I am an Assistant Professor of Pathology at the University Of Utah Department Of Pathology and Medical Director of clinical laboratories at University of Utah Hospital and Clinics. Linearity and Calibration Verification Clinical Assays Quality control materials used to calibrate baseline values, verify and validate the analytical measurement range, and demonstrate linearity for clinical assays. It is fairly common to encounter situations where an assay is linear over the tested range, however, the samples tested at the low end or the high end of the AMR are problematic. There are numerous useful resources available for assistance with meeting regulatory requirements for calibration verification and linearity, many of which are listed on this slide. This slide shows many examples of such applicable assays, some of which are often available in routine or stat laboratory settings as well as reference laboratory settings. An assay may be proven to be linear but show unacceptable bias. Pearls of Laboratory Medicine Thank you for joining me on this Pearl of Laboratory Medicine on “Calibration Verification & Linearity: Regulatory Requirements and Application to Coagulation Assays.”. The samples must include a minimal value near the lower limit, a mid-point value, and a maximum value near the upper limit of the AMR. : following relocation of the instrument or after major maintenance) or calibration verification may be performed in accordance with CLIA guidelines, to verify continued acceptable performance of calibration and stated reportable range of the analyzer … CVA/CVA for CELL-DYN ®. The linearity experiment I will show in the following slides consisted of analyzing five samples spanning the AMR, each measured in triplicate. • Linear Regression: The r value is the correlation coefficient for the linearity of the parameter. Once a linearity study has been performed to determine the linear reportable range for a test method, it may be repeated as recommended by the manufacturer (i.e. It is the combined effect of calibration and verification but the final result is in the final output of the process. The CAP Calibration Verification/Linearity Surveys provide specimens and statistical evaluations of the reported results for verification of your current calibration settings as well as for assessing the analytical measurement range (AMR) of your laboratory method. If patient samples were used, were they processed according to standard operating procedure prior to testing to ensure adequate mixing, centrifugation, or were other necessary processing steps were taken? These may be control solutions that have assigned values, proficiency testing samples that have assigned target values, or special series of “linearity” materials that have assigned values. Calibration Verification and Linearity: Regulatory Requirements and Application to Coagulation Assays, The Journal of Applied Laboratory Medicine, HLA Testing for Solid Organ Transplantation, Laboratory Testing for Transgender Individuals, Maple Syrup Urine Disease and Other Disorders of Branched Chain Amino Acid Catabolism, Procalcitonin Testing and Antibiotic Stewardship, Setting Analytical Quality Goals with Biological Variation Data, Tyrosinemias Biochemistry and Clinical Laboratory Investigation, Clinical Chemistry Guide to Scientific Writing, Commission on Accreditation in Clinical Chemistry. We will first begin this Pearl with some relevant definitions. In this example, the source of the samples was a commercially produced kit. If a kit was used, were the kit’s instructions followed? The source of materials as well as the acceptability criteria for accepting or rejecting tests during calibration verification are determined by the laboratory director. Here is a table listing the mean observed values of the raw data for the measurements for D- dimer obtained for each sample. We will now discuss what to do if you observe that an assay is not linear over its AMR, or if unexpected bias or imprecision is present. Continuing without changing Cookie settings assumes you consent to our use of cookies on this device. // 900 Seventh Street, NW Suite 400 Calibration Verification Is there a new requirement for calibration verification? In this example, the AMR of the assay is 0.27-4.0 micrograms per milliliter. • Calibration Verification*: Verifies the accuracy of your instrument's calibration status throughout the reportable range. These standards can be found on the Joint Commission internet site. If the lower or upper end of the presumed AMR cannot be verified, then labs have the option of using a narrower AMR. The data appear to be linear visually, and the plot demonstrates Pearls of Laboratory Medicine minimal scatter of the data points, with even coverage of the AMR throughout the range and adequate coverage to the limits at the high and low ends. Were any flags or errors generated by the instrument during testing? Samples can be tested in duplicate for calibration verification which may be slightly different than the process for testing patient samples. Calibration material is a solution that contains a known amount of analyte. The product (Order No. How can labs meet the regulatory requirements? You can change these settings at any time, but that may impair functionality on our websites. The AMR is the range of concentrations of an analyte that a method can directly measure without any dilution, concentration, or other pretreatment. LGC Maine Standards is a market leader for linearity and calibration verification products. AMR validation is a process used to verify the linear relationship between the analytical results of a method and the concentration of analyte over the entire measurement range. the measured concentration. College of American Pathologists (CAP) checklist requirements break this down into calibration verification and AMR validation (linearity). Calibration verification confirms that an assay has remained stable throughout the reportable range of patient test results. What constitutes acceptable bias is at the discretion of the laboratory director. Phone // +1.202.857.0717 or 800.892.1400 Washington, DC 20001 CVA (Calibration Verification Assessment) and CVA for CELL-DYN are assayed linearity control kits used to determine the patient reportable range and linear performance of three- and five-part differential hematology analyzers by testing the upper and lower limits. Learn More About Calibration Verification/Linearity Programs, Laboratory Professionals Learning Programs, Archives of Pathology & Laboratory Medicine, Read more about Verifying Performance Characteristics. CUMBERLAND FORESIDE, Maine, Dec. 22, 2020 /PRNewswire/ -- LGC Maine Standards¹ announces the release of VALIDATE ® IL-6 to meet the linearity and calibration verification needs of clinical laboratories running the Roche cobas ® platform. Dr. Pearson is employed by the University of Utah and ARUP Laboratories. Samples can be tested in duplicate for calibration verification which may be slightly different than the process for testing patient samples. For the former, the lab may need to acquire additional samples near the low end and the high end for analysis. Examples of exempt assays include clot-based assays and platelet function tests. Methodology has evolved since then and many coagulation laboratories use methods which may be calibrated and measure a concentration of an analyte. This program, designed for laboratories, satisfies the requirements for scheduled calibration verification and verification of the analytical measurement range as specified in the CAP Laboratory Accreditation Program and Current Clinical Laboratory Improvement Amendments (CLIA) Regulations Section 493.1255 for most analytes. Bias is evident when the linear regression analysis produces a slope that is not equal to 1, a non-zero intercept, or differences on a bias plot. CLIA Calibration Verification vs LinearityCLIA Calibration Verification vs. Linearity • Calibration verification is the ppygrocess of verifying agreement between calibrators (or other materials of known analyte concentrations) and measured values • Calibrators should ideally be traceable to a reference method to ensure accuracy Patient samples may be used, so long as they sufficiently challenge the upper and lower ends of the AMR and are of acceptable quality and stability. CCTC (English) The slope and intercept indicate minimal proportional and constant bias. The minimum requirement is to analyze three samples in duplicate that span the AMR of the assay. Examples of assays which meet this criteria include EIA methods, immunoturbidity methods, and chromogenic methods. Source: Trainee Council in English, Hello, my name is Lauren Pearson. Our modern laboratory and streamlined processes allow us to consistently manufacture products that are of the highest quality, are easy-to-use and are incredibly efficient. By performing a linearity experiment! VALIDATE® products allow clinical laboratories to complete their required linearity and calibration verification, maximizing the reportable range while minimizing manual dilutions. Calibration verification and linearity and analytical measurement range verification should be performed using suitable materials with assessment of results using well-defined evaluation protocols. Commercial kits, control materials, calibrators of a different lot than the current calibration, proficiency testing materials, and reference materials are an alternative to using patient samples, and are available for purchase from a number of vendors. The checklist also states that linearity studies are not required for calibration and calibration verification of CBC instruments. Thank You from www.TraineeCouncil.org Were reagents used within stability? The values obtained for calibration verification should be within acceptable limits set by the manufacturer or laboratory. This is because in the past, coagulation testing was primarily clot-based testing using instruments that were not calibrated to measure the concentration of an analyte. The range of values reported on patient specimens may need to be changed accordingly. // Calibration verification is required by CLIA, but why else is it important? Tax Planning; Personal Finance; Save for College; Save for Retirement; Invest in Retirement It is important to ensure that samples of the appropriate matrix are used.  // The calibration verification discussion includes a brief reference to the hematology instrument calibration verification and a more extensive discussion of the process and criteria for calibration verification of instruments and methods that are not exempt. Were the samples used for testing stored appropriately? Calibrated tests that directly measure activity or concentration of an analyte by enzyme immunoassay, immunoturbidity, or chromogenic methods require AMR verification. Related to linearity is the concept of the analytical measurement range (AMR). Date: FEB.25.2019 AUDIT MicroControls, Inc. is pleased to announce the following new addition to our line of calibration verification/linearity and daily quality control products: Linearity FLQ Troponin T for Roche Systems. The concept of “linearity” is not separately designated by CLIA. It is a check on linearity as well as calibration. For other problems with high or low specimens, assess pre-analytic variables including sample handling and degradation. Slide 3: Linearity refers to the relationship between the final analytical result for a measurement and the concentration of the analyte being measured. If the results show that the assay is non-linear over the full range or even a partial range, there are three areas to focus your troubleshooting steps. Notice that for each sample, the mean observed measurement is close to, or equal to the expected value. We will now transition to applying these concepts to a specific example, quantitative D-dimer. The College of American Pathologists (CAP) instrumentation validation tools provide laboratories with high-quality Surveys that focus on the accuracy of test results for patients. Yes, VALIDATE® linearity and calibration verification products can be used to meet the JCAHO requirements for calibration verification. Liquid, ready-to-use, multi-level sets Shipping on your schedule Not all coagulation assays are calibratable, and thus these requirements will not apply.  // These concepts are comfortable and familiar to many laboratorians in clinical chemistry, but are newly applied to other areas of laboratory medicine, such as thrombosis and hemostasis testing. Each of the individual measurements for each sample are plotted. If the calibration changes, patient results will change. It is different from calibration, which is the process of establishing a correlation between the measurement signal generated by the instrument and the true concentration of the analyte in the sample. The application in the calibration field is more on the development (design and development) of a calibration procedure in order to meet certain requirements. Calibration verification is also indicated in the following situations: whenever there is a complete change in the set of reagents to a new lot, there is major preventative maintenance or replacement of critical parts of the instrument, relocation of the instrument, quality control data show a trend, shift, or are outside of acceptable limits. Trouble at the low and high end is observed when the samples don’t come close enough to the limits of the AMR, or when samples do adequately challenge the ends but the observed values are different than expected. Clot-based tests do not require AMR verification. Linearity refers to the relationship between the final analytical result for a measurement and the concentration of the analyte being measured. Welcome to this Pearl of Laboratory Medicine on “Calibration Verification & Linearity: Regulatory Requirements and Application to Coagulation Assays.”. Here is a scatter plot of the data. Calibration Verification / Linearity Training Sponsored by: Maine Standards , Maine Standards Speaker Highlights, from the standard QC.1.170, concerning linearity and calibration … Calibration verification is helpful for monitoring assay performance over time and maintaining quality results. Begin the investigation by reviewing specimen handling steps and quality control data. If the assay is shown to be non- linear within the AMR, the laboratory is alerted to possible problems with reagents, specimen handling, or the instrument itself. If the observed values are different than expected, it could be the case that the analyte concentrations of the samples were not within the AMR of the instrument, so this should be verified as well. Was testing performed by an individual deemed competent to perform testing? VALIDATE® products allow clinical laboratories to complete their required linearity and calibration verification, maximizing the reportable range while minimizing manual dilutions. Additionally (not cited here), there is a Clinical Laboratory Standards Institute document, EP-6, which may be useful. Possible manifestations include unexpected increased scatter in the data, large differences between replicates for specimens, or a standard deviation which exceeds allowable error. It may also detect accuracy and precision problems earlier than quality control or proficiency testing data. And calibration verification products can be tested in duplicate for calibration verification should be within acceptable limits set by instrument. Dr. Pearson is employed by the laboratory has always been responsible for calibration verification not apply linearity... Lastly, consider the possibility of clerical errors if results from the instrument during testing we will first begin Pearl! Is at the discretion of the analyte being measured University of Utah and ARUP.! Analyze three samples in duplicate that span the AMR of the analyte, protocols... 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