CLSI eNews - 1 August 2007 (Plain Text Version)

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News
Executive Vice President's Message
CLSI President-Elect to Meet With JCCLS in Tokyo
CLSI's The Key to Quality
Lois Schmidt, DA Appointed CLSI’s Vice President of Standards
James Nichols, PhD, DABCC, FACB To Serve as CLSI’s Editorial Review Board Representative for Lab Tests Online
Honoring the Life and Accomplishments of Richard R. Miller, Jr.
Recent Changes to CLSI Membership Categories
Press Releases
Standards Status
Vote and Deadlines
Recently Approved Documents
Recently Distributed ISO Standard
Call for Nominations
Events and Exhibits
Upcoming Events
Upcoming Presentations
CLSI Meetings Calendar
Participate in CLSI
Volunteer
New and Sustaining Members
Update Your Subscription

Call for Nominations

How to Construct an Error Grid for Diagnostic Assays; Evaluating Between Reagent Lot Variation; Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (EP6-A); Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline (EP21-A)

The Clinical and Laboratory Standards Institute requests volunteers to serve as subcommittee members for a new voluntary consensus project. The project description and specific qualifications needed are provided below:

NEW PROJECT:
How to Construct an Error Grid for Diagnostic Assays

Description:

Although there are many evaluation protocols, one can always ask the question, is the estimated performance “good enough”. This is a difficult question to answer and previous attempts from CLSI and ISO/TC212 to establish analytical performance goals for assays have failed to be completed. The proposed project will provide a new approach by leveraging the longstanding, existing glucose error grids. The project will explain how to construct error grids for any diagnostic assay, with focus on

* The region that should include most (95%) of the data – the acceptable result region
* The region(s) that should include (0%) of the data – the erroneous result region

Moreover, these grids will be illustrated for different diseases and uses (e.g., screening vs. monitoring). This can lead to different error grids for the same assay. These grids will be graphed in a spreadsheet, so that existing CLSI Evaluation Protocols documents can have data displayed in the error grid. It is intended to provide guidance on how to quantify the amount of data and the corresponding confidence interval in each error grid region.

In addition, the document is geared towards manufacturers with respect to construction of error grids. However, it is also applicable to clinical laboratories, since data from protocols such as CLSI document EP15-A2—User Verification of Performance for Precision and Trueness; Approved Guideline—Second Edition can be displayed in an error grid.

Whereas this project provides a means to construct error grids, it is important to note that it will not attempt to provide a list of completed error grids for assays, which is another way of saying that it will not attempt to provide goals for assays, but rather the format for how goals can be produced.

Guideline Content:

1. Forward
2. Scope
3. Introduction
4. Definitions
5. Error grids and assays
a. Different diseases
b. Different uses (screening, monitoring)
c. Confirmation assays
6. Sources to establish limits
7. How to translate the information into a graph
8. Quantifying the percentage of results in each error grid region
9. Examples
    a. For EP9—Method Comparison and Bias Estimation Using Patient Samples
    b. For EP15—User Verification of Performance for Precision and Trueness
    c. For EP21—Estimation of Total Analytical Error for Clinical Laboratory Methods

Specific Expertise/Work Experience Needed:

Statisticians with experience/expertise in constructing error grids for diagnostic assays.
Laboratorians with significant experience/expertise in performing and assuring quality of clinical laboratory assays.
Clinical laboratory directors responsible for quality of assays performed in their laboratories
IVD manufacturers of reagent and test systems and their government relations personnel
National and international representatives familiar with regulatory and accreditation requirements for IVD assays and test systems to assist with harmonization and global application of the guidelines.

The deadline to submit a nomination form, including a curriculum vitae and disclosure of interests form, is 1 September 2007. Send to Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, PA 19087.

NEW PROJECT:
Evaluating Between Reagent Lot Variation

Description:

Prior to the 1992 enactment of CLIA 88, reagent lot validation practices were highly variable. General guidelines for measuring and responding to lot-related shifts in control and patient data were not widely applied and very few laboratories validated new reagent lots by re-analyzing retained patient specimens. Section 493.1255 of the CLIA 88 Standard specifies that whenever a complete change of reagents occurs, “the laboratory . . . demonstrate that changing reagent lot numbers does not affect the range used to report patient test results, and control values are not adversely affected by reagent lot number changes”. Soon after the enactment of CLIA 88, the requirement for lot validation was promulgated in the accreditation checklists of various professional organizations including that of the College of American Pathologists (CAP). The rigor in fulfilling lot validation depends on the knowledge, confidence and prior practices of the laboratory directors and the supervisory technologists.

While some CLSI guidelines are being developed for demonstrating equivalence in analyzers operated within a health care system, the evaluation of between lot variation has not been yet addressed by CLSI.

This guideline will address the following quality control issues:

One of the most frequent quality control issues faced by laboratorians is how to respond appropriately to a shift in quality control (QC) following a reagent lot change. Possible actions include adjusting the control range, checking for shifts in patient data or simply ignoring the QC shift.
The laboratorian should use a systematic, statistically sound approach to gathering information for investigating shifted quality control and /or patient data following a reagent lot change.
Depending on whether QC and / or patient data have shifted, the laboratorian must be able to know when to reset the qc mean ( isolated quality control shift) or evaluating the clinical importance of the shift if the patient results have also shifted.

Guideline Content:

Classification of different test systems according to reagent / analyte stability; frequency and magnitude of between reagent lot shifts;
Approaches to measuring between lot shifts – QC, patients,
Approaches to defining maximum allowable error in reagent lot shifts
Suggestions for action if QC and/or patients have shifted significantly

Specific Expertise/Work Experience Needed:

Laboratorians with significant experience/expertise in performing and assuring quality of clinical laboratory assays.
Laboratory directors responsible for verification and validation of assays performed in their laboratories
Statisticians with experience/expertise in performing assay verification and validation analyses
IVD manufacturers of reagent and test systems and their government relations personnel
National and international representatives familiar with regulatory and accreditation requirements for reagent lot verification and validation to assist with harmonization and global application of the guidelines.

Clinical and Laboratory Standards Institute’s Area Committee on Evaluation Protocols has requested nominations to serve as subcommittee members to revise the CLSI guideline described below:

PROJECT REVISION:
Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (EP6-A)

Description:

EP6-A, which was published in 2003 provides an economical and user-friendly method of establishing or verifying the linear range for use by both manufacturers and users of quantitative analytical methods. This guideline also can be used to demonstrate the extent to which a quantitative analytical method meets clinical requirements or manufacturer's linear range claims.

In revising EP6 the following updates/revisions will be considered:

A clear statement on the need to test the full measuring interval for the instrument under test. This might also include directions on testing linearity across the full physiologic range, which would include non-linearity due to the auto-dilutor calculations.
A section on actions to take when the method is nonlinear. Currently the document describes reducing the range of testing, but not actions to take to investigate the source of non-linearity, or as indication of a need for recalibration.
A non-statistical, non-parametric alternative for “ad hoc” verification of linearity (consecutive slopes), or checking corrective actions.
A section on the use of peer group statistics, as in current CAP Surveys and some commercial products. This should discuss linearity relative to peers, and the linearity of the method. It should also include considerations for the generation of peer group statistics.
More guidance on setting goals for nonlinear error.

Specific Expertise/Work Experience Needed:

Statisticians with experience/expertise in performing assay verification and validation analyses.
Laboratory directors responsible for verification and validation of assays performed in their laboratories
Laboratorians with significant experience/expertise in performing method evaluations.
IVD manufacturers of reagent and test systems and their government relations personnel
National and international representatives familiar with regulatory and accreditation requirements for IVD assay and test system verification and validation.

Clinical and Laboratory Standards Institute’s Area Committee on Evaluation Protocols has requested nominations to serve as working group members to revise the CLSI guideline described below:

PROJECT REVISION:
Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline (EP21-A)

Description:

EP21-A, which was published in 2003 provides manufacturers and end users a means to estimate total analytical error for an assay. The procedure includes a data collection protocol and analysis method, which is largely graphical. The result is compared to a total analytical error goal.

Specific Expertise/Work Experience Needed:

Statisticians with experience/expertise in performing assay verification and validation analyses.
Laboratory directors responsible for verification and validation of assays performed in their laboratories
Laboratorians with significant experience/expertise in performing method evaluations.
IVD manufacturers of reagent and test systems and their government relations personnel
National and international representatives familiar with regulatory and accreditation requirements for IVD assay and test system verification and validation.