EUnetHTA has published assessment of C-reactive protein point-of-care testing (CRP POCT)

In early February 2019, the network of European HTA agencies, EUnetHTA, announced the final report of the project OTCA12 “C-reactive protein point-of-care testing (CRP POCT) to guide antibiotic prescribing in primary care settings for acute respiratory tract infections (RTIs).”

Traditionally CRP testing has been undertaken in the laboratory setting; CRP point-of-care testing (POCT) refers to testing at or near the site of the patient encounter with the result being available within minutes to inform decision-making. In the context of patients presenting to primary care with acute respiratory tract infections (RTIs), the aim of CRP POCT is to provide reliable test results which assist the clinician rule out a severe bacterial infection thereby supporting a decision not to prescribe an antibiotic to those who are unlikely to benefit from treatment. It may also help identify patients who could benefit from an antibiotic. The test is indicated if, after clinical assessment, there is uncertainty as to whether an antibiotic should be prescribed. Fifteen CE marked CRP POCT systems were identified for inclusion in this assessment.

There are multiple research questions:

• Does CRP POCT in primary care lead to a significant reduction in antibiotic prescribing without compromising patient safety?
• What is the diagnostic test accuracy (DTA) of CRP in patients presenting with acute RTIs in primary care?
• How does the analytical performance of the commercially available CE marked CRP point-of-care tests marketed for use in primary care compare with standard laboratory CRP measurement and with each other? That is, are they are they interchangeable in terms of accuracy, precision, and ease of use?

The HTA Core Model Application for Rapid Relative Effectiveness Assessments (REA, v 4.2) will be followed for the selection of assessment elements. A systematic literature search will be performed for the effectiveness and safety domains. The strength of evidence for all critical outcomes will be rated according to GRADE methodology. The Risk of bias (RoB) assessment of the included studies will be done according to the Cochrane Risk of bias tool on study and outcome level. Data was searched for in the various databases: Cochrane library, EBSCO Host (Cinhal), Pubmed, Embase.

Key takeaway messages regarding clinical effectiveness:

• Twelve studies were included (4 individual RCTs, 3 cluster RCTs, and 5 non-randomised studies), ten out of which were conducted in Europe
• The 7 RCTs (n=5,320) were included in the meta-analysis, and the pooled estimate showed a statistically significant reduction in antibiotic prescribing at index consultation in the CRP POCT group compared with usual care (relative risk (RR) 0.76, 95% CI: 0.67–0.86, I2 = 70%). When grouped based on the method of randomisation (individual or cluster randomisation), the substantial heterogeneity in the pooled estimate (I2 = 70%) reduced to 0% for cluster randomised trials (RR 0.68, 95% CI: 0.61, 0.75, I2 = 0%; n=3). Quality of evidence was marked as moderate according to GRADE methodology
• The non-randomized studies (n=4,839) show a similar effect of CRP POCT on antibiotic prescribing with a pooled RR of 0.61 (95% CI: 0.54–0.69, I2 = 74%) but with low quality of evidence
• The authors are moderately confident that the use of CRP POCT leads to a significant reduction in the number of patients presenting to primary care with an RTI being given an antibiotic prescription at their index consultation. Furthermore, they are also confident that this reduction is achieved without compromising patient safety

Key takeaway messages regarding the diagnostic test accuracy (DTA):

• Thirteen DTA studies were included, all conducted in Europe
• A high level of heterogeneity was noted across studies, reflecting differences in the criteria used to define test positivity, diagnostic criteria, patient populations and the absence of a universal reference standard for the diagnosis of RTIs requiring antibiotics
• Most (9) studies reported on the usefulness of CRP in lower respiratory tract infections (LRTI) and/or specifically in pneumonia, while others report on the usefulness of CRP in patients with sore throat (2) and sinusitis (2)
• there is very limited evidence for the use of CRP to support antibiotic prescribing decisions in patients presenting with acute RTIs in primary care. In patients with ambiguous clinical findings, CRP testing may be useful when used in conjunction with clinical examination or as part of a clinical decision rule to identify those patients who are unlikely to benefit from an antibiotic, particularly where there is diagnostic uncertainty based on clinical examination alone. However, the authors note that further validation of prediction rules incorporating CRP measurement is required

Key takeaway messages regarding analytical performance:

• Eighteen studies were included in the assessment of analytical performance:
• The analytical performance of the CE marked quantitative CRP POCT devices evaluated in this assessment is broadly comparable to laboratory CRP testing when used in idealized circumstances. Performance may be poorer at extreme levels, but this is unlikely to impact decision-making in primary care where the decision to prescribe or not to prescribe an antibiotic applies to all values above or below a threshold
• There is evidence of greater variability in performance when used by nonlaboratory trained healthcare staff in primary care, with the variation most likely due to operator error

Key takeaway messages regarding safety:

• The same twelve studies, like in the efficacy part, were considered
• No study reported death of the patient
• The authors conclude that this method is safe

Key takeaway messages regarding reimbursement:

• The use of CRP POCT in patients with suspected LRTI has been included in guidelines in the UK, Norway, Sweden, the Netherlands, Germany, Switzerland, Czech Republic and Estonia to determine severity of infection and to guide antibiotic prescribing
• CRP POCT to inform prescribing in primary care was noted to have been indicated in 16 out of 19 countries for which data were provided, and to be reimbursed for this indication in nine of these countries (Denmark (about €9.5), Germany (€1.15 in general laboratory; €4.9 in special laboratory), Hungary, Italy (about €3.8, but not in primary care), Lithuania, the Netherlands (about €3.9), Norway (around €4.3), Poland, Slovenia, Switzerland (CHF 10))
• It is only negatively recommended (non-mandatory recommendation in the guidelines) in the UK

The authors also note that further research is required to validate the long-term effectiveness of CRP POCT to change prescribing behavior and to validate its effectiveness and safety in specific sub-populations such as children and older adults (>65 years) and in different primary care settings (out-of-hours clinics and long-term care facilities) where the spectrum of patients may differ

See the full details (assessment details, external experts’ and manufacturers’ comments) in English here.

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