C-reactive protein point of care testing in the management of acute respiratory infections in the Vietnamese primary healthcare setting – a cost benefit analysis

It is estimated that 80–90% of antibiotic prescription occurs in primary care, of which half are for acute respiratory infection (ARI) [1, 2]. Antibiotic use is unrestricted in Viet Nam, and prescription and sales of antibiotics for ARI is very common in- and outside primary health care settings [3] despite a predominantly viral etiology [4]. Approximately 70% of primary care patients in Viet Nam are prescribed antibiotics, and ARI is the reason for 51% of these [5]. Treatment decisions are at best based on clinical examination, which in both low and high income settings is of poor accuracy in identifying when antibiotics are required, and is often inadequately performed [3, 6, 7].

The interaction between antimicrobial consumption and antimicrobial resistance (AMR) is complex, however, it is widely accepted that safe reductions in consumption will have the desirable effect of mitigating the burden of AMR [8]. A recent modelling study estimated the economic costs of AMR per antibiotic consumed, equating with the societal gains for every course of antibiotics averted [9]. For example, in the Thai context, the consumption of a full course of beta-lactams was associated with an economic cost of $10.8 due to AMR.

Several biomarker tests have been evaluated for this purpose in the context of ARIs in primary care, and C-reactive protein (CRP) has been shown to have high discriminatory power in distinguishing between viral and bacterial infections, in the range of 85–95% sensitivity and 50–75% specificity [10–12]. A meta-analysis of clinical trials concluded that CRP tests can safely reduce antibiotic prescribing [13].

Point-of-care (PoC) CRP tests are commercially available and can be performed in primary care using capillary blood samples, with results available within minutes [14, 15]. This approach is already taken in a number of high income countries such as Norway and Sweden [16] and is recommended by Public Health England and the National Institute for Health and Clinical Excellence (NICE) [17]. In low and middle income countries (LMICs), and in Asia in particular, no such tests are in routine use and antibiotic dispensing is often unregulated or regulation is poorly enforced and resistance levels are high and increasing [18–21]. Despite the urgent need to improve antibiotic targeting in these settings, the necessary evidence on the cost-effectiveness of biomarker testing is scarce.

A randomised control trial in Viet Nam compared CRP PoC testing with routine care in the management of ARIs in primary care, finding significant reductions in antibiotic prescription without compromising patient recovery and satisfaction [22]. To determine whether the incremental cost of introducing CRP tests is economically justifiable, this needs to be compared with the societal costs of AMR the tests could avert. In this short report, we use primary cost data collected in the trial and the output of the modelling analysis of the economic costs of AMR per antibiotic consumed to perform a cost-benefit analysis of CRP testing in primary care in the Vietnamese setting.

This cost-benefit analysis of CRP testing takes a societal perspective. Primary cost data were collected in a clinical trial on CRP testing in primary care as described in the Additional file 1: Tables S1 and S2, comparing the costs of managing ARI in the intervention group as compared with controls. The CRP readers and reagents used in the study were donated by the manufacturer, with a purchase cost per kit of approximately $3 and for a single reader $1000. If implemented at scale, CRP testing could be carried out using simple lateral flow devices that can be used by relatively untrained personnel. Such tests have been shown to be accurate and available at under $0.5 [15, 23]. By way of comparison World Health Organisation (WHO) pre-qualified lateral flow malaria rapid diagnostic tests (RDTs) are available at under $0.3. We conservatively assume here a unit cost of $1 per test, allowing for added costs for import tariffs, shipment, training, and other peripheral expenses.

where NMB is the net monetary benefit of CRP testing, ∆pAB is the percentage difference in prescribing between patients in the CRP group and controls; cAMR is the cost of AMR per antibiotic consumed; ∆DC is the difference in direct medical care as observed in the trial; and Ct is the direct cost of the CRP tests. A positive net monetary benefit indicates that CRP testing is cost-beneficial. All costs are assumed to be incurred at the time patients are presenting at the health centre, therefore no discounting is applied.

A three-way sensitivity analysis was carried out for key drivers of the net-monetary benefit: 1) the cost of the CRP tests, ranging from $0.5 to $3; 2) adherence to test results indicating low CRP (i.e. not prescribing antibiotics to patients with low CRP concentrations, which occurred in 64% of cases in the trial context) ranging from 50 to 100%; and 3) the economic cost of AMR, ranging from $0 to $14 per course of antibiotics, using the upper bound of the range of costs of AMR per full course of broad spectrum beta-lactam as described in Shrestha et al. (2018) [9], adjusted by the per-capita GDP ratios of Viet Nam and Thailand.

The data were analyzed and the cost-benefit analysis were run in R version 3.2.2 (R Foundation for Statistical Computing, Vienna, Austria) and using the R Color Brewer package.

The trial demonstrated that CRP testing could safely reduce antibiotic prescription in primary health care settings. The primary cost data indicate that other than the cost of the test, there were no added direct medical costs and potential cost savings associated with the intervention. Assuming a unit cost per test of $1, the incremental cost per patient would be $0.93. With an estimated societal cost of AMR of $4.1 per course of a broad spectrum beta-lactam, the use of the tests would not appear to be cost-beneficial due to the limited adherence to their results. The sensitivity analysis, however, indicated that the tests could be cost-beneficial if healthcare workers refrained from prescribing to patients with low CRP at higher rates than observed in the trial.

Use of CRP test in the context of primary care in LMICs is likely to incur a modest incremental cost, but this can be offset by the economic costs of AMR averted, providing adherence to their results is high. Whether patients or health providers in LMICs can and should shoulder the tangible costs is contestable; this study suggests that international donor support for these purposes is economically warranted. With low cost tests available and validated, large scale implementation of CRP point of care tests is feasible. Implementation of CRP testing on national scales will pave the way for novel and better systems that are currently cost-prohibitive once these are better validated and available at affordable price ranges.