Cost-effectiveness of a rapid point-of-care test for diagnosing patients with suspected bloodstream infection in Ireland

Speed is of the essence for sepsis management and faster diagnosis of specific pathogens may help ensure that patients receive the most appropriate treatments as soon as possible. In addition, reducing the use of broad-spectrum antibiotics is an essential part of antibiotic stewardship to prevent the emergence of antibiotic resistance. This work explored the potential use of a novel diagnostic test to detect Gram-negative or Gram-positive bacterial or fungal infections rapidly to aid in the diagnosis of sepsis in severely ill, hospitalised adult patients.

A rapid point-of-care (PoC) test as an adjunct to blood culture to aid the diagnosis of sepsis patients with bloodstream infections may decrease the use of broad-spectrum antibiotics and reduce rates of inappropriate antimicrobial therapy (IAAT) use. Through a decision tree model, taking the perspective of the Irish healthcare provider, the cost-effectiveness of such an intervention was evaluated against the current standard of care (SoC) in hospitalized adults in Ireland. The base-case scenario showed that using a rapid PoC test was cost-saving and lifesaving, with €8188 saved per death averted. The results were sensitive to the length of hospital stay for patients with true-positive and true-negative results and to the length of stay (LOS) in the intensive care unit. The threshold analysis showed that even at lower sensitivities, the rapid PoC test could be cost-effective due to the substantial impact of starting earlier targeted and appropriate treatment in patients with bloodstream infection (BSI) and sepsis. Clinical studies are ongoing to determine the clinical impact in practice.

The results of this work are published in Informatics in Medicine Unlocked and the full text can be accessed here.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 967968. Novus Diagnostics (SepTec) funded Aquarius Population Health to conduct the study.

Vankelegom M, Burke D, Mohammed AMF, et al. Cost-effectiveness of a rapid point-of-care test for diagnosing patients with suspected bloodstream infection in Ireland. Informatics in Medicine Unlocked [Internet]. 2022 Jan 1;32:101056. Available from: https://www.sciencedirect.com/science/article/pii/S2352914822001952

A cost effectiveness analysis of repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK

Syphilis is a treatable sexually transmitted infection (STI) which can be passed from mother to foetus during pregnancy resulting in congenital syphilis. Syphilis infection also increases the risk of adverse pregnancy outcomes such as stillbirth and pre-term delivery. Most cases of congenital syphilis and adverse pregnancy outcomes can be avoided if the infection is diagnosed and correctly treated during pregnancy.

In the UK, pregnant women are offered screening for syphilis, HIV and hepatitis at their first antenatal appointment, typically at or before 12 weeks gestation. Despite the very high coverage of these routine screens plus repeat screening in some higher risk women, a handful of congenital syphilis cases still occur each year, either in women who miss screening or in women who become infected with syphilis after their antenatal screen. For this reason, the UK National Screening Committee (UK NSC) commissioned Aquarius to assess the cost effectiveness of offering a repeat screen to all pregnant women later in pregnancy.

We worked closely with a small group of experts to compare the current strategy – screening in the first trimester only – with an alternative strategy – screening in the first trimester and a repeat screen later in pregnancy. We developed a decision tree and model inputs which accounted for the sensitivity and specificity of the syphilis assay, the small number of women who do not attend antenatal care until their third trimester (thereby missing the opportunity for repeat screening) and the costs associated with screening, delivery and antenatal care for all women delivering in the UK in one year.

The model revealed that repeat screening would prevent 5.5 cases of congenital syphilis each year but at cost of £1.8 million per case avoided. When a lifetime horizon was considered, the incremental cost-effectiveness ratio (ICER) for the repeat screening strategy was £120,494 per QALY gained – well above the £20k-30k cost per QALY threshold that NICE uses to assess interventions.

The paper concludes that in the UK setting, where prevalence of syphilis is very low, repeat screening for syphilis in pregnancy would not be a cost-effective strategy and alternative strategies should be sought to prevent congenital syphilis.

This is the first published study from outside the US to compare these two screening strategies. The results will be used to inform national screening policy and are relevant countries with similar syphilis prevalence and healthcare costs.

Huntington S, Weston G, Seedat F, et al Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK: a cost-effectiveness analysis BMJ Open 2020;10:e038505. doi: 10.1136/bmjopen-2020-038505

Cost-effectiveness and impact of five different point of care strategies to preserve last line treatment for gonorrhoea

Antimicrobial resistance (AMR) has developed to every class of antibiotic used for the treatment of gonorrhoea – and in recent years several multi-drug resistant strains of gonorrhoea have been reported in the UK and elsewhere. Once the prevalence of resistance to a first-line treatment reaches 5%, an alternative drug is selected as first-line treatment. In the UK, as with many other countries, ceftriaxone is the current first-line treatment for gonorrhoea. There are few alternative treatments available should ceftriaxone resistance become widespread and therefore steps are being taken to preserve the effectiveness of ceftriaxone by avoiding its use for infections that could be treated using other antibiotics.

Aquarius was commissioned by the Applied Diagnostic Research and Evaluation Unit (ADREU) at St. Georges London to compare the cost and effectiveness of five different strategies to test for antibiotic susceptibility in NG infections. We developed a decision tree model to assess how point-of-care (POC) testing could be used to diagnose gonorrhoea and at the same time test for antibody susceptibility, allowing the use of previously abandoned antibiotics for the majority of patients, thereby sparing ceftriaxone use.

The results of the model showed that all five strategies cost more than the current strategy of not testing for AMR. The paper concludes that AMR POC testing may enable improved antibiotic stewardship but would require investment into the health system.

The article was published in October in Eurosurveillance and is available free online [link].

Harding-Esch EM, Huntington SE, Harvey MJ, Weston G, Broad CE, Adams EJ, et al. Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics. Eurosurveillance [Internet]. 2020;25(43). Available from: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.43.1900402

Examining the acceptability of offering STI screening in higher educational settings

Uptake of screening for STIs, such as chlamydia and gonorrhoea, is often inadequate in young people despite provision of open-access sexual health services. Offering STI tests outside medical settings is currently being explored as a way to increase uptake in this group.

In 2017, St George’s University of London ran the ‘Test n Treat’ feasibility trial where free, confidential on-site testing for chlamydia and gonorrhoea was offered to students at six higher-education colleges in South London. We have previously reported on the main results of the trial and the cost estimates of providing such a service .

As part of the trial, the research team wanted to understand the acceptability of this type of service among students as well as the barriers and facilitators to its use. They interviewed a small sample of students, some of whom used the service and some of whom did not, as well teachers and the research team. The results of this qualitative study, which Aquarius Population Health gave advisory support to, were published in August 2020.

The paper reports that students who used the service had a very positive opinion of it. There were a number of barriers to using the service identified, including embarrassment about STI testing and the perceived view that individuals would be viewed negatively by their peers if they had an STI test. On the flip side, peers also acted as facilitators to uptake, for example, if a group of friends encouraged each other to get tested. A lack of understanding of STIs was another major barrier, with many students lacking understanding about the long-term consequences of STIs or having the misconception that only people with symptoms should get tested. Where a £5 honorarium was given to students using the service, this acted as a legitimate incentive for testing, mitigating the (perceived) social stigma of testing.

The paper concludes that if a similar service were provided in future, uptake could be improved if education about sexual health was offered alongside testing, if small cash incentives were given and if peer influencers were engaged to promote the service.

Fleming, C., Drennan, V.M., Kerry-Barnard, S. et al. Understanding the acceptability, barriers and facilitators for chlamydia and gonorrhoea screening in technical colleges: qualitative process evaluation of the “Test n Treat” trial. BMC Public Health 20, 1212 (2020). https://doi.org/10.1186/s12889-020-09285-1

Modelling the choice of high-risk human papillomavirus (HR-HPV) assay in the English cervical screening programme

Aquarius developed a decision tree model to compare the use of the Aptima mRNA HR-HPV assay to a DNA HR-HPV assay in the HPV primary screening algorithm in England. Robust results from the model demonstrate that using the mRNA HR-HPV assay is cost saving and avoids unnecessary HPV recall tests, cytology tests and colposcopies compared to using a DNA HR-HPV assay.

In England, women are invited for cervical cancer screening starting at age 25 and are recalled at regular intervals until age 64. In the HPV primary screening algorithm, cervical samples are tested first for HR-HPV. Positive HPV samples are then tested using liquid based cytology to identify abnormal cells.

Aquarius developed a cost consequence analysis decision tree taking the perspective of NHS England and modelling the HPV primary screening algorithm for one simulated cohort of 2,247,439 women aged 25-64 from baseline screen through recall visits. The model endpoint was discharge to routine recall, loss-to-follow up, or referral to colposcopy. A micro-costing approach was used to estimate costs for screening in England, using published data. Head-to-head comparison of mRNA to DNA tests at baseline and with follow-up was not available for the English population. Therefore, data from the HORIZON study in Denmark with similar positivity to that in England was used.

The model indicated that using an mRNA versus DNA assay in the HPV primary screening algorithm in England can save an estimated £15.4 million and require 28,009 fewer unnecessary colposcopies, 90,605 few HR-HPV tests and 253,477 fewer cytology tests. Uncertainty and scenario analyses demonstrate cost and resource savings will almost certainly be achieved using the mRNA assay.

Weston G, Dombrowski C, Harvey MJ, et al Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation BMJ Open2020; 10:e031303. doi: 10.1136/bmjopen-2019-031303

Cost analysis of near patient chlamydia and gonorrhoea screening and treatment in further education/technical colleges

Aquarius collaborated with St George’s University of London on an NIHR-funded study, ‘Test n Treat’ (TnT). In this cluster randomised feasibility trial, rapid chlamydia (CT) and gonorrhoea (NG) testing and same day on-site chlamydia treatment in six technical colleges in South London was delivered.

Using process data from the trial (the main results of which were published last year) and NHS cost data, the overall cost of providing the TnT service was calculated, as well as the cost per CT/NG screen and the cost per CT/NG infection diagnosed. These took into account the fixed daily costs, such as staff time and equipment use, and the per screen costs, i.e. the consumables used to collect and test samples, and were dependent on uptake of screening. Since the average cost per screen was higher if uptake was low as per what was observed in the trial, and lower if uptake was high, costs for a range of update scenarios were assessed. If daily capacity for screening was achieved (calculated as 49 screens/day), the cost per screen was £47 (including the £10 incentive given to students to encourage participation). This increased to £91, if uptake was equivalent to the average uptake observed on the trial (19 screens/day). The paper concluded that delivering this type of service is more expensive per person than CT and NG screening in sexual health clinics but could be more comparable in areas of high CT/NG prevalence.

Kerry-Barnard S, Huntington, S, Fleming C, et al. Near patient chlamydia and gonorrhoea screening and treatment in further education/technical colleges: a cost analysis of the ‘Test n Treat’ feasibility trial. BMC Health Services Research. https://doi.org/10.1186/s12913-020-5062-5

Cluster-randomised feasibility trial of a chlamydia test and treat (TnT) service in further education colleges

Aquarius were involved in a recent cluster-randomised feasibility trial looking at whether provision of a same day test and treatment (TnT) service for chlamydia in further education colleges could be used to improve uptake of chlamydia testing in sexually active 16-24 year olds. The trial found that despite a high prevalence of chlamydia among sexually active students at the colleges, uptake of the free confidential TnT service was low. At the three colleges, 13% of students were tested when the service was first offered and 10% when it was offered again three months later. Interviews with students revealed that low uptake was associated with not feeling at risk of a sexually transmitted infection, perceptions of stigma, and lack of knowledge about sexually transmitted infections, while all students interviewed were positive about the TnT service itself.

Oakeshott P, Kerry-Barnard S, Fleming C, et al. “Test n Treat” (TnT): a cluster randomised feasibility trial of on-site rapid Chlamydia trachomatis tests and treatment in ethnically diverse, sexually active teenagers attending technical colleges. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2018.10.019.

Modelling cost-effectiveness of multipathogen POC tests for sexually transmitted infections

In this BMJ Open article, we report on health economic modelling results that compare three possible strategies for point-of-care (POC) sexually transmitted infection (STI) testing with the current practice of microscopy and lab-based testing. Results showed that testing for STIs with either a dual, triple or quadruple POC test provided more patient benefit than current practice but may cost more. The quadruple POC test was the least expensive POC strategy relative to standard care – with an incremental cost-effectiveness ratio of £36,585 per quality adjusted life years gained, when taking the clinic’s perspective. When taking the commissioners’ perspective, who pay for the services delivered through tariffs, over £26 million in savings could be achieved using the 4-bug test, mainly because patients were treated appropriately on their first testing visit rather than having to re-attend.

Huntington SE, Burns RM, Harding-Esch E, et al. ‘Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees.’ BMJ Open 2018;8:e020394. doi:10.1136/bmjopen-2017-020394

To request a copy of the published article, please email caroline.dombrowski@aquariusph.com.

Three simple tests could save the NHS nearly £6.9 billion

This year marks the 70^th birthday of the NHS – a time to celebrate its achievements and the dedicated staff who keep its wheels turning. Yet, there is increasing concern about the future of the NHS, and particularly its funding. In this article, jointly commissioned by the British In Vitro Diagnostics Association (BIVDA) and Innovate UK, we showcase three tried and tested in vitro diagnostics, which, if more widely adopted, could save the NHS an estimated £6.9 billion over the next five years.

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Test n Treat – rapid STI testing and treatment in colleges: study protocol

Sexually active young people attending London further education (FE) colleges have high rates of chlamydia, but screening rates are low. We describe the study protocol for “Test and Treat” (TnT), an NIHR-funded research study. This is a cluster randomised feasibility trial of frequent, rapid, on-site chlamydia testing using the Cepheid GeneXpert system and same-day treatment in six FE colleges. As part of the study we also conducted qualitative and economic assessments to assess the feasibility of conducting a future large-scale trial to investigate if TnT reduces chlamydia rates. The methods for recruitment, participant data collection, sample collection and testing are described, for baseline and follow-up in the control and intervention groups. The statistical analysis plan for TnT has been published separately.

Kerry-Barnard S, Fleming C, Reid F, et al. ‘Test n Treat (TnT)’- Rapid testing and same-day, on-site treatment to reduce rates of chlamydia in sexually active further education college students: study protocol for a cluster randomised feasibility trial. Trials. 2018 Jun 5;19(1):311. doi: 10.1186/s13063-018-2674-8.