The final article in our series about molecular diagnostics looks at best practices for analytical sensitivity and analytical specificity. Both are additional characteristics for laboratory-developed tests and modified FDA-cleared or approved tests.
Analytical sensitivity is a quantitative and qualitative measure
Also referred to as the limit of detection (LOD), this performance characteristic is expressed as a concentration. The lower the detectable concentration, the greater the analytical sensitivity. It is essential in molecular infectious disease tests.
Analytical sensitivity can be determined by measuring samples at different concentrations or by testing dilutions of multiple replicates with a known target substance concentration. The amount of analyte is crucial because too much can cause incorrect genotype results, and too little can cause allele drop-out and false-negative results.
Best practices:
- 20 measurements at, above, and below the likely analytical sensitivity
- Assays using a nucleic acid extraction procedure must include a control to detect errors in the extraction process; CAP requires it for all nucleic acid isolation/preparation processess
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Use whole bacteria or viruses as the control material for nucleic acid isolation, preparation, or process
Analytical specificity is determined through interference studies
Cross-reactivity and interference are the two aspects of analytical specificity. Performing interference studies allows you to determine a test’s ability to detect only the target, distinguish it from other sequences, and provide a normal result in specimens without the mutation. These studies use specimens spiked with interfering agents and non-spiked specimens.
Best practices:
- Conduct studies for each specimen matrix used with the assay
- Assess a panel of related alleles to identify potential false-positive results
This wraps up our series on molecular diagnostics verification. Our white paper, Assay Verification Procedures for Molecular Diagnostics, offers a deeper look at what’s required, the steps in developing a solid program, and best practices for each performance characteristic that labs need to verify.
Missed earlier posts in the series?
- Part 1 - Know What to Verify
- Part 2 - Tackling the How
- Part 3 - Accuracy and Precision
- Part 4 - Reportable Range and Reference Interval Best Practices
Download Assay Verification Procedures for Molecular Diagnostics to learn more or speak with a representative today by calling 800-676-1881.
Support for you and your verification process
Laboratory directors are responsible for determining the required verification experiments, the number required, the type of specimens, and the methodology for evaluating the data. LGC Clinical Diagnostics can help you sort through the myriad of verification guidelines and standards.
Our ACCURUN molecular controls are whole-cell or whole-organism low positive controls that can appropriately challenge your assay from extraction through detection. Our AccuSeries linearity and performance panels offer comprehensive out-of-the-box solutions to expedite and simplify assay verification and installation activities. ACCURUN and AccuSeries are ideal solutions to ensure complete control over assay performance monitoring.
Questions?
Speak to an LGC Clinical Diagnostics representative today by emailing CDx-Sales@lgcgroup.com, or by calling 800-676-1881.