Skip to content
Publicly Available Published by De Gruyter November 16, 2022

The harmonization issue in laboratory medicine: the commitment of CCLM

  • Martina Zaninotto EMAIL logo , Maria Stella Graziani and Mario Plebani ORCID logo

Abstract

The analytical quality of the clinical laboratory results has shown a significant improvement over the past decades, thanks to the joint efforts of different stakeholders, while the comparability among the results produced by different laboratories and methods still presents some critical issues. During these years, Clinical Chemistry and Laboratory Medicine (CCLM) published several papers on the harmonization issue over all steps in the Total Testing Process, training an important number of laboratory professionals in evaluating and monitoring all the criticisms inherent to the pre-analytical, as well as analytical and post analytical phases: from the consensus statement on the most informative testing in emergency setting, to the prevention and detection of hemolysis or to patients identification and tube labeling procedures, as far as to different approaches to harmonize hormones measurements or to describe new reference methods or to harmonize the laboratory report. During these years the commitment of the journal, devoted to the harmonization processes has allowed to improve the awareness on the topic and to provide specific instruments to monitor the rate of errors and to improve patients safety.

Introduction

While the analytical quality of the clinical laboratory results has shown a notable improvement over the past decades, thanks to the joint efforts by companies, laboratory professionals and various institutional bodies, the comparability among the results produced by different laboratories still deserves attention.

Actually, to guarantee that each single patient could obtain the maximum benefit and the best possible treatment from the laboratory information, the harmonization of the laboratory results is at least as important as their analytical quality. This requires that all the different aspects of the total testing process (TTP) (i.e. terminology, units of measurements, reference ranges, decisions limits, report format, together with the accuracy of the analytical results) should be comparable, standardized and harmonized [1].

Quite often, the terms standardization and harmonization are used interchangeably, probably because the aim is the same: to provide the clinicians and patients with laboratory results that are comparable and equivalent among different laboratories and over the time. However, it should be taken into account that the two terms refer to different concepts. Standardization should be used when the results are uniform among routine measurement procedures and traceable to a recognized standard reference material defined by the International System of Units (SI) through a high-order primary reference material and/or a reference measurement procedure. Harmonization is aimed to make the results comparable irrespective of the measurement procedure, mainly because neither a reference measurement procedure nor a primary reference material are available [2]. Notably, this is the case of the vast majority of the measurands determined every day in clinical laboratories. The other important difference between the two terms is that the harmonization process includes all the aspects of TTP besides the analytical quality.

The Clinical Chemistry and Laboratory Medicine (CCLM) Editor-in-Chief and Editorial Board believed that the topic was of such relevance to dedicate a great effort encouraging the publication of several contributions on the matter in the last decade. Two aspects of this series of contributions should be emphasized: first, besides the traditional area of clinical chemistry, other laboratory medicine subspecialties have been considered (hematology, hemostasis, autoimmunity, molecular diagnostics, microbiology); second, the full spectrum of the processes involving in the laboratory activity and organization have been included such as external quality assessment, IVD regulation, education and training of the personnel.

In particular, a pivotal CCLM initiative should be underlined: the publication of two special issues entirely dedicated to the topic of hamonization in 2018 and 2019; the two issues contain an impressive amount of data and information about the advancement of the harmonization process in laboratory medicine that represent still an important source of knowledge on this topic [3, 4].

Aim of this paper is to illustrate and comment this specific CCLM activity, focusing on the articles that could be considered as milestones on the subject.

Methods

The articles have been selected searching on PubMed for the term “harmonisation” or “harmonization” in the CCLM publications, for the years 2012–2022. In addition, all the articles included in the two CCLM special issues on harmonization [3, 4] have been added, regardless if they had “harmonisation” or “harmonization” in the title. The papers related to the EFLM initiatives to harmonize the education and training of the Laboratory Medicine Specialists have been also considered. The total number of the obtained articles is 86.

In the following paragraphs, the papers published in this last decade, are divided in four major areas, to include all the laboratory activities, even those not directly connected to the production of the laboratory data and in particular:

  1. Harmonization activities at global level

  2. Pre-pre and pre-analytical phase

  3. Analytical phase

  4. Post and post-post analytical phase

Activities at global level

As indicated before, to achieve the goal of obtaining laboratory results that can be totally comparable, there is a strong requirement to harmonize the laboratory activities far beyond those needed to produce the laboratory results (i.e. the TTP), focusing on the global organization of the clinical laboratories [5]. These aspects, together with the specific activities in the different branches of the laboratory medicine, have been considered by CCLM in the recent years and are discussed in this paragraph [6, 7].

A significant role in the harmonizing projects is played in Europe by the European Federation of Laboratory Medicine (EFLM), promoting relevant initiatives in the field [8, 9] such as biological variation studies, pre-analytical phase guidelines and harmonization of the laboratory medicine specialist’s education and training. At international level, the International Federation of Clinical Chemistry (IFCC) also has worked on projects related to harmonization (mainly on accreditation, quality indicators, external quality assessment). These documents and the related results will be discussed in the dedicated sections.

The total testing process of the different laboratory medicine branches

Considering that the ultimate goal of the harmonizing activities is to guarantee the best patient outcomes, an approach including all the branches of the laboratory medicine is mandatory [10]. Furthermore, it should be always remembered that all the aspects producing the laboratory results have to be harmonized [6, 10]. The first CCLM special issue on “Harmonization in Laboratory Medicine” dedicated many contributions to these aspects [3]. A good example of a collaborative effort embracing all the aspects of the TTP, is the paper by Samuel Vasikaran on the IFCC harmonization activities on markers of bone turnover [11]. The article illustrates the joint effort by IFCC, International Osteoporosis Foundation (IOF) as well as the US National Bone Health Association (NBHA) to achieve the harmonization of each step of TTP for the laboratory determination and reporting biomarkers results in osteoporosis. The study produced later, important practical results, published in the following years [12, 13].

About the different branches of laboratory medicine, the special issue on harmonization [3] includes autoimmune testing [14], [15], [16], hemostasis [17, 18], hematology [19], microbiology [20], and point of care testing (POCT) [21] giving a complete picture of the complex world of laboratory medicine.

The editorial on autoimmune testing [14] is followed by a review summarizing the major achievements by the European Autoimmunity Standardisation Initiative (EASI) in the standardization of autoantibody tests, and in the harmonization of testing algorithms [15] and by a second review on TTP thyroid autoantibody testing focusing on tests request, retesting intervals, terminology, measurement units and definition of reference limits [16]. The Authors of the review stress the concept that while the standardization of the autoimmune assays is more complicated than that of the clinical chemistry tests, the harmonization of behaviors and procedures is a more feasible target. Therefore, it is absolutely worthwhile to pursue these specific goals.

A more complicated issue seems to be represented by the harmonization of the hemostasis tests [17, 18] that may be attributable not only to the high variety of reagents and methods available to investigate the hemostasis process but also to the high number of drivers involved in the stage. Actually, various groups play significant roles in the harmonization of hemostasis testing (i.e. International Council for Standardization in Hematology, International Society on Thrombosis and Haemostasis, British Committee for Standards inHaematology, plus a number of regional thrombosis and hemostasis societies). This provided a plethora of initiatives and documents and, consequently, a lack of “harmonization” among these different groups has often created barriers to international harmonization activities. Much work is therefore still to be done in this field of laboratory medicine because. In some cases, the unresolved issues generated non trivial problems to the patient management, as reported for D dimer testing in the recent COVID-19 pandemic [22].

The harmonization in the hematology branch is also an issue [19]. In this case the complications arise from the enormous technical advancements in the field which made available new generation hematological analyzers (the so called hemocytometers) that allow a combination of first level tests (the classical complete blood count) with more sophisticated second level morphological analysis. While the basic blood count parameters have reached a reasonable inter-instruments comparability, the challenge posed by the new morphological parameters, the algorithms to generate the second line testing and the interpretative/descriptive comments to be included in the laboratory report, remain unresolved questions, in spite of some relevant initiatives reported in the following sections.

Biological variation (BV) is a field of Laboratory Medicine that embrace the TTP (from the analytical performance specifications [APS] to the determination of reference change value [RCV])-and has many applications covering the different branches; so, it can be included among the activities at global level. EFLM has launched a number of initiatives [23] and CCLM published all the related documents over the years. Essentially, the EFLM Study Group on BV worked with the aim of delivering robust and reliable BV data harmonizing at the same time the approaches of the future studies on BV, the terminology, the reporting and the applications. Many tools are now available for the scope: the Biological Variation Data Critical Appraisal Checklist (BIVAC), the publication of a Medical Subject Heading term for BV and the Biological Variation Database at the EFLM website.

Quality indicators and regulatory activities

The accuracy and efficiency of the clinical laboratories testing are key factors to guarantee the best outcome for patients. So, there is a stringent need to enable laboratory users to measure the quality of the laboratory services; to this purpose, a set of quality indicators (QIs) has been identified and proposed to the international community. The process of harmonizing the QIs use, measurement and terminology started some years ago [24] and thank to the joint effort of a number of experts working together in a dedicated IFCC WG (Laboratory Errors and Patient Safety-WG-LEPS) and collaborating with the EFLM Task and Finishing Group “Performancespecifications for the extra-analytical phases”, an important target has been reached [25], [26], [27]. A benchmarking program based on a Model of Quality Indicators which has been defined and approved by a scientific consensus, is currently available; the QIs in the list are: patient centered, consistent with the requirements of the International Standard for medical laboratory accreditation (ISO 15189: 2012), addressed to all stages of the TTP [26] and easily measurable (a rather essential attribute) [28]. This tool is freely available to all laboratories and could efficiently identify and monitor errors (and the risk of) in laboratory medicine, enhancing the patient safety [26, 27].

In addition, two further papers are worth to be mentioned: one dedicated to the harmonization of the medical tests and IVD regulation [29] and the other to the contribution of accreditation (ISO 15189) to the harmonization process [30]. In fact, the technological advancements make available an impressive number of new tests to measure new biomarkers; however, it is still lacking a proper engagement of all the involved stakeholders in the process of standardization and harmonization of medical tests [29, 30]. Laboratory professionals should be strictly involved in the task and for this reason the paper concludes with a call to the professional societies to “…have a strong voice in their (inter-)national governments to negotiate long-lasting public policy commitment and funds for global standardization of medical tests” [29].

A similar message to the scientific or professional societies is included in the paper on the role of accreditation [30]. The universal adoption of the ISO 15189 standard has increased over the years and largely contributed to the harmonization of the laboratory processes worldwide. However, as underlined by the authors, this unifying role is endangered by the constant request from different scientific societies, for more specific standards to meet the needs of all the sub-specialties of the laboratory medicine. The cooperation between scientific societies and different National Accreditation Bodies in order to produce the future versions of the standard, is therefore mandatory, to preserve the harmonizing function of the standard that should not be affected by any border between nations or between sub-specialties [30].

The harmonization of the profession in Europe

It is well shared that the harmonization process is a responsibility of the clinical laboratory personnel. This task requires that education and training of laboratory specialists and their continuous professional development to be harmonized in turn. In fact, the differences in the education of professionals will hamper not only the free movements of professionals across nations, but also could impact on the laboratory ability to harmonize the TTP, endangering the patient outcomes and safety. The journey towards the harmonization of laboratory specialists’ education and training in Europe started some years ago [31], [32], [33] being a long and not easy journey, but very successful at the end, thanks to the effort of the EFLM Profession Committee which worked in strict cooperation with European government bodies. In the last 10 years, CCLM published all the EFLM papers on this subject [34], [35], [36], but even before all the EFLM documents and papers about this topic have been hosted by CCLM. This process begins with the precise definition of the profession, and the adoption a common name at the European level: since 2010, the EFLM (then the European Federation of Clinical Chemistry; EFCC) has introduced the title “EFLM Register of Specialists in Laboratory Medicine in Europe” (EUSpLM) after voting by the National Societies [33, 37].

In the following years, the EFLM has worked on the creation of a common Syllabus, whose last version has been published in 2018 [34]. A key driver for a unified European Syllabus is to harmonize the education and training principles across Europe and to establish defined standards of practice. The Syllabus can help to define a common set of competence for EUSpLM enabling thus the free movement across Europe borders of the specialists, assuring that patients can obtain the same standard of treatment and care. The last version of the Syllabus [34] built on the fourth edition (2012) [38], details more specifically the knowledge requirements in clinical biochemistry/immunology, haematology/blood transfusion, microbiology/virology/infection prevention and control, cytogenetics/molecular genetics, underlying the skills required in the new generation analytical techniques and in the use of the statistical evaluations. In this version, the sections on leadership have been expanded to highlight the competencies needed to provide services beyond the traditional laboratory activities, facing with the patient needs and expectations [39].

A fundamental step forward is represented by EUSpLM. After its origin, dated 1988 [40], the register was integrated into the different configurations of the European Federation of Societies of Clinical Chemistry and Laboratory Medicine until its dissolution and transfer to EFLM in 2018 [35]. Actually, the setting of Register’s Equivalence of Standards across Europe and the assessment of the country’s ability to meet them, falls into the activities of specific WG, Register, of EFLM’s Profession Committee. In 2020, in conjunction with the Register, EFLM launched the Academy, with the aim of supporting education, training and continuous professional development (CDP) for EUSpLM: the EFLM Register is now incorporated into the Academy [35]. Essentially, the Register has set an Equivalence of Standards to deliver laboratory medicine services across Europe, offering to patients uniform treatment, assurance of high-quality performances and improvement in safety. Furthermore, the Register allows the recognition of the profession across Europe, particularly for specialists coming from Countries lacking of a national register or where the profession is not regulated. The establishment of the Equivalence of Standards reflects the pivotal role of EFLM in harmonizing the practice of Laboratory Medicine in Europe.

The most recent EFLM document concerning the profession in Europe is dedicated to the contribution of the Federation to the definition of a Common Training Framework (CTF) for EUSpLM, in agreement with the European Directive 2013/55/EC (The Recognition of Professional Qualifications) [36, 41]. The proposed CTF [36] is based on the Syllabus [34] and represents the EFLM contribution to the single Member States in order to present to the European Union their submission for the recognition of the CTF for Specialists in Laboratory Medicine.

All in all, the EFLM activity in this topic has to be recognized as a fundamental contributor to the harmonization of the practice of Laboratory Medicine in Europe, enhancing patient safety and better outcomes.

Pre-analytical phase

Pre-pre-analytical phase

It is well known and widely shared in clinical and laboratory communities that the efficiency and efficacy of the laboratory information provided by the specific test results start not only from the appropriateness of tests requesting but also from the appropriate and efficient management of repetitive testing. In the time in which the laboratory activities and services are increasingly under pressure to cut cost and savings resources, seems to be of particular value the Editorial from Lang published in CCLM in 2013 [42], stressing the need to define the “minimum retesting interval” and to harmonize the approach in the clinical and laboratory communities in order to guarantee to the patients worldwide the accurate and timely monitoring of the different biomarkers measurement according to clinical and therapeutic need. Since 2013, this specific issue has been underlined in several occasions focusing the attention about the opportunity to share with the clinicians this approach but also to provide the most effective criteria to accurately estimate the clinically significant variations in biomarkers concentrations during monitoring. About the harmonization of these issues, and in particular the appropriateness of test request and the minimum retesting interval, as well as the proposal of the “reference change values, RCV” calculated from the biological variability studies [23], the CCLM journal has been constantly involved to spread and to discuss the limits and the advantages of these approaches.

A relevant and interesting example of this commitment, may be represented by the “consensus report” from SIBioC and AcEMC published in 2018 by Lippi et al. [43] that describes a tentative consensus about the most informative diagnostic tests in emergency setting. The need to harmonize these laboratory activities starts from the results of a survey carried out between contact professionals of two societies involved in the task, demonstrating the poor agreement at national level in available panel tests and in test requesting in emergency setting.

As the pre-pre-analytical phase of the TTP includes different and well known activities potentially inducing diagnostic errors and inequity in the patient care, all most critical steps should be assessed, harmonized and monitored adopting specific quality indicators. Indeed, the well-known cause and effect relationship between all activities in the different phases of the TTP and possible occurrence of errors, forces to promote and to harmonize all phases in order to provide objective rules and algorithms to allow the errors reduction.

Specific activities

In this context, the journal published relevant papers aiming to define and harmonize specific critical issues covering the quality in pre-analytical phase [44] such as the prevention and detection of hemolysis [45], the color-coding for blood collection tube closure [46], the patients identification and tube labeling [47] as well as the “old-age” question about the assessment of in vitro stability to allow a “real” comparison of the obtained results across studies [48]. Thanks to the punctual and consistent publications concerning these topics, CCLM trained a lot of laboratory professionals in evaluating and monitoring all the criticisms inherent the preanalytical phase, allowing to improve the knowledge and to provide specific instruments to monitor the rate of errors and to improve patients’ safety [44].

Analytical phase

The harmonization issues related to the analytical steps, represent for all laboratory professional a challenge that still today shows several and different shadows. During these years, CCLM gave space to National and European Scientific Societies [49] as well as to several authors aiming to analyze different aspects and to suggest new solutions for overcoming well known criticisms. Starting from the publications of the specific approach such as the standardization project for the insulin measurement [50], the innovative statistical model and the use of “consensus mean value from EQA” or recalibrations function to harmonize the thyroid hormone stimulating immunoassay [51], [52], [53], [54], as far as the description of the reference methods for specific biomarkers measurement, carbohydrate-deficient-transferrin [55], procalcitonin [56], Parathyroid hormone [57], 17-hydroxyprogesterone [58], the journal work allows to improve the state-of-art of the harmonization process, highlighting as well the relevant criticisms and the incomplete pictures existing [59], [60], [61]. Noteworthy, the tireless activity carried out by CCLM to stress the relevance of EQA in TTP but in particular in the analytical phase should be underlined [62, 63]: several papers have been published concerning the suggestion of EQA approach as tool to obtain harmonized results in enzyme [64] and in general clinical chemistry methods [65, 66], as well as in specific hormone measurement [67], stressing at the same time the need to assure the commutability of the control materials [65] and the harmonization of EQA schemes itself [68, 69] to support the laboratory professionals in the accreditation project [70]. Further contributions have been promoted in some specific and more specialized fields of the laboratory medicine such as coagulation [71, 72], therapeutic drug monitoring [73], molecular diagnostics [74, 75] and more recently, autoimmunity, not only in standardization and harmonization of the analytical procedure [76], [77], [78], [79], [80], [81] but also in defining the “consensus strategy” in the classification of some peculiar patterns diseases-related [82], [83], [84].

Post-analytical phase

The correct interpretation of the laboratory results is the final phase of TTP: until the information contained in the laboratory report is conceived by the physician brain and generate an action, the TTP is not concluded and the desired patient outcome is not reached [6, 85].

The laboratory report is a valuable source of information, not only when accurate analytical results are reported, but also (and probably in particular) when the numerical data are accompanied by other parameters (mainly, but not only, terminology, units of measurements, reference values, interpretative comments) aimed to make the data “actionable”. The harmonization of the post analytical phase is a rather complicated issue chiefly because it implies an exercise of communication that involves parties speaking different languages (i.e. laboratorians, physicians, information technologies specialists). Many initiatives have been carried on the subject over the years by the laboratory experts and regulatory agencies and these have been regularly reported by CCLM.

Harmonized reporting

A notable opinion paper summarizing the reasons why the content of the laboratory reports should be consistent across the different laboratory services has been published in 2019 by Flatman [86] as the opening paper of the special issue on harmonization, part 2 [4]. The variations encountered in laboratory practice in nomenclature, units, reference intervals, and flagging are not only “illogical and inefficient” but also constitute a risk for patient safety mainly because patients (and clinicians) expect and assume that the results from different laboratories are comparable and are therefore disoriented and get confused when they discover that they differ greatly [86].

A following paper in the same issue deals with of the need of harmonized laboratory reports [87]. The paper, using Australian laboratories as an example, discusses the possible future developments to improve the report harmonization. These include the standardization of laboratory format (like HL7 or PDF), but the authors themselves recognize that it is not sufficient to guarantee the report harmonization. In Australia, national guidelines on the topic are available [88], but the harmonization of the laboratory report format has not been reached yet and much work is still required to achieve the goal.

An interesting approach to harmonize the laboratory report in autoimmune testing, can be found in a Letter to the Editor by the EFLM Task and Finish Group Autoimmunity Testing, the EASI and the European Consensus Finding Study Group [89]. Recognizing the importance of the antineutrophil cytoplasmic antibodies (ANCA) testing for the diagnosis of vasculitis and that the standardization of the ANCA determinations is sub-optimal, the Authors recommend harmonizing clinical interpretation of ANCA test results by providing test result-specific likelihood ratios (LRs).

Immunoassay for ANCA usually apply a dichotomous interpretation (positive/negative); the proposal is to employ test specific LRs to overcome the lack of assay standardization thus harmonizing test results interpretation across assays and manufacturers [90]. It will be compelling to verifying the near future if the suggestion has been widely adopted and reached the aim.

Reference values

Reference intervals (RIs) are a fundamental part of the laboratory report; they are used by healthcare professionals to interpret the patient test results with the main scope to differentiate healthy from non-healthy people. The verification of the RIs used by the single laboratory is therefore mandatory and it is prescribed by the ISO 15189 standard for clinical laboratory accreditation.

In the special issue on harmonization, part 2 [4], a couple of papers deal with the topic, containing both useful recommendations on the procedures the clinical laboratories should use. The first is a review on the use of indirect methods for RIs determination by the IFCC Committee on Reference Intervals and Decision Limits [91] and the second one offers recommendations on how to transfer and verify the RIs received by laboratories from external source [92], illustrating the content of the Clinical Laboratory Standards Institute (CLSI) EP28-A3c guideline. If universally adopted, these recommendations could allow a uniform approach to the RIs determination, usage and verification, helping the harmonization of the laboratory report also in this aspect.

Specific experiences are also worth to be mentioned; four papers report about national initiatives for harmonizing RIs. The reports are from Belgium [93], Australasia [94], Netherlands [95] and Canada [96]. They are all very interesting and give to the CCLM readership useful hints on how to proceed towards this goal. However, it should be emphasized that only the paper from Belgium [93] illustrates the results of the initiative. We all read often about attractive projects and initiatives on harmonization, but seldom we are informed about the results of the projects themselves. The Belgian project was a success and the Authors could verify that the majority of laboratories in Belgium now adopt the suggested units of measurement [93].

Interpretative comments

The activity of including interpretative comments in the laboratory report is a post-analytical activity of considerable value and it is aimed to facilitate the interpretation of laboratory results by the clinicians closing the brain-to-brain loop, reducing at the same time the possibility of errors and ameliorating the patient outcome [97]. To serve to this scope, the comments should be of high quality and provided by trained and qualified laboratory personnel; it is therefore largely intuitive that harmonization activities in this specific field are a definite need. The inclusion of interpretative comments in a laboratory report is an add-on value in a number of circumstances: in case of analytical interferences influencing the results, when reflex testing is necessary and mainly when the description of particular patterns is mandatory, as it happens for serum electrophoresis patterns and differential count morphology. It should be however emphasized that the sub-optimal harmonization of reference intervals, units of measurements and terminology is another (and important) reason to provide interpretative comments. The interpretative comments are of such value that there is a specific requirement in the ISO 15189 standard and that they are included in the European Syllabus for training of specialists in Laboratory Medicine [34]. Among the articles CCLM dedicated to the topic, it can be cited the IFCC WG Harmonization of Quality Assessment of Interpretative Comments position paper [98]. In this paper a particular attention is dedicated to the importance of creating and using EQA schemes specifically dedicated to interpretative comments. The participation to these schemes will be of help for improving the quality and the harmonization of the comments and ultimately the patient outcome. Two valuable examples to help with the provision of interpretative comments can be found in CCLM. The first is dedicated to serum and urine protein electrophoresis [99] and the second one to the hematology laboratory reporting [100]. These two Opinion papers include specific recommendations for the inclusion of comments in the report and provide good examples of comments for specific situations. These articles deserve an extensive diffusion and certainly the application of the suggestion in the daily practice will improve the harmonization of this activity. It is well recognized that resistance to adopt a harmonized approach in this activity is largely due to longstanding personal habits and local preferences: the attentive reading and the reception of the indications included in the papers will result in the recognition that harmonized interpretative comments facilitate the tasks rather than complicating them.

Critical values

The critical values, also known as high-risk or panic or alarm values, are another fundamental component of the laboratory reports and of the connections between the clinical laboratory and the clinicians and patients. The adoption of an efficient procedure for the communication of critical values/results and the creation of a specific list is crucial for clinical, ethical, and organizational reasons. However, there is no uniform consensus on which values and for which parameters should be considered “critical”. This lack of harmonization is partly due to the specific population of patients and the type of hospital served by the laboratory; therefore, the list of parameters, the related results and the procedure of communication are to be developed locally. The harmonization in this field is thus related to the process of establishing the list and the values, rather than the list itself. Two papers [101, 102] describe the experience of producing the list of parameters and the related values and, rather importantly, one of them [101] report about the results obtained after the adoption of the list. The two initiatives are based in USA [101] and in Australia/New Zealand [102] and both contain important suggestions on how to proceed and could serve as good examples.

Conclusions

The impressive number of articles on the harmonization in all phases of the TTP in laboratory medicine, published in CCLM in the last decades, demonstrates not only the relevance of the specific topic but also the criticisms and the incomplete pictures still existing. In this paper, aiming to review the most interesting contributions to improve the knowledge on the harmonization in laboratory medicine, it appears that a lot of work should be carried out from the laboratory medicine professionals to reach the goal: several position papers and consensus statement from national and international groups published in the journal, still need development and further application activities. Accordingly, the journal will remain a strategic partner to move the harmonization issue to a further development and concrete applications, supporting the opportunity to publish new insights and new goals achieved in this topic of laboratory medicine.


Corresponding author: Martina Zaninotto, QI.LAB.MED, University of Padova, Padova, Italy, E-mail:

  1. Research funding: None declared.

  2. Author’s contribution: All authors have contributed equally to the drafting of the paper.

  3. Competing interests: The authors declare no conflicts of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

References

1. ICHCLR. International consortium for harmonization of clinical laboratory results annual report 2021. https://www.harmonization.net/media/1165/ichclr-annual-report-2021.pdf [Accessed 28 Aug 2022].Search in Google Scholar

2. Plebani, M. Harmonization in laboratory medicine: requests, samples, measurements and reports. Crit Rev Clin Lab Sci 2016;53:184–96. https://doi.org/10.3109/10408363.2015.1116851.Search in Google Scholar PubMed

3. Special Issue. Harmonization in Laboratory Medicine: the request, the sample, the measurement and the report-an update. Part 1. Clin Chem Lab Med 2018;56:1559–802.Search in Google Scholar

4. Special Issue. Harmonization in Laboratory Medicine: the request, the sample, the measurement and the report-an update. Part 2. Clin Chem Lab Med 2019;57:1–142.Search in Google Scholar

5. Tate, JR, Johnson, R, Barth, JH, Panteghini, M. Harmonization of laboratory testing – a global activity. Clin Chim Acta 2014;432:1–3. https://doi.org/10.1016/j.cca.2014.02.006.Search in Google Scholar PubMed

6. Plebani, M. Harmonization in laboratory medicine: the complete picture. Clin Chem Lab Med 2013;51:741–51. https://doi.org/10.1515/cclm-2013-0075.Search in Google Scholar PubMed

7. Plebani, M, Graziani, MS, Tate, J. Harmonization in laboratory medicine: Blowin’ in the wind. Clin Chem Lab Med 2018;56:1559–62. https://doi.org/10.1515/cclm-2018-0594.Search in Google Scholar PubMed

8. Ceriotti, F, Barhanovic, NG, Kostovska, I, Kotaska, K, Perich Alsina, MC, On behalf of the EFLM Working Group on Harmonisation of total testing process. Harmonization of the laboratory testing process: need for a coordinated approach. Clin Chem Lab Med 2016;54:e361–3.10.1515/cclm-2016-0244Search in Google Scholar PubMed

9. Eric, S, Kilpatrick, ES, Sandberg, S. An overview of EFLM harmonization activities in Europe. Clin Chem Lab Med 2018;56:1591–7. https://doi.org/10.1515/cclm-2018-0098.Search in Google Scholar PubMed

10. Plebani, M. Harmonization in laboratory medicine: more than clinical chemistry? Clin Chem Lab Med 2018;56:1579–86. https://doi.org/10.1515/cclm-2017-0865.Search in Google Scholar PubMed

11. Vasikaran, S. Assessment of bone turnover in osteoporosis: harmonization of the total testing process. Clin Chem Lab Med 2018;56:1603–7. https://doi.org/10.1515/cclm-2017-1109.Search in Google Scholar PubMed

12. Vasikaran, SD, Bhattoa, HP, Eastell, R, Heijboer, AC, Jørgensen, NR, Makris, K, et al.. Harmonization of commercial assays for PINP; the way forward. Osteoporos Int 2020;31:409–12. https://doi.org/10.1007/s00198-020-05310-6.Search in Google Scholar PubMed PubMed Central

13. Bhattoa, HP, Cavalier, E, Eastell, R, Heijboer, AC, Jørgensen, NR, Makris, K, et al.. IFCC-IOF Committee for Bone Metabolism. Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and β-CTX in blood. Clin Chim Acta 2021;515:16–20. https://doi.org/10.1016/j.cca.2020.12.023.Search in Google Scholar PubMed PubMed Central

14. Jacobs, JFM, Bossuyt, X. Standardization and harmonization of autoimmune diagnostics. Clin Chem Lab Med 2018;56:1563–7. https://doi.org/10.1515/cclm-2018-0807.Search in Google Scholar PubMed

15. Damoiseaux, J, Olschowka, N, Shoenfeld, Y. EASI – European Autoimmunity Standardisation Initiative: facing the challenges of diagnostics in autoimmunity. Clin Chem Lab Med 2018;56:1620–3. https://doi.org/10.1515/cclm-2017-0826.Search in Google Scholar PubMed

16. Tozzoli, R, Bizzaro, N. Harmonization in autoimmune thyroid disease diagnostics. Clin Chem Lab Med 2018;56:1778–82. https://doi.org/10.1515/cclm-2018-0037.Search in Google Scholar PubMed

17. Favaloro, EJ, Lippi, G. On the complexity of hemostasis and the needfor harmonization of test practice. Clin Chem Lab Med 2018;56:1568–74. https://doi.org/10.1515/cclm-2018-0174.Search in Google Scholar PubMed

18. Emmanuel, J, Favaloro, EJ, Gosselin, R, Olson, J, Jennings, I, Lippi, G. Recent initiatives in harmonization of hemostasis practice. Clin Chem Lab Med 2018;56:1608–19. https://doi.org/10.1515/cclm-2018-0082.Search in Google Scholar PubMed

19. Buoro, S, Lippi, G. Harmonization of laboratory hematology: a long and winding journey. Clin Chem Lab Med 2018;56:1575–8. https://doi.org/10.1515/cclm-2018-0161.Search in Google Scholar PubMed

20. Samul, LP. Harmonization of microbiology processes and standards: work in progress. Clin Chem Lab Med 2018;56:1624–8. https://doi.org/10.1515/cclm-2017-1074.Search in Google Scholar PubMed

21. Stavelin, A, Sandberg, S. Harmonization activities of Noklus – a quality improvement organization for point-of-care laboratory examinations. Clin Chem Lab Med 2019;57:106–14. https://doi.org/10.1515/cclm-2018-0061.Search in Google Scholar PubMed

22. Favaloro, EJ, Thachil, J. Reporting of D-dimer data in COVID-19: some confusion and potential for misidentification. Clin Chem Lab Med 2020;58:1191–9. https://doi.org/10.1515/cclm-2020-0573.Search in Google Scholar PubMed

23. Aarsand, AK, Røraas, T, Bartlett, WA, Coşkun, A, Carobene, A, Fernandez-Calle, P, et al.. On behalf of the European Federation of Clinical Chemistry and LaboratoryMedicine (EFLM) Working Group on Biological Variation. Harmonization initiatives in the generation, reporting and application of biological variation data. Clin Chem Lab Med 2018;56:1629–36. https://doi.org/10.1515/cclm-2018-0058.Search in Google Scholar PubMed

24. Plebani, M, Chiozza, ML, Sciacovelli, L. Towards harmonization of quality indicators in laboratory medicine. Clin Chem Lab Med 2013;51:741–51. https://doi.org/10.1515/cclm-2012-0582.Search in Google Scholar PubMed

25. Plebani, M, Astion, ML, Barth, JH, Chen, W, de Oliveira Galoro, CA, Escuer, MI, et al.. Harmonization of quality indicators in laboratory medicine. A preliminary consensus. Clin Chem Lab Med 2014;52:951–8. https://doi.org/10.1515/cclm-2014-0142.Search in Google Scholar PubMed

26. Sciacovelli, L, Panteghini, M, Lippi, G, Sumarac, Z, Cadamuro, J, de Oliveira Galoro, CA, et al.. Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a consensus statement on behalf of the IFCC Working Group “Laboratory Error and Patient Safety” and EFLM Task and Finish Group “Performance specifications for the extra-analytical phases”. Clin Chem Lab Med 2017;55:1478–88. https://doi.org/10.1515/cclm-2017-0412.Search in Google Scholar PubMed

27. Aita, A, Sciacovelli, L, Plebani, M. Extra-analytical quality indicators – where to now? Clin Chem Lab Med 2019;57:127–33. https://doi.org/10.1515/cclm-2017-0964.Search in Google Scholar PubMed

28. Aita, A, Sciacovelli, L, Plebani, M. Laboratory-related errors: you cannot manage what you don’t measure. You manage what you know and measure. Diagnosis 2017;4:193–5. https://doi.org/10.1515/dx-2017-0038.Search in Google Scholar PubMed

29. Cobbaert, C, Smit, N, Gillery, P. Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century. Clin Chem Lab Med 2018;56:1598–602. https://doi.org/10.1515/cclm-2018-0343.Search in Google Scholar PubMed

30. Thelen, MHM, Huisman, W. Harmonization of accreditation to ISO15189. Clin Chem Lab Med 2018;56:1637–43. https://doi.org/10.1515/cclm-2017-0820.Search in Google Scholar PubMed

31. Cobbaert, C. Time for a holistic approach and standardization education in laboratory medicine. Clin Chem Lab Med 2017;55:311–3. https://doi.org/10.1515/cclm-2016-0952.Search in Google Scholar PubMed

32. Beastall, GH. Harmonisation of specialist training and continuing professional development in laboratory medicine: a long but necessary journey. Clin Chem Lab Med 2015;53:1–3. https://doi.org/10.1515/cclm-2014-1005.Search in Google Scholar PubMed

33. Oosterhuis, WP, Zerah, S. Laboratory medicine in the European union. Clin Chem Lab Med 2015;53:5–14. https://doi.org/10.1515/cclm-2014-0407.Search in Google Scholar PubMed

34. Jassam, N, Lake, J, Dabrowska, M, Queralto, J, Rizos, D, Lichtinghagen, R, et al.. The European federation of clinical chemistry and laboratory medicine syllabus for postgraduate education and training for specialists in laboratory medicine: version 5. Clin Chem Lab Med 2018;56:1846–63. https://doi.org/10.1515/cclm-2018-0344.Search in Google Scholar PubMed

35. Wieringa, G, Jassam, N, Homsak, E, Rako, I, Racek, J. The Academy of the European Federation of Clinical Chemistry and Laboratory Medicine and the European register of Specialists in Laboratory Medicine: guide to the Academy and the register, version 4. 2020. Clin Chem Lab Med 2021;59:499–503. https://doi.org/10.1515/cclm-2020-1507.Search in Google Scholar PubMed

36. Wieringa, G, Queraltó, J, Homšak, E, Jassam, N, Cavalier, E, Svinarov, D, et al.. A proposed common training framework for specialists in laboratory medicine under EU directive 2013/55/EC (the recognition of professional qualifications). Clin Chem Lab Med 2021;59:505–12. https://doi.org/10.1515/cclm-2020-1504.Search in Google Scholar PubMed

37. Zerah, S, Murray, J, Horvath, A. EFLM position statement – our profession now has a European name: specialist in laboratory medicine. Biochem Med (Zagrab) 2012;22:272–3. https://doi.org/10.11613/bm.2012.029.Search in Google Scholar

38. Wieringa, G, Zerah, S, Jansen, R, Simundic, AM, Queralto, J, Solnica B, et al.. The EC4 European syllabus for post-graduate training inclinical chemistry and laboratory medicine: version 4 – 2012. Clin Chem Lab Med 2012;50:1317–28. https://doi.org/10.1515/cclm-2012-0019.Search in Google Scholar PubMed

39. Watson, ID, Wilkie, P, Hannan, A, Beastall, GH. Role of laboratory medicine in collaborative healthcare. Clin Chem Lab Med 2019;57:134–42. https://doi.org/10.1515/cclm-2017-0853.Search in Google Scholar PubMed

40. Jansen, RTP. The EC4 register of European clinical chemists and EC4 activities. Clin Chim Acta 2002;319:143–8. https://doi.org/10.1016/s0009-8981(02)00035-9.Search in Google Scholar PubMed

41. European Parliament and EU Council. Directive 2013/55/EU of the European parliament and of the Council of 20 November 2013 amending directive 2005/36/EC on the recognition of professional qualifications and regulation (EU) No 1024/2012 on administrative cooperation through the internal market information System (‘the IMI regulation’). https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=celex%3A32013L0055 [Accessed Sep 2022].Search in Google Scholar

42. Lang, T. Laboratory demand management of repetitive testing-time for harmonisation and an evidence-basedapproach. Clin Chem Lab Med 2013;51:1139–40. https://doi.org/10.1515/cclm-2013-0063.Search in Google Scholar PubMed

43. Lippi, G, Panteghini, M, Bernardini, S, Bonfanti, L, Carraro, P, Casagranda, I, et al.. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and Academy of Emergency Medicine and Care consensus report. Clin Chem Lab Med 2018;58:1655–9. https://doi.org/10.1515/cclm-2017-0077.Search in Google Scholar PubMed

44. Lippi, G, Banfi, G, Church, S, Cornes, M, De Carli, G, Grankvist, K, et al.. Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE). Clin Chem Lab Med 2015;53:357–70. https://doi.org/10.1515/cclm-2014-1051.Search in Google Scholar PubMed

45. Fernandez, P, Llopis, MA, Perch, C, Alsina, MJ, Alvarez, V, Biosca, C, et al.. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience. Clin Chem Lab Med 2014;52:1557–68.10.1515/cclm-2013-0935Search in Google Scholar PubMed

46. Simundic, AM, Cornes, MP, Grankvist, K, Lippi, G, Nybo, M, Ceriotti, F, et al.. Colour coding for blood collection tube closures-a call for harmonisation. Clin Chem Lab Med 2015;53:371–6. https://doi.org/10.1515/cclm-2014-0927.Search in Google Scholar PubMed

47. van-Dongen-Lases, E, Cornes, MP, Grankvist, K, Ibarz, M, Kristensen, GBB, Lippi, G, et al.. Patient identification and tube labelling-a call for harmonisation. Clin Chem Lab Med 2016;54:1141–5.10.1515/cclm-2015-1089Search in Google Scholar PubMed

48. Bastin, P, Favresse, J, Streel, C, Maisin, D, Fillè, C, Gruson, D. Assessment of in vitro stability: a call for harmonization across studies. Clin Chem Lab Med 2018;56:e121–4. https://doi.org/10.1515/cclm-2017-1024.Search in Google Scholar PubMed

49. Myers, GL, Miller, WG. The road map for harmonization: status of the International Consortium for Harmonization of Clinical Laboratory Results. Clin Chem Lab Med 2018;56:1667–72. https://doi.org/10.1515/cclm-2017-0907.Search in Google Scholar PubMed

50. Van Houcke, SK, Van Aelst, S, Van Uytfanghe, K, Thienpont, LM. Harmonization of immunoassays to the all-procedure trimmed mean-proof of concept by use of data from the insulin standardization project. Clin Chem Lab Med 2013;51:e103–5. https://doi.org/10.1515/cclm-2012-0661.Search in Google Scholar PubMed

51. Stockl, D, Van Uytfanghe, K, van Aelst, S, Thienpont, LM. A statistical basis for harmonization of thyroid stimulating hormone immunoassays using a robust factor analysis model. Clin Chem Lab Med 2014;52:965–72. https://doi.org/10.1515/cclm-2013-1038.Search in Google Scholar PubMed

52. Clerico, A, Ripoli, A, Zucchelli, GC, Plebani, M. Harmonization protocols for thyroid stimulating hormone (TSH) immunoassays: different approaches based on the consensus mean value. Clin Chem Lab Med 2015;53:377–82. https://doi.org/10.1515/cclm-2014-0586.Search in Google Scholar PubMed

53. Clerico, A, Ripoli, A, Fortunato, A, Alfano, A, Carrozza, C, Correale, M, et al.. Harmonization protocols for TSH immunoassays: a multicenter study in Italy. Clin Chem Lab Med 2017;55:1722–33. https://doi.org/10.1515/cclm-2016-0899.Search in Google Scholar PubMed

54. Padoan, A, Clerico, A, Zaninotto, M, Trenti, T, Tozzoli, R, Aloe, R, et al.. Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results. Clin Chem Lab Med 2020;58:1663–72. https://doi.org/10.1515/cclm-2019-1167.Search in Google Scholar PubMed

55. Weykamp, C, Wielders, JPM, Helander, A, Anton, RF, Bianchi, V, Jeppson, JO, et al.. Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: III. Performance of native serum and serum spiked with disialo transferrin proves that harmonization of CDT assay is possible. Clin Chem Lab Med 2013;51:991–6.10.1515/cclm-2012-0767Search in Google Scholar PubMed

56. Huynh, HH, Boeuf, A, Pfannkuche, J, Schuetz, P, Thelen, M, Nordin, G, et al.. Harmonization status of procalcitonin measurements: what do comparison studies and EQA schemes tell us? Clin Chem Lab Med 2021;59:1610–22. https://doi.org/10.1515/cclm-2021-0566.Search in Google Scholar PubMed

57. Couchman, L, Taylor, DR, Krastins, B, Lopez, MF, Moniz, CF. LC-MS candidate reference methods for the harmonisation of parathyroid hormone (PTH) measurement: a review of recent developments and future considerations. Clin Chem Lab Med 2014;52:1251–63. https://doi.org/10.1515/cclm-2014-0150.Search in Google Scholar PubMed

58. Graves, RF, Ho, CS, Loh, TP, Chai, JH, Jolly, L, Graham, P, et al.. Current state and recommendations for harmonization of serum/plasma 17-hydroxyprogesterone mass spectrometry methods. Clin Chem Lab Med 2018;56:1685–97. https://doi.org/10.1515/cclm-2017-1039.Search in Google Scholar PubMed

59. Zhang, K, Lin, G, Wang, L, Sun, Y, Zhang, R, Xie, J, et al.. Harmonization of results has not been fully achieved for serum immunoglobulin measurements. Clin Chem Lab Med 2015;53:e309–12. https://doi.org/10.1515/cclm-2015-0145.Search in Google Scholar PubMed

60. Ferraro, S, Borille, S, Carnevale, A, Fruciante, E, Bassani, N, Panteghini, M. Verification of the harmonization of human epididymis protein 4 assays. Clin Chem Lab Med 2016;54:1635–43. https://doi.org/10.1515/cclm-2015-1142.Search in Google Scholar PubMed

61. Aloisio, E, Serafini, L, Chibireva, M, Dolci, A, Panteghini, M. Hypoalbuminemia and elevated D-dimer in COVID-19 patients: a call for results harmonization. Clin Chem Lab Med 2020;58:e255–6. https://doi.org/10.1515/cclm-2020-1038.Search in Google Scholar PubMed

62. Graves, RF. The central role of external quality assurance in harmonisation and standardisation for laboratory medicine. Clin Chem Lab Med 2017;55:471–3.10.1515/cclm-2016-0782Search in Google Scholar PubMed

63. Coucke, W, Tanaskovic, JV, Hecimovic, A, Honovic, L, Vlah, SH, Ferencak, G, et al.. A new method for monitoring harmonization of laboratory results within EQA schemes. Clin Chem Lab Med 2020;58:e217–9. https://doi.org/10.1515/cclm-2020-0121.Search in Google Scholar PubMed

64. Weykamp, C, Franck, P, Gunnewiek, JK, deJonge, R, Kuypers, A, van Loon, D, et al.. Harmonisation of seven common enzyme results through EQA. Clin Chem Lab Med 2014;52:1549–55.10.1515/cclm-2014-0458Search in Google Scholar PubMed

65. Don-Wauchope, A, Kavsak, PA. Commutable samples with assigned target concentrations may help us harmonise general chemistry results. Clin Chem Lab Med 2017;55:165–6. https://doi.org/10.1515/cclm-2016-0558.Search in Google Scholar PubMed

66. Cwiklinska, A, Dabrowska, H, Kowalsi, R, Kuchta, A, Kortas-Stempak, B, Fijalkowska, A, et al.. Harmonization of urinealbumin/creatinine ratio (ACR) results: a study based on an external quality assessment program in Polish laboratories. Clin Chem Lab Med 2018;56:1728–33. https://doi.org/10.1515/cclm-2018-0102.Search in Google Scholar PubMed

67. Graves, RF, Jolly, L, Hartmann, MF, Ho, CS, Kam, RKT, Joseph, J, et al.. Harmonisation of serum dihydrotestosterone analysis: establishment of an external quality assurance program. Clin Chem Lab Med 2017;55:522–9.10.1515/cclm-2016-0394Search in Google Scholar PubMed

68. Ceriotti, F, Cobbaert, C. Harmonization of external quality assessment schemes and their role-clinical chemistry and beyond. Clin Chem Lab Med 2018;56:1587–90. https://doi.org/10.1515/cclm-2018-0265.Search in Google Scholar PubMed

69. Badrick, T, Stavelin, A. Harmonising EQA schemes the next Frontier: challenging the status quo. Clin Chem Lab Med 2020;58:1795–7. https://doi.org/10.1515/cclm-2020-0343.Search in Google Scholar PubMed

70. Sciacovelli, L, Secchiero, S, Padoan, A, Plebani, M. External quality assessment programs in the context of ISO 15189 accreditation. Clin Chem Lab Med 2018;56:1644–54. https://doi.org/10.1515/cclm-2017-1179.Search in Google Scholar PubMed

71. Meijer, P, Kynde, K, van den Besselaar, AMHP, Van Blerk, M, Woods, TAL. International normalized ratio (INR) testing in Europe: between-laboratory comparability of test results obtained by Quick and Owren reagents. Clin Chem Lab Med 2018;56:1698–703. https://doi.org/10.1515/cclm-2017-0976.Search in Google Scholar PubMed

72. Ruhhak, LR, Romijn, FPHTM, Smit, NPM, van der Laarse, A, Pieterse, MM, deMaat, MPM, et al.. Detecting molecular forms of antithrombin by LC-MRM-MS: defining the measurands. Clin Chem Lab Med 2018;56:1704–14. https://doi.org/10.1515/cclm-2017-1111.Search in Google Scholar PubMed

73. Robijns, K, van Luin, M, Jansen, RTP, Neef, C, Touw, DJ. A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities. Clin Chem Lab Med 2018;56:1715–21. https://doi.org/10.1515/cclm-2018-0116.Search in Google Scholar PubMed

74. Schuurs, TA, Koelewijn, R, Brienen, EAT, Kortbeek, T, Mank, TG, Mulder, B, et al.. Harmonization of PCR-based detection of intestinal pathogens: experiences from the Dutch external quality assessment scheme on molecular diagnosis of protozoa in stool samples. Clin Chem Lab Med 2018;56:1722–7. https://doi.org/10.1515/cclm-2017-1057.Search in Google Scholar PubMed

75. Ruiz, MS, Sanchez, MB, Contersa, YMV, Agrielo, E, Alonso, M, Altuna, ME, et al.. Programme for harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations. Clin Chem Lab Med 2020;58:2025–35. https://doi.org/10.1515/cclm-2019-1283.Search in Google Scholar PubMed

76. Monogioudi, E, Martos, G, Hutu, DP, Schimmel, H, Meroni, PL, Sheldon, J, et al.. Standardization of autoimmune testing-is it feasible? Clin Chem Lab Med 2018;56:1734–42. https://doi.org/10.1515/cclm-2017-1077.Search in Google Scholar PubMed

77. Meroni, PL, Borghi, MO. Diagnostic laboratory tests for systemic autoimmune diseases: unmet needs towards harmonization. Clin Chem Lab Med 2018;56:1743–8. https://doi.org/10.1515/cclm-2018-0066.Search in Google Scholar PubMed

78. Falkenburg, WJJ, von Ricthofen, HJ, Koers, J, Weykamp, C, Schreurs, MWJ, et al.. Clinically relevant discrepancies between different rheumatoid factor assays. Clin Chem Lab Med 2018;56:1749–58. https://doi.org/10.1515/cclm-2017-0988.Search in Google Scholar PubMed

79. Damoiseaux, J, Heijnen, I, Van Campenhout, C, Fabien, N, Herold, M, van der Molen, RG, et al.. An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice. Clin Chem Lab Med 2018;56:1759–70. https://doi.org/10.1515/cclm-2017-0306.Search in Google Scholar PubMed

80. Perez, D, Gliburd, B, Cabrera-Marante, O, Martinez-Flores, JA, Serrano, M, Naranjo, L, et al.. Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies. Clin Chem Lab Med 2018;56:1771–7. https://doi.org/10.1515/cclm-2017-0241.Search in Google Scholar PubMed

81. Nevejan, L, Dobbels, P, Norman, GL, Voreck, A, Bossuyt, X, Van Hoovels, L. Necessity of harmonization of tissue transglutaminase IgA assays to align clinical decision making in coeliac disease. Clin Chem Lab Med 2022;60:e81–4. https://doi.org/10.1515/cclm-2021-1207.Search in Google Scholar PubMed

82. Andrade, LEC, Klotz, W, Conrad, K, Ronnelid, J, Fritzler, MJ, von Muhlen, CA, et al.. International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I. Clin Chem Lab Med 2018;56:1783–8. https://doi.org/10.1515/cclm-2018-0188.Search in Google Scholar PubMed

83. Calise, SJ, Zheng, B, Hasegawa, T, Satoh, M, Isailovic, N, Ceribelli, A, et al.. Reference standards for the detection of anti-mitochondrial and anti-rods/rings autoantibodies. Clin Chem Lab Med 2018;56:1789–98. https://doi.org/10.1515/cclm-2017-1152.Search in Google Scholar PubMed PubMed Central

84. Herold, M, Klotz, W, Andrade, LEC, Conrad, K, de Melo Cruvinel, W, Damoiseaux, J, et al.. International Consensus on Antinuclear Antibody Patterns: defining negative results and reporting unidentified patterns. Clin Chem Lab Med 2018;56:1799–802. https://doi.org/10.1515/cclm-2018-0052.Search in Google Scholar PubMed

85. Tate, J, Johnson, R, Barth, J, Panteghini, M. Harmonization of laboratory testing – current achievements and future strategies. Clin Chim Acta 2014;432:4–7. https://doi.org/10.1016/j.cca.2013.08.021.Search in Google Scholar PubMed

86. Flatman, R. Terminology, units and reporting – how harmonized do we need to be? Clin Chem Lab Med 2019;57:1–11. https://doi.org/10.1515/cclm-2017-1083.Search in Google Scholar PubMed

87. Jones, GRD, Leggs, M. Report formatting in laboratory medicine – a call for harmony. Clin Chem Lab Med 2019;57:61–5. https://doi.org/10.1515/cclm-2017-1165.Search in Google Scholar PubMed

88. Royal College of Pathologists of Australasia (RCPA). Standards for Pathology Informatics in Australia (SPIA) (v3.0). Sydney: RCPA; 2017. https://www.rcpa.edu.au/Library/PractisingPathology/PTIS/APUTS-Downloads/Standards-and-Guidelines/SPIA-(APUTS)-Standards-for-Pathology-Informatics-i [Accessed Sep 2022].Search in Google Scholar

89. Bossuyt, X, Damoiseaux, J, Rasmussen, N, van Paassen, P, Hellmich, B, Baslund, B, et al.. Harmonization of antineutrophil cytoplasmic antibodies (ANCA) testing by reporting test result specific likelihood ratios: position paper. Clin Chem Lab Med 2021;59:e35–9. https://doi.org/10.1515/cclm-2020-1178.Search in Google Scholar PubMed

90. Bossuyt, X, Rasmussen, N, van Paassen, P, Hellmich, B, Baslund, B, Vermeersch, P, et al.. A multicentre study to improve clinical interpretation of proteinase-3 and myeloperoxidase antineutrophil cytoplasmic antibodies. Rheumatology 2017;56:1533–41. https://doi.org/10.1093/rheumatology/kex170.Search in Google Scholar PubMed

91. Jones, GRD, Haeckel, R, Ping Loh, T, Sikaris, K, Streichert, T, Katayev, A, et al.. On behalf of the IFCC Committee on Reference Intervals and Decision Limits. Indirect methods for reference interval determination – review and recommendations. Clin Chem Lab Med 2019;57:20–9.10.1515/cclm-2018-0073Search in Google Scholar PubMed

92. Ozarda, Y, Higgins, V, Adeli, K. Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations. Clin Chem Lab Med 2019;57:30–7. https://doi.org/10.1515/cclm-2018-0059.Search in Google Scholar PubMed

93. Demarteau, M, Cammaert, P, Vandevelde, NM, Callewaert, N, Coucke, W, Bernard China, B, et al.. A pragmatic bottom-up approach to harmonize the units of clinical chemistry tests among Belgian clinical laboratories, focusing on immunoassays. Clin Chem Lab Med 2019;57:12–9. https://doi.org/10.1515/cclm-2017-0824.Search in Google Scholar PubMed

94. Koerbin, G, Sikaris, K, Jones, GRD, Flatman, R, Tate, JR, On behalf of the AACB Harmonization Committee for Common Reference Intervals. An update report on the harmonization of adult reference intervals in Australasia. Clin Chem Lab Med 2019;57:38–41. https://doi.org/10.1515/cclm-2017-0920.Search in Google Scholar PubMed

95. den Elzen, WPJ, Brouwera, N, Thelen, MH, Le Cessie, S, Haagen, IA, Christa, M, et al.. NUMBER: standardized reference intervals in the Netherlands using a ‘big data’ approach. Clin Chem Lab Med 2019;57:42–56. https://doi.org/10.1515/cclm-2018-0462.Search in Google Scholar PubMed

96. Parker, ML, Adeli, K, On behalf of the CSCC Working Group on Reference Interval Harmonization. Pediatric and adult reference interval harmonization in Canada: an update. Clin Chem Lab Med 2019;57:57–60. https://doi.org/10.1515/cclm-2017-0965.Search in Google Scholar PubMed

97. Plebani, M. Interpretative commenting: a tool for improving the laboratory-clinical interface. Clin Chim Acta 2009;404:46–51. https://doi.org/10.1016/j.cca.2009.03.012.Search in Google Scholar PubMed

98. Vasikaran, S, Sikaris, K, Kilpatrick, E, French, J, Badrick, T, Osypiw, J, et al.. On behalf of the IFCC WG Harmonization of QualityAssessment of Interpretative Comments. Assuring the quality of interpretative comments in clinical chemistry. Clin Chem Lab Med 2016;54:1901–11.10.1515/cclm-2016-0709Search in Google Scholar PubMed

99. Moss, MA. Moving towards harmonized reporting of serum and urine protein electrophoresis. Clin Chem Lab Med 2014;52:1129–35.Search in Google Scholar

100. Buoro, S, Da Rin, G, Fanelli, A, Lippi, G. Harmonization of interpretative comments in laboratory hematology reporting: the recommendations of the Working Group on Diagnostic Hematology of the Italian Society of Clinical Chemistry and Clinical Molecular Biology (WGDH-SIBioC). Clin Chem Lab Med 2019;57:66–77. https://doi.org/10.1515/cclm-2017-0972.Search in Google Scholar PubMed

101. Hashim, IA, Cuthbert, JA, for the Critical Values Working Group. Establishing, harmonizing and analyzing critical values in a large academic health center. Clin Chem Lab Med 2014;52:1129–35. https://doi.org/10.1515/cclm-2014-0029.Search in Google Scholar PubMed

102. Campbell, CA, Lam, Q, Horvath, AR. An evidence- and risk-based approach to aharmonized laboratory alert list in Australia and New Zealand. Clin Chem Lab Med 2019;57:89–94. https://doi.org/10.1515/cclm-2017-1114.Search in Google Scholar PubMed

Received: 2022-11-02
Accepted: 2022-11-03
Published Online: 2022-11-16
Published in Print: 2023-04-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 25.2.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2022-1111/html
Scroll to top button