Analytical Phase of Diagnostic Testing – Quality Control & ISO 15189

Review of Previous Lecture and Context

• The lecturer (Youping) greets the audience and reminds them:
  • Last lecture focused on Pre-Analytical Phase of the Total Testing Process (TTP).
  • Emphasized that pre-analytical steps account for the majority of testing errors.
• Current lecture objective: step forward to the Analytical Phase.
  • Guiding questions:
  • What is the analytical phase and how is it distinct from the pre-analytical phase?
  • How do labs evaluate quality during the analytical phase?
  • How are Internal Quality Control (IQC) and External Quality Assurance (EQA) implemented?
  • Which statistical rules (e.g., Westgard rules) determine run acceptance/rejection?
  • How does one read a Levey–Jennings control chart and interpret EQA reports?

Total Testing Process (TTP) – Placement of Analytical Phase

• TTP begins with a clinical question and ends with a diagnostic action.
• Pre-Analytical Phase:
  • Many intermediate processes outside the lab (patient prep, specimen collection, transport, accessioning).
  • Accounts for the vast majority of errors (≈ 70\% of unexpected or erroneous results).
• Analytical Phase (today’s focus):
  • Activities performed inside the laboratory.
  • Starts with analytical quality design.
  • Goal: assure/ improve measurement quality and reliability.
  • Error contribution relatively low: only ≈ 10\text{–}15\% of total mistakes.

Improving Analytical Quality

• Automation
  • Modern laboratories deploy automated lines and robotic sample handlers.
  • Benefits:
  • Repeatability & consistency.
  • Reduced human variability → decreased error rate.
  • Illustrated by a schematic of a laboratory automation system.

Common Analytical Phase Errors

• Undetected IQC failure
• Instrument / equipment malfunction
  • E.g., probe clogs, hardware wear-out.
• Sample probe failure → mis-identification, mix-up
• Analytical interference
  • Endogenous: hemolysis, lipemia, icterus, paraproteins.
  • Exogenous: medication, anticoagulants, contaminants.
• Scope limitation of this lecture: focus on Quality Control (QC) only (other errors to be covered separately).

Quality Control & Quality Assurance Framework

• Internal Quality Control (IQC)
  • Routine checking of analytical run validity.
  • Uses control materials with known target ranges.
  • Results plotted on Levey–Jennings charts.
• External Quality Assurance (EQA / Proficiency Testing)
  • Inter-laboratory comparison.
  • Periodic, blind samples sent by a scheme provider.
  • Lab receives performance report and peer group statistics.
• Statistical Decision Rules: Westgard Rules
  • Provide acceptance/rejection criteria for daily runs.
  • Examples (not yet elaborated here): 1_2s, 1_3s, 2_2s, R_4s, 4_1s, 10_x.

Regulatory & Standards Landscape

1. Clinical and Laboratory Standards Institute (CLSI)

• Global, non-profit, consensus-based organisation.
• Develops best-practice guidelines for:
  • Sample types: blood, body fluids (urine, saliva, CSF), tissues, hair, etc.
  • Technical procedures, QC, QA, safety, informatics.
• Recognised by labs, accreditors, regulators worldwide.

2. National Association of Testing Authorities (NATA) – Australia

• Provides accreditation for:
  • Clinical laboratories, inspection bodies.
  • Calibration services, reference material producers.
  • Proficiency testing scheme providers.
• Broader scope beyond healthcare: food, construction, environment.
• Endorsed by Australian Government as benchmark for “better regulation, good governance & fair markets.”

3. International Organization for Standardization (ISO) – Standard 15189

• ISO = worldwide federation of national standards bodies.
• ISO 15189: “Medical laboratories – Requirements for quality and competence.”
  • Prepared by Technical Committee on clinical lab testing & in-vitro diagnostics.
• Publication timeline:
  • 1st edition: 02/2003.
  • 3rd/current edition: 2012 (still in use).
• Purpose & scope:
  • Sets QMS requirements tailored to medical laboratories.
  • Helps labs self-assess competence & seek accreditation.
  • Universal: applies to any division or organisational structure of a medical lab.
• Core goals:
  • Develop failure-resistant environment – detect mistakes early.
  • Continuous quality improvement through staff empowerment & process optimisation.

ISO 15189 Structure

• Divided into 2 main parts:
  1. Management Requirements (QMS focus)
  • Regular management reviews.
  • Scheduled internal audits.
  • Objective: ensure activities remain effective & meet client needs.
  • Foster culture of proactive improvement (identify opportunities before issues arise).
  • Example components (left column of lecture table):
    • Quality policy & objectives.
    • Document control.
    • Contract review.
    • Corrective & preventive actions.
  1. Technical Requirements (competence focus)
  • Personnel qualifications & training.
  • Method validation/verification.
  • Equipment calibration & maintenance.
  • Pre-examination, examination, post-examination processes.
  • Measurement uncertainty, traceability.

Laboratory Duties Under ISO 15189 (summarised from slide)

• Maintain comprehensive policies and Standard Operating Procedures (SOPs).
• Ensure all staff are trained & competent in technical, quality-management, and clinical tasks.
• Instrument performance must be documented:
  • Calibration schedules.
  • Maintenance logs.
  • QC statistics.
• Environmental monitoring:
  • Incubator temp/humidity.
  • Refrigerator/freezer temps.
  • Logbooks for verification & alarms.

Key Take-Home Points

• Analytical phase contributes smaller error proportion but still requires rigorous QC.
• Automation enhances consistency yet cannot replace formal QC/QA systems.
• Implementation of IQC, EQA, Westgard rules, and Levey–Jennings charts are core to error detection during analysis.
• CLSI, NATA, ISO 15189 provide layered governance ensuring labs deliver reliable, competent diagnostic services.
• Building a failure-resistant environment entails proactive monitoring, staff empowerment, and continual quality improvement.

Upcoming Content (Teaser)

• Detailed walkthrough of:
  • Westgard rule interpretation.
  • Levey–Jennings chart diagnostics (shift, trend, random error detection).
  • Reading & acting on EQA proficiency reports.
• Expanded discussion on analytical interferences and troubleshooting strategies.