Introducing new tests to a laboratory’s repertoire

Expert opinions from Dr Heidi Mendoza
There are many assessments to make when adding a new test to a lab’s collection. Dr Heidi Mendoza, acting consultant clinical biochemist at Raigmore Hospital, Inverness, UK, shares her experiences and observations of doing exactly that in both ordinary circumstances and during a pandemic, as well as having to contend with the geographic challenges imposed by the nature of life in the Scottish Highlands.
Can you provide a little background about yourself and where you work, please?
I am a clinical biochemist based in Raigmore Hospital, which is a small hospital in the Scottish Highlands. In my current role I provide clinical advice and interpretation for biochemistry tests for general practitioner (GP) practices and three hospitals across the Highlands. Working in the Highlands is incredibly rewarding, but also very challenging! It can take between 2 and 6|hours to travel between hospitals and our patients may have to travel by plane or boat to be seen, with journey times of +12|hours depending on where they live. It really puts the laboratories under pressure to get it right for the patient. Repeat testing isn’t as simple or straightforward as it would be in a city and we have to have excellent systems in place for reporting critical results and getting patients into hospital or transferring them between hospitals. Getting the right test, in the right place, with the right turnaround time is really important for our patients and for our clinicians.
What are the usual circumstances in which you would think about bringing a new test into the lab’s repertoire?
Any new test is a cost pressure on our National Health Service (NHS) and can only be brought in when it demonstrates clear benefits for patients. We have brought in two new tests in the last 12|months that are good examples of the different ways we can bring in new tests to our laboratory.
The first test is the NT-proB-type natriuretic peptide (NTproBNP) test. NTproBNP is used to investigate patients with suspected heart failure and the results can be used to determine whether a patient needs an echocardiogram (ECHO) or not. If they do need an ECHO the NTproBNP result can be used to split patients into those who need urgent ECHO (2|weeks) or routine ECHO (6|weeks). In theory this is a perfect test to implement as it will benefit patients and is cost-effective with respect to the more expensive ECHO investigation. However, NTproBNP has been implemented in other hospitals without reducing ECHO waiting times or the number of ECHOs performed! To ensure that this didn’t happen in our service, I spent 6|months before implementation of the test liaising with cardiologists and GP representatives from across the Highland region. We changed the ECHO referral pathway to include NTproBNP and created useful guidance for GPs on when to, and importantly when not to, request NTproBNP. We implemented the test just under 1|year ago and have seen a positive effect on ECHO referrals. We will still have to attend a 1|year post-implementation review with the Hospital Board to present our audit data and show that investment in the service by introducing a new test has benefited patients and other areas of the service.
Procalcitonin is the second example. Procalcitonin is a test that can be used in the investigation of sepsis and guide the use of antibiotics. Procalcitonin was not a test available in our hospital before the COVID-19 pandemic. Procalcitonin is not increased in the majority of adult patients with COVID-19; however, an elevated procalcitonin may suggest superimposed bacterial infection and be used to guide treatment of these patients and improve patient outcomes. Early in the COVID-19 pandemic we were approached by our Intensive Care Unit (ITU) and Microbiology consultants who requested that procalcitonin be available for our COVID-19 patients in ITU to guide their antibiotic treatment. We implemented procalcitonin in less than 4|weeks with help from our instrument manufacturer, external quality assessment providers and other Scottish hospitals who provided anonymized patient serum with known values so that we could verify our assay as quickly as possible. We are now in the process of putting together a business case and following the evidence base which will determine whether we continue to offer the procalcitonin test.
How would you usually go about adopting a new test?
As highlighted in the two examples above, we must agree a clinical need for a test and then liaise with the users of the service to find out how the test should be implemented into the patient-care pathway. Once we have worked out the clinical utility of the test, then we can carry out the laboratory verification of the test and the laboratory workflow. Verification is very straightforward. For example, the between-batch and within-batch precision, accuracy, linearity on dilution, interferences and sample stability for a test need to be evaluated. The implementation of the test then must be followed by an audit which shows that the test is being used as intended and giving the benefits predicted. If not, the test may need to be withdrawn. The hardest part of the entire process is agreeing how a test is going to be used and fitting it in to the patient-care pathway.
In the situation of the COVID-19 pandemic, we have a new disease, caused by a new virus, and new tests that have been created very quickly. How do you start to use a new test in these circumstances – are there any differences in procedure?
There is no difference in the steps that need to be performed we just need to be able to do everything in a much shorter time frame. That is actually much easier than it sounds. In the NHS, the laboratories from different parts of the country are great about helping other laboratories. We regularly share protocols, data and learning. If a new test is released we’ll contact another laboratory and they’ll share their local experience and any problems they have had with the test.
For procalcitonin implementation I contacted the laboratory in Dundee, UK, and they helped us out by lending us kits and reagents, sending us anonymized patient serum with known procalcitonin values, and sharing their data and verification protocols. This allowed us to complete verification incredibly quickly. We will still have to gather the data and evaluate whether the test is providing the benefit that we predicted when we established the clinical need.
What are the challenges regarding validation, reference levels, results interpretation and reporting?
Verifying tests is straightforward as we are always evaluating tests in clinical laboratories so are very experienced. Results interpretation can be quite difficult. If we need clinicians to change patient management based on a result then we have to provide them with very clear local guidance on what we want them to do with a result. This might be different from the action they would take in another hospital with different patient pathways, different pressures on patient turnaround times, and different diagnostic facilities. This is where good working relationships with users of the service are key to test implementation. If you just implement a new test without working out where it fits in the patient pathway, it doesn’t matter how great the test is, as it is unlikely to be used well and may not improve patient care.
What do you have to think about in terms of logistics?
Many laboratories are understaffed due to a combination of unfilled vacancies and staff on long-term absence. The additional work involved in verifying and implementing a new test does put pressure on staff. However, NHS laboratory staff are highly trained and dedicated. When the staff know how a test is going to be used and the benefit to the local community, they support the implementation and the extra work involved.
Biocontainment and staff safety have been important considerations during the COVID-19 pandemic. We had to adhere to government guidance in the transport, analysis and disposal of samples from patients with suspected COVID-19. This changed laboratory workflows and slowed us down, creating longer turnaround times.
Logistics are a serious consideration for us owing to our geography. Reagent shortages or delays in deliveries have a big impact on small laboratories as they can’t store much surplus reagent stocks because of expiry dates. Unexpected overuse or underuse of a new test can be quite challenging and leave the laboratory short of tests or with expired, wasted kits. There are also several times during the year when the roads are impassable between our central and rural laboratories. We have been down to single numbers of tests remaining several times over the last few years or had failed delivery from manufacturers in winter. There was also a shortage of procalcitonin reagent as there was such a surge in the use of the test during the COVID-19 pandemic. Again, working closely with users of our laboratory services has enabled us to rationalize the use of the test until the global shortage of reagent ended. On a number of occasions we have also shared reagents with other Scottish laboratories to ensure that none of the laboratories were left without reagents.
What has been learnt from the current coronavirus situation about diagnostic testing during a pandemic that would help to improve the process in future?
The coronavirus pandemic has shown how robust the infrastructure of the NHS is in Scotland and how adaptable laboratories can be when required. The laboratories really pulled together and worked towards a common goal delivering testing to COVID patients and non-COVID patients during a crisis. The two things that made this possible were: (1) Having a very clear goal – delivery of a service with new testing during a pandemic; and (2) Finances changes which needed to be made to deliver the service got rapid financial approval. How do we take these lessons learned and apply it to the routine delivery of laboratory services? Finance will always be a limiting factor – as it should be! Healthcare is expensive and it is up to us as healthcare professionals to deliver a cost-effective and affordable service. In contrast, having a clear goal, is definitely something that we could do better in the future. In the case of the pandemic, laboratories found different solutions based on local geography, resources and incidence of COVID. The changes made by laboratories in the remote Highlands and Islands were similar, but different than those made by laboratories in major cities. The staff that delivered the service found the best solutions to the goals set by the government – that is the real lesson we need to take away. We need to give very clear goals to services and let local expertise and knowledge drive the changes to solve the problem.
The expert
Heidi Mendoza BSc MSc PhD RCPath
Blood Sciences Department, Raigmore Hospital, Inverness IV2 3UJ, UK