Evolution of Translational Omics Lessons Learned and the Path Forward (2012) / Chapter Skim
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3 Best Practices for Omics-Based Test Validation Prior to Use for Patient Management Decisions in a Clinical Trial Setting
3 Best Practices for Omics-Based Test Validation Prior to Use for Patient Management Decisions in a Clinical Trial Setting
Pages 65-78
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From page 65... ...
into a validated test ready for use in a clinical trial setting is the same validation process used for other new tests performed in clinical laboratories. This chapter references the current standards used for regulation of clinical laboratories and clinical tests, specifically the Clinical Laboratory Standards defined under the Clinical Laboratory Improvement Amendments of 1988 (CLIA)
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From page 66... ...
The bright line signifies the point in test development where a fully defined, validated, and locked-down clinical test method is necessary. Changes to the test after the bright line is crossed require a return to the test validation phase, approval by the Institutional Review Board (IRB)
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From page 67... ...
However, FDA is the federal regulatory agency with authority for oversight of testing and should be seen as a partner in the test validation phase. Therefore, the committee uses the CLIA and FDA regulatory standards as a minimum for assuring the quality of a test prior to use in a clinical trial to direct patient management.
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From page 68... ...
BACKGROUND Translation of a candidate omics-based test from the discovery phase into a clinical test requires confirmation of the research findings using a defined assay and fully specified computational procedures performed in the setting of a clinical laboratory certified under CLIA through the Centers for Medicare & Medicaid Services (CMS) or an accreditation organization with deeming authority under CLIA.
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From page 69... ...
However, if any test result, including an omics-based test result, is used for patient care, even in the setting of a clinical trial, the test must be performed in a CLIA-certified laboratory and must meet all the regulatory requirements for performance of a clinical test under CLIA regulations. These regulations state that a clinical laboratory must validate the test to define the test method and the performance characteristics of the test, and then the validated test must be performed and regularly assessed using specific quality standards.
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From page 70... ...
, investigators can work with the director and staff of a CLIA-certified laboratory to transition the test to the clinical laboratory setting in preparation for studies to evaluate the test for clinical use. The investigators should be able to provide the clinical laboratory with the defined assay method and the fully specified and locked-down computational procedures used to interpret the omics measurements in the research setting.
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From page 71... ...
Clinical laboratories prefer to use existing instruments and methods familiar to the laboratory staff for financial and workflow reasons. When the clinical laboratory does not have appropriate instruments for a new omics-based test, either a new method can be developed and performed on instruments already available in the clinical laboratory, the appropriate instruments can be purchased for the clinical laboratory, or the research instruments can be brought under CLIA standards and used by the clinical laboratory for test validation and eventual performance of the test in a clinical trial setting.
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From page 72... ...
The defined test method should include the fully specified computational procedures that were locked down at the end of the discovery phase, which will be used for analysis of the assay results to yield the final test result that is used as the interpretive criteria for the omics-based test. Once the test method, including the interpretive criteria, is established and documented, the methods can be assessed for their analytical and clinical performance characteristics in a test validation process.
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From page 73... ...
For omicsbased tests, the usual interpretive criteria used to produce a final test result will generally be replaced by these computational procedures, although the specific cutoff values and potentially definition of indeterminate results may need to be defined as the test method is developed within the CLIA-certified laboratory. Finally, for test validation processes that warrant publication because of the novel or new aspects of the test, the appropriate guidelines for reporting of biomarker study results should be considered at the planning phase of the test validation process and be used to ensure consistency in the reporting of the test validation process results (Surinova et al., 2011)
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From page 74... ...
. For an omics-based test, the precisely defined computational procedures used for interpretation of the assay results must be included in the validation process to ensure that it performs well on the assay results yielded by the test method in the clinical laboratory.
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From page 75... ...
for the test that describes the specimens and specimen handling requirements, assay methods, data handling procedures, fully specified computational procedures used to interpret the assay results in order to yield clinically actionable results, and methods for reporting results. The SOP also should describe the procedures for quality control and quality assurance, including issues related to the preanalytical, analytical, and postanalytical aspects of testing; quality indicators to be monitored such as turnaround time, documentation, and investigation of test failures; and trends in test results, as well as ongoing calibration processes for the instruments and the test.
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From page 76... ...
Sometimes testing still can be performed in a single laboratory, even with multiple clinical trial sites, if the specimen handling requirements and the turnaround times required for clinical care can be accommodated with specimen transport to the single laboratory. If testing is to be performed in laboratories at each clinical site, then each laboratory must complete a test validation process, and a plan to compare findings from the different laboratories should be defined.
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From page 77... ...
Investigators need to include this phase of test development and validation in their grant proposals, and as recommended in Chapter 5, funding agencies should provide appropriate support for this phase of test development that addresses analytical and clinical/biological validation, in anticipation of assessment of the test in a prospective clinical trial to direct patient management. SUMMARY AND RECOMMENDATION Any test that is used for patient management decisions, whether in a clinical trial or patient care setting, should be performed in a clinical laboratory certified under CLIA through CMS or an accreditation organization with deeming authority under CLIA.
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From page 78... ...
2011. Discussion with the Science and Technology Working Group of the IOM Committee to Review Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials, Conference Call with Alberto Gutierrez, Washington, DC, August 19.
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