UnityDesktop_BioRad

Reference Guide for Easy QC Data Management

with Unity Desktop

Contents

Getting Started 11 Welcome to Unity Desktop ................................................11

How to Contact Us .................................................12 Organization of this Guide ........................................12 Typographical Conventions .......................................13 A Note About Screen Shots........................................13 Service Packs........................................................13

Where Do I Begin? ...........................................................14 Essential Startup Tasks for New Users ...................................15

First Time Log In....................................................16 Add Users ............................................................16 Add a Lab Number..................................................17 Add a Lot Number ..................................................17 Add Tests ............................................................18 Enter Data ...........................................................18

Introduction to Quality Control Statistics 21 What is Quality Control? ...................................................21

How Are QC Results Used? ........................................22 Basic QC Statistics ..........................................................24

Mean..................................................................25 Standard Deviation .................................................26 Calculating a Control Mean and Range..........................27 Standard Deviation Index..........................................27 Bias ...................................................................28 Coefficient of Variation ...........................................29 Total Error and TEa ................................................30 Coefficient of Variation Ratio ....................................31 z-score ...............................................................31

SPC Rules .....................................................................31 1-2s ...................................................................32 1-2.5s.................................................................33 1-3s ...................................................................34 1-3.5s.................................................................34 1-4s ...................................................................35 2-2s ...................................................................35 R-4s ...................................................................36 3-1s and 4-1s ........................................................37 7-T ....................................................................38

4 Bio-Rad Laboratories

Easy QC Data Management

N-x Rules ............................................................ 38

Choosing a QC Procedure 41 Recommended Steps ....................................................... 41

Determine Quality Requirements for the Test ................ 42 Evaluate Test Performance....................................... 43

Troubleshooting QC Results ............................................... 46 Good Habits ......................................................... 47 Keys to a Productive Review of the Laboratory Quality System........................................................................ 50

Program Basics 53 Starting and Exiting the Program ........................................ 53 Current Lab, Lot, Test, and Panel ....................................... 53 Toolbars ...................................................................... 54 Unity Desktop Menu Bar ................................................... 55 Bio-Rad Laboratories From the Windows Start Menu ................. 57 Shortcut Keys................................................................ 57 Functions and Where to Find Them...................................... 59

User Profiles and Security 61 Defining, Modifying, and Deleting Users ................................ 61

To Add a User....................................................... 62 To Modify a User ................................................... 63 To Delete a User ................................................... 63

Passwords .................................................................... 63 To Change Your Password......................................... 65

Choosing Permissions....................................................... 65 Administration/Setup Permissions............................... 65 Data Permissions ................................................... 66 Database Permissions.............................................. 66 Rules and Settings Permissions .................................. 67 Labs, Lot, Tests, and Panels Permissions ...................... 67 Data Handling Permissions........................................ 68

Labs and Lots 69 Labs ........................................................................... 69

Adding and Updating Labs ........................................ 70 Duplicating Labs.................................................... 71 Deleting Labs ....................................................... 72 Opening and Closing Labs......................................... 72

Bio-Rad Laboratories 5

Contents

Lots............................................................................73 Adding Bio-Rad Lots ................................................73 Adding Non-Bio-Rad Lots ..........................................74 Duplicating Lots.....................................................75 Deleting Lots ........................................................77 Editing Lots ..........................................................77 Closing and Opening Lots..........................................78 Lot Expiration Notifications.......................................79

Tests 81 Overview of Tests ...........................................................81 Adding Tests .................................................................82

To Add Tests Manually .............................................83 Adding Tests With Instrument Setup ............................84 Adding Tests With an Other Code................................86

Test Rules and Settings ....................................................87 Rules Tab of the Test Settings Dialog Box ......................87 Settings Tab of the Test Settings Dialog Box...................87

Duplicating Tests............................................................88 Updating Tests...............................................................88

To Update a Test ...................................................88 Closing and Opening Tests .................................................89

To Close Tests.......................................................89 To Open Tests.......................................................90

Deleting Tests ...............................................................90 To Delete Tests .....................................................91

Sorting Tests .................................................................91 To Sort Tests in Lab Mode.........................................91 To Sort Tests in Panel Mode ......................................92

VITROS Slide Generations..................................................92 Changing VITROS Slide Generations .............................93 Update VITROS Slide Generations................................94

Panels and Data Groups 95 Panels .........................................................................95 Panel Tests Dialog Box .....................................................95

To Add a Panel......................................................97 To Update a Panel..................................................97 To Delete a Panel ..................................................97 To Sort Tests in a Panel ...........................................98

Data Groups..................................................................98 To Change the Default Current Data Selection ................99 To Define or Edit a Group .........................................99



Applying QC Rules 101 Overview of Rule Evaluation .............................................101

Rule Statuses ......................................................102 Rule Precedence When Displaying Rule Violations...........103

Setting SPC Rules ..........................................................104 To Set SPC Rules at the Test Level.............................104 To Set SPC Rules at the Lot Level ..............................105

Using Fixed Means and SDs with SPC Rules ............................105 To Set a Fixed Mean and/or Standard Deviation .............106

SPC Rules: Tabular Summary ............................................107

Entering Data 109 Data Entry Overview ......................................................109 Useful Features of Data Entry ...........................................110

Navigating within Data Entry....................................110 Viewing Charts and Reports within Data Entry ...............111 Viewing Rules/Settings and AGs within Data Entry ..........111 Changing a Data Row's Date-Time ..............................112 Specifying a Default Data Entry Mode .........................112 Set Date ............................................................113

Unity Desktop Data Screens..............................................114 Data Screen Header...............................................115 Data Entry Grid....................................................115 Statistics/Chart Area .............................................115 Fixed Mean and SD (on Data Screens)..........................116

Point Data Entry ...........................................................117 Point Data Grid ....................................................118 Entering Point Data ...............................................122

Summary Data Entry ......................................................123 Entering Summary Data ..........................................124

Qualitative Data Entry ....................................................125 Adding Qualitative Tests .........................................125 Rejection Logs .....................................................126 Entering Qualitative Data........................................127 Sending Qualitative Data to the Unity Interlaboratory Program.......................................................................128

Managing Your Data 129 Overview of Data Management ..........................................129 Changing Values and Date/Times .......................................130

To Edit the Date-Time............................................130 To Edit a Value ....................................................130


Contents

Changing a Data Point's Accepted/Rejected Status ................. 131 To Change the Accepted/Rejected Status.................... 131

Inserting Data Rows....................................................... 131 To Insert a Data Row............................................. 132

Deleting Data .............................................................. 132 To Delete a Row(s) of Data ..................................... 133 To Delete a Range of Data ...................................... 134

Reviewing and Annotating Data 135 Overview of Actions and Comments.................................... 135

Actions ............................................................. 136 Comments ......................................................... 139 Actions and Comments by Instrument......................... 139

Importing and Exporting Data 143 Importing Data............................................................. 143

Customizing Import .............................................. 144 Import File Status ................................................ 148 Autoimport ........................................................ 148 Rejection Logs .................................................... 149 Operator Setup ................................................... 149

Exporting Data............................................................. 152

Unity Desktop Charts 155 Viewing, Printing, and Saving Charts .................................. 155 Chart Options .............................................................. 156

General Chart Options ........................................... 157 Chart Headers..................................................... 157

Levey-Jennings Charts.................................................... 158 Customizing Your L-J Charts .................................... 158

Multi-L-J Charts ........................................................... 161 To Display Multi-L-J Charts ..................................... 161

Bar Charts .................................................................. 161 Youden Charts ............................................................. 162

Youden Chart Options............................................ 163 Using Youden Charts ............................................. 164

Unity Desktop Reports 165 Useful Features of Unity Desktop Reports ............................ 165

Choosing a Report Format....................................... 165 Selecting the Data to Appear on Reports ..................... 166 Configuring Intralaboratory Report Headers ................. 167



Documenting Report Reviews ...................................167 Individual Unity Desktop Reports ...............................168

Sending Data to the Unity Interlaboratory Program 173 Transmission Files .........................................................173

To Transmit Data Manually for Monthly Unity ................174 To Activate Automatic Monthly Transmission for Monthly Unity.......................................................................174

Using Write Transmission File ...........................................174 To Write a Transmission File ....................................175 To Email a Transmission File to Bio-Rad.......................176

Unity Interlaboratory Reports 177 Overview of Unity Interlaboratory Reports ............................177

Viewing Interlaboratory Reports on QCNet ...................178 Standard Reports ..........................................................178

Monthly Evaluation Report.......................................178 Laboratory Performance Overview Report ....................179 Laboratory Comparison Report .................................180 Laboratory Histogram ............................................182 Bias and Imprecision Histogram Report........................183 Data Rejection Report............................................184

Optional Interlaboratory Reports .......................................185 Worldwide Report.................................................185 Manufacturer Report .............................................186 Statistical Profile Report.........................................187

Affiliated Reports..........................................................189 Affiliated Laboratory Comparison Report .....................190 Affiliated Laboratory Comparison Report: Abbreviated Summary............................................................190 Affiliated Data Exception Report ...............................192


Contents

Urinalysis Reports ......................................................... 193

Regulatory Requirements and Reports 197 Overview of Regulatory Requirements and Reports ................. 197 CLIA Requirements........................................................ 198 Accreditation Requirements (Paraphrased)........................... 202 ISO 15189................................................................... 210

Unity Desktop Database Basics 211 Database Basics ........................................................... 211 Updating Database Information......................................... 211

Manual Database Updates....................................... 212 Backup and Restore....................................................... 213 Condensing Data .......................................................... 214

To Condense Data by Lab, Lot, or Test ....................... 214 To Condense Data for All Labs.................................. 215

Reconciling Your Database .............................................. 215

Installation and Setup 217 Before You Begin .......................................................... 217 Installation ................................................................. 217 Activation Keys and Licensing........................................... 218

Activation Keys ................................................... 218 Licensing ........................................................... 220

Upgrading to Unity Desktop ............................................. 220 Upgrading from QC OnCall, Unity Plus/Pro, or Unity-PC... 220 Upgrading From Unity Post...................................... 221 Steps to Import Historical Data ................................ 221

The Setup Dialog Box ..................................................... 222 The Configure Unity Desktop Tab.............................. 223 Unity Interlaboratory Reports Tab............................. 225

Changing the Main Screen Graphics .................................... 226 To Change the Main Screen Graphics.......................... 226



Windows Hints 229 Tree Views..................................................................229 Command Buttons .........................................................229 Check Boxes and Option Buttons ........................................230 Selecting Items in Lists ...................................................231 Available/Unavailable Items.............................................232 Drag-and-Drop Sorting ....................................................232 Paging Arrows ..............................................................233 Using Calendars ............................................................233 Creating Shortcuts.........................................................234 Setting a Short Date Format .............................................234 Removing Unity Desktop..................................................235

Supplemental Information 237 Manual Interfacing and Standard Import Files ........................237

Create a Properly Formatted Data File........................238 Give Each File a Unique Name ..................................240 Define Paths for Interface Data.................................241 Alternatives to Interfacing ......................................242

Messages ....................................................................242 Rejection Log Messages ..........................................242 Action Messages ...................................................243

License, Warranty, and Trademark Information......................246

References 249 QC References .............................................................249

Glossary of Terms 251

Index 263

In This Chapter

Welcome to Unity Desktop ............................................ 11 Where Do I Begin? ...................................................... 14 Essential Startup Tasks for New Users............................... 15

Welcome to Unity Desktop Welcome to Unity Desktop. New users will find this powerful, user-friendly software provides access to advanced tools and functions that are designed to meet or exceed clinical laboratory quality requirements for data access, analysis, review, management, storage, and reporting reliable results. Existing users of other Bio-Rad programs will find the software provides familiar functionality plus several new features, including:

Qualitative Data Entry (on page 125) that allows you to enter qualitative and semi-quantitative data and send it to the Unity Interlaboratory Program.

Automatic monthly transmission (see "To Activate Automatic Monthly Transmission for Monthly Unity" on page 174) to ensure that your data always arrives at Bio-Rad on time.

Notification when software updates are available with installation or download.

Expanded charting options.

One of the most powerful utilities of Unity Desktop is its ability to connect your laboratory to the worldwide clinical laboratory community. Bio-Rad's Unity Interlaboratory Program collects data from thousands of labs worldwide and combines it to create consensus groups to which your data is compared.

C H A P T E R 1

Getting Started



How to Contact Us

We have made every attempt to ensure that this guide is accurate and complete. However, if you need to contact Bio-Rad directly for assistance, you can:

Search our knowledge base at support.qcnet.com.

Send an email to [email protected]. Inside the U.S., phone a Bio-Rad software support representative at 1-

800-854-6737, option 6. Software support representatives are available Monday through Friday from 5 am to 5 pm (Pacific Standard Time).

If you phone Bio-Rad outside of normal working hours, please leave a message and a software support representative will contact you, typically within 24 hours.

Outside the U.S., please contact your local Bio-Rad software support representative.

Organization of this Guide

This guide is organized with the information that you are expected to use more frequently listed at the beginning of the guide and the information that you are expected to use less frequently, or only when installing and configuring Unity Desktop, at the end of the guide.

Because Unity Desktop's major function is to oversee your QC data, QC information appears first in this guide; the mechanics of using the program appear next; and installation and set up instructions appear last because they are usually performed only once.

Please be aware of the following when using this guide:

Unity Desktop frequently provides multiple ways to access program functions; however, this guide generally provides only the simplest way to perform a task.

Windows instructions are provided based on Windows XP. If you are using another operating system, such as Windows 2000, you may need to adapt some instructions to suit your operating system.

When providing paths, installation is expected to be to the default locations, usually to your local hard disc drive. So C:\ in the path description refers to your local hard disc drive.


Getting Started

Typographical Conventions

This guide uses consistent styles to aid readability. Throughout this document:

Items you see on the screen, such as check box names and dialog box titles, are enclosed in double quotes. For example, the Setup dialog box.

Menu items are shown in a bold font and appear in the order you select them with each item separated by a vertical bar (|). For example, Tools | Security | Administrator.

Buttons that you click appear in a bold font. For example, click Close to exit the dialog box and return to the main screen.

Names of keys on the keyboard appear in bold and in all capital letters. For example, CTRL, SHIFT, DELETE.

Keys that you press together (i.e. shortcut keys) appear in bold and are separated by a plus sign (+). For example, "Press SHIFT+F11 to exit the program."

Notes are separated from the surrounding text by horizontal lines above and below the note. For example:

This feature is only available when the test is being evaluated by an analytical goal.

Warnings are shown shaded. For example:

To prevent data loss, always archive or backup your database before installing new software.

A Note About Screen Shots

The user interfaces for Unity Real Time and Unity Desktop are virtually identical. (The appearance of the data entry screens vary only slightly.) Because of this, screen shots of the two programs are used interchangeably throughout this guide.

Service Packs

Occasionally, Bio-Rad releases updates for its existing software products. When an update is available, Unity Desktop notifies you at login using one of two screens based on whether or not you have selected the "Automatic



product updates" check box on the "Configure Unity Desktop" tab of the "Setup" dialog box (see "The Setup Dialog Box" on page 222).

When the "Automatic product updates" check box is selected The "Product Update" dialog box appears when you log in to Unity Desktop. From the "Product Update" dialog box, you can:

Click Install to download and install the update.

Click Download to download the update to a location you specify for installation at a later time.

Click Close to close the dialog box without taking any action. Unity Desktop will notify you again of the update the next time you log in.

When the "Automatic product updates" check box is not selected

A message that a service pack is available appears when you log in to Unity Desktop. The message requests that you contact your Bio-Rad software support representative. Your representative can give you instructions on how to access the service pack.

Where Do I Begin? Once you have completed Installation and Setup, what you do next depends on what Bio-Rad QC data management software, if any, you were previously using:

If you are a Unity-PC or Unity Plus/Pro user and want to move your existing data into Unity Desktop, follow the instructions for moving the data into Unity Desktop.

If you are a Unity Post user, contact your Bio-Rad software support representative to request an import disk of data you have submitted to the Unity Interlaboratory Program.


Getting Started

If Unity Desktop is your first Bio-Rad QC data management software, you will need to define users, labs, lots and tests before you can begin using Unity Desktop. Essential Startup Tasks for New Users (on page 15) should supply enough information to get you up and running quickly. It also provides links to more information should you need it.

Essential Startup Tasks for New Users If you have never submitted data to the Bio-Rad Unity Interlaboratory Program using an earlier Bio-Rad software or Unity Post, you must perform the tasks in the following list before you can start entering data into Unity Desktop.

If you have ever submitted data to the Unity Interlaboratory Program by any means, including Unity Post, see Upgrading From UNITY-PC and Unity Plus/Pro, you may be able to avoid some or all of these tasks.

Essential Startup Tasks First Time Log In (on page 16) Add Users (on page 16) Add a Lab Number (on page 17) Add a Lot Number (on page 17) Add Tests (on page 18) Enter Data (on page 18)

Once you have created tests, you can begin data entry. Unity Desktop begins evaluating a point data test against its default rules after the test has the number of data points specified on the "Settings" tab of the "Test Settings" dialog box.

If you want to begin rule evaluation with the first data point, you need to specify a fixed mean and SD (see "Using Fixed Means and SDs with SPC Rules" on page 105).

When the test has a statistically significant number of data points, you might want to change the default rules as described in Choosing a QC Procedure (on page 41). If your lab uses the optional Westgard Advisor, it will suggest rules for you. (Twenty is generally considered the minimum number of data points for statistical significance.)



If you laboratory wants to have rules suggested for you, contact your Bio-Rad Representative to receive information regarding Unity Real Time and the optional Westgard Advisor.

First Time Log In 1 Start Unity Desktop. The "Login" dialog box appears with "admin" in the

"User" field.

The "Password" field should be active (i.e. the cursor appears in it.) If the password field is inactive, click in the field to select it.

2 Type sa in the password field, and click OK.

The default administrator login allows new users initial access to the software. After you create other users, you should delete this user or change the password.

Add Users

Unity Desktop uses passwords and user profiles to control which program functions users can access. User initials appear on the data screen, with actions and comments, and other areas within the software to document which user performed the activity. User's initials, combined with audit trails, document who did what and provide useful information when investigating problems; hence, we strongly recommend that you create a unique user profile and password for each person who uses Unity Desktop.

3 Log in to Unity Desktop as a user with permission to manage users. (The admin/sa login provides this permission.)

4 Choose Tools | Security | Administrator or press ALT+F11. The "Administrator" dialog box appears.

5 Click New in the User profile area. All fields on the dialog box are cleared.

6 Type the user ID, user name, password, and initials you want to assign to the new user.

7 Select the "Set password expiration period to" check box if you want the user's password to expire after the number of months you choose from the drop-down list.


Getting Started

Password expiration periods are entirely optional and their use depends on the level of security required in your laboratory.

8 Click the "Administrator" check box to give the new user all permissions or select the individual permissions you want the user to have.

9 Click Apply to create the new user and leave the dialog box open so that you can add another user or click OK to create the user and close the dialog box.

Add a Lab Number

You need to define a lab number before you can add lots to it. All lab numbers must be provided by Bio-Rad.

Use the lab number included in your startup packet or contact your Bio-Rad software support representative, who can provide you with additional lab numbers.

10 Log in to Unity Desktop as a user with permission to manage labs, lots, and tests. (The default admin/sa login provides this permission.)

11 Click the Lab icon on the toolbar. The "Lab" dialog box appears.

12 Type the requested information in each field. An asterisk (*) indicates a required field.

13 Click Add when the information is complete and correct.

The lab number appears in the "Open labs" list. If this is the first lab number you have added, this lab number becomes your primary lab number and is shown in bold text.

14 At this point, you can:

Type a new lab number and edit the fields as necessary. Then click Add to add an the lab number.

Click Lot to display the "Lot" dialog box to add a lot number(s) to the lab number.

Click Close to exit the dialog box.

Add a Lot Number 1 Log in as a user with permission to manage labs, lots, and tests.

2 Select the lab number you want to add lots to in the navigation tree.



The navigation trees appear as tabs on the left of the main screen. The "Lab" tree presents a hierarchical arrangement by lab numbers, lot numbers, and tests. The "Panel" tree organizes tests by panel name. See Tree Views (on page 229) for more information.

3 Click the Lot icon on the toolbar. The "Lot" dialog box appears. Notice that the selected lab number and lab description appear under the dialog box title.

4 Select a control product from the drop-down list under "Control product." The list will contain all Bio-Rad control products and any "Other" lots you have previously defined.

5 Select a lot number from the drop-down list under "Lot number." The list will contain all unexpired lot numbers.

6 Click Add. The lot number appears in the open lots list.

7 Repeat steps 4 6 to add additional lots as needed.

8 When all lots are added, click Close to exit the dialog box or click Test to add tests to the currently selected lot number.

Add Tests 1 Select the appropriate lab/lot combination in the "Lab" or "Panel"

navigation trees.

2 Click Test on the toolbar. The "Test" dialog box appears.

3 Make a selection for each item in the left "Test information" pane.

4 Click Add when your selections are complete and correct.

Alternatively you can add groups of tests for an instrument using Instrument Setup. (This feature is not available when the RiLiBK module is installed.)

Enter Data

You can enter data for a test as individual data points (point data entry) or as a monthly mean, SD, and number of points (summary data entry). Rule evaluation occurs only for point data.

To Enter Point Data

See Point Data Entry for more information.


Getting Started

1 Double-click the test in either the "Lab" or "Panel" trees. (Nothing appears in the "Panel" tree until you define a panel or panels.) The data entry screen appears with either the "Point Data" or "Summary Data" tab selected.

You can specify which tab is active from the "Configure Unity Desktop" tab of the "Setup" dialog box. Choose Tools | Setup and click the Point or Summary option under "Default data entry mode (see "Specifying a Default Data Entry Mode" on page 112)".

2 Click the appropriate tab if not already displayed.

The first cell in the first blank data entry row will be the active cell and is surrounded by a dark border. This is the cell where you will type your value. If you do not have a value to enter for the selected level, you can press Tab to move to the appropriate cell.

3 Type values for each level of control you have results for and press Tab to move to the next data row.

4 Click Save when all your values are entered.

To Enter Summary Data

See Summary Data Entry for more information.

1 Double-click the test in either the Lab or Panel tree. The data entry screen appears with either the "Point Data" or "Summary Data" tab selected.

2 Click the "Summary Data" tab if not already displayed.

3 Type your mean, SD, and number of points for each level, pressing Tab to move between the cells.

4 When all values for a row are entered, press Tab to move to the next blank data entry row.

5 Click Save when all your values are entered.

In This Chapter

What is Quality Control? ............................................... 21 Basic QC Statistics ...................................................... 24 SPC Rules................................................................. 31

What is Quality Control? Quality control in the medical laboratory is a statistical process used to monitor and evaluate the analytical process which produces patient results. The statistical process requires:

Regular testing of quality control products along with patient samples Good laboratory practice requires testing normal and abnormal controls at least daily when patient testing is performed. If the test is stable for less than 24 hours or some change has occurred which could potentially affect the test stability, controls should be assayed more frequently. All labs in the U.S. must comply with CLIA Requirements (on page 24).

Generation of QC results for evaluation When a diagnostic test is performed in the medical laboratory, the outcome of the test is a result. The result may be a patient result or a quality control (QC) result. The result may be quantitative (a number) or qualitative (positive or negative) or semi-quantitative (limited to a few different values).

Unity Desktop currently provides QC rule evaluation only for quantitative tests. (You can enter data from qualitative/semiquantitative tests; however, the data is not evaluated against any rules.)

C H A P T E R 2

Introduction to Quality Control Statistics



How Are QC Results Used?

QC results are used to validate patient results. Once validated, patient results can be used for diagnosis, prognosis, or treatment planning. For example, when a patients serum is assayed (tested) for potassium, the test result tells us how much potassium (what concentration) is present in the blood. This result is then used by the physician to determine whether the patient has a low, normal, or high potassium level.

Lets assume that the measured value of potassium in a patients serum is 2.8 mmol/L (a unit of measure, millimoles per liter). This result is abnormally low and indicates an inappropriate loss of potassium.

But how does the person performing the test know that this result is truly reliable? It could be possible that the instrument is out of calibration and the patients true potassium value is 4.2 mmol/La normal result.

The question of reliability for most testing can be resolved by regular testing of quality control materials and the application of statistical process control values.

As you test QC materials, you develop a database of values from which you can calculate a mean and range (i.e. mean 3SD). You can then compare your QC results to this range using statistical process control (SPC) rules and make decisions to accept or reject patient results based on the outcome of rule evaluation.

Normal and Abnormal Controls

A normal control product contains normal levels for the analyte being tested. An abnormal control product contains the analyte at a concentration above or below the normal range for the analyte. For example, the normal range for a potassium level is about 3.5 5.0 mmol/L. A normal control would contain potassium at a level within this range. An abnormal control would contain potassium at a level below 3.5 mmol/L or above 5.0 mmol/L.



The following example QC log shows normal and abnormal control results and patient results for a seven-day period.

Test: Potassium

Instrument: Instrument No.1 Unit of measure: mmol/L Level 1 (Normal

Control) Level 2 (Abnormal Control)

Patient Results

Range: 3.7-4.3 mmol/L 6.7-7.3 mmol/L

Date: 11/1 4.0 7.0 4.2, 4.0, 3.8, 5.0, 5.8, 4.2

11/2 4.1 7.0 3.8, 4.4, 4.6, 3.9, 4.6, 4.4, 3.9

11/3 4.0 6.9 4.4, 3.9, 3.7, 4.7

11/4 4.2 7.1 4.7, 5.6, 4.2, 3.7, 4.3

11/5 4.1 7.0 4.2, 4.3, 4.1, 4.3

11/6 4.1 7.0 4.6, 4.4, 5.5, 3.8, 3.2

11/7 4.2 8.0 2.8, 4.6, 4.2, 3.2, 3.9, 4.1, 6.0, 4.3

The acceptable range for the Level I (normal control) is 3.7 4.3 mmol/L. The range for Level II (abnormal control) is 6.7 7.3 mmol/L. When the daily QC result obtained for the normal control is compared to the range calculated for the normal control, it becomes apparent that each result lies somewhere within the expected range. This indicates that the analytical process is "in control" at the normal level on that day of testing.

When the daily QC result for the Level II (abnormal control) is compared to the defined range for the abnormal control, the analytical process is shown to be in control for each day of testing except for the last day (11/7). On November 1 through November 6, both controls were "in control," and patient values could be reliably reported.

However, the laboratory was "out of control" for abnormal high potassiums on November 7 because the value obtained for the QC material (8.0 mmol/L) was outside the acceptable range (6.7 7.3 mmol/L). This result indicates that some error occurred which may have produced abnormally high patient results that are unreliable. The laboratory should not report any patient samples with an abnormally high potassium until the error is resolved and the abnormally high sample(s) are re-tested.



Hence, it is now apparent that the range defined for each level of control is fundamental to the quality control system. Basic QC Statistics (on page 24) describes the calculations required to develop an acceptable control range.

CLIA Requirements

In the United States, the Clinical Laboratory Improvement Amendments of 1988 (CLIA), as modified by the final CLIA Rule, require two levels of control (one normal and one abnormal) be assayed on each day the test is performed for all non-waived tests, unless the Centers for Medicare & Medicaid Services (CMS) approves the procedure specified in Appendix C of the State Operations Manual that provides equivalent quality testing.

In other words, if you test patient samples for potassium on Wednesday, you must assay at least one normal and one abnormal control product for potassium on Wednesday unless an equivalent QC Procedure has been approved by CMS. Blood gas testing is slightly different.

For instruments that verify calibration internally, the U.S. laboratory must run one control every eight hours using a combination of materials that include both low and high values on each day of testing.

If the instrument does not verify calibration internally, the laboratory must assay these same controls with each patient sample.

As with any government regulation, these requirements can undergo change as a result of the regulatory or political process.

Basic QC Statistics A total QC system must control both trueness and precision. Your goal is for a test to have both low bias and low imprecision. Since problems with imprecision are less likely to cause analytical failure in the modern laboratory because of computerization and mechanization of the analytical process, bias is brought to the forefront.

The following figure illustrates low bias and low imprecision as a target, where the center of the bulls eye represents the target value.



The following figures show two other possibilities:

The first figure illustrates the situation where your standard deviation for a test is small (good precision), but is shifted away from the target value (high bias).

The second figure represents poor precision and, believe it or not, low bias because the average of the results is close to the bull's eye. Of course, individually none of the points are close, and their individual z scores would reflect this.

Bias and imprecision are most important at the clinical decision levels. For example, -hCG clinical decision levels are at low concentrations (corresponding to early pregnancy in the female and early testicular cancer in the male) or at moderate concentrations (to diagnose the progression of pregnancy).

Useful Statistics

Evaluation of a test's bias and imprecision utilizes several calculations. Although Bio-Rad's QC evaluation software performs these calculations for you, it's useful to understand the math behind the calculations, which includes:

Mean (on page 25) Standard Deviation (on page 26) Standard Deviation Index (on page 27) Accuracy (Bias) (see "Bias" on page 28) Coefficient of Variation (on page 29) Coefficient of Variation Ratio

Mean

The mean of a group of data points is simply their arithmetic average. Your calculated mean provides your laboratorys best estimate of the analytes "true" value for a specific level of control. The mean a predetermined number of standard deviations represents the error you expect to see in a test when the analytical system is stable.



The following formula is used to calculate the Mean:

Where =sum and Xn=all observed values

Standard Deviation

The standard deviation measures a test's precision or how close individual measurements are to each other. (The standard deviation does not measure bias, which requires that you compare your results to a target value, such as your peer group.) The standard deviation provides an estimate of how repeatable a test is at specific concentrations. Test repeatability can be consistent (low standard deviation, low imprecision) or inconsistent (high standard deviation, high imprecision).

Obviously, we want repeated measurements of the same specimen to give results that are as close to each other as possible. Good precision is especially needed for tests which are repeated regularly on the same patient to track treatment or disease progress. For example, a diabetic patient in a critical care situation may have glucose levels run every 2 to 4 hours. In this case, it is important for the glucose test to be precise because lack of precision can cause loss of test reliability. If there is a lot of variability in the test performance (high imprecision, high standard deviation), the glucose result at different times may not be true.

Standard deviation is often abbreviated as SD or s.

The following formula is used to calculate the SD:

( )1

2

=

nxx

SD n

A high standard deviation can be attributed to:

Inherent variability in the test, which represents expected error Analytical system malfunction, which represents unexpected error that

the laboratory must investigate and correct

Levey-Jennings Charts allow you to visually review data points plotted against a 3SD range.



Calculating a Control Mean and Range 1 Collect a minimum of twenty data points for each level of control.

Data points should be obtained from twenty separate analytical runs* which reflect variables such as calibration frequency, change of reagent or reagent lot, operator technique, temperature/humidity of testing location, daily/weekly maintenance, etc.

*Based on the Clinical and Laboratory Standard Institute (CLSI) recommendation for the minimum number of data points necessary to calculate a range.

All new control products should be compared to previously validated controls (parallel testing).

2 Calculate the mean and standard deviation from the data points collected.

Use a statistical test for outliers before eliminating any questionable data points.

Calculate the statistical control limits from the mean 2s and the mean 3s.

Use product insert ranges only as guidelines. Ranges are based on reagent lots and materials available at the time of value assignment. During the life of the control lot, manufacturers may reformulate tests or begin using a new source of raw materials for kit/reagent production. Published ranges cannot account for variables such as instrumentation software updates or performance differences over time.

Standard Deviation Index

The Standard Deviation Index (SDI) is a measurement of bias (how close your value is to the target value). Bio-Rad's Unity Interlaboratory Program uses the consensus group value as the target value. The following formula is used to calculate the SDI:

=

group

grouplab

SDMeanMean

SDI



Interpreting the SDI

The target SDI is 0.0, which indicates no difference between the lab mean and the consensus group mean. An SDI greater than 1 indicates a possible problem with the test.

The SDI essentially expresses bias as increments of standard deviation. An SDI of -1.8 indicates that the laboratory has a negative bias of 1.8 standard deviations from the group mean which is not a good situation.

Bias will increase or decrease the percentage of patients outside defined reference limits. For example, a positive analytical bias will decrease the percentage of patients normally outside the lower limit and increase the percentage of patients normally outside the upper reference limit, creating an increase in false positive test results. Negative bias has an opposite effect, decreasing true positives and creating false negatives.

An SDI of 0.0 indicates a perfect comparison with the consensus group.

The following guidelines can be used to interpret SDIs:

SDI value Interpretation 0.0 Perfect comparison with consensus group

1.25 Acceptable

1.25 1.49 Acceptable to marginal performance Some investigation of the test system may be required

1.5 1.99 Marginal performance Investigation of the test system is recommended

2.0 Unacceptable performance Remedial action usually required

Bias

Bias (%) measures how far your observed value is from a target value, which can be determined by some reference value or estimated from outside sources such as proficiency testing results or interlaboratory groups such as Bio-Rads Unity Interlaboratory Program.



Bias (%) can be calculated as:

100% Bias Lab

=

group

grouplab

MMM

Where Mlab is your lab's mean and Mgroup is the reference value (i.e. proficiency or interlaboratory value).

Coefficient of Variation

The Coefficient of Variation (CV) is the ratio of the standard deviation to the mean and is expressed as a percentage as follows:

100%

=

meandeviation standardCV

The CV allows the laboratorian to make easier comparisons of the overall precision of two analytical systems.

The CV is a more accurate comparator than the standard deviation because the standard deviation typically increases as the concentration of the analyte increases. If the laboratorian is comparing precision for two different methods and uses only the standard deviation, he or she can be easily misled.

Using only the standard deviation to compare analytical systems (e.g. by instrument, method, reagent, etc.) can be misleading.

For example, you need to compare a hexokinase and glucose oxidase method for measuring glucose. The standard deviation for the hexokinase method is 4.8 and 4.0 for glucose oxidase. Based on just the standard deviation, you might conclude that the glucose oxidase method is more precise than the hexokinase method.

However, a comparison of CVs might show that the methods are equally precise. Assume the mean for the hexokinase method is 120 and the glucose oxidase mean is 100. The CV then for both methods is 4%, and they are equally precise.



Determining an Acceptable CV

How do you determine an acceptable CV? Several sources can provide expected levels of precision, including:

Precision information provided in the product insert or instrument manual

Interlaboratory comparison programs Proficiency surveys Evaluations of instruments and methods published in professional

journals

These sources are useful for evaluating your CV for a test or when comparing two test systems.

Total Error and TEa

The concepts of total error (TE) and total allowable error (TEa) are useful when choosing the SPC rule(s) to apply to a test. Rules can be chosen to alert you when the total error for a test exceeds a quality specification (TEa) that you choose. Total error for a test includes both bias and imprecision as shown by the following formula (at a 99% confidence interval):

labbiaslab CVLabTE 33.2(%) +=

TEa specifications are available from several sources as discussed in Determine Quality Requirements for the Test (on page 42). Once you have chosen a TEa, you can calculate a TEbudget as shown by the following formula:

100(%)

=

a

labbudget TE

TETE

The optional Westgard Advisor allows you to choose a TEa and then suggests SPC rules based on your test data and Unity Interlaboratory information.

If you laboratory wants to have rules suggested for you, contact your Bio-Rad Representative to receive information regarding Unity Real Time and the optional Westgard Advisor.



Coefficient of Variation Ratio

The Coefficient of Variation Ratio (CVR) compares your lab's precision for a specific test to that of other laboratories performing the same test. This comparison is useful for comparing your laboratory's precision to that obtained by other labs.

The CVR is calculated using the following formula:

group

lab

CVCVCVR =

The CVR appears on several Unity Interlaboratory reports, including:

Laboratory Comparison Reports Monthly Evaluation Reports Affiliated Laboratory Comparison Report: Abbreviated Summary

includes CVRs based on your affiliated group as well as the peer and method consensus groups.

z-score

The z-score is the number of standard deviations a control result is from the expected mean and is calculated as follows:

=

expected

expectedobserved

SDMeanResult

scorez

A z-score of 2.3 indicates that the observed value is 2.3 SD away from the expected mean. A data point with this z-score would violate the 1-2s rule, but not the 1-3s rule. The z-score appears on the point data screen.

SPC Rules In 1981 Dr. James Westgard of the University of Wisconsin published an article on laboratory quality control that set the basis for evaluating analytical run quality for medical laboratories. The Westgard system is based on the principles of statistical process control used in manufacturing nationwide since the 1950s. There are six basic rules in the Westgard



scheme: 1-3s, 2-2s, R-4s, 1-2s, 4-1s, and 10x. These rules are used individually or in combination (multi-rule) to evaluate the quality of analytical runs.

The rationale for applying these rules is:

Reduce false rejections made when applying just the 1-2s rule for run rejection

Increase error detection over that provided when applying just the 1-3s rule for run rejection

Include rules to detect and distinguish random and systematic error (1-3s and R-4s to detect random error and 2-2s, 4-1s, and 10x to detect systematic error)

Westgard devised a shorthand notation for expressing quality control rules. Most quality control rules can be expressed as NL, where N represents the number of control observations to be evaluated and L represents the statistical limit for evaluating the control observations. Thus, 1-3s represents a control rule that is violated when one control observation exceeds the 3s control limits.

1-2s

The 1-2s rule is usually a warning rule that is violated when a single control observation is outside the 2s limits.

Some laboratories consider any quality control value outside its 2s limits to be out of control, and therefore incorrectly decide that the patient specimens and QC values are invalid.

An analytical run usually should not be rejected if a single quality control value is outside the 2s QC limits but within the 3s QC limits. Approximately 4.5% of all valid QC values will fall somewhere between 2 and 3 standard deviation limits. Laboratories that universally reject values outside the 2s limit end up rejecting good runs too frequently.

The 1-2s rule was originally designed as a warning rule for manual application of the Westgard Rules. If one control measurement within a run exceeds the mean 2 standard deviations in a manual application of Westgard rules, you should evaluate other controls in the run (within the run) and in previous runs (across runs) before accepting the run and reporting the results. With computer-based applications of Westgard rules, the 1-2s rule is usually not necessary.



Using this rule alone in performing quality control tests causes frequent rejection of valid runs. According to Dr. Westgard, failure to allow for valid points between 2s and 3s may result in falsely rejecting:

5% of all analytical runs when using one level of control 10% of all analytical runs when using two levels of control 14% of all analytical runs when using three levels of control

These false rejections mean that patient samples are repeated unnecessarily; labor and materials are wasted; and patient results are unnecessarily delayed.

The following figure shows an L-J chart with a data point between +2s and +3s.

1-2.5s

Violation of the 1-2.5s rule indicates random error and may also point to systematic error. This rule is applied within the run only. The following figure shows an L-J chart with a data point outside the 2.5s limits.



1-3s

The 1-3s rule identifies unacceptable random error or possibly the beginning of a large systematic error. Any QC result outside 3s violates this rule. Since only 0.3% or 3 out of 1000 points will fall outside the 3s limits, any value outside of 3s is usually considered to be associated with a significant error condition.

While a value outside 3s may be statistically significant, it may not be biologically or medically relevant due to the fact that modern laboratory instruments are often more precise than what is needed medically.

The following figure shows an L-J chart with a data point outside the 3s limits.

1-3.5s

Violation of the 1-3.5s rule indicates random error and may also point to systematic error. The run is considered out of control when one control value exceeds the mean 3.5s. This rule is applied within the run only. The following figure shows an L-J chart with a data point outside the 3.5s limits.



1-4s

Violation of the 1-4s rule indicates random error and may also point to systematic error. The run is considered out of control when one control value exceeds the mean 4s. This rule is applied within the run only. The following figure shows an L-J chart with a data point outside the 4s limits.

2-2s

The 22s rule detects systematic error only.

The 2-2s rule is violated when two consecutive QC results are: Greater than 2s On the same side of the mean

The rule is applied both within a run and across runs: Within run violationTwo control values in the same run are >2s on the

same side of the mean. Violation of the within run application indicates that systematic error is present that potentially affects the entire analytical curve.

Across run violationIn one run, a single level of control is >2s from the mean and, in the next run, the same level of control is >2s on the same side of the mean. Violation of the across run application indicates that systematic error is present, but affects only a single portion of the analytical curve.

The following figures show an L-J chart with a data point violating the 2-2s rule, within and across a run.



Within run violation:

Across run violation:

R-4s

The R-4s rule identifies random error only and is applied only within the current run. This rule is violated when there is at least a 4s difference between control values within a single run.

For example, assume both Level I and Level II have been assayed within the current run. Level I is +2.8s above the mean and Level II is -1.3s below the mean. The total difference between the two control levels is greater than 4s (i.e. +2.8s (-1.3s) = 4.1s).



The following figure shows an L-J chart with two points that violate the R-4s rule.

3-1s and 4-1s

These rules are violated when three or four consecutive results:

Exceed 1s Are on the same side of the mean

The 3-1s and 4-1s rules can be violated both within a control material (e.g. all Level I control results) and across control materials (e.g. Level I, II, and III control results in combination).

Violations within a control material indicate systematic bias in a single area of the method curve.

Violations across control materials indicate systematic error over a broader range of concentrations.

The following figures show an L-J chart with a data point violating the 3-1s rule within a run and a 4-1s rule across a run.

3-1s Within Run



4-1s Across Run

7-T

The 7-T rule is violated when a group of seven consecutive data points for a single level of control show either a "strict" increasing or decreasing pattern. A "strict" increasing pattern is defined as a series of points that increase incrementally from the previous point (each point greater than the last) without a break in the pattern. A "strict" decreasing pattern is the same pattern in a negative direction.

The following figure shows an L-J chart with points that violate the 7-T rule.

N-x Rules

The N-x rules are violated when there are 7, 8, 9, 10, or 12 control results on the same side of the mean.

Each of these rules has two applications: within a control material (e.g. all Level 1 control results) or across control materials (e.g. Level 1, 2, and 3 control results in combination).



Within a control material violations indicate systematic bias in a single area of the method curve while violation of the across control materials application indicates systematic bias over a broader concentration.

The 7-x control rule is far more sensitive to analytical bias than the 12-x rule, and the chances of finding seven consecutive control observations on one side of the mean are much higher than finding twelve.

The following figures show an L-J chart with data points that violate the 8-x rule within a run and the 9-x rule across a run.

8-x Within Run

9-x Across Run

In This Chapter

Recommended Steps ................................................... 41 Troubleshooting QC Results ........................................... 46

Recommended Steps Ensuring that your SPC Rules (on page 31) are chosen to maximize error detection while minimizing false rejections is crucial when setting up your QC system. CLSI (C24-A2, section 5) recommends that you follow these steps when setting up your QC system:

1 Determine quality requirements for the test

2 Evaluate test performance

3 Identify possible QC procedures, which include determining the:

Rules to apply

Control materials to be used

Number of control samples to be analyzed in each run

Location in the run where the control samples are tested (e.g. at the beginning, in the middle, at the end, or distributed throughout the run)

4 Predict the performance of the identified QC procedures (This step requires probability calculations or computer simulations.)

5 Choose goals based on your required quality

6 Select a QC procedure

Obviously, this is not a simple process, which may explain why many laboratories fall back on the 1-2s rule. Although the 1-2s rule produces too many false alarms, it feels safe.

The optional Westgard Advisor makes this arduous task easier.

C H A P T E R 3

Choosing a QC Procedure



Determine Quality Requirements for the Test

How good does a test need to be? Answering this question will help you determine the total allowable error (i.e. the error that the test can have and still be considered "in control"). There are several models you can use for quality specifications, including:

1 Medical usefulness requirements based on the effect of analytical performance on clinical decisions:

Biological variation information

Clinicians' opinions

2 Published professional recommendations from:

National and international expert bodies and agencies

Expert local groups or individuals

3 Performance goals set by:

Regulatory bodies and agencies

Organizers of External Quality Assessment (EQA) schemes

4 Goals based on the current state of the art, including:

Interlaboratory comparison programs such as the Unity Interlaboratory Program

EQA or Proficiency Testing schemes

Current published information on methodology

The preceding hierarchy is based on the consensus agreement published in the Scandinavian Journal of Clinical and Laboratory Investigation 1999; 59: 585.

When available and appropriate, models higher in the list are preferred to those lower in the list.

In general, proficiency testing requirements define the minimum standards for performance, because they are based on requirements needed to maintain accreditation. However, proficiency testing may be appropriate for some tests. Medical usefulness requirements are usually more stringent, but may be required for some tests.



Evaluate Test Performance

After you determine the quality required for a test, you need to evaluate the test's bias and imprecision in order to quantify its total error (TE). Unity Desktop uses the following formula to calculate laboratory total error (TE) for p



SD range Defect rate (%) Defects per million 2 SD 4.5 45,400

3 SD < 0.27 ~2,700

4 SD 0.0063 63

5 SD 0.0057 0.57

6 SD 0.000002 0.002

The advantage of controlling a process to six sigma is that the process can tolerate small shifts without significantly increasing the defect rate. In an ideal world, all our processes would be six sigma, and we could monitor them with very simple QC.

Unfortunately, not all processes are six sigma, and, as process capability decreases, our choice of QC procedures becomes increasingly important in detecting significant errors. In fact, some processes may have such low process capacity (i.e. high total error) that they cannot be controlled to a defined level of quality. This condition would trigger a maximum QC condition within the optional Westgard Advisor.

For clinical lab tests, the total error (TE) for a test provides an indication of the test's process capability, because it combines bias and imprecision. This allows us to calculate sigma using the following formula:

CVBiasTEaSigma =

The optional Westgard Advisor calculates and displays sigma based on your data for a test and your selected TEa and consensus group.

We can correlate sigma with the TEa as shown in the following table. (The table assumes that bias is zero.)

Process classification Process capability criterion 4-sigma process TEa > bias + 4SD

3-sigma process TEa > bias + 3SD

2-sigma process TEa > bias + 2SD

When bias is not zero, the sigma classification of a process decreases as its bias increases.



The information in this chapter was abstracted from the Six Sigma Quality Management and Desirable Laboratory Precision lesson available on Westgard.com. Dr. Westgard provides an eye-opening correlation between CLIA performance requirements and those required for a 5 or 6-sigma process. As Dr. Westgard concludes, "Six Sigma Quality Management sets demanding standards of performance for laboratory testing processes."

How Do I Use Six Sigma?

The sigma value for a test is a good indication of its process capability because it considers both bias and imprecision. Unfortunately, most clinical lab tests are below six sigma processes.

So how do we get to six sigma? The obvious answer is to choose a test method whose process is six sigma. Labs can take steps to control precision (e.g. proper training, instrument maintenance, etc.) However, to a large extent, method precision is a function of instrument methodology.

While you may not be able to control method precision, you can choose a QC procedure that detects small changes in the testing system so you reject runs having defects and perform corrective actions to prevent further defects.

The optional Westgard Advisor calculates sigma values and displays them on both the "Grid" and "Chart" tabs of the "Design QC Rules" tab. The sigma value also appears on Westgard Advisor Reports.

Qualitative Evaluation of a Test's Bias and Imprecision

Laboratories can access information about imprecision using interlaboratory comparison reports supplied by the vendor of their control materials. While these reports may also be used to evaluate bias, some laboratories prefer proficiency report data for this purpose.

Participants in Bio-Rads Unity Interlaboratory Program can use the Laboratory Comparison Report, the Laboratory Performance Overview Report, or the Statistical Profile Report. These reports contain two relevant statistics that laboratories can use as a qualitative assessment of their laboratory bias and imprecision:

CVR (coefficient of variation ratio)-represents a peer-based evaluation of imprecision.

This ratio is calculated as the laboratory CV for the test divided by the average CV reported for the consensus group.



SDI (standard deviation index)-provides a relative peer-based estimate of bias.

SDI describes or quantifies bias (difference between the laboratorys observed mean and the consensus group mean) in terms of standard deviation.

OPSpecs Charts and sigma values, which are available if you are using the optional Westgard Advisor, provide information about a test's maximum allowable bias (inaccuracy) and imprecision.

Troubleshooting QC Results Inevitably, your QC system will eventually indicate an out-of-control situation. What do you do then? In a lesson titled "QC - The Out-of-Control Problem" available on Dr. Westgard's web site (Westgard.com), Elsa F. Quam BS, MT (ASCP) discusses two prevalent bad habits and then provides five good habits to develop when troubleshooting QC problems.

The two bad habits listed by Ms. Quam will be familiar to anyone working in a clinical laboratory. They represent the incorrect, yet easy-way-out approach to solving QC problems.

Repeat the Control

In the past, labs frequently applied the 1-2s rule, which yields a false rejection rate of 5% for N=1, 9% for N=2, and 14% for N=3, where N is the number of control materials tested in the run. Using the 1-2s rule, it might be reasonable to simply repeat the test for the control. However, with carefully chosen rules, this approach is unnecessary. For example, the false rejection rate for a 1-3s rule is only 0.3 %. It is also important to remember that even if the repeat value is within control limits, allowing us to accept the run, we could be ignoring a problem until a future run.

Try a New Control

Another poor approach is to test a different vial of control and repeat it until it falls within range. A bad vial of control material is unlikely, although it can occur, such as when controls are not properly reconstituted, are stored improperly, are used beyond their expiration date, etc. These are issues that should be addressed by training. Cost is another issue. A new vial of control material is usually much less expensive than repeating a patient run.



As Ms. Quam concludes, "Automatically repeating controls or blaming the control itself are often attempts to resolve the problem without the hassle and time delay necessary in finding and eliminating the true cause of the QC failure. These practices have become habit because they are easy and we often do not have or do not teach the skills necessary to resolve the problem using a more systematic approach."

Recalibrate A third risky habit not mentioned by Ms. Quam is frequent recalibration. Laboratories should be concerned about the number of times a test is recalibrated because each calibration or recalibration potentially introduces new or additional systematic errors. Frequent recalibrations may indicate a defective SPC protocol (rules applied, mean, and range in use) set by the laboratory, instrument malfunction, sub-optimal reagent quality, or failure to follow the manufacturers instructions and schedule for maintenance.

So what are the good habits?

Good Habits

If we eliminate the bad habits, what do we replace them with? In her article "QC - The Out-of-Control Problem ", Ms. Quam lists five good habits:

1 Inspect the control charts or rules violated to determine type of error.

2 Relate the type of error to possible causes.

3 Consider factors in common on multitest systems.

4 Relate the problem to recent changes.

5 Verify the solution and document the remedy.

A sixth good habit, not mentioned by Ms. Quam, is to perform a regular review of your quality system to assess its effectiveness. Keys to a Productive Review of the Laboratory Quality System (on page 50) provides a list of questions that may be helpful for these reviews.

Determine the Type of Error

Determining the type of error (random or systematic) is a good first step when investigating a QC problem. Different rules are sensitive to different error types. For example:



The 1-3s and the R-4s rules usually indicate increased random error because they test the tails or width of a distribution

The 2-2s, 4-1s, and 10-x rules usually indicate systematic error, because they examine consecutive QC results that exceed the same limit

Looking at L-J charts will also indicate the type of error.

When possible, always identify the type of error before trying to identify the cause of the problem. Further classification of systematic error as a shift or trend is also useful.

Relate the Error to Possible Causes

Random errors (imprecision) and systematic errors (bias) have different causes. Systematic errors are more common and usually easier to investigate.

Systematic error is evidenced by a change in the mean of the control values. The change in the mean may be gradual and demonstrated as a trend or it may be abrupt and demonstrated as a shift. Causes of systematic error include change in reagent lot, change in calibrator lot, wrong calibrator values, improperly prepared reagents, deterioration of reagents, deterioration of calibrator, inadequate storage of reagents or calibrators, change in sample or reagent volumes due to pipettor misadjustments or misalignment, change in temperature of incubators and reaction blocks, deterioration of a photometric light source, and change in procedure from one operator to another.

Random error is any deviation away from an expected result. For QC results, any positive or negative deviation away from the calculated mean is defined as random error. Random error can be acceptable (or expected) as defined by your acceptable range or unacceptable (unexpected) random error, which is any data point outside the expected population of data (e.g. a data point outside the 3s limits). Random errors may be caused by bubbles in reagents and reagent lines, inadequately mixed reagents, unstable temperature and incubation, unstable electrical supply, and individual operator variation in pipetting, timing, etc.

Erratic performance due to occasional air bubbles in sample cups or syringes or defective unit-test devices are a different kind of random error, often called "flyers", because they aren't really caused by a change in the imprecision of the method, but rather represent an occasional disaster. It is very difficult to catch flyers by QC. Patient replicate determinations may be a better way of detecting these kinds of events.



Consider Common Factors on Multitest Systems

When using a multitest system, you may have a problem with a single test or with several tests.

Only one test involved Apply the first two steps (i.e. determine the type of error and relate it to possible causes).

Several tests involved Consider what, if anything, the tests have in common. The following list includes some questions you might want to ask:

Do all the tests have small or large sample sizes?

Do all the tests use the same filter?

Do all the tests with the problem use the same lamp and tests without the problem use a different lamp?

Do all the tests use the same mode of detection (endpoint vs. rate, MEIA vs. FPIA)?

Do all the tests have certain mechanical components in common or certain optical components in common?

Relate the Problem to Recent Changes

A good question to ask yourself when QC problems arise is, "What changed?" You should have already classified the error as random or systematic, which gives you clues about what to investigate first.

Use a systematic logical troubleshooting approach in isolating the cause, making only one change at a time and documenting each action taken.

Systematic Error

If you observe a sudden shift, inspect the reagent, calibration, and maintenance records, and note recent actions. For example, if the shift occurred immediately following a reagent replacement, verify that the lot number is correct and has been checked out or calibrated, and that the reagent has been prepared properly, that the reagent is indeed the correct reagent.

If you observe a systematic trend, review QC records, including documentation of function checks, prior to taking actions to resolve the cause. Trends can be caused by a slowly deteriorating reagent, a calibration



shift, a change in instrument temperature, or a deteriorating filter or lamp. Unfortunately, systematic trends can be more difficult to resolve than shifts because they occur over a longer time period.

Random Error

The causes of increased random error are generally much more difficult to determine because of their random nature. Random errors are more likely due to bubbles in the reagent, reagent lines, sampling or reagent syringes, or improperly mixed/dissolved reagent, pipette tips not fitting properly, a clog in the pipettor, imprecise pipettor, the power supply, and even power fluctuations.

Many of these problems can be detected by inspecting the machine during operation. If a careful inspection provides no clues, you can consult troubleshooting guides and manufacturer recommendations.

If you repeat the run, and the controls are acceptable, but you are still concerned that a problem may exist, you may want to perform a precision run using 10 back-to-back determinations on the same patient sample. This precision run may identify further imprecision problems. Duplicate analysis of patient specimens is also recommended when monitoring random error problems.

Verify and Document

After you identify and correct a problem, the correction should be verified by retesting controls. Generally, you will run controls at the beginning of a run. If the new QC values are in control, you should repeat patient samples from the out-of-control run as necessary. Finally, document the out-of-control event along with the corrective action.

Troubleshooting reports, especially for unusual problems, provide useful information for future problem solving.

You can correlate problems with your reports including intralaboratory, InstantQC, and Unity Interlaboratory reports.

Keys to a Productive Review of the Laboratory Quality System

Your laboratory quality system should include regular reviews of your QC results. CAP-accredited laboratories must review and document QC



performance at least weekly. These reviews, which are often done retrospectively, offer an excellent opportunity to critically assess the SPC rules applied to a test.

Issues that reviewers should consider include: Statistical out-of-control events Frequency of outliers (QC values outside the established total allowable

error limits) during the period or across periods

The amount of bias present, if any

Assessing these issues is key to a productive review and can be facilitated by asking the following questions: Are the statistical process control (SPC) rules in effect for the test too

restrictive when the capability of the methodology or technology and total allowable error are jointly considered?

Should another more stringent single rule or more complex multi-rule be applied to improve error detection?

Should the mean for the test be adjusted? How much imprecision is present and is it a significant contributor to

total error? Should the laboratory focus its efforts on improving precision?

How much comparative bias is present and is it a significant contributor to total error? Should the laboratory focus its efforts on removing or reducing analytical bias?

Is the appropriate consensus group (Peer, Method, All Laboratories) being used to estimate the laboratorys comparative bias for the test?

Are the performance goals for imprecision and bias for the test, which also affect total allowable error, appropriately set?

How frequently do SPC error flags occur for the test during this review period? Across review periods? Are these frequent error flags due to inappropriate selection of SPC rules, larger than expected imprecision, or the presence of bias, do the mean and range need adjustment?

How frequently is the test being recalibrated? Does calibration exceed the frequency recommended by the manufacturer?

There is probably not enough time to ask all of these questions during each review cycle. However, each of these questions represents an opportunity to measure and appraise the effectiveness of the process control in effect for a specific test.

In This Chapter

Starting and Exiting the Program .................................... 53 Current Lab, Lot, Test, and Panel ................................... 53 Toolbars .................................................................. 54 Unity Desktop Menu Bar ............................................... 55 Bio-Rad Laboratories From the Windows Start Menu ............. 57 Shortcut Keys............................................................ 57 Functions and Where to Find Them.................................. 59

Starting and Exiting the Program If you created a shortcut when installing Unity Desktop, simply double-click the shortcut on your desktop to display the "Login" dialog box. Otherwise, choose Start | All Programs | Bio-Rad Laboratories | Unity Desktop.

If you did not create a shortcut during installation, the following steps describe how to create a shortcut from the Windows Start menu.

1 Select Start | All Programs | Bio-Rad Laboratories | Unity Desktop.

2 Right-click Unity Desktop. A popup menu appears.

3 Select Create Shortcut. The shortcut appears on the desktop.

Current Lab, Lot, Test, and Panel The left pane of the Unity Desktop screen has tabs for the lab and panel navigation trees. The lab, lot, or test selected in the tree is the current lab, lot, or test. See Tree Views (on page 229) for additional information.

Because trees are hierarchical:

Selecting a test also determines the current lab and lot.

C H A P T E R 4

Program Basics



Selecting a lot number also determines the current lab, but there is no current test.

Selecting a lab number determines only the current lab. There is no current lot or current test.

The current lab, lot, and test selections determine the active lab, lot, and test. For example, if you select a test in the tree and then click the L-J icon on the toolbar, Unity Desktop displays the Levey-Jennings chart for the selected test.

Because selecting a test also determines the current lab and lot, these items will be active if you access the "Lab" or "Lot" dialog boxes. In addition, menu and toolbar items become available or unavailable depending on which item (lab, lot, or test) is selected in the tree. For example, charts and reports are available only when a test is selected in the tree. Similarly, selecting a lot selects its associated lab number.

Toolbars The Unity Desktop toolbar contains icons (buttons) that you click to activate specific program functions. The icons themselves are self-explanatory, especially when using large icons, but you can hover your mouse over an icon to display a short description. The default toolbar contains commonly used icons; however, you can customize your toolbar to contain the functions you use most frequently.

When you choose View | Toolbar, the "Toolbar" dialog box appears.


Program Basics

Your current toolbar icons appear below the dialog box's title bar. The "Large toolbar" and "Small toolbar" option buttons control the appearance of the toolbar icons. Small icons take up less room on the screen; however, large icons contain labels, which may be useful until you become familiar with the program. In the preceding figure, the "Large toolbar" option is selected.

The lower part of the dialog box contains an "Available list" and a "Selected list" of icons with several buttons:

AddSelect an icon in the "Available list", and click Add to move the icon to the "Selected list."

RemoveSelect an icon in the "Selected list" and click Remove to remove the icon from the "Selected list". The icon reappears in the "Available list."

CTRL + Click and SHIFT + Click are active and operate as described in Selecting Items in Lists (on page 231).

RefreshClick to change the icon display under the title bar to your current selections.

DefaultClick to return the selections to the program defaults. OKClick to save your changes. CancelClick to cancel any changes and close the dialog box.

Unity Desktop Menu Bar The Unity Desktop menu bar contains menus each of which opens to a submenu. The menu bar is not customizable. This section provides a reference for which items are accessible from each main menu. Functions of each menu item are discussed elsewhere in this guide.



Menu Item Submenus File Open

Save ChartVi

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