Laboratory Quality Control Based on Risk Management

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Laboratory Quality Control Based on Risk Management John A. Gerlach, Ph.D., D(ABHI) Professor and Director Biomedical Laboratory Diagnostics Program MSU Tissue Typing Laboratory gerlach@msu.edu

EP23-A Guidance for developing quality control plans for measuring systems. Monitor to: Detect trends Identify corrective actions Provide CQI

EP23-A Up front information gathering: Regulatory requirements Manufacturer support Laboratory environment Medical necessity/utility

EP23-A Risk management principles

Principles of Risk Management (ISO) create value be an integral part of organizational processes be part of decision making explicitly address uncertainty and assumptions be systematic and structured be based on the best available information Be adaptable/able to be tailored take into account human factors be transparent and inclusive be dynamic, iterative and responsive to change be capable of continual improvement and enhancement

Risk Management Process (ISO) Context Assessment Rate of occurrence X impact = risk magnitude Composite Risk Index = Impact X Probability Treatments Avoidance eliminate or withdraw Reduction optimize or mitigate Sharing transfer or outsource Retention accept and budget Management plan Implementation Monitor, review and adjust

Context Identify risk Source analysis Internal or external to the system Problem analysis Risks related to identified threats

EP23-A Use risk management principles to develop a quality control plan tailored to the particular combination of: Measuring system Laboratory environment Clinical application

EP23-A Guidance for developing quality control plans for measuring systems. Monitor to: Detect trends Identify corrective actions Provide CQI

Realities of clinical testing Manufacturer is responsible for quality in design of measuring system and reagents.

Realities of clinical testing Manufacturer is responsible for quality in design of measuring system and reagents. Laboratory director is accountable for the quality of the test system.

Effective plan needs: Regulatory requirements Manufacturer provided information Laboratory environment Medical application of the test Risk assessment process

Risk assessment process: Identifies weakness in the measuring system Environmental weaknesses Probability of error estimates a measure of the effectiveness of the control process built into the measuring system Laboratory s tolerance for risk in context of the clinical use of the test result

EP23-A Establish QCP Monitor Modify in response to: Unanticipated failure modes Underestimated risks of error Unnecessary procedures based on establishing reliability of the system based on performance

Risk Management

Risk Management Manufacturer s Risk

From EP23-A: Process to develop and continually improve a QCP (corrective and preventative Action [CAPA] and CQI)

Risk Management

Risk Management Risk estimation is probability of occurrence and severity

Risk Management Determine whether risk is acceptable taking into account medical application of the test

Risk Management Develop QCP to reduce risk to acceptable level by preventing failure and implementing monitoring system to detect before harm occurs.

Residual risk Risk that remains after all control measures have been implemented. Decision on acceptability All laboratory tests have residual risk If deemed unacceptable.back to the drawing board

Final QCP Aggregate of all laboratory-applied control procedures required to remove or achieve a clinically acceptable risk. Must comply with all regulatory and accreditation requirements Must comply with manufacturer requirements Laboratory is ultimately responsible to ensure that testing processes and QCP s are capable to provide the analytical quality of results required for patient care

Quality Control Historically, two level controls How often they were run depended on: Assay Frequency of operation Test volume Clinical use Calibration

Traditional QC limitations Only monitor the portion of the system that they are exposed to Only alert to a problem once they fall out of range Shelf life Matrices

Controls built into the measuring system Integrated QC samples System function checks Electronic system checks Calibration checks

Controls techniques using patient test results Repeat testing Monitor aggregated patient results Implausible values Delta checks Correlation of results

Process mapping Operator training and competency Sample acceptability System startup Reagent and supply procurement/storage Calibration Analysis Result review

Example of fishbone diagram to map potential areas for problems:

Composite Risk Index = Impact X Probability

Composite Risk Index = Impact X Probability Impact: What will care provider do with result? What other information is used to corroborate the result? Will confirmatory test be implemented before the result is used? How quickly will a medical decision be made? What interventions are initiated based on result? What is risk of inappropriate intervention or action? How severe might the harm be?

Composite Risk Index = Impact X Probability Impact: Negligible inconvenience or temporary discomfort Minor temporary injury or impairment not requiring medical intervention Serious injury or impairment requiring medical intervention Critical permanent impairment or life-threatening injury Catastrophic results in patient death ISO 14971

Composite Risk Index = Impact X Probability Probability: Historical failure data Method evaluation Method verification Reliability estimates Site environmental assessments QC/PT data Failure rejection experiments Failure simulations Medical literature Health hazard evaluations Adverse event reports Medical judgment List servers Word of mouth Social networks.

Composite Risk Index = Impact X Probability Probability: Frequent = once/week Probable = once/month Occasional = once/year Remote = once every few years Improbable = once in the lifetime of the measuring system ISO 14971

Composite Risk Index = Impact X Probability Probability of harm Severity of harm Negligible Minor Serious Critical Catastrophic Frequent Unacceptable Unacceptable Unacceptable Unacceptable Unacceptable Probable Acceptable Unacceptable Unacceptable Unacceptable Unacceptable Occasional Acceptable Acceptable Acceptable Unacceptable Unacceptable Remote Acceptable Acceptable Acceptable Acceptable Unacceptable Improbable Acceptable Acceptable Acceptable Acceptable Acceptable ISO 14971

Composite Risk Index = Impact X Probability Probability of harm Severity of harm Negligible Minor Serious Critical Catastrophic Frequent Unacceptable Unacceptable Unacceptable Unacceptable Unacceptable Week Probable Acceptable Unacceptable Unacceptable Unacceptable Unacceptable Month Occasional Acceptable Acceptable Acceptable Unacceptable Unacceptable Year Remote Acceptable Acceptable Acceptable Acceptable Unacceptable Years Improbable Acceptable Acceptable Acceptable Acceptable Acceptable Rare ISO 14971

QCP evaluation Monitor for trends Monitor complaints Monitor rejected runs

QCP evaluation Corrective actions Revise QCP

QCP Haven t told you much new information beyond what a good laboratory or prudent laboratory or a compliant laboratory is currently practicing.

QCP Haven t told you much new information beyond what a good laboratory or prudent laboratory or a compliant laboratory is currently practicing. Except.

Composite Risk Index = Impact X Probability Probability of harm Severity of harm Negligible Minor Serious Critical Catastrophic Frequent Unacceptable Unacceptable Unacceptable Unacceptable Unacceptable Probable Acceptable Unacceptable Unacceptable Unacceptable Unacceptable Occasional Acceptable Acceptable Acceptable Unacceptable Unacceptable Remote Acceptable Acceptable Acceptable Acceptable Unacceptable Improbable Acceptable Acceptable Acceptable Acceptable Acceptable ISO 14971

HLA laboratories Three assays: Typing Antibody detection and identification Compatibility testing

HLA typing Where can the system fail:

HLA typing Where can the system fail: Sample collection DNA isolation Amplification Hybridization/gels/luminex Data interpretation Reporting Entering into UNET

HLA typing Where can the system fail: Sample collection DNA isolation Amplification Hybridization/gels/luminex Data interpretation Reporting Entering into UNet Severity of harm Probability of harm Negligible Minor Serious Critical Catastrophic Frequent Unacceptable Unacceptable Unacceptable Unacceptable Unacceptable Probable Acceptable Unacceptable Unacceptable Unacceptable Unacceptable Occasional Acceptable Acceptable Acceptable Unacceptable Unacceptable Remote Acceptable Acceptable Acceptable Acceptable Unacceptable Improbable Acceptable Acceptable Acceptable Acceptable Acceptable

Example of fishbone diagram to map potential areas for problems:

QCP Impact of errors: Typing Ab screening/id Compatibility Comparison of results: Compatibility is the ultimate double check

QCP Crossmatch: Sources of error or risk.. Cross-check? DSA based on typing and Ab screening and ID

QCP How do the risks of the crossmatch change if it is a VIRTUAL CROSSMATCH? Severity of harm Probability of harm Negligible Minor Serious Critical Catastrophic Frequent Unacceptable Unacceptable Unacceptable Unacceptable Unacceptable Probable Acceptable Unacceptable Unacceptable Unacceptable Unacceptable Occasional Acceptable Acceptable Acceptable Unacceptable Unacceptable Remote Acceptable Acceptable Acceptable Acceptable Unacceptable Improbable Acceptable Acceptable Acceptable Acceptable Acceptable

QCP Develop in conjunction with assay development, validation, verification and implementation. Design assessment tools into the process to monitor for identified risks. a priori.it would be easier, I think.

CLSI EP23-A November 4, 2011 Formal announcement: CMS adoption of EP-23 for CLIA QC as a QC option. EP-23 is the product of the CLSI and CLIA partnership: The CLSI standards document development utilizes a consensus process among affected constituencies to engender technical and scientific validity and credibility. CMS will announce the date in 2012 on which laboratories may begin to implement EP-23: After that date, laboratories may implement EP- 23, or continue to follow those existing QC policies and procedures that are currently allowed, until the end of the education and transition period. EP-23 will be voluntary: As with all new CLIA requirements, laboratories will be provided ample time and education to adopt EP-23 policies. It will also be voluntary for accrediting organizations (AO) and exempt States (ES).

We have lived and adapted to the quality assurance mantra for quite awhile now is this the next step in a logical progression? Thank you for your attention.

bld.msu.edu