Terminology, units and reporting - how harmonized do we need to be?

Harmonization initiatives in laboratory medicine seek to eliminate or reduce illogical variations in service to patients, clinicians and other healthcare professionals. Significant effort will be required to achieve consistent application of terminology, units and reporting across laboratory testing providers. Current variations in practice for nomenclature, reference intervals, flagging, units, standardization and traceability between analytical methods, and presentation of cumulative result data are inefficient and inconvenient, or worse yet, patient safety risks. All aspects of laboratory service across the "total testing process" ultimately depend on concise, reliable communication. Clinical terminologies (e.g. SNOMED-CT, LOINC, IFCC/IUPAC NPU) provide a mechanism to correctly identify an analyte or panel of tests within a request for testing and communicate the results back to the clinician or electronic health record (EHR). Electronic systems for requesting and reporting laboratory testing are said to be interoperable when reliable connection and communication of content occur. Modern electronic reports and EHRs will provide greater flexibility and functionality, but also require effective guidelines or standards to ensure consistent representation of laboratory data. Programs to harmonize service in these areas require ongoing local, national and international efforts and should incorporate stakeholders from laboratories, medical staff, information technology and informatics specialists, patient representatives and government. The process of identifying harmonized best practice, then ensuring uptake across many laboratory testing providers, is generally iterative rather than "one off". New opportunities for additional harmonization will be generated as analytical performance, standardization and traceability, and diagnosis and treatment continue to evolve.

An update report on the harmonization of adult reference intervals in Australasia.

The Australasian Association of Clinical Biochemists (AACB) has over the past 5 years been actively working to achieve harmonized reference intervals (RIs) for common clinical chemistry analytes using an evidence-based checklist approach where there is sound calibration and metrological traceability. It has now recommended harmonized RIs for 18 common clinical chemistry analytes which are performed in most routine laboratories and these have been endorsed by the Royal College of Pathologists of Australasia (RCPA). In 2017 another group of analytes including urea, albumin and arterial blood gas parameters were considered and suggested harmonized RIs proposed. This report provides an update of those harmonization efforts.

Oral glucose tolerance test to diagnose gestational diabetes mellitus: Impact of variations in specimen handling.

To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.

Indirect derivation of biological variation data and analytical performance specifications for therapeutic drug monitoring activities.

We applied the indirect approach using anonymised data from an Australian and a Singapore laboratory to derive biological variation data for a group of 10 therapeutic drugs routinely monitored. A series of inclusion and exclusion criteria were applied on the data. The within- (CVi) and between-individual (CVg) biological variation data were then derived as previously described. The corresponding index of individuality and analytical performance specifications were also calculated. The biological variation data were overall very similar between the two study sites. Moreover, the biological variation data were also comparable between males and females, as well as whether the data originated from patients who only had two episodes of measurement during the study period or from the last two results from patients who had more than two episodes of measurement during the study period. The results presented in this study contribute towards the biological variation data for therapeutic drugs, which can be used to inform discussions about the setting of harmonised analytical performance specifications for these measurands.

Understanding the 'Silver Book' - An important reference for standardised nomenclature in clinical laboratory sciences.

Clinical laboratories perform a wide menu of testing (examinations). Successful requesting, examination, and ordering in this environment requires clear standardised nomenclature. The Silver Book (SB) is an IUPAC (International Union of Pure and Applied Chemistry) publication, produced with the support of both IUPAC and the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), that makes recommendations on logical standardised nomenclature, symbols, properties, and units in many disciplines of the clinical laboratory sciences. These recommendations are founded on and in agreement with the principles and work of the International Organization for Standardization (ISO), Bureau International des Poids et Mesures (BIPM), IUPAC, and the IFCC. Practical applications described are based on those scientific principles. The SB recommendations apply to all types of examination, not only to measurement of quantities but also examination of nominal properties where no magnitude is involved. The SB is applicable not only to clinical chemistry, but to many other clinical laboratory disciplines. For examples, reports regarding haemostasis, toxicology, clinical microbiology, reproduction and fertility, clinical pharmacology, clinical allergology, clinical molecular biology, and clinical immunohaematology have been published by the IUPAC and the IFCC. Peak scientific bodies such as the IUPAC and the IFCC have important roles in the development of sound international standards for nomenclature of examinations. Such standards support safe and effective representation of patient health information, foster portability, and empower future decision support systems.

Calculated Chemistry Parameters - do they need to be harmonised?

In clinical chemistry, harmonisation of the testing process is a global initiative with the purpose of improving patient safety, allowing better integration of research data and enabling the use of national electronic heath records. In Australia, as in other countries, the initial focus has been on the harmonisation of the more commonly measured analytes. There are also a number of calculated parameters, derived from these measured analytes, which could also be considered for harmonisation. Calculated parameters that are reported by laboratories and used for clinical decision-making should undergo the same robust process of harmonisation as is the case for the measured analytes. Aspects that should be considered for harmonisation are: terminology, the formulae used and where possible the use of common reference intervals. To investigate pathways towards the harmonisation of calculated parameters, three commonly reported parameters are considered. Calculated osmolality, the anion gap and albumin-adjusted calcium are all derived from common analytes which have individually been considered for harmonisation. They present different methodological, measurement uncertainty and terminological hurdles to harmonisation and are likely to require different pathways and solutions.

Consensus Statement for the Management and Communication of High Risk Laboratory Results.

Ineffective test follow-up is a major source of harm for patients around the world. Unreliable communication from medical laboratories (henceforth termed 'laboratories') to clinicians of results that represent critical or significant risk to patients (collectively termed 'high risk results') is a contributing factor to this problem. Throughout Australasia, management practices for such results vary considerably. The recommendations presented in this document are based on best practice derived from the published literature and follow consultation with a wide range of stakeholders. These recommendations were created to harmonise Australasian practices by guiding laboratories in the design and implementation of safe and effective communication procedures for managing high risk results which require timely notification.

Limited clinical utility of high-sensitivity plasma C-reactive protein assays.

Many recent studies have shown a relationship between plasma C-reactive protein (CRP) concentrations and risk of cardiovascular disease. However, the intra-individual variation in plasma CRP concentrations is large. Use of plasma CRP measurement in individual patients is likely to result in many being misclassified in their risk status. Use of repeated measurements is not a practical solution to this problem.

Recommendations for reporting and flagging of reference limits on pathology reports.

Surveys by the RCPA PITUS Project have shown significant variations in report rendering between Australasian Pathology Providers. The same project collected anecdotal evidence that this variation has led to the misunderstanding and misreading of results - a clinical safety issue. Recommendations are given for the rendering of reference limits on pathology reports, determination and rendering of result flags, and the documentation of sub-population partitions for reference intervals. These recommendations apply equally for paper or electronic reporting, but should not limit the use of novel techniques within electronic reports to convey additional meaning. PITUS Working Group 4 will publish draft recommendations for peer review and comment in relation to the above in the second half of 2014.

Coding for pathology tests - strengths and weaknesses.

Laboratory professionals will increasingly find themselves called upon to assist with the coding of pathology test requests and reported results in the era of the e-Health Record (EHR). EHR users from outside pathology, including patients and clinicians, will expect seamless integration of pathology services, and question variations in test nomenclature, units, reference intervals, and interpretive comments. Scientists and pathologists will need to be ready to work with colleagues outside their traditional scientific disciplines, along with IT and terminology experts, to resolve illogical historical variations, highlight differences that might endanger patient safety, and help lay the foundations for evolving e-health systems that enhance healthcare without eroding the interpretive value of pathology reports from different laboratories. An overview of medical terminologies and Australasian eHealth harmonisation programs is also provided.