EP10-A3 定量临床检验方法的初步评价

临床检验

EP10-A3

Vol. 26 No. 34

Replaces EP10-A2

Vol. 22 No. 29 Preliminary Evaluation of Quantitative Clinical Laboratory Measurement Procedures; Approved Guideline—Third Edition

This guideline provides experimental design and data analysis for preliminary evaluation of the performance of a measurement procedure or device.

A guideline for global application developed through the Clinical and Laboratory Standards Institute consensus process.

临床检验

EP10-A3

ISBN 1-56238-622-0

Volume 26 Number 34 ISSN 0273-3099 Preliminary Evaluation of Quantitative Clinical Laboratory

Measurement Procedures; Approved Guideline—Third Edition

Jan S. Krouwer, PhD

George S. Cembrowski, MD, PhD

Daniel W. Tholen, MS

Abstract

Clinical and Laboratory Standards Institute document EP10-A3—Preliminary Evaluation of Quantitative Clinical Laboratory Measurement Procedures; Approved Guideline—Third Edition is intended to facilitate a limited, preliminary evaluation of the performance of a measurement procedure or device. Using the experimental design and data analysis procedure described, determination of whether a device has problems that require further evaluation or referral to the manufacturer can be done with a minimum expenditure of time and material. Included in Appendixes A and B are sample data sheets that should facilitate the analysis of the data. Appendix C contains a more sophisticated, powerful, statistical method for determining the possible causes of imprecision.

Clinical and Laboratory Standards Institute (CLSI). Preliminary Evaluation of Quantitative Clinical Laboratory Measurement Procedures; Approved Guideline—Third Edition . CLSI document EP10-A3 (ISBN 1-56238-622-0). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2006.

(Formerly NCCLS)

临床检验

Volume 26 EP10-A3 Contents Abstract (i)

Committee Membership (iii)

Foreword (vii)

Laboratory Error Sources and CLSI Evaluation Protocols Documents (viii)

1Scope (1)

2Introduction (1)

3Standard Precautions (1)

4Terminology (2)

4.1 A Note on Terminology (2)

4.2Definitions (2)

5Materials (5)

5.1Reference Procedures (5)

6Calibration and Sequence of Samples in a Run (6)

7Number of Days and Runs (6)

8Preliminary Procedures (6)

9Collection and Recording of Data (6)

10Initial Data Plotting and Inspection (6)

10.1Difference Plot of Data vs. Concentration (6)

10.2Visual Inspection for Outliers (9)

10.3Visual Inspection for Linearity (9)

11Analysis of the Data for Imprecision (9)

11.1Interpretation (9)

12Preliminary Assessment of Bias (10)

12.1Assigned Values (10)

12.2Calculation of Bias (10)

12.3Interpretation (10)

13Full Data Analysis Procedures (10)

13.1 A Comment on the Model (11)

13.2Summarizing the Five Runs (11)

14An Alternative Procedure (11)

15Use of EP10 by Manufacturers (11)

16How to Perform Multiple Regression for EP10 in Excel (11)

v

临床检验

Number 34 EP10-A3 Contents (Continued) References (14)

Symbols Used in Appendixes (15)

Appendix A. Preliminary Performance Acceptability Check (16)

Appendix B. Example Use of Data Sheets (22)

Appendix C. Statistical Explanation (43)

Summary of Consensus Comments and Committee Responses (46)

Summary of Delegate Comments and Committee Responses (48)

The Quality System Approach (50)

Evaluation Protocols Documents, Descriptions, and Key Words (51)

vi

临床检验

Volume 26 EP10-A3 Foreword

Before using a new measurement procedure or instrument for in vitro diagnostic use, the laboratory must make a preliminary decision about its acceptability. This initial performance check is neither a rigorous characterization of long-term performance nor an evaluation of the many factors that can affect results produced by the device. Rather, this experiment is a quick check to rule out major problems and a starting point for accumulating data and experience that will enable the user to make a final decision. The primary purpose of this document is to help detect performance problems that would warrant immediate correction, referral to the manufacturer, or expanded investigation before a new device is placed into service.

This document may also now be used by manufacturers to either establish the magnitude of factors that can affect performance or verify that such magnitude is acceptable.

Additional revisions since the last edition of EP10 (2002) include:

?a figure to illustrate which error sources the EP10 protocol can detect with respect to all error sources and other EP documents (see page viii);

?suggested sample sizes, so now the document is useful for manufacturers;

?instructions for the multiple regression calculations in Excel;

?revised references; and

?revised definitions.

Key Words

Carry-over, comparison of methods, drift, evaluation protocol, experimental design, linearity, multiple regression, outlier, precision

vii

临床检验

Number 34 EP10-A3 Laboratory Error Sources and CLSI Evaluation Protocols Documents

Laboratory Error Sources and CLSI Evaluation Protocols Documents.a This figure illustrates the relationship among parameters estimated by EP documents. Items higher up in the figure are more comprehensive whereas lower level items are more specific. Overall, the figure is much like a cause-and- effect diagram. Documents marked (d) provide guidance for demonstrating that a source of measurement inaccuracy is within acceptable limits. Documents marked (v) provide guidance for more rigorous evaluation of inaccuracy components.

a For a description of each of the documents listed, please see page 53.

viii

临床检验

Volume 26 EP10-A3 Preliminary Evaluation of Quantitative Clinical Laboratory Measurement Procedures; Approved Guideline—Third Edition

1Scope

Before starting a complete evaluation of a new measurement procedure, kit, or instrument for in vitro diagnostic use, it is often necessary to make a preliminary decision about its acceptability. This initial performance check is neither a rigorous investigation into the procedure’s long-term performance, nor an evaluation of the many factors that can affect results produced by the device. The primary purpose of this document is to help detect problems that are severe enough to warrant immediate correction, referral to the manufacturer, or expanded investigation. Accreditation bodies may have requirements for verification or validation that exceed the procedures in this document (see the most current edition of CLSI document EP15—User Verification of Performance for Precision and Trueness).

Manufacturers can also benefit by performing this protocol either as assays are developed or when they are validated. By performing more than five runs, manufacturers can detect trends in the effects estimated by EP10 or document their absence.

2Introduction

This document describes a procedure for the preliminary evaluation of linearity, proportional and constant bias, linear drift, sample carry-over, and precision of a clinical laboratory measurement procedure. Preliminary evaluations should be performed before new procedures are used to test patients’ samples and when any modifications of procedures are made. This guideline is based on a protocol and procedure developed for continuous flow analyzers.1 The rationale for recommending a protocol based on so old a system is explained in Section 13.1. The experiment is intended primarily for evaluating automated instruments but may be appropriate for kits, manual procedures, or other in vitro diagnostic devices. By repeating a sequence of only ten samples, performance characteristics may be evaluated by plotting the data and performing some simple calculations. Using a statistical technique called multiple linear regression analysis, further information about the factors influencing accuracy (such as sample carry-over linear drift, and nonlinearity) can be obtained. Instructions are given for simple data analysis, in case a computer is not available.

The experiment is intended to provide preliminary estimates of those performance characteristics that may be used to determine the ultimate acceptability of the device. The results should be used only to determine whether the device has grossly unacceptable performance.

The following sections outline the materials and procedures to be used. Many variations on this basic experiment are possible (such as extending the number of days or eliminating the priming samples when appropriate). Variations should be dictated by the complexities of the device, the particular characteristics of the measurement procedure, and the resources available to the user.

3Standard Precautions

Because it is often impossible to know what isolates or specimens might be infectious, all patient and laboratory specimens are treated as infectious and handled according to “standard precautions.” Standard precautions are guidelines that combine the major features of “universal precautions and body substance isolation” practices. Standard precautions cover the transmission of all infectious agents and thus are more comprehensive than universal precautions which are intended to apply only to transmission of blood-borne pathogens. Standard and universal precaution guidelines are available from the U.S. Centers for Disease Control and Prevention (Garner JS, Hospital Infection Control Practices Advisory Committee. ©Clinical and Laboratory Standards Institute. All rights reserved.1

临床检验

Volume 26

EP10-A3

©Clinical and Laboratory Standards Institute. All rights reserved. 51Evaluation Protocols Documents, Descriptions, and Key Words

EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline—Second

Edition (2004). This document provides guidance for designing an experiment to evaluate the precision performance of quantitative measurement methods; recommendations on comparing the resulting precision estimates with manufacturers’ precision performance claims and determining when such comparisons are valid; as well as manufacturers’ guidelines for establishing claims.

Evaluation protocol, experimental design, medical devices, outlier, precision, quality control

EP6-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved

Guideline (2003). This document provides guidance for characterizing the linearity of a method during a method evaluation; for checking linearity as part of routine quality assurance; and for determining and stating a manufacturer's claim for linear range.

Allowable difference, allowable error, linearity, matrix effects, measurement error, total error, uncertainty

EP7-A2

Interference Testing in Clinical Chemistry; Approved Guideline—Second Edition (2005). This document provides background information, guidance, and experimental procedures for investigating, identifying, and characterizing the effects of interfering substances on clinical chemistry test results.

Evaluation, hazard analysis, interference, interferent, matrix effects, performance claims, risk management, specificity, validation, verification

EP9-A2 Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline—Second

Edition (2002). This document addresses procedures for determining the bias between two clinical methods, and the design of a method comparison experiment using split patient samples and data analysis.

Bias, evaluation protocol, experimental design, linear regression, method comparison, quality control, residuals

EP12-A User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline (2002). This document

contains a protocol to optimize the experimental design for the evaluation of qualitative tests; to better measure performance; and to provide a structured data analysis.

Analytical goals, qualitative test, semiquantitative test

EP14-A2 Evaluation of Matrix Effects; Approved Guideline—Second Edition (2005). This document provides guidance

for evaluating the bias in analyte measurements that is due to the sample matrix (physiological or artificial) when two measurement procedures are compared.

Analytical interference, bias, matrix, matrix effect, physicochemical interference

EP15-A2 User Verification of Performance for Precision and Trueness; Approved Guideline—Second Edition (2005).

This document describes the demonstration of method precision and trueness for clinical laboratory quantitative methods utilizing a protocol designed to be completed within five working days or less.

Bias, precision, repeatability, trueness, verification of performance

EP17-A Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline (2004).

This document provides guidance for determining the lower limit of detection of clinical laboratory methods, for verifying claimed limits, and for the proper use and interpretation of the limits.

Limit of blank, limit of detection, limit of quantitation, nonparametric statistics

EP18-A Quality Management for Unit-Use Testing; Approved Guideline (2002). This guideline recommends a quality

management system for unit-use devices that will aid in the identification, understanding, and management of sources of error (potential failure modes) and help to ensure correct results. It is targeted for those involved in the supervision of laboratory-testing quality management, and it addresses issues related to specimen collection through reporting of test results.

Quality assurance, quality control, quality management, quality system, unit-use system

临床检验

Number 34

EP10-A3

©Clinical and Laboratory Standards Institute. All rights reserved. 52 Evaluation Protocols Documents, Descriptions, and Key Words (Continued)

EP19-R

A Framework for NCCLS Evaluation Protocols; A Report (2002). This document describes the different types of performance studies that are conducted to evaluate clinical assays.

Demonstration, evaluation protocol, validation, verification

EP21-A Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline (2003). This

document provides manufacturers and end users with a means to estimate total analytical error for an assay. A data collection protocol and an analysis method which can be used to judge the clinical acceptability of new methods using patient specimens are included. These tools can also monitor an assay’s total analytical error by using quality control samples.

Error, error of measurement, measurement error, total analytical error, total analytical error interval

GP10-A Assessment of the Clinical Accuracy of Laboratory Tests Using Receiver Operating Characteristics (ROC)

Plots; Approved Guideline (1995). This document provides a protocol for evaluating the accuracy of a test to discriminate between two subclasses of subjects where there is some clinically relevant reason to separate them. In addition to the use of ROC plots, the importance of defining the question, selecting the sample group, and determining the “true” clinical state are emphasized.

Clinical accuracy, false-negative fraction, false-positive fraction, medical decision analysis, performance evaluation, receiver operating characteristic (ROC) plot, sensitivity, specificity, true-negative fraction, true-

positive fraction

Other Related Publication

X5-R

Metrological Traceability and Its Implementation; A Report (2006). This document provides guidance to

manufacturers for establishing and reporting metrological traceability.

Calibrator, certified reference material, commutability, metrological traceability, reference measurement procedure, uncertainty of measurement, validation, value assignment

本文来源：https://www.bwwdw.com/article/gw91.html