Point of Care Testing

Point of care testing

WHY DO WE TEST?

When we think of consultations with patients, we may have a range of tasks to accomplish, some of which may be explicit, such as an immunisation or a specific follow-up of a long-term condition. Some may be implicit, such as a general review of progress after surgery or may be part of a hidden agenda which the patient may have.

Common to all consultations is the need for professional care, diagnosis, and treatment. Key to these considerations is the need for tests or investigations. These tests can do several things including advancing our understanding of the person’s physiological response to treatments, and perhaps also to gain a clearer view of what might be wrong.

Some tests are so commonplace and non-invasive that we may no longer recognise them as such, e.g., blood pressure measurement and recording of core temperature. Others exist in a far off and remote setting with limited opportunity for general practice nurses to access them, such as magnetic resonance imaging (MRI) scans. Between these two extremes we have other investigations, such as spirometry and ECG, and biochemical tests such as full blood count, urea and electrolytes and cancer markers.

There is, however, a group of tests which have come to be known as ‘point of care’ or ‘near patient’ tests. These include urine diptesting, random blood glucose and pulse oximetry. What these tests have in common is the rapid analysis of some pathological or physiological parameters to provide evidence for the presence, or absence of disease. These tests have given practice nurses the ability to diagnose disease or exclude it, to monitor and advise patients with diabetes, chronic kidney disease, COPD, and other long-term conditions. The benefits that these tests have conferred for clinicians have led manufacturers to expand the range of point of care tests (POCT) into previously unconsidered areas of testing, including D-dimer to diagnose thrombosis and thromboembolism and rapid C-reactive protein to exclude serious infection.

However, with every test comes a responsibility to use the information the test result provides to deliver the best patient care. When considering when to undertake a particular test we should always ask ourselves the question ‘Why am I doing this test?’. There are many good reasons for doing a test, including disease monitoring, finding, or excluding a diagnosis. There are also less well-qualified justifications, such as running a battery of all the tests available and patient or family pressure to undertake specific tests without clinical need.

A person requesting a test has certain responsibilities. They need to:

• Understand the clinical need and justification for the test
• Understand how the test is performed or requested
• Provide sufficient information in the request for the service to deliver the test
• Understand the result of the test
• Act on the result to deliver the best patient care.

This last responsibility also extends to understanding how to refer, and to whom, if the result of the test and the clinical presentation of the patient determines that referral is needed.

These same responsibilities are relevant when we consider point of care testing. Which brings us to the features of the ideal POCT.

FEATURES AND REQUIREMENTS OF THE IDEAL POCT

When we consider the ideal POCT we can envisage that we should have a test which is ideally:^1,2

• Easy to use with minimal training
• Non-invasive
• Simple to interpret
• Always gives an accurate result, which is unambiguous
• Gives replicable results when used by different people
• Confers a benefit on diagnosis or treatment
• Cheap – both in capital outlay and consumables
• Reliable over time and with no need for regular calibration.

Clearly anyone who has used any of the current POCT tools available will know that this list is idealised and not necessarily a practical reality in primary care. Even blood glucose testing requires a small skin prick and is therefore not entirely ‘non-invasive’ and that at times interpretation can be a challenge, especially when you compare results between different clinicians, the so-called interobserver variation.

It is at this point we should consider the issue of false positives and false negatives, or specificity and sensitivity of POCT.

SENSITIVITY AND SPECIFICITY

It is clearly important that, when we undertake any test, we want a reliable answer to our clinical question. When we test for an infection or for pregnancy, we want a test that says ‘yes, this patient has a streptococcal infection’ or ‘no, this patient is definitely not pregnant’. What we do not need is a test which provides a result indicating that ‘this patient has a raised level of x which could mean six different things, one of which is very serious and needs immediate admission to hospital.’

Sensitivity

Sensitivity is the ability of a test to correctly identify those with the disease (true positive rate). In essence we want a test to be highly sensitive, which means that it gives an answer to the clinical question ‘Is this a streptococcal infection?’ positively (‘yes’) all the time when that is the case. In other words, there will be no false negatives.

Specificity

Specificity is the ability of the test to correctly identify those without the disease (true negative rate).

As well as wanting a test to be sensitive we also want it to be highly specific. This means, for example, that it gives an answer to the clinical question ‘Can I exclude streptococcal infection in this person?’ . Someone who has the infection will not be told ‘No, you don’t have this infection’ wrongly. In other words that there are no false positives. In essence most tests will have a degree of reduced sensitivity and/or specificity. However, it is beholden on us when we use a test to understand what these limitations are and to use our clinical judgement to determine when we feel that the test has not delivered the level of confidence we expected.

ADVANTAGES AND DISADVANTAGES OF POCT

The advantages of POCT are that we can gain important information about the person’s physiological status, which can inform decision making about drug monitoring, diagnosis, referral strategy and treatment – all done in primary care, which can be cost-effective and timely.

The disadvantages are that the tests can end up giving information which is confusing, contradictory, unhelpful and costly, particularly when the patient pathway results in unnecessary additional investigations and secondary care referrals.^3,4

As outlined earlier it is therefore important not to undertake tests where we feel that the clinical picture is not going to be helped by such a test. A good question at this juncture in a consultation is to ask yourself, ‘Is this test going to change my management of this person?’. If the answer is ‘No’ then there is little point in ordering or undertaking it.

THE CURRENT STATE OF POCT

There is a wide range of POCTs available in primary care in the UK. These include:^5,6

• Pregnancy test – beta human chorionic gonadotrophin (b-hCG)
• Urine diptesting – glucose, nitrites, ketones, and leucocytes
• Blood glucose
• International Normalised Ratio (INR) for warfarin control
• Haemoglobin
• Throat swab for streptococcus A
• C- reactive protein
• HbA1c for diabetes
• Nose/throat swab for influenza
• Platelet count.

Some are used more widely and regularly than others and some are also used by patients for self-monitoring. Some are part of diagnostic and monitoring protocols and others used ad-hoc, as required, depending on the clinical situation.

THE FUTURE OF POCT

There are clearly diagnostic conundrums, which we face every day in practice, that could be aided by new POCTs; for example, a test to diagnose sepsis and to differentiate upper from lower respiratory tract infections. One research paper asked an international sample of primary care practitioners which tests would be most useful to them to assist with monitoring treatments and improving diagnosis. Respondents provided both a list of the tests they currently used, and a wish list of tests they would like to have access to. The wish list included chlamydia, white cell count and B-type natriuretic peptide (to exclude heart failure).⁷ The medical devices industry will no doubt evaluate the needs and the scientific possibilities of such tests as part of their horizon scanning and future workplans.

However, we should exercise a note of caution in our enthusiasm to grasp these potential new technologies. We will all have read or heard news items proclaiming a great and novel advance in medical technology only for a quieter and more muted fanfare when the benefits claimed are not realised when subjected to the real working environment and real patients.

The published research indicates that the quality of the POCT technology is usually high but the evaluation of the benefits to patients has rarely been assessed as part of the technology appraisal for POCT.3,7 This includes an overall cost-benefit or cost-effectiveness analysis of the entire patient journey, especially when the next POCT may drive a need for more appointments, more investigations, additional medications, and further referrals.

WHERE DOES TESTING FOR COVID-19 FIT?

Rapid testing for COVID-19 or SARS-CoV-2 has been a key part of the public health strategy for many countries. These test results are relied upon for sustaining work patterns in key roles, attendance at educational establishments, care homes and other critical facilities. There have been a range of POCT technology approaches used for these tests and include PCR (polymerase chain reaction) and LFIA (lateral flow immunoassay).^8-10

Most COVID-19 POCTs use LFIA as it is extremely versatile. This system detects high-molecular-weight proteins and gives a result within 20 minutes of the test. However, although these tests have been found to be highly specific (very few false positives) they have also been shown to have a very poor level of sensitivity with only 49% of people detected to have COVID-19 when they were tested. In other words, 51% of those who had the infection were not accurately detected as having it using this test.¹¹

This lack of sensitivity of LFIA presents us with an important dilemma. If you test positive you can be quite sure that you do indeed have COVID-19. However, if you test negative then there is an almost 50:50 chance that you may still have COVID-19 despite the negative test result. At the time of writing this is where we find ourselves. It is to be hoped that further developments will improve the sensitivity of this particular test so that our confidence in the results and the ability to rely on this test to support public health measures for COVID-19 is improved.

CONCLUSION

It would be difficult to imagine doing the work of a practice nurse without access to POCT for urine, blood glucose or pregnancy testing. Newer and improved tests can bring additional potential benefits, for practice nurses and patients alike, with better reliability, greater accuracy, and higher degrees of confidence in the results. It is to be hoped that this translates into better outcomes for patients. However, as we have seen with the COVID-19 LFIA, just because we wish a test to give us clear and reliable information does not necessarily make it so.

FURTHER READING AND RESOURCES David Spiegelhalter. The Art of Statistics. 2019 Pelican Books ISBN: 978-0-241-25876-7 NHS Health Check. Point of Care Testing. National Guidance https://www.healthcheck.nhs.uk/commissioners-and-providers/delivery/point-of-care-testing/

References

1. Price CP. Point of care testing BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7297.1285

2. St John A. The Evidence to Support Point-of-Care Testing. Clin Biochem Rev. 2010 Aug;31(3):111-9. PMID: 24150515; PMCID: PMC2924123. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924123/

3. Verbakel JY, Turner PJ, Thompson MJ, et al Common evidence gaps in point-of-care diagnostic test evaluation: a review of horizon scan reports BMJ Open 2017;7:e015760. doi: 10.1136/bmjopen-2016-015760 Available from: https://bmjopen.bmj.com/content/7/9/e015760

4. Schols AMR, Dinant G-J, WL Cals J Point-of-care testing in general practice: just what the doctor ordered? British Journal of General Practice 2018; 68 (673): 362-363. DOI: 10.3399/bjgp18X698033 Available from: https://bjgp.org/content/68/673/362#ref-8

5. St John A, Price CP. Existing and Emerging Technologies for Point-of-Care Testing. Clin Biochem Rev. 2014 Aug;35(3):155-67. PMID: 25336761; PMCID: PMC4204237. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204237/

6. Kozel TR, Burnham-Marusich AR Point-of-Care Testing for Infectious Diseases: Past, Present, and Future Journal of Clinical Microbiology Jul 2017, 55 (8) 2313-2320; DOI: 10.1128/JCM.00476-17 Available from: https://jcm.asm.org/content/55/8/2313

7. Howick J, Cals JWL, Jones C, et al Current and future use of point-of-care tests in primary care: an international survey in Australia, Belgium, The Netherlands, the UK and the USABMJ Open 2014;4:e005611. doi: 10.1136/bmjopen-2014-005611 Available from: https://bmjopen.bmj.com/content/4/8/e005611.info

8. Wang, D., He, S., Wang, X. et al. Rapid lateral flow immunoassay for the fluorescence detection of SARS-CoV-2 RNA. Nat Biomed Eng 4, 1150–1158 (2020). Available from: https://doi.org/10.1038/s41551-020-00655-z

9. Wu JL, Tseng WP, Lin CH, Lee TF, Chung MY, Huang CH, Chen SY, Hsueh PR, Chen SC. Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2. J Infect. 2020 Sep;81(3):435-442. doi: 10.1016/j.jinf.2020.06.023. Epub 2020 Jun 15. PMID: 32553841; PMCID: PMC7295501. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295501/

10. Flower B, Brown JC, Simmons B, et al Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey Thorax 2020;75:1082-1088. Available from: https://thorax.bmj.com/content/75/12/1082

11. Wise Jacqui. Covid-19: Lateral flow tests miss over half of cases, Liverpool pilot data show BMJ 2020; 371 :m4848 Available from: https://www.bmj.com/content/371/bmj.m4848