Advice
Clinical and technical evidence
Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. The literature search strategy, evidence selection methods and detailed data extraction tables are available on request by contacting mibs@nice.org.uk.
Published evidence
Six studies are summarised in this briefing. These include a randomised controlled trial (Andreeva and Melbye 2014), a retrospective diagnostic nested case-control study (Minnaard et al. 2015) 2 analytical performance studies (Brouwer and van Pelt, 2015; Minnaard et al. 2013), a mixed-methods study (Van den Bruel et al. 2016) and a prospective observational study (Minnaard et al. 2016).
The randomised controlled trial by Andreeva and Melbye (2014) used an open-cluster design to evaluate the effect of CRP testing on the prescribing of antibiotics, referral for radiography and recovery outcome of patients presenting to general practice with acute cough and respiratory tract infections.
The mixed-methods study by Van den Bruel et al. (2016) comprised an observational cohort of 297 children presenting with an acute illness. A nested randomised controlled trial was done (n=54) which compared CRP testing with no testing. This study included an embedded qualitative interview study to explore the acceptability of CRP testing.
The nested case-control study by Minnaard et al. (2015) aimed to determine the diagnostic accuracy of 5 point-of-care CRP tests, including the Alere Afinion CRP test, and whether they added diagnostic value in predicting radiographic-diagnosed pneumonia in adults presenting with acute cough in primary care.
The prospective observational study by Minnaard et al. (2016) included a total of 939 patients presenting to primary care with acute cough.
Two studies assessed the analytical performance of the Alere Afinion CRP test (Brouwer and van Pelt, 2015, Minnaard et al. 2013).
Table 2 summarises the clinical evidence as well as its strengths and limitations.
Table 2: Summary of the selected studies
|
Study size, design and location |
Intervention and comparator(s) |
Outcomes |
Strengths and limitations |
|
n=179. Cluster randomised controlled trial. Multicentre (18 general practices). Russia. |
CRP-guided therapy using the Alere Afinion CRP test (n=101), compared with non-CRP guided therapy (n=78). |
Antibiotic prescribing rate and referrals for chest X-ray were significantly lower in the intervention group than in the control group. A similar recovery rate was observed in both groups. |
Cluster design reduces risk of contamination. There were some significant differences between groups at baseline, suggesting the presence of confounding factors (that was not controlled for). The study was adequately powered to detect a 20% reduction in antibiotic prescribing. The trial was not blinded, increasing the risk of performance bias. |
|
n=297 children. Mixed methods study: observational cohort with a nested randomised controlled trial (n=54) and embedded qualitative study. Two out-of-hours general practices. UK. |
Alere Afinion CRP test (not explicitly stated within the study, but confirmed by manufacturer; n=26) compared with no CRP test (n=28). |
No statistically significant difference was reported in any outcome during the index consultation between those tested or not tested with the CRP test. In the 10‑day follow-up period, significantly more children randomised to CRP testing had antibiotic prescriptions. |
Open-label trial, but assessors were blinded to the group allocation. No power calculations were done to determine sample size. Relatively low number of children randomised. No information on diagnostic accuracy was reported. Nine patients were lost to follow-up at 10 days for both groups. |
|
n=200. Retrospective diagnostic case-control study. Multinational (16 primary care research networks across 12 European countries). Belgium, Finland, Germany, Hungary, Italy, Netherlands, Norway, Poland, Spain, Slovakia, Sweden, UK. |
5 point-of-care devices including the Alere Afinion CRP test, and a laboratory analyser (Vitros 5.1 FS, Ortho Diagnostics; Dimension Vista Systems, Siemens). Diagnostic accuracy outcomes were determined from 200 patient blood samples (100 with pneumonia, 100 without pneumonia). A clinical algorithm was used to determine the incremental predictive power of each CRP test to predict pneumonia. |
The sensitivity and specificity of Alere Afinion CRP in predicting pneumonia was consistent with other point-of-care tests and a laboratory reference test. In all cases the discriminatory power of the tests to predict pneumonia were reduced when a higher threshold of CRP (>100 mg/litre) was used. Sensitivity was 55% and 20% for low (20 mg/litre) and high (100 mg/litre) thresholds respectively for the detection of radiographic pneumonia, and specificity as 73% and 99%. |
Retrospective case-control design subject to inherent bias (likely to overestimate effect). Radiographs were used as the reference standard. Samples were analysed retrospectively at a central laboratory. A diagnostic model was used to evaluate the incremental predictive power of CRP when added to symptoms and signs. This may not completely represent clinical judgement in real life. |
|
n=939. Prospective observational study. Multicentre, 9 general practices. Netherlands. |
Comparison of GPs' 'pre-test decision' to prescribe antibiotics (following routine history-taking and physical examination) with their 'post-test decision' after reviewing the CRP test result using Alere Afinion CRP. |
In 41% of tested patients, the indication for testing was in accordance with Dutch guidelines. Point-of-care CRP test results prompted changes in antibiotic prescribing decisions in 27% of all CRP-tested patients. There was no significant reduction in net antibiotic prescribing decisions before and after CRP testing. |
No comparator group was included and no diagnostic information was reported. Decision to perform CRP test was according to Dutch guidelines, which may not be generalisable to current UK practice. Baseline antibiotic prescribing rate was low in comparison to international data from other studies and may not be representative for the UK population. Case registration forms were not completed for patients who did not have a CRP test. |
|
Analytical performance study. Netherlands. |
8 point-of-care devices including Alere Afinion CRP, compared with a comparative laboratory method (Synchron CRP). All blood samples were from GPs' patients, aged over 18 years, with CRP concentrations ranging from 5 to 200 mg/litre, determined with the Synchron analyser. |
The linear regression equation of the Alere Afinion CRP test revealed an underestimation of CRP values compared with the laboratory method. However, the correlation and coefficient of variance of the Alere Afinion CRP test met the set acceptability criteria. The correlation of the CRP tests to the reference standard varied considerably. The Alere Afinion CRP test was considered to be one of the preferred analysers for point of care. |
Patient blood samples were used with CRP values determined from an appropriate reference standard. Patient characteristics and diagnosis were not reported. |
|
Analytical performance study. The Netherlands. |
5 point-of-care devices including Alere Afinion CRP compared with a laboratory method (Olympus AU2700). Residual stored material from routinely done laboratory blood tests was pooled to obtain lithium heparin plasma pools with CRP concentrations of approximately 10, 15, 20, 25, 50, 90, 100 and 110 mg/litre. |
The analytical performance and agreement of the CRP tests to the laboratory method varied considerably, but was considered adequate. For high CRP values (>100mg/litre), agreement with the laboratory standard systematically decreased for all 5 point-of-care tests. |
Lithium heparin plasma samples were used instead of blood obtained by finger-prick. |
|
Abbreviation: CRP, C-reactive protein. |
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Strengths and limitations of the evidence
Two of the studies were randomised controlled trials that provided direct comparative data on the use of point-of-care CRP testing with the Alere Afinion CRP test compared with standard practice (Andreeva and Melbye, 2014 and Van den Bruel et al. 2016). However, neither of these provided diagnostic accuracy data on the system and clinical follow-up was limited. Furthermore, the study by Van den Bruel et al. (2016) only included children with acute illness. There are currently no UK guidelines that recommend CRP testing in this population.
A diagnostic case-control study did provide diagnostic accuracy information, but had important methodological weaknesses in its design (Minnaard et al. 2015), as outlined in table 2. The observational study by Minnaard et al. (2016) reported the potential effect of the Alere Afinion CRP test on prescribing practice, but lacked a comparator group.
The diagnostic case-control study (Minnaard et al. 2015) and analytical performance study (Brouwer and van Pelt, 2015) also did measurements in a laboratory setting, and may not be representative of the primary care setting for which the test is intended.
Recent and ongoing studies
There are 2 large clinical trials currently investigating the Alere Afinion CRP test:
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ERNIE2 – Investigating point-of-care CRP in children in primary care and the emergency department (study protocols published by Verbakel et al. 2014 and Lemiengre et al. 2014).
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PACE – Investigating use of a CRP point-of-care test in patients with chronic obstructive pulmonary disease in primary care to help target antibiotic prescribing to patients who are most likely to benefit.
The manufacturer also highlighted 2 recent pilot studies which are due for publication:
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Cross et al. (2016) – Responsible antibiotic prescribing in primary care: implementing point-of-care CRP testing in the management of acute lower respiratory tract infection.
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Evaluation of C-reactive protein in primary care settings to support reduction in antibiotic prescribing for self-limiting respiratory infections by the Scottish Antimicrobial Prescribing Group – This has evaluated the feasibility of using CRP testing in primary care and unscheduled care settings (such as out-of-hours service).