The New Zealand Approach to Harmonised Reference Intervals

Introduction

When patients consistently attend the same laboratory for all their testing, and any referred test is sent to the same site every time, the need for reference interval (RI) harmonisation is scarcely apparent. However, in many cases the need to attend hospital or a hospital clinic interspersed with primary care at the general practitioner (GP) surgery will mean that testing will be carried out by more than one laboratory. Moreover, with competitive commercial environments, more mobile patients and the potential for natural disasters or industrial action in the sector, the need for harmonisation becomes more readily apparent. Health reforms too have had an impact with centralisation of services meaning that patients have to travel further afield for treatment and associated laboratory testing.

In New Zealand, the unsung heroes of RI harmonisation are the regional quality assurance groups (QAGs). These groups are similar to the Australasian Association of Clinical Biochemists (AACB) QC subcommittees in that they are regionally based, but different as they do not come under the governance of a single organisation like the AACB. Predominantly they are the result of gathering together a group of like-minded individuals, with a concern for patient welfare as their driving influence.

Currently we have three of these groups in New Zealand, the Auckland Regional Quality Assurance Group (ARQAG), the Lower North Island Quality Assurance Group (LNIQAG) and the South Island Quality Assurance Group (SIQAG) (see Figure). ARQAG is the longest running of these groups, followed by LNIQAG and SIQAG. Each group has approached its harmonisation activities from different angles, depending on which particular drivers are active in their region at a particular time, but the groups communicate with each other and co-operate wherever possible. Meeting minutes and associated information are exchanged, allowing the groups to benefit from shared method comparisons and other commutable data. A New Zealand representative from one of the regional QAGs also attends the annual AACB Scientific and Regulatory Affairs Committee (SRAC) meeting to take part in the AACB QC subcommittee meeting, maintaining links with our Australian counterparts.

Figure.

Approximate geographical areas covered by the New Zealand Quality Assurance Groups.

Auckland Regional Quality Assurance Group¹

The group, originally formed in the 1970s, is made up of scientific and technical staff, registrars and pathologists from hospital and community laboratories, directly representing 10 laboratories, with oversight of a number of smaller satellite laboratories. Meeting minutes are distributed to all group participants, to the other QAGs within New Zealand, the AACB convener of QC subcommittees in Australia, and the RCPA QAP. The ARQAG has survived health reforms, laboratory mergers and the competitive environment and continues to flourish.

The objectives of ARQAG are to:

• Standardise (wherever possible) RIs and result reporting, including nomenclature, units and comments, and to aid in the synchronisation of significant changes to reporting, both regionally and nationally.

• Provide a forum for discussing technical problems, share knowledge and expertise, and alert others to reagent or QC problems that have the potential to affect results.

• Facilitate inter-laboratory surveys using patient samples to identify platform bias as part of RI review and/or as external quality assurance when other options are unavailable.

Like other New Zealand QAGs, meetings occur in work time and are considered an important and core part of the laboratories’ contribution to patient care and continuing quality improvement. The key to the success of this group has been open collaboration and co-operation between laboratories, both private and public, without regard for competitive advantage.

ARQAG RI reviews now not only look at the numerical limits, but many other details including significant figures, rounding, limits for reporting results (‘less than’ and ‘greater than’ results), comments and use of the Logical Observation Identifiers Names and Codes (LOINC) recommended code and test name. All have become significant factors in providing commutable results from the many laboratories that will ultimately be collated in one central database.

Successes

• More than 35 years of continued activity sharing ideas and information and achieving quality improvements.

• Completed RI reviews that have resulted in harmonised ranges and comments in many cases, and identification of where harmonisation is currently impossible in others.

Future ARQAG activities

Vendors of GP patient management systems (PMS) have created systems to be flexible so that the GP can customise result configuration, seemingly without regard as to whether results are harmonised. Although laboratories carry out random audits of results sent to confirm accuracy, the check is performed on a single report while the unseen cumulative report may include a clinically significant error brought about by an alignment of results that should remain separate. A project for 2012 is to discover how the GP PMS are capturing the Health Level Seven (HL7) electronic messages and storing laboratory results and to what extent individual GPs can configure their own systems. As a result, the group might be able to advise GPs on formats that preserve appropriate alignments of results.

Lower North Island Quality Assurance Group

LNIQAG was originally formed in May 1989, as the Wellington QA group, with the encouragement of ARQAG and the Waikato QA group (which is no longer active). The group became LNIQAG in 1993 and has been described by its participants as a group of ‘ageing’ medical laboratory scientists with a passion for Clinical Biochemistry, plus a couple of pathologists! Meetings are held 6-weekly, less frequently than the ARQAG due to the geographical distance between contributors. Seven laboratories are regularly represented, with occasional contribution from smaller laboratories in the region. This group has also survived health reforms, laboratory mergers and the competitive environment, and it includes hospital and private laboratory participants.

The original aim of LNIQAG was ‘to encourage dialogue for troubleshooting and to work towards producing accurate and reliable results in the region’. To this end, the group operates on the basis of collegial support, sharing experiences, information and problems, providing ongoing education and networking in an open and honest environment.

Successes

LNIQAG has developed and supported common Biochemistry RIs following a huge data mining project in 2001, was proactive in the introduction of uncertainty of measurement, and has also reviewed alert/panic or critical limits and standardised haemolysis index commenting regionally. At a national level, it was actively involved from both the analytical and information technology (IT) perspectives in implementation of the highly sensitive Troponin T assay and in the recent cessation of dual reporting of HbA_1c.

Future challenges

As well as supporting common regional RIs, the challenge is to ensure their continued use over time and to extend into more problematic areas such as paediatric and pregnancy-related RIs. The group continues to be busy with ongoing review of critical values, keeping haemolysis index comments in step with technology and working towards standardised comments for selected tests to give more consistent reporting to referrers.

South Island Quality Assurance Group²

Unlike the other two groups, SIQAG was established in 2008/2009 specifically as part of a comparability project between Canterbury Health Laboratories, Southern Community Laboratories, Med Lab South and Grey Hospital Laboratory. This project was completed as part of a larger program of work looking at the development of a regional results repository in the Canterbury region. The scope of work was initially limited to tests from the Ministry of Health schedule (that specifies tests funded in community laboratories) although it was agreed that other tests identified by SIQAG could be reviewed. Consultants and senior Medical Laboratory Scientists from each discipline met and pragmatically assessed tests for comparability.

In order to ensure that results reported to a regional repository would cumulate and display correctly, each test that was deemed comparable had the following reviewed and agreed:

• Name (standardised to LOINC recommendation).

• Reference interval.

• Reporting units.

• Number of decimal places reported.

The idea of acting as a forum similar to ARQAG to deal with ongoing issues was an extension of this original project, and this group includes both Biochemistry and Haematology disciplines. SIQAG has its own website, reflecting the deliberate involvement of a specialist IT person from the beginning. Representatives from West Coast, South Canterbury and Canterbury were initially on board, with Nelson and Marlborough, and Otago and Southland participating at later stages.

Purpose²

The purpose of SIQAG is to review and ensure the on-going comparability of Biochemistry RIs between the South Island laboratory providers sending results into the Éclair Regional Results repository.

Objectives

The objectives of SIQAG are as follows:

1. To maintain the SIQAG Biochemistry RI document, which details what tests are deemed comparable, current agreed RI/units and the analysers used to perform these tests at each of the laboratory service providers. This document will be maintained by the incumbent Chairperson and it is the responsibility of all SIQAG Biochemistry members to ensure that it is kept current.

2. To be proactive in reviewing the comparability of RIs wherever possible with a focus on agreeing RIs nationally if possible.

3. To run comparative studies using patient samples to confirm comparability, in line with the Clinical and Laboratory Standards Institute (CLSI) guideline ‘Verification of comparability of patient results within one health care system; approved guideline’.³

4. To promote the use of LOINC codes locally for cumulating results in Éclair.

5. To facilitate discussion with other relevant external groups as appropriate with a view to promoting the use of agreed RIs.

Successes

Definite successes include the precise definition of RIs for those tests that can use common intervals, in conjunction with the creation of a website which has a ‘living’ SIQAG Biochemistry RI document and complete terms of reference (TOR) for the group. For each test, where a common RI has been shown to be applicable, the website has a list of the laboratories using the range, the analytical platform and method type, along with the appropriate LOINC code, result format, specimen type, units and whether or not paediatric ranges are required. A change log gives justification for the RI in use as well as a history of previous intervals. A table of tests that are unable to use common RIs is also included.

Challenges

The Christchurch earthquakes have had a huge impact on laboratories in the Christchurch region and, consequently, on the work of SIQAG, but the group continues to function, meeting annually as per its TOR, to the credit of its members. The recent contractual changes in provision of private laboratory services in the Canterbury region may impact on this group.

While called the South Island QAG, the Otago and Southland regions were not initially involved in the group, but representatives have attended more recently with the potential for a truly ‘South Island’ group in the future.

National Harmonisation Activities

At a national level there are several harmonisation activities that are ongoing.

• In 2009 a comparison study was undertaken, at the request of the New Zealand Growth Hormone Committee, to determine the comparability of human Growth Hormone (GH) assays in New Zealand. The adoption of a recombinant GH standard (IS 98/574) calibrated in mass units (μg/L) and the co-operation of the four laboratories performing GH assays, has allowed this assay to be harmonised between the two analytical platforms in use, resulting in comparable results on patient samples (also refer to commentary by James Davidson in this issue).

• The Waikato National Quality Surveys is a QC initiative begun in the mid-1980s by Waikato Hospital. The program utilises fresh human specimens and began as a QC exercise by Waikato Hospital in Hamilton and the smaller hospitals that it oversees in the surrounding region. It has now grown to more than 70 participants within New Zealand and several more in Australia.⁴ The surveys span 19 different subspecialties across multiple laboratory disciplines, and allow laboratories to assess comparability of results between different analytical platforms and methods on a weekly basis.

• Labnet is an alliance of hospital board laboratories that have agreed to work together in order to benefit from common systems and economies of scale, with the aims of improving and promoting the services which they provide.⁵ This alliance supports and integrates smaller laboratories by providing access to standardised infrastructure and processes, including clinical and scientific education, pathologist support and information technology.

Three of the current key areas of Labnet activity are:

1. Using the same laboratory information system, that is, a common LIS.

2. Standardising methods, reference ranges and report formats.

3. Standard reporting under the individual laboratory header.

Summary

Ongoing review of RIs by the QAGs in a climate of everchanging assay performance has highlighted not only the importance of being vigilant with analytical performance but also that the correct reporting of results is often beyond the control of laboratory scientists and pathologists. A common problem is the difficulty of implementing change once it has been agreed, which emphasises the importance of vigilance in auditing the reporting of results. It is increasingly apparent that there is a requirement for Laboratory IT expertise either within QA groups or easily available to them. It seems that while harmonisation is a noble principle, in practice it is difficult to achieve and the realisation of ‘National’ or ‘Australasian’ Harmonisation may still be some way off. It is widely recognised that some analytes, notably immunoassay results from different platforms, cannot be readily harmonised and, in the interim, should be differentiated in any central result repository. However it is often difficult to ensure that this happens. While harmonisation is the goal, ways of managing less amenable analytes must also be considered carefully.

The cessation of dual reporting of HbA_1c in New Zealand highlighted the differences in reporting formats from different laboratories for a supposedly harmonised analyte with ‘agreed upon cutpoints’. This exercise has served to broaden the focus of laboratories from results and RIs to how the results appear for our end users, as well as the context in which they appear. It has also demonstrated the importance of communication between laboratory staff, IT staff and GP PMS vendors, as well as regulatory bodies that access data from GP PMS databases for statistical purposes. The care and attention paid to pre-analytical and analytical issues can easily be unwittingly undone by careless or uninformed IT, and patient safety could be compromised by misinterpretation of cumulative results.