PF1 - Quality Assurance and Assessment Lecture Notes

Quality Assurance (QA)

A systematic process to ensure reliable, accurate laboratory results, involving policies, procedures, and monitoring to minimize errors.

Components of QA in Laboratory Operations

Patient/client prep, sample collection, pre-analytical phase, analytical phase, and post-analytical phase.

Role of QA Programs

Establishing standardized workflows and protocols

Conducting routine audits and proficiency testing

Training personnel to maintain competency

Compliance with regulatory bodies (e.g., ISO, CLSI, CAP, DOH-HFSRB)

Pre-analytical Errors

Incorrect patient ID and sample contamination.

Analytical Errors

Instrument malfunction and procedural errors.

Post-analytical Errors

Misinterpretation and delayed reporting.

Error Prevention Strategies

Implementing strong internal QC programs, using automation, encouraging ongoing staff training, and promoting a culture of quality.

Quality Control (QC)

Examining “control” materials of known substances along with patient samples to monitor the accuracy and precision of the complete examination (analytic) process.

The goal of QC is to detect errors and correct them before patients’ results are reported.

Quantitative Examination Methods

Measure the quantity of a particular substance in a sample, requiring accuracy and precision.

Qualitative Examination Methods

Examinations that do not have numerical results, such as growth/no growth or positive/negative, reactive/non-reactive, color change

Semi-Quantitative Examination Methods

Results expressed as an estimate of the measured substance, like 'trace amount' or '1+, 2+, or 3+', number of cells per microscopic field, titers and dilutions in serologic tests

Steps for Quantitative QC Implementation

Establish policies, assign responsibility, select high-quality controls, establish control ranges, develop graphs, monitor control values, develop corrective action procedures, and record all actions.

Control

Material that contains the substance being analyzed (include patient samples when performing a test), used to validate the reliability of the test system (run after calibration, run periodically during testing)

Calibrators

A substance with a specific concentration and calibrators are used to set (calibrate) the measuring points on a scale

Controls

Substances similar to patients’ samples with an established concentration and used to ensure the procedure is working properly.

Assayed Controls

Target value pre-determined; requires verification and use.

Unassayed Controls

Target value not pre-determined; requires a full assay before using.

Steps in Implementing Quantitative QC

Obtain control material, run each control 20 times over 30 days, and calculate mean and standard deviations.

Accuracy

The closeness of the measurements to the true value.

Precision

The amount of variation in measurements.

Bias

The difference between the expectation of a test result and an accepted reference value.

Standard Deviation (SD)

Principle measure of variability used in the laboratory.

Coefficient of Variation

Used to monitor precision and compare methods, ideally less than 5%.

Levey-Jennings Chart

Graphically representing control ranges over a 20-30 day period to ensure procedural variation is represented and calculate mean and SD

Random Error

Variation in QC results with no pattern; only a cause for rejection if outside 2SDs.

Systematic Error

Not acceptable- shift and trend.

External Quality Assessment (EQA)

A system for objectively checking the laboratory’s performance using an external agency or facility.

EQA method: Proficiency Testing

An external provider sends unknown samples for testing to a set of laboratories; results are analyzed, compared and reported to the laboratories

EQA Methods

Comparison among different test sites, early warning for systemic problems, objective evidence of testing quality, areas that need improvement and training needs

On-Site Evaluation

A periodic visit by evaluators for on-site laboratory assessment is a type of EQA that has been used when other methods of EQA are not feasible/effective

EQA Management Process

Includes handling of samples, analyses of samples, appropriate record keeping, investigation of deficiencies, taking corrective action, and communication of outcomes.

EQA Performance Problems (Pre-Analytical)

Sample may have been compromised during preparation, shipping, or after receipt in the laboratory by improper storage or handling

EQA Performance Problems (Analytical)

The EQA challenge materials may exhibit a matrix eect in the examination system used by the participating laboratory

EQA Performance Problems (Analytical)

Possible sources of analytical problems include reagents, instruments, test methods, calibrations and calculations

EQA Performance Problems (Analytical)

Competency of sta will need to be considered and evaluated

EQA Performance Problems (Analytical)

Analytical problems should be investigated to determine whether error is random or systematic.

EQA Performance Problems (Post-Analytical)

The report format can be confusing, Interpretation of results can be incorrect and Clerical or transcription errors can be sources of error.

EQA Performance Problems (Pre-Analytical)

The sample may have been processed or labelled improperly in the laboratory

Quality Assurance (QA)

Involves policies, procedures, and monitoring to minimize errors.

Importance of QA in Laboratory Operations

Ensures patient safety, improves efficiency and consistency in testing and enhances regulatory compliance.

Laboratory operations (pre-analytical phase)

Personal Competency Evaluations

Sample Receipt and Accessioning

Sample Transport

Laboratory operations (analytical phase)

Quality Control Testing

Laboratory operations (post-analytical phase)

Record Keeping

Reporting

internal QC programs (error preventing strategies)

Routine QC Testing

Instrument calibration and Maintenance

Implementation and strict adherence to standard operating procedures (SOPs)

Data monitoring and Statistical analysis

Consequences of impact of lab errors on patient outcomes

Misdiagnosis and incorrect treatment

Delayed interventions

Increased healthcare costs and patient dissatisfaction.

Quality assurance

not a one-time process; it’s an ongoing commitment to excellence

CHARACTERISTICS OF CONTROL MATERIALS

Appropriate for the diagnostic sample

Values cover medical decision points

Similar to test sample

Available in large quantity

Ideally enough for one year

Can store in small aliquots

Control materials (types of control materials)

May be frozen, freeze- dried, or chemically preserved

Requires very accurate reconstitution if this step is necessary.

Control materials (sources of control materials)

Commercially prepared

Made “in house”

Obtained from another laboratory, usually central or reference laboratory

IN-HOUSE CONTROLS

pooled sera

Full assay, validation

CHOOSING CONTROL MATERIALS

Values cover medical decision points similar to the test sample

Controls are usually available in high, normal, and low ranges

PREPARATION AND STORAGE OF CONTROL MATERIAL

Adhere to manufacturer’s instructions

Keep adequate amount of same lot number

Store correctly

MEASUREMENT OF VARIABILITY

Variability is a normal occurrence when a control is tested repeatedly

Aected by: ○ Operator technique ○ Environmental conditions ○ Performance characteristics of the measurement

The goal is to dierentiate between variability due to chance from that due to error

MEASUREMENT OF VARIABILITY - MODE

The value which occurs with the greatest frequency

MEASUREMENT OF VARIABILITY - MEDIAN

The value at the center or midpoint of the observations

MEASUREMENT OF VARIABILITY - MEAN

The calculated average of the values

NORMAL DISTRIBUTION

All values symmetrically distributed around the mean

Characteristic “bell-shaped” curve

Assumed for all quality control statistics

STANDARD DEVIATION

Principle measure of variability used in the laboratory

INTERPRETATION OF CONTROLS

Dependent on the number of controls run with patients' samples.

When using only one QC sample: Values outside 2 SD = out of control = reject

If it is possible to use only one control, choose one with a value that lies within the normal range of the analyte being tested. When evaluating results, accept all runs where the control lies within +2 SD.

In order to improve efficiency and accuracy, a system using two or three controls for each run can be employed: Apply Westgard multirole system.

QC TROUBLESHOOTING

If QC is out of control: STOP testing

Identify and correct problem

Repeat testing on patient samples and controls after correction

Do not report patient results until the problem is solved and controls indicate proper performance

BASIC TROUBLESHOOTING (QC OUT OF LIMITS - ACTIONS TO BE TAKEN)

If unresolved - Repeat with the same vial

If unresolved - Repeat with new vial

If unresolved - Repeat with new reagents

If unresolved - Recalibrate If unresolved Refer to support

SOURCES OF ERROR AND POSSIBLE REASONS

RANDOM ERROR - SYSTEMATIC ERROR

Unstable power supply - Improper alignment of probes

Double pipetting of sample - Drift/shift in incubation temperature

Air bubbles in water supply - Change in reagent lot number

Air bubbles in reagent/sample - Deterioration of reagent

Operator technique - Use of non-compliant consumables

- Recent calibration

- Change in test procession

- Improper handling of reagents

EQA method: Rechecking or retesting

slides that have been read are rechecked by a reference laboratory; samples that have been analyzed are retested, allowing for interlaboratory comparison.

EQA method: on-site evaluation

usually done when it is difficult to conduct traditional proficiency testing or to use the rechecking/retesting method.

EQA

important for improvement of the laboratory QMS, as it is a measure of lab performance

ISO/IEC GUIDE 43-1:1997

“Proficiency testing schemes (PTS) are interlaboratory comparisons that are organized regularly to assess the performance of analytical laboratories and the competence of the analytical personnel.”

CLSI GP27-A2 27:8

“A program in which multiple samples are periodically sent to members of a group of laboratories for analysis and/or identification; whereby each laboratory’s results are compared with those of other laboratories in the group and/or with an assigned value, and reported to the participating laboratories and others.”

Lung Center of the Philippines

Clinical Chemistry

San Lazaro Hospital

National Reference Laboratory/STD AIDS Cooperative Central Laboratory (SLH-NRL/SACCL)

ROLES OF LABORATORY

Information received from PT participation must be directed toward improvement in the laboratory to receive the full value.

PROFICIENCY LIMITATIONS

PT results are affected by variables not related to patient samples.

PT will not detect all problems in the laboratory.

PT may not detect problems with pre- and post examination procedures

other QA methods - RETESTING

Tested by reference laboratory

Performed on serum

Not blinded

Statically significant

other QA methods - RECHECKING

Samples must be collected randomly

Avoid systematic sampling bias

Satirically significant

Resolve discrepancies

Effective feedback

ON-SITE EVALUATION

Obtain a realistic picture of laboratory practices by observing the laboratory under routine conditions in order to check that it is meeting quality requirements.

Provide information for internal process improvement.

Measure gaps or deficiencies—learn “where we are”;

Assist the laboratory in collecting information for planning and implementation of training, monitoring and corrective actions

management process - handling of samples

These will need to be logged, processed properly and stored as needed for future use.

management process - analyses of samples

Consider whether EQA samples can be tested so that sta do not recognize them as dierent from patient samples (blinded testing).

management process - appropriate record keeping

Records of all EQA testing reporting should be maintained over a period of time, so that performance improvement can be measured.

management process - investigation of any deficiencies

For any challenges where performance is not acceptable.

management process - taking corrective action when performance is not acceptable

The purpose of EQA is to allow for detection of problems in the laboratory, and to therefore provide an opportunity for improvement.