External quality assurance (EQA): navigating between quality and sustainability

My professional career has been strongly influenced by a paper published three decades ago in Clinical Chemistry by Renè Dybkaer, who highlighted the evidence that demonstrable quality of laboratory services consists of two parts. First, a statement of quality policy that addresses “the identification of user needs, the selection of measurement procedures, reference measurement systems … and proficiency testing with materials having reference measurement assigned values”. Second, the need for “recognition of competence through systems such as good laboratory practice, ISO 9000 certification and professional accreditation” (ISO 15189 did not exist at that time) [1]. After many decades, I still believe that external quality assurance (EQA)/proficiency testing (PT) programs and accreditation according to the specifically developed international standard for medical laboratories (ISO 15189:2022) [2] are fundamental and mandatory tools for any clinical laboratory. They represent unavoidable and essential competencies for laboratory professionals that must be maintained and improved over time to ensure quality in laboratory medicine. In addition, EQA/PT programs and accreditation are interrelated, as interlaboratory comparisons are mandatory requirements for accreditation according to the international standard for medical laboratories (ISO 15189: 2022), and laboratory performance in EQA/PT programs plays a fundamental role in accreditation survey processes [3]. However, there are still many controversial issues regarding EQA/PT programs that require more attention and open debate to ensure a bright future for these programs. In this issue of the Journal, a paper by Amann et al. on “an IFCC global laboratory quality project” should stimulate a discussion on the relationship between quality and sustainability in EQA [4]. Indeed, the IFCC project aimed to implement an EQA program in low- and middle-income countries, using a study design, namely the type of control materials and the assignment of target values, that may be of major concern. According to the authors, “commercially available lyophilized human-based material was used for which the manufacturer did not make a commutability claim. Commutability was not evaluated and was considered unlikely. For this reason, peer assessment was used rather than comparison with a reference method or overall mean. The method peer group mean of participants’ results after exclusion of outliers was therefore used as the target value for each sample” [4]. In a seminal paper published some years ago, Miller and Coll. classified EQA/PT programs into 6 categories according to 3 characteristics: sample commutability, procedure for target value assignment, and inclusion or non-inclusion of replicate samples. In particular, the first 4 categories are the most desirable because they use commutable samples with target values established by a reference system and can evaluate both individual laboratories and measurement procedures for reproducibility, calibration traceability, and inter-laboratory and inter-procedural agreement. Conversely, “programs in categories 5 and 6 use samples that are unlikely to be commutable, thereby limiting the evaluation to peer group comparisons and failing to provide information on bias between different measurement procedures” [5]. There is no doubt that the IFCC pilot program falls into such categories 5 and 6 and that it provides participating laboratories with limited information on analytical standardization and inter-method agreement. In a recent paper by Theodorsson and Coll entitled “External quality assurance in the era of standardization”, the authors emphasize that “EQA organizers should also strive to develop and maintain EQA schemes for the assessment of metrological traceability, as traceability is a cornerstone in achieving equivalence of measurement results and minimizing risks to patients” [6]. Therefore, sample commutability and target values established by reference systems appear to be “mandatory” for EQA programs aimed at assessing metrological traceability and analytical standardization. However, in the same paper, the authors highlight the evidence that “standardized results represent less than 20 % of the measurands analyzed in current medical laboratories” [6]. The first question, therefore, is whether it is really necessary to organize EQA/PT programs for 20 % of the measurands currently analyzed, using costly commutable materials with target values established by reference measurement procedures, while participation in EQA/PT programs in resource-limited settings is hampered by several challenges, including the cost of commutable materials and other logistical issues [7]. In other words, can we forget about 85 % of the world’s population?

The second question is about the evidence that, while sound criteria have been established for small homogeneous molecules whose measurement results have been standardized using the first three categories of higher-order metrological reference, consensually defined criteria should be identified for all other measurands, also because some of these laboratory tests play an increasing role in clinical decision-making and patient management. COVID-19 was a paradigmatic challenge to raise our awareness of the need to identify valuable criteria for the implementation of reliable EQA/PT programs dealing with coagulation, serology, molecular, genetic and even point-of-care testing (POCT), moving from traditional “clinical chemistry” to laboratory medicine [8]. The third issue is the evidence that quality in clinical laboratories requires the assessment not only of analytical results but also of pre- and post-analytical issues, especially since sample integrity and valuable comparators (units of measurement, reference intervals and decision levels) strongly influence the ultimate quality of laboratory information [9]. Unfortunately, few programs are available to assess pre- and post-analytical issues. A further, but essential, question relates to the dilemma of the nature of EQA programs, namely whether their scope should be “regulatory” or “educational” [10]. Different settings, governmental and regulatory issues, and different scenarios may require “ad hoc” answers, but certainly we must share the principle that participation in EQA/PT programs is not enough. After decades of EQA/PT programs, clinical laboratories need to use the data to discuss “out-of-range” results and implement corrective and preventive actions, thus using EQA/PT as a valuable tool for quality improvement.

Another fundamental issue is that of harmonization. In particular, it should be important to achieve greater harmonization between EQA/PT programs and to better discuss the role of programs in improving harmonization in laboratory medicine. In other words, harmonization of EQA/PT programs should promote harmonization in clinical laboratories, and harmonization efforts in laboratory medicine should promote harmonization of EQA/PT programs.

In my opinion, there is no answer to all the questions raised above, but I strongly believe that the International Federations (namely, IFCC and EFLM), should assure closer cooperation with the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM), other relevant professional bodies and all providers of EQA/PT programs to emphasize the essential role of these programs in laboratory medicine and arrive at consensual recommendations to be adopted in high, low and middle income countries.