The Approach to Pathology Harmony in the UK

Introduction

The Pathology Harmony initiative is now established nationally and internationally as a driver to take out unwarranted variation in the work of the clinical laboratory. Pathology Harmony was first conceived in Birmingham, UK in 2007. At that time, three major laboratories in the city had procured identical clinical biochemistry analysers. Despite using the same methods for essentially the same population group, these laboratories were using different reference intervals to help interpret results. In most cases the scientific basis justifying these differences was found to be lacking. This led 20 laboratories in the West Midlands and North West Manchester region of England together with all laboratories in Wales to form the Pathology Harmony group, with a remit to examine in detail the variation in reference intervals to see if it could be overcome. In addition, the group identified other areas of pathology that required harmonisation including units of measurement, test names, advice on protocols for simple tests, criteria for telephoning out-of-hours urgent results to primary care, and guidelines for the appropriate use of tumour markers.

Here the approaches taken by the UK Pathology Harmony group and examples of the work done are presented to help demonstrate the way harmonisation works, and the potential benefits to service quality and our users.

External Drivers for Change

There are many pressures on UK laboratories which encourage harmonisation across a broad range of pathology laboratory activity. In recent years there has been a drive towards linking laboratory results to enable them to be viewed by a range of users in primary and secondary healthcare. Such joining up of information technology (IT) solutions is greatly hindered by laboratories applying different reference intervals to their results. Variation in test names and reporting units is also slowing progress.

In addition to differences in reference intervals, variations in other aspects of pathology services can impact on users, for example the different criteria for telephoning abnormal results out-of-hours to a primary care location. This is despite the availability of guidelines such as those published by the Royal College of Pathologists.¹ Users are becoming more vocal about these issues and the need for these differences to be addressed by pathology professionals.

Role of Pathology Harmony Group

The role of the Pathology Harmony group has included acting as a forum for discussion between pathology laboratories that have moved apart as competition between healthcare providers has increased. As pathology provision in the UK is becoming increasingly diverse and the process of pathology commissioning gathers momentum, there is increasing pressure to look for consistent approaches across pathology, enabling a variety of service providers to interact to ensure service optimisation.

Harmonisation Techniques

Pathology Harmony has so far evolved through three phases of work. Phase one, which was completed in November 2007, has concentrated on clinical biochemistry; phase two, completed in 2009, included haematology and immunology; and phase three, which is ongoing, is concentrating on pathology guidelines and test units. For each phase the approach to harmonisation is the same. Firstly the degree of variation is identified. This includes sampling what actually happens in a number of laboratories to determine the extent of variation. Once the variation is quantified, the supporting scientific basis is then examined. Finally, based on all evidence collected, the group makes its recommendations.²

Harmonisation of Reference Intervals

Users are increasingly calling for the issue of non-uniformity of reference intervals to be addressed and this has been highlighted in a recent editorial.³ Determining how laboratories have ended up with their current reference intervals requires an open and candid approach, and here defending the indefensible has no place. Reference intervals can be based on historical ranges developed using very different analytical equipment many years ago. People cling to modifications of this earlier work as it gives a feeling that reference intervals have been based on a foundation of a population study. The results of a survey of Birmingham laboratories on how reference intervals for common tests have been derived are shown in the Table. Approaches include using ranges provided by the reagent kit insert and using published reference intervals in popular clinical chemistry textbooks, sometimes modified locally and based on a whole range of reasons. Certainly once these unsound foundations are out in the open, it is much easier to agree to a pragmatic scientific approach to achieving consensus reference intervals. Where the underlying science does not convincingly explain identified variation, the harmonisation process can move forward without further hindrance.

Table.

Summary responses by laboratories in Birmingham UK to a questionnaire on how reference intervals have been established.

Test	Manufacturer	Literature	In-House	Not Known
Sodium	6	1	3	6
Potassium	6	2	4	5
Urea	6	2	3	6
Creatinine	5	2	3	6
Chloride	7	2	1	5
Bicarbonate	6	1	1	6
Calcium	5	3	4	4
Adjusted Calcium	5	3	2	6
Phosphate	5	3	4	4
Magnesium	5	3	3	6

The converse is also true, and the identification of a valid scientific basis to variation curtails any further consideration of harmonisation. A good example of this is the analysis of alkaline phosphatase where, due to fundamental assay differences, it is not possible to harmonise reference intervals.

With the exception of an occasional outlier, for most tests the Pathology Harmony group has examined, the variation in reference intervals used has been very small. This is demonstrated for serum magnesium in Figure 1 which summarises data collected from 16 laboratories in the greater Birmingham area. These data, together with evidence from a wider group of laboratories, led to the Pathology Harmony recommendation of a serum magnesium reference interval of 0.7–1.0 mmol/L.

Figure 1.

Variation in serum magnesium reference intervals in 16 laboratories in the greater Birmingham area.

Harmonisation of Reporting Units

Phase two harmonisation of haematology highlighted the issue of laboratories using different reporting units. This increases the potential for clinical interpretation errors and unnecessary clinical risks. Of particular concern was the reporting of haemoglobin in both g/dL and g/L. The recommendation of the Pathology Harmony group was to report haemoglobin in g/L. This decision demonstrates that Pathology Harmony recommendations do not always reflect paths of least resistance, as g/dL is the unit traditionally used in the UK for haemoglobin and is currently still used by most laboratories.

The Pathology Harmony group has made many recommendations for standardisation of reporting units. This work is crucial to enabling consistent IT approaches across different computer platforms, and can be viewed on the Pathology Harmony website.⁴

Harmonisation of Guidelines

Phase three of the Pathology Harmony initiative is ongoing. Most recently the group has examined the use of tumour markers in oncology practice for which currently there is no standard guidance in the UK. This contrasts with countries with health insurance-based medical systems where there are often much clearer evidence-based guidelines for the use of such tests. For example, the Blue Cross Blue Shield website offers very clear guidelines on the use of a range of tumour markers.⁵ Best practice has been determined for each of the common tumour markers by interaction with professionals with appropriate expertise. The result is agreed guidance which is being produced in the form of a bookmark (Figure 2). This bookmark, which has an initial print run of 50,000, is now being distributed by UK laboratories to their users. An electronic version can also be downloaded.⁴

Figure 2.

The Pathology Harmony bookmark offers a novel way of communicating guidelines on the use of tumour markers.

Communicating Harmony

Recommendations of the Pathology Harmony initiative have been widely circulated and commented on, and this has included presentations at meetings with representatives from across the UK. The later stages of the Pathology Harmony process have had strong support from the Department of Health in England and from key professional groups, and similar initiatives have now commenced around the world. Understanding the political dimension is absolutely vital for successful local implementation and has been a key part of the success of the Pathology Harmony approach. Appropriate communication at a number of levels has also enabled a wide cross-section of the pathology community to feel involved in the process.

Ways Forward

Harmonisation of reference intervals, test names and units of measurement can offer practical advantages to help optimise current services. Although there is no legal requirement for clinical laboratories to implement Pathology Harmony recommendations, we have found that there is an increasing understanding of the approach and willingness to move into line. Not least, this has been due to the Pathology Harmony arguments being logical and for the most part about things that we know need addressing but never quite get around to.

As traditional pathology services see alternative styles of service, it is increasingly likely that basic adherence to nationally agreed standards, including relevant harmonisation, will be included in the specifications drawn up by commissioners for pathology service provision. Our approach to pathology harmonisation has been broadly based on consensus, though where needed, it has included challenging those that argue the indefensible.

Conclusions

In the UK, the success of the Pathology Harmonisation process has included a mix of science, pragmatism and political buy-in from key professional groups. We have also used professional marketing communication techniques such as printed media, websites and word-of-mouth to promote the work and outcomes of the Pathology Harmony project. Success so far has been due to an understanding of the importance of each of these elements to help achieve our fundamental aim of continual service improvement in the changing world around us.