for LDL-cholesterol.
BACKGROUND: Homogeneous LDL-cholesterol methods from Genzyme, Reference Diagnostics, Roche, and Sigma were evaluated for precision, accuracy, and specificity for LDL in the presence of abnormal lipoproteins. METHODS: Each homogeneous method was performed by a Roche/Hitachi 911 according to the vendors' instructions, and the results were compared with the beta-quantification reference method. We measured precision over 20 days using quality-control and frozen serum specimens. Sera from 100 study participants, including 60 with hyperlipidemias, were assayed by each method. Accuracy was evaluated from regression and total error analysis. Specificity was evaluated from the bias (as a percentage) vs concentration of triglycerides. RESULTS: The total CV was <2% for all methods. Regression slope and intercept (with 95% confidence intervals) were as follows: Genzyme, 0.955 (0.92 to 0.99) and 30.3 (-12 to 73) mg/L; Reference Diagnostics, 0.975 (0.93 to 1.02) and -8 (-63 to 47) mg/L; Roche, 1.067 (1.02 to 1.11) and -101 (-161 to -42) mg/L; and Sigma, 0.964 (0.91 to 1.02) and 164 (89 to 239) mg/L. The percentages of individual results with >12% bias were as follows: Genzyme, 8.0%; Reference Diagnostics, 11.0%; Roche, 10.0%; and Sigma, 30.0%. Total error calculated from mean systematic bias and all-sources random bias was as follows: Genzyme, 12.6%; Reference Diagnostics, 16.5%; Roche, 41.6%; and Sigma, 38.3%. Slopes of bias (as a percentage) vs triglycerides were P <0.001 for all methods except the Roche method, which was P = 0.094. CONCLUSIONS: The evaluated methods show nonspecificity toward abnormal lipoproteins, thus compromising their ability to satisfy the National Cholesterol Education Program goal for a total error of <12%. These homogeneous LDL-cholesterol results do not improve on the performance of LDL-cholesterol calculated by the Friedewald equation at triglyceride concentrations <4000 mg/L.