The cost-effectiveness of Magnetic Resonance-Guided Focused Ultrasound compared to Deep Brain Stimulation for the treatment of essential tremor

Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the United Kingdom and causing considerable societal impact (1). Medical treatment has mixed efficacy with approximately 25%-55% response to treatment (2). Deep Brain Stimulation (DBS) is a proven neurosurgical treatment. However, the risks of surgery and anaesthesia mean some patients are ineligible.

Magnetic Resonance Guided Focused Ultrasound (MRgFUS) is an emerging non-invasive technique to treat tremor (3). MRgFUS causes tremor suppression by thermal ablation of tremor-sensitive brain tissue without general anaesthesia. Several international clinical trials have demonstrated MRgFUS a safe and clinically effective mrET treatment (4–6). This study aims to ascertain the cost-effectiveness of MRgFUS for the treatment of medically refractory Essential Tremor (mrET) in England.

A Markov model was used to assess two sub-populations of mrET, those eligible and those ineligible for neurosurgery, in the context of England’s healthcare system. MRgFUS treatment for mrET in England was found to have a favourable cost-effectiveness profile for both groups of ET patients.

The introduction of MRgFUS as a widely available ET treatment in the UK is currently undergoing the necessary stages of regulatory approval. As this is the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE’s WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

The paper reporting this work is published in the British Journal of Radiology. The full text can be accessed here.

Jameel A, Meiwald A, Bain P, et al. The Cost-Effectiveness of unilateral magnetic Resonance-Guided focused ultrasound in comparison to unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England. BJR [Internet]. 2022 Sep 20 [cited 2022 Sep 27];20220137. Available from: https://doi.org/10.1259/bjr.20220137

References

1. Essential Tremor NEW [Internet]. Tremor | The National Tremor Foundation. [cited 2021 Oct 4]. Available from: https://tremor.org.uk/essential-tremor

2. Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, et al. Correlates of functional disability in essential tremor. Mov Disord Off J Mov Disord Soc. 2001 Sep;16(5):914–20.

3. Meng Y, Hynynen K, Lipsman N. Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nat Rev Neurol. 2021 Jan;17(1):7–22.

4. Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, et al. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016 Aug 25;375(8):730–9.

5. Halpern CH, Santini V, Lipsman N, Lozano AM, Schwartz ML, Shah BB, et al. Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology. 2019 Dec 10;93(24):e2284–93.

6. Jameel A, Gedroyc W, Nandi D, Jones B, Kirmi O, Molloy S, et al. Two year data from a preliminary study of double lesion site MRgFUS treatment of Essential Tremor targeting the thalamus and the posterior subthalamic area. MedRxiv Prepr. 2021 Jan 2;2020.12.27.20248723.

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

Health economic evaluation of an mRNA HR-HPV assay versus a DNA HR-HPV assay for the proposed French cervical screening programme

Persistent infection with high-risk human papillomavirus (HR-HPV) has been linked to precancerous lesions which may progress to cervical cancer. Guidance was issued in 2020 in France to include the use of assays to detect HR-HPV infections in a national cervical screening programme.

A decision tree model simulating the French cervical screening algorithms was developed to evaluate the effect of using a similarly sensitive, but more specific, mRNA HR-HPV assay (Aptima HR-HPV assay) compared to a DNA HR-HPV test (cobas 4800 HPV assay) in the proposed cervical screening algorithm for a hypothetical cohort of women aged 25 to 65 years in France.

Results showed using an mRNA assay could yield an estimated annual cost saving of €6.5 million and reduces the total number of colposcopies, HPV and cytology tests. As mRNA and DNA assays have similar test sensitivity, true positives will not be missed, and total costs are reduced by eliminating unnecessary colposcopy referrals, HR-HPV and cytology tests.

The choice of high-risk human papillomavirus assay makes a significant difference in resource use and costs and is important to consider when implementing cervical screening in France. Using an mRNA versus DNA assay can result in cost savings and reductions in unnecessary testing and procedures, which in turn benefits women and the health care system.

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

Dombrowski CA, Weston GM, Descamps PP, et al. Health economic evaluation of an mRNA high-risk human papillomavirus (HR-HPV) assay versus a DNA HR-HPV assay for the proposed French cervical screening programme. Medicine (Baltimore). 2022 Jul 22;101(29):e29530.

Identifying the common barriers to optimal COPD care in Japan, Canada, England, and Germany through Evidenced Care Pathways

COPD was the third leading cause of mortality worldwide in 2019 (1), responsible for 3.23 million deaths (2). Improved understanding of the common barriers to care delivery could inform international approaches to improving care standards and patient outcomes.

Evidence Care Pathways (ECPs) were created to bring to life the story of how COPD care is currently delivered in Japan, Canada, England and Germany. Published epidemiological, clinical, and economic data was used to populate the ECPs. Thematic content analysis was performed on the clinician interviews (twenty-four respiratory healthcare professionals in primary and secondary care) to inform and validate the ECPs.

The results of this work published in the International Journal of Chronic Obstructive Pulmonary Disease identified three key themes relating to barriers to optimal COPD management across the countries: journey to diagnosis, treatment and management, and the impact of COVID-19. Presentation to healthcare with advanced COPD, low consideration of COPD by patients and healthcare professionals, and sub-optimal acute and chronic disease management were common across all countries. COVID-19 has negatively impacted disease management across the pathway – but has also opened opportunities for virtual consultations.

COPD is a significant public health issue that needs urgent prioritisation. The common barriers to optimal COPD care identified across the four studied countries highlight the continued need for strategies to optimise COPD care, particularly as the burden of COPD continues to grow.

The Evidenced Care Pathways for the four countries can be downloaded h ere. Please download this document and open it in a PDF reader such as Adobe for full functionality.

This study was funded and commissioned by AstraZeneca.

Meiwald A, Gara-Adams R, Rowlandson A, et al. Qualitative Validation of COPD Evidenced Care Pathways in Japan, Canada, England, and Germany: Common Barriers to Optimal COPD Care. Int J Chron Obstruct Pulmon Dis. 2022;17:1507-1521 https://doi.org/10.2147/COPD.S360983

References

1. WHO. The top 10 causes of death. Accessed October 22, 2021. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death

2. WHO. Chronic obstructive pulmonary disease (COPD) fact sheet. Published 2021. Accessed August 18, 2021. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)

A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada

While cervical cancer cases in Canada have decreased recently due to cytology primary screening, cervical cancer remains a relatively common and preventable cause of cancer in women. Cervical cancer is primarily caused by persistent genital infection with high-risk human papillomaviruses (HR-HPV). Ontario Health has been evaluating implementing HPV-based testing in cervical screening.

A decision tree model was developed to evaluate the impact of using a similarly sensitive, but more specific, mRNA HR-HPV assay (Aptima HR-HPV assay) compared to a DNA HR-HPV assay (Hybrid Capture 2 HPV assay) in a hypothetical cervical screening algorithm in Ontario, Canada. Results indicated that screening using an mRNA assay could yield cost savings of $4M CAD and a reduction in unnecessary colposcopies, HPV, and cytology tests. These results indicate that the choice of HR-HPV test is important when implementing a primary HPV screening program to avoid unnecessary resource use and cost, which will benefit both women and healthcare providers.

Weston G, Dombrowski C, Steben M, et al.A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada. Preventive Medicine Reports [Internet]. 2021 Sep 1 [cited 2021 Jul 29];23:101448. Available from: https://www.sciencedirect.com/science/article/pii/S2211335521001388

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

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.

Aquarius PopulationHealth

Project Type: Journal Article