How should genelabs define and operationalize specimen adequacy reportable range

Establishing a clear and operationalized specimen adequacy reportable range is essential for ensuring the reliability and validity of laboratory test results. This can be achieved through standardized definitions, acceptance criteria, and systematic integration into laboratory workflows.

Why it matters

• Quality Assurance: Ensures that only specimens meeting predefined adequacy criteria are analyzed, reducing the risk of erroneous results.
• Regulatory Compliance: Aligns with CLIA and FDA requirements for performance specifications in laboratory testing.
• Improved Outcomes: Enhances the reliability of diagnostic and prognostic information provided to clinicians, ultimately benefiting patient care.
• Operational Efficiency: Streamlines laboratory processes by integrating quality checks into existing workflows, reducing time spent on re-testing or handling inadequate specimens.
• Data Integrity: Maintains traceability and accountability from specimen collection to reporting, ensuring that all data can be audited and verified.

How to apply

1. Define Specimen Adequacy:

   • Establish criteria based on specimen type (e.g., blood, saliva, FFPE).
   • Set quantitative thresholds for metrics such as DNA yield, DNA Integrity Number (DIN), RNA Integrity Number (RIN), and purity.
   • Define contamination limits that are acceptable for each specimen type.

2. Implement Pre-Analytic Checklists:

   • Develop checklists that include adequacy criteria to be reviewed at the time of accessioning.
   • Link these checklists to barcode systems to ensure accurate tracking of specimens.

3. Integrate into LIMS:

   • Create specific fields in the Laboratory Information Management System (LIMS) to capture adequacy metrics.
   • Establish workflows for rejecting or flagging specimens that do not meet adequacy criteria.

4. Define Reportable Range:

   • Document the classes of analytes/variants (e.g., SNV, indel, CNV, SV) and the loci or breadth of analysis (e.g., exome, genome).
   • Specify performance metrics at lower and upper bounds, including allele fractions.

5. Validate Analytical Sensitivity and Specificity:

   • Perform validations for each variant class and specimen type using contrived and mixed samples.
   • Ensure batch-level quality control (QC) checks are in place for coverage, uniformity, and duplication, linked to sensitivity claims.

6. Establish Change Control Protocols:

   • Implement a system where any changes (e.g., kit lot, chemistry, aligner) necessitate targeted verification or revalidation of adequacy and reportable ranges.

7. Communicate Performance Specifications:

   • Create a one-page summary of performance specifications for each assay to be shared with clinicians and internal users.
   • Ensure that limitations and adequacy criteria are clearly stated in test catalogs and final reports.

Metrics to track

• Specimen Adequacy Rates: Percentage of specimens meeting defined adequacy criteria.
• Rejection Rates: Frequency of specimens rejected due to inadequacy.
• Analytical Sensitivity and Specificity: Performance metrics for each variant class and specimen type.
• Batch-Level QC Metrics: Coverage, uniformity, and duplication rates for each batch of tests.
• Change Control Incidents: Number of instances requiring revalidation or verification due to changes in protocols or materials.

Pitfalls

• Inadequate Definitions: Failing to establish clear and specific definitions for specimen adequacy can lead to inconsistent results.
• Poor Integration: Not fully integrating adequacy checks into LIMS and workflows can result in overlooked specimens.
• Lack of Training: Insufficient training for staff on the importance of specimen adequacy can lead to non-compliance with established protocols.
• Neglecting Change Control: Ignoring the need for revalidation after changes in processes or materials can compromise test integrity.
• Insufficient Communication: Failing to communicate performance specifications to clinicians can lead to misunderstandings regarding test limitations.

Key takeaway: Establishing a robust framework for defining and operationalizing specimen adequacy is critical for ensuring the reliability of laboratory results and compliance with regulatory standards.