CLSI EP23 ™ —Laboratory Quality Control Based on Risk Management

1. CLSI EP23™—Laboratory Quality Control Based on Risk Management James H. Nichols, PhD, DABCC, FACB Chairholder EP23 Document Development Committee Professor of Clinical Pathology, Microbiology and Immunology Vanderbilt University School of Medicine Medical Director, Clinical Chemistry Nashville, Tennessee, USA

2. Objectives • Review key aspects of risk management. • Describe the various types of control processes. • Identify CLSI document EP23 as a resource for developing a laboratory quality control (QC) plan based on risk management. • Use CLSI document EP23 to develop a quality control plan (QCP) based on risk management for a simple, moderate complexity device.

3. Risk Would you walk underneath this piano?

4. Risk Management • Risk management is not a new concept; laboratories: • Evaluate the performance of new devices. • Troubleshoot instrument problems. • Respond to physician complaints. • Estimate harm to a patient from incorrect results. • Take actions to prevent errors. • Risk management is a formal term for what clinical laboratories are already doing every day.

5. Risk Management Definition Systematic application of management policies, procedures, and practices to the tasks of analyzing, evaluating, controlling, and monitoring risk (ISO 14971)

6. Risk Definition Risk – the chance of suffering or encountering harm or loss (Webster's Dictionary and Thesaurus. Ashland, OH: Landall, Inc.; 1993). Risk can be estimated through a combination of the probability of occurrence of harm and the severity of that harm (ISO/IEC Guide 51). Risk, essentially, is the potential for an error to occur that could lead to patient/staff harm.

7. What could go wrong?

8. Sources of Laboratory Error • Environmental: • – Temperature • – Humidity • – Light intensity • – Altitude • Operator: • – Improper specimen preparation, handling • – Incorrect test interpretation • – Failure to follow test system instructions • Specimen: • – Bubbles • – Clots • – Incorrect tube additive • Analysis: • – Calibration factor incorrect • – Mechanical failure

9. Managing Risk With a Quality Control Process

10. Quality Control Advantages QC monitors the end product (result) of the entire test system. QC has target values: if assay recovers the target, then everything is assumed stable (ie, instrument, reagent, operator, sample). Disadvantages When a problem is detected, one must go back and reanalyze patients since the last “good” QC. If results are released, then results may need to be corrected. Need to get to fully automated analyzers that eliminate errors up front Until that time, need a robust QC plan (QCP)

11. Types of Quality Control “On-Board” or Analyzer QC – built-in device controls or system checks Internal QC – laboratory-analyzed surrogate sample controls External QC – blind proficiency survey Other types of QC – control processes either engineered by a manufacturer or enacted by a laboratory to ensure result reliability

13. Quality Control Limitations No single QC procedure can cover all devices, because the devices may differ. QC practices developed over the years have provided laboratories with some degree of assurance that results are valid. Newer devices have built-in electronic controls, and “on-board” chemical and biological controls. QC information from the manufacturer increases the user’s understanding of device’s overall quality assurance requirements. ISO. Clinical laboratory medicine – In vitro diagnostic medical devices – Validation of user quality control procedures by the manufacturer. ISO 15198. Geneva, Switzerland: International Organization for Standardization; 2004.

14. Laboratory-Manufacturer Partnership Developing a quality plan surrounding a laboratory device requires a partnership between the manufacturer and the laboratory. Some sources of error may be detected automatically by the device and prevented, while others may require the laboratory to take action, such as analyzing surrogate sample QC on receipt of new lots of reagents. Clear communication of potential sources of error and delineation of laboratory and manufacturer roles for how to detect and prevent those risksis necessary.

15. Quality Control

16. CLSI Document EP23 • Laboratory Quality Control Based on Risk Management; Approved Guideline (EP23-A™) • James H. Nichols, PhD, DABCC, FACB, Chairholder of the document development committee • EP23 describes good laboratory practice for developing a QCP based on the manufacturer’s risk mitigation information, applicable regulatory and accreditation requirements, and the individual health care and laboratory setting.

17. The Scenario • CLSI document EP23 provides guidance on developing an appropriate QCP that will: • – Save time and money. • – Use electronic and/or integrated QC features. • – Use other sources of QC information. • – Conform to one’s laboratory and clinical use of the test.

18. Developing a QCP

19. The Quality Control Toolbox • Every QC tool has its strengths and weaknesses (there is no perfect QC tool). • Implement a combination of tools in order to properly control a test. • EP23 explains the strengths and weaknesses of the different QC processes.

20. Examples of Quality Control Tools Intralaboratory QC Interlaboratory QC Integrated (built-in) QC Measuring system function checks Electronic system checks Calibration checks Repeat testing of patient samples Monitoring aggregated patient results Implausible values Delta checks Correlation of multiple analytes in same sample

21. What Could Go Wrong?

22. Gather Information for the Risk Assessment • Gather information from several sources: • – Regulatory and accreditation requirements • Clinical Laboratory Improvement Amendments Test/test system information • User’s manual, reagent package insert, literature • – Health care and testing site settings • Temperature conditions, operator training programs • – Medical requirements for the test results • Allowable performance specifications via physicians

23. Developing a Process Map • Break down all phases of the test or test system into steps, so that weak points can be identified. • Each step can be analyzed to find potential failure modes that could present significant risk to patients. • Process can then be further analyzed to see if controls can be put into place to avoid the failures.

24. Process Map

25. Key Process Steps • View the preexamination (preanalytical), examination (analytical), and postexamination (postanalytical) areas of the laboratory. • Think about what steps can be taken to reduce potential errors “unrelated” to the actual testing of the sample.

26. Where Is the Risk in the Process? What could possibly go wrong?

27. Identify the Risks

28. Hazard or Risk Identification Some areas to consider for weaknesses in the process: System startup System calibration Loading and testing of patient samples Proper device function Test result review • Testing personnel training and competency • Reagent/calibrator/parts procurement and storage • Patient sample acceptability

29. Risk Assessment

30. Perform the Risk Assessment • Identify the potential failures and their causes. • – Review the process map, fishbone diagram, manufacturer’s instructions, etc. • Assess each potential failure. • Where a failure could occur, add an element to the QCP that will reduce the possibility of that failure, making residual risk acceptable. • – For some types of failures, the manufacturer’s information may already have a quality check in place.

31. Perform the Risk Assessment (cont’d) • Construct a table; see which types of errors are detected and which ones are not. • – If not detected, it must be included in the QCP. • For each possible failure, assess the possibility of that failure. • – Do this for each identified failure. • – Use all of the information gathered in order to make these assessments.

32. Assemble the Quality Control Plan • Use the information gathered earlier to assess all of the identified risks and their control measures. • Construct the QCP. • Include each of the identified QCP actions in the QCP.

33. What could go wrong?

34. Monitor Quality Control Plan for Effectiveness • Verify that the QCP that is put in place actually works. • Continue to monitor errors and control failures. • If an error occurs: • – Take the appropriate corrective action. • – Investigate the cause of the error. • – Once the cause is understood, evaluate whether any changes need to be made in the QCP.

35. Monitor Quality Control Plan for Effectiveness (cont’d) • Review any complaints that the laboratory receives from health care providers. • – These complaints may include pointing out another source of QC “failure” that must be addressed. • For patient safety, the QCP should be reviewed and monitored on an ongoing basis to ensure that the QCP is optimal.

36. Don’t Be Discouraged—Risk Management Is Documenting Much of What We Already Do!

37. Polling Question #1 What is a QCP? The frequency of liquid controls for a test A form that defines required specifications of materials from suppliers A document that describes the practices, processes, and sequences of specified activities to control the quality of a particular measuring system None of the above

38. The Scenario • A laboratory director wants to develop a QCP • – Incorporates the right QC processes for the specific test • – Uses adequate QC to control for their potential error sources • – Follows manufacturer’s instructions • A unit-use blood gas analyzer will be used as the example.

39. Developing a Quality Control Plan

40. Polling Question #2 Raise your hand if you are responsible for blood gas or electrolyte testing in your facility, or if you are a manufacturer or distributor of blood gas/electrolyte test systems.

41. Gather the Information

42. Blood Gas and Electrolytes Generic unit-use blood gas/lytes analyzer in a same-day surgical center Low volume: 0 - 5 tests/day Need for daily liquid QC uses two kits ($10 each) and adds to turnaround time (TAT). Adoption of nontraditional QC through EP23 would improve cost, test, and labor efficiency.

43. Blood Gas and Electrolytes Portable clinical analyzer for in vitro quantification of various analytes in whole blood Analyzers and cartridges should be used by healthcare professionals trained to use the system according to the facility’s policies and procedures.

44. System consists of: Portable clinical analyzer Test cartridges sealed in foil pouch for protection during storage Quality assurance materials Control solutions Calibration verification set Data Management System Server class computer Data management software Wireless connectivity and LIS/HIS interfaces Blood Gas and Electrolytes Device Device Device Device

45. BloodGas and Electrolytes • Unit use cartridge contains all components to perform the testing • – Calibrating solution • Reagents • Sample handling system • Sensors • Analyzer automatically controls all steps of the testing process: • Fluid movement • Calibration • Reagent mixing • Thermal control

46. Cartridge Operations • Cartridges are standardized to plasma core lab methods using multi-point calibration curves stored in the device memory that are stable over many lots • Upon insertion, a calibrant solution in the cartridge is passed across the sensors. • Signals produced by the sensor’s responses to calibrant are measured – A one-point calibration adjusts the offset of stored multi-point calibration curve. • Analyzer then moves sample over sensors, and the signal of the sensor responses to the sample are measured off the adjusted calibration curve

47. Polling Question #3 What types of quality control processes can help laboratories manage their risk of errors for a blood gas/electrolyte test system? Liquid quality control samples Manufacturer checks and simulated internal electronic controls Staff training and competency All of the above

48. Internal Control Processes Simulated internal QC - diagnostic check of the edge connector, internal electronics, and analyte circuitry. Internal QC simulates electronic signals produced by the sensors during a cartridge test. An isolated region of the internal circuit board sends a range of simulated sensor signals through the cartridge measurement channels Range of signals encompasses entire linear range expected from blood analytes Next, conductivity out of the connector pins is measured, insuring no contamination is present in the edge connector which would interfere with the test. Signal measurements must fall within strict predetermined thresholds to pass.

49. Quality Control Recommendations Internal Simulated QC: Automatically performed by device every 8 hrs If significant change in analyzer temp (cold to hot) Whenever performance of device in question Liquid QC: Each shipment of cartridges New lots of cartridges If cartridges experience temperature shift >8°C (15°F) Periodically as required by facility policies Temperature Verification Monitored continuously during each patient test, but verification cartridge available and recommended annually, or as required by facility policy

50. Identify Weak Steps for Hazards or Risk of Error Create a Process Map