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Method Evaluation

CLSI EP49

Framework for Developing Evidence of Clinical Validity of Medical Laboratory Test Methods

CLSI EP49 provides a framework for establishing evidence of a medical laboratory test method’s clinical validity, with a focus on designing clinical performance studies and key measures of clinical performance.

March 19, 2026
Michelle Campbell, MS, MLS(ASCP)CM, MBCM, SCCM; Natalya Benina, MS

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Abstract

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.

Product Details
EP49Ed1E
978-1-68440-322-6
68
Authors
Michelle R. Campbell, MS, MLS(ASCP)CM, MBCM, SCCM
Natalya Benina, MS
Romiya Barry, PhD
J. Rex Astles, PhD, FADLM
Marvin Berman, PhD
Kate L. DeRosa, PhD, MA
Mark Kellogg, MLS(ASCP), PhD, DABCC
Marina V. Kondratovich, PhD
Dana Li, MD, PhD
Kristen Meier, PhD
Aimee Tan Aleksei Tikhonov, PhD, MS
Brigit Quinn, MS
Min Yu, MD, PhD, MBA
Abstract

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.

Authors
Michelle R. Campbell, MS, MLS(ASCP)CM, MBCM, SCCM
Natalya Benina, MS
Romiya Barry, PhD
J. Rex Astles, PhD, FADLM
Marvin Berman, PhD
Kate L. DeRosa, PhD, MA
Mark Kellogg, MLS(ASCP), PhD, DABCC
Marina V. Kondratovich, PhD
Dana Li, MD, PhD
Kristen Meier, PhD
Aimee Tan Aleksei Tikhonov, PhD, MS
Brigit Quinn, MS
Min Yu, MD, PhD, MBA