As medical laboratory tests involving detection of nucleic acids become more common, well-designed and implemented proficiency schemes are needed to assure quality and to further the development of this complex and rapidly growing area of laboratory medicine. CLSI MM14—Design of Molecular Proficiency Testing/External Quality Assessment has been developed to guide the individuals and organizations responsible for providing proficiency testing (PT)/external quality assessment (EQA). It will also serve medical laboratories with a benchmark for evaluation of new programs or to facilitate development of laboratory-based PT/EQA or alternative assessment schemes when appropriate schemes are not available from formal programs. Specific subchapters discuss the design of PT/EQA programs; sources of materials; production, manufacture, and QA of samples; sample distribution; receipt and evaluation of data; and reporting responsibilities. Also discussed are examples of method-based PT/EQA programs and alternative assessment strategies and how they can be used to evaluate laboratory test performance. CLSI MM14 also lists and describes relevant regulatory and guidance documents related to PT/EQA.

CLSI MM14-Ed3 was revised in 2025 under the Limited Revision Process and replaces CLSI MM14-A2, which was published in 2013. Several changes were made in this edition, including: 
• Improving the terminology to also accommodate CLSI’s recommendation for harmonization of terms 
• Including additional types of reference samples, such as in silico modified nucleic acid sequence data files, clustered regularly interspaced short palindromic repeat–engineered cell lines, cell-free tumor DNA, and formalin-fixed, paraffin-embedded tissue sections or cores 
• Including additional sources of reference samples from commercial and other sources
• Discussing different formats for PT and EQA

The purpose of CLSI MM14 is to complement currently available regulatory and guidance documents regarding the management and operations of proficiency testing (PT)/external quality assessment (EQA) programs. Presently, these documents guide the administration of such programs, but consideration of panel selection, analysis of data for evolving technologies and tests with many possible measurands, method-based PT/EQA, and reporting to participants are not addressed. For molecular methods, these issues are important for all stakeholders, including regulatory agencies, accrediting agencies, PT/EQA providers/organizations, PT/EQA materials manufacturers, medical (clinical) laboratories, and test/reagent manufacturers. CLSI MM14 addresses both large formal PT/EQA programs as well as medical laboratorians who produce, distribute, and administer PT/ EQA schemes, and should provide guidance for the development and implementation of new PT/EQA programs for nucleic acid testing or modifying existing schemes. 

CLSI MM14 does not address the process of testing and reporting PT/EQA in the medical laboratory, medical laboratory inspection, accreditation, or other regulatory processes. 

CLSI MM14 focuses on nucleic acid (DNA and RNA) PT/EQA in the areas of human genetics, infectious diseases, molecular oncology, and pharmacogenetics. Although written specifically to address needs in this area, the principles stated may be applicable to programs outside of nucleic acid testing. 

Organizations and programs that send blinded samples to laboratories and analyze the submitted results carry several different names. These challenge programs may be called PT/EQA, quality assessment or assurance programs, QC programs, ring trials, sample exchange, and EQA/assurance. Countries or regions may place regulatory distinctions on these names. To facilitate the readability of CLSI MM14, the terms PT/EQA, PT/ EQA provider/organization, and PT/EQA program have been chosen to describe such activities, and regulatory categorization is not implied unless specifically noted.