Caring, Concern, and Consistency

Quality control is a recurring – and vital – theme throughout pathology and laboratory medicine. It is particularly evident in the field of blood coagulation, a precision science that requires careful testing of samples, and equally careful testing of the tests themselves. And that’s where quality assurance (QA) processes come in – both internal to the user or facility in question, and external to the test itself. As point-of-care testing (POCT) evolves and is increasingly adopted into healthcare practice, it becomes increasingly important for pathologists to understand the QA methods that go into ensuring that both laboratory-based and point-of-care tests are accurate, precise, and consistent.

The resurgence of UK NEQAS for Blood Coagulation

Coagulation is a constantly developing field of work, a fact that was no less true during the dynamic decades of the 1980s and 1990s. In July 1988, I left my position as head of the coagulation laboratory at St Bartholomew’s Teaching Hospital in London to move to the revitalized UK National External Quality Assessment Service for Blood Coagulation (UK NEQAS BC). The program had recently been revived under the guidance of Peter Kernoff, Director of the Katharine Dormandy Haemophilia Centre at the Royal Free Hospital in London, so was to be located there – but due to a lack of available space in the busy facility, a “NEQAS Portacabin” was installed and became a feature outside the entrance to the Haemophilia Centre.

In November 1993, my colleague Ian Jennings and I relocated UK NEQAS BC northward to work with Eric Preston and Steve Kitchen (hemophilia center director and laboratory scientist, respectively, at the Royal Hallamshire Hospital in Sheffield). Following the move, registration and participation in the laboratory program rapidly increased – not only within the UK, but also by cohorts of participating laboratories in Europe and further afield. In 1996, the Near Patient Testing (now known as Point of Care Testing) EQA program for oral anticoagulant control was piloted to 25 centers; this program alone grew to encompass over 5,000 registrations today, and additional POCT programs for activated clotting time (ACT) and D-dimer are now well-established and overseen by Dianne Kitchen, Lead Scientist for POCT programmes. Following Eric Preston’s retirement, UK NEQAS BC has continued to grow under the guidance of the current Director, Isobel Walker.

Who we are

As part of the national network of 24 EQA centers (also known as proficiency testing centers) within the National Health Service that make up UK NEQAS, each constituent program offers not only test samples for an extensive array of evaluated analytes, but also advice and assistance for laboratory science, medical, pharmacy, and nursing healthcare professionals. Programs are operated on a not-for-profit basis, each being led by dedicated healthcare professionals with expertise in their respective specialties. Educational aspects are of paramount importance for UK NEQAS, and centers regularly hold scientific meetings for their participants.

EQA programs vary in their processes and types of sample that are distributed, according to their pathology specialty, but normally consist of a biological material (whole blood, plasma, serum, cerebrospinal, or other body fluid or solid) stabilized by buffers, fixatives, or freeze-drying. An aliquot of the same material is sent to the testing laboratory or clinic for analysis according to the facility’s routine method of testing. The sample should be integrated into an existing run of patient samples wherever possible, rather than being accorded any special treatment.

Following testing, results are sent to the EQA provider for data and statistical analysis, comparing the participants’ results against all others for the same sample using the same methodology. Normally, the provider issues an individual participant report soon after the closing date, followed later by a more comprehensive report based on all results received. Performance criteria are established prior to testing by steering committees with expertise in the relevant field of biomedical science, and each participant’s results are compared with these criteria to determine compliance.

Participants experiencing performances outside the consensus from their peer group in any test may be offered assistance in the form of advice, together with repeat samples to check their results. Where persistent unsatisfactory or poor performance surfaces – thankfully a rare occurrence –participants will be offered further assistance, and those who are UK-based may ultimately be referred to the appropriate National Quality Assurance Advisory Panel for additional professional advice to improve performance.

Laboratory testing versus POCT

Unsurprisingly, there are often differences between the processes of laboratory testing and POCT, but – contrary to perceived ideas regarding performances within testing systems – one is certainly just as “satisfactory” as the other. In a number of cases, POCT precision in EQA surveys has been comparable  to  an equivalent laboratory method. This can be seen, for example, in the January 2018 UK NEQAS BC distributions for prothrombin time/INR testing. In the laboratory program exercise, the coefficient of variation (CV) for results from a sample with an overall INR of 3.4 returned by 914 participating centers was 6.4 percent, compared with a POCT program survey distribution (although not the same sample) with an overall INR of 5.7 returned by 4,166 participating centers, with a CV of 6.6 percent for the most widely used POCT system.

QA processes for laboratory testing and POCT are not only covered by EQA, but also internal quality control (IQC). IQC is generally purchased from a commercial manufacturer – often, though not always, the producer of the testing device – and compares the result obtained on the IQC sample to a range. The range may be specific for the reagent or test kit used (in the case of a laboratory test), or a range for the POCT device, test strip or cartridge. It should provide an answer to the question, “Is my result the same today (or in this testing session) as it was yesterday (or in the previous testing session)?”

EQA is a service ideally provided by an organization independent from commercial entities, although some EQA programs are also available from equipment or reagent manufacturers. As noted, EQA compares a result from the provided sample for the laboratory or POCT process with results from other users of the same reagent, kit or POCT device. EQA provides an answer to the question, “Are my results the same as those obtained by other users of the same test?”

One of the major differences between laboratory-based and POCT analyses relates to the fact that POCT measurements are, more often than not, performed by members of a clinical team and not by laboratory-trained scientists. Healthcare professionals, not having received laboratory training, may lack an understanding of the importance of complete QA. POCT is an analytical process and, as such, the full testing process (from the preanalytical to the post-analytical phase) should be understood and carefully adhered to by all healthcare professionals using POCT systems.

The five Ws

Who should be responsible for POCT quality control?

Whoever is carrying out the testing: a biomedical or clinical scientist, a clinician, a nursing professional, or any other healthcare professional trained in the use of the POCT system.

What should the quality control process for POCT look like, and what information should be collected?

The operator of the POCT system should record IQC information including:

• the date and time of the test

• the batch of IQC used

• the range for that IQC batch

• the batch of test strips used

• the operator’s identification.

It is the POCT system operator’s responsibility to check IQC results before continuing to test patients and, if the IQC is out of range, to repeat. If it is then still out of range, the operator should suspend testing and contact the POCT system manufacturer or distributor for advice. The POCT system should, of course, always be enrolled in an accredited EQA program (where one exists for the analyte under test).

Where and when should quality assessment take place?

IQC should be tested wherever the POCT system is being used, be that near a patient on an inpatient ward, in an outpatient clinic, or in a phlebotomy or laboratory area. There are several time points at which IQC testing should take place:

• when starting a new batch of POCT system test strips or cartridges
• when maintenance has been carried out on the POCT device
• when there has been physical disruption to the system
• when there are unexpectedly high or low patient results 
• at least once per clinic or testing session, with additional IQC tests carried out if a high number of patients are being tested
• if a POCT system is used infrequently or for only a small number of tests, IQC should be carried out for each batch of tests, even if it is a single patient test
• EQA should be performed whenever the provider schedules a distribution to be circulated to their participants, which is usually within a given time period before the closing date of the survey exercise, but may be specifically defined to have all participants test the EQA sample(s) on a set day.

When and how should the quality control processes themselves be evaluated?

EQA is a complementary tool to IQC in the QA toolbox, and results from both processes should be continuously monitored. National accreditation bodies, such as the United Kingdom Accreditation Service offer registration in a program of compliance with, and ongoing surveillance to, international standards (ISO 15189:2012 for laboratories and ISO 22870:2016 for POCT-based registrations). EQA programs register to achieve accreditation to ISO 17043:2010, and I strongly recommend participation in an EQA program that has maintained its accreditation status.

Why are EQA and accreditation necessary, and how can laboratories access these services?

The many benefits of participating in an EQA program include:

• the comparison of performance against other participating sites, especially where using the same methodology
• the identification of problems - especially where systematic - that may be associated with reagents, kits or testing systems
• the flagging up of processes that require improvement.

EQA may also be used by participating centers to identify where there may be deficiencies in method practice. When such situations arise, the EQA provider may even offer corrective assistance in the form of advice and previously distributed samples to check on test systems. Participation in an EQA program is normally required for laboratory or POCT accreditation, with the EQA program itself having ideally been accredited against standards to ISO 17043:2010 with continuing surveillance by the accreditation body.

EQA services, including POCT programs, are available from UK NEQAS, with details available on the UK NEQAS website (ukneqas.org.uk).

Questions and concerns

A number of qualitative POCT tests have raised concerns regarding their performances, and some semi-quantitative POCT methods have been known to fall short in their detection abilities. However, following discussion with – and intervention from – overseeing organizations, such as the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), these are  under greater control, and standards for new tests are strictly maintained. If a particular POCT method is ever questioned and taken under investigation, a Europe-wide Field Safety Notice can be issued to ensure that users curtail testing with that system. An example of this situation is a recent a POCT D-dimer test (1). An investigation by MHRA resulted in the issuance of a Field Safety Notice and the withdrawal of the D-dimer rapid test from the market (2)(3).

Pathologists’ and laboratory scientists’ concerns regarding the validity of results from POCT systems have now thankfully disappeared, along with the fear that POCT would diminish these professionals’ working practices. POCT methods have been successfully integrated into many laboratories, and pathologists and lab scientists are often involved with the POCT coordinators and committees that many hospitals have established. Greater concerns in the UK now center on the conversion of the existing pathology system to a series of “networks” – hub-and-spoke models that centralize and reallocate laboratory services – and what role POCT methods can play in this process.

Quality assurance, and particularly EQA, was not too long ago seen as an “evaluation evil” – a blunt instrument with which to penalize users. Fortunately, we have seen the processes evolve to be embraced as a precision tool to assist healthcare professionals in obtaining the best test results for their patients. It’s a trend that can only improve our work, and I hope it will be long-lived.