CLSI EP49, Framework for Developing Evidence of Clinical Validity of Medical Laboratory Test Methods provides test developers (both manufacturers and laboratories that create laboratory-developed tests) with a framework for establishing evidence of clinical validity for a medical laboratory test method. Clinical validation is defined and discussed in the context of clinical utility and analytical validation during the establishment of a test method. CLSI EP49 focuses on evaluating clinical validity through a clinical performance study, comparing a candidate test method with a comparator for assessing a target condition based on the test method’s intended use. Purposes and categories of tests are described along with measures of a test method’s clinical performance. Considerations are outlined for components of a study protocol and clinical performance study report, as well as for monitoring clinical validity postlaunch. 

Additional topics discussed in CLSI EP49 include obtaining samples for clinical performance studies, use of real-world data, potential biases in subject selection, and ethical considerations.

CLSI EP49 provides a framework to aid test developers (both manufacturers and laboratories that create laboratory-developed tests [LDTs]) in establishing evidence of clinical validity for medical laboratory test methods using noninterventional clinical performance studies. Examples of measures of clinical performance to support a test method’s clinical validity are provided, as well as considerations for the design of clinical performance studies, based on the test’s purpose. Categories of tests covered include qualitative, quantitative, semiquantitative, and multianalyte assays with algorithmic analysis. Lastly, general considerations for preparing study protocols and reporting results from clinical performance studies are provided. 

CLSI EP49 does not include a step-by-step protocol for studies to establish evidence of clinical validity and is not a substitute for consultation with the test developer’s applicable regulatory authority when studies or other methods are designed for demonstrating a test method’s clinical validity. CLSI EP49 does not include in-depth discussions of interventional studies related to clinical validation (ie, clinical performance studies in which results from the test method are used for the clinical management of subjects in the clinical study) or provide guidance for establishing a test method’s analytical validity (see CLSI EP191), verifying clinical validity or agreement (see CLSI EP122), or developing evidence for clinical utility. 

NOTE: Studies performed during clinical validation to support regulatory submissions for a test method might be subject to compliance with human subject protection regulations beyond the scientific quality standards for designing, conducting, recording, and reporting clinical performance studies.