Network Meta-analysis and Economic Evaluation of Neurostimulation Interventions for Chronic Nonsurgical Refractory Back Pain.

OBJECTIVES: Different types of spinal cord stimulation (SCS) have been evaluated for the management of chronic nonsurgical refractory back pain (NSRBP). A direct comparison between the different types of SCS or between closed-loop SCS with conventional medical management (CMM) for patients with NSRBP has not been previously conducted, and therefore, their relative effectiveness and cost-effectiveness remain unknown. The aim of this study was to perform a systematic review, network meta-analysis (NMA) and economic evaluation of closed-loop SCS compared with fixed-output SCS and CMM for patients with NSRBP. METHODS: Databases were searched to September 8, 2023. Randomized controlled trials of SCS for NSRBP were included. The results of the studies were combined using fixed-effect NMA models. A cost-utility analysis was performed from the perspective of the UK National Health Service with results reported as incremental cost per quality-adjusted life-year (QALY). RESULTS: Closed-loop SCS resulted in statistically and clinically significant reductions in pain intensity (mean difference [MD] 32.72 [95% CrI 15.69-49.78]) and improvements in secondary outcomes (Oswestry Disability Index [ODI] and health-related quality of life [HRQoL]) compared with fixed-output SCS at 6-month follow-up. Compared with CMM, both closed-loop and fixed-output SCS resulted in statistically and clinically significant reductions in pain intensity (closed-loop SCS vs. CMM MD 101.58 [95% CrI 83.73-119.48]; fixed-output SCS versus CMM MD 68.86 [95% CrI 63.43-74.31]) and improvements in secondary outcomes (ODI and HRQoL). Cost-utility analysis showed that closed-loop SCS dominates fixed-output SCS and CMM, and fixed-output SCS also dominates CMM. DISCUSSION: Current evidence showed that closed-loop and fixed-output SCS provide more benefits and cost-savings compared with CMM for patients with NSRBP.

Does industry funding and study location impact findings from randomized controlled trials of spinal cord stimulation? A systematic review and meta-analysis.

BACKGROUND/IMPORTANCE: Concerns have been raised that effects observed in studies of spinal cord stimulation (SCS) funded by industry have not been replicated in non-industry-funded studies and that findings may differ based on geographical location where the study was conducted. OBJECTIVE: To investigate the impact of industry funding and geographical location on pain intensity, function, health-related quality of life and adverse events reported in randomized controlled trials (RCTs) of SCS. EVIDENCE REVIEW: Systematic review conducted using MEDLINE, CENTRAL, EMBASE and WikiStim databases until September 2022. Parallel-group RCTs evaluating SCS for patients with neuropathic pain were included. Results of studies were combined in random-effects meta-analysis using the generic-inverse variance method. Subgroup meta-analyses were conducted according to funding source and study location. Risk of bias was assessed using Cochrane RoB 2.0 tool. FINDINGS: Twenty-nine reports of 17 RCTs (1823 participants) were included. For the comparison of SCS with usual care, test for subgroup differences indicate no significant differences (p=0.48, moderate certainty evidence) in pain intensity score at 6 months for studies with no funding or funding not disclosed (pooled mean difference (MD) -1.96 (95% CI -3.23 to -0.69; 95% prediction interval (PI) not estimable, I2=0%, τ2=0)), industry funding (pooled MD -2.70 (95% CI -4.29 to -1.11; 95% PI -8.75 to 3.35, I2=97%, τ2=2.96) or non-industry funding (MD -3.09 (95% CI -4.47 to -1.72); 95% PI, I2 and τ2 not applicable). Studies with industry funding for the comparison of high-frequency SCS (HF-SCS) with low-frequency SCS (LF-SCS) showed statistically significant advantages for HF-SCS compared to LF-SCS while studies with no funding showed no differences between HF-SCS and LF-SCS (low certainty evidence). CONCLUSION: All outcomes of SCS versus usual care were not significantly different between studies funded by industry and those independent from industry. Pain intensity score and change in pain intensity from baseline for comparisons of HF-SCS to LF-SCS seem to be impacted by industry funding.

Diagnostic accuracy and clinical impact of MRI-based technologies for patients with non-alcoholic fatty liver disease: systematic review and economic evaluation.

Background: Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease. Objectives: The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing. Data sources: The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment. Methods: A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results. Results: The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters. Limitations: Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited. Conclusions: Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only. Study registration: This study is registered as PROSPERO CRD42021286891. Funding: Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.

Non-alcoholic fatty liver disease includes a range of conditions that are caused by a build-up of fat in the liver, and not by alcohol consumption. This build-up of fat can cause inflammation. Persistent inflammation can cause scar tissue (fibrosis) to develop. It is important to identify patients with fibrosis because severe fibrosis can cause permanent liver damage (cirrhosis), which can lead to liver failure and liver cancer. In the National Health Service, patients with non-alcoholic fatty liver disease undergo tests to determine whether they have fibrosis. The test results are not always accurate and multiple tests can give conflicting results. Some of the tests may not be suitable for patients who have a very high body mass index. In the National Health Service, a liver biopsy may be offered to patients with inconclusive or conflicting test results or to those patients for whom other tests are unsuitable. However, liver biopsy is expensive, and is associated with side-effects such as pain and bleeding. Magnetic resonance imaging-based testing could be used as an extra test to help clinicians assess non-alcoholic fatty liver disease and identify patients who may need a liver biopsy. We assessed two magnetic resonance imaging-based diagnostic tests, LiverMultiScan and magnetic resonance elastography. LiverMultiScan is imaging software that is used alongside magnetic resonance imaging to measure markers of liver disease. Magnetic resonance elastography is used in some National Health Service centres to assess liver fibrosis; however, magnetic resonance elastography requires more equipment than just an magnetic resonance imaging scanner. We reviewed all studies examining how well LiverMultiScan and magnetic resonance elastography assess patients with non-alcoholic fatty liver disease. We also built an economic model to estimate the costs and benefits of using LiverMultiScan to identify patients who should be sent for a biopsy. Results from the model showed that LiverMultiScan may not provide good value for money to the National Health Service.

Cost-utility Analysis of Evoke Closed-loop Spinal Cord Stimulation for Chronic Back and Leg Pain.

OBJECTIVES: The effectiveness of Evoke closed-loop spinal cord stimulation (CL-SCS), a novel modality of neurostimulation, has been demonstrated in a randomized controlled trial (RCT). The objective of this cost-utility analysis was to develop a de novo economic model to estimate the cost-effectiveness of Evoke CL-SCS when compared with open-loop SCS (OL-SCS) for the management of chronic back and leg pain. METHODS: A decision tree followed by a Markov model was used to estimate the costs and outcomes of Evoke CL-SCS versus OL-SCS over a 15-year time horizon from the UK National Health Service perspective. A "high-responder" health state was included to reflect improved levels of SCS pain reduction recently reported. Results are expressed as incremental cost per quality-adjusted life year (QALY). Deterministic and probabilistic sensitivity analysis (PSA) was conducted to assess uncertainty in the model inputs. RESULTS: Evoke CL-SCS was estimated to be the dominant treatment strategy at ~5 years postimplant (ie, it generates more QALYs while cost saving compared with OL-SCS). Probabilistic sensitivity analysis showed that Evoke CL-SCS has a 92% likelihood of being cost-effective at a willingness to pay threshold of £20,000/QALY. Results were robust across a wide range of scenario and sensitivity analyses. DISCUSSION: The results indicate a strong economic case for the use of Evoke CL-SCS in the management of chronic back and leg pain with or without prior spinal surgery with dominance observed at ~5 years.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis.

OBJECTIVES: Recent recommendations on starting dose, smaller dose increments, and longer intervals between dose increase have the potential to increase the safety of ziconotide administration in addition to improving its value for money. Ziconotide is not routinely commissioned in England, with one of the concerns being whether it represents the best use of resources. The aim of this project is to conduct a budget impact analysis to estimate the costs or savings associated with the changes in ziconotide dosage in addition to its use in combination with morphine for the management of cancer pain. MATERIALS AND METHODS: An open, Markov-like cohort decision analytic model was developed to estimate the budget impact of ziconotide in combination with morphine (ziconotide combination therapy) vs morphine monotherapy through intrathecal drug delivery (ITDD) for the management of cancer pain. The perspective adopted was that of the UK National Health Service, with a five-year time horizon. Sensitivity analyses were conducted to evaluate different scenarios. RESULTS: Ziconotide combination therapy was more expensive than treatment with morphine monotherapy. The total costs of ziconotide combination therapy and morphine monotherapy for the first year were £395,748 and £136,628 respectively. The estimated five-year cumulative budget impact of treatment with ziconotide combination therapy for the five-year time horizon was £2,487,539, whereas that of morphine monotherapy was £913,804. The additional costs in any of the first five years are below the resource impact significance level of £1 million for medical technologies in England. CONCLUSIONS: The results of this budget impact analysis suggest that although a combination of intrathecal ziconotide in combination with morphine is associated with higher costs to the health care system in England, the incremental costs are not significant. Routine commissioning of ziconotide alone or in combination with morphine would provide an alternative for a population with limited ITDD treatment options.

Screening trials of spinal cord stimulation for neuropathic pain in England-A budget impact analysis.

Screening trials of spinal cord stimulation (SCS) prior to full implantation of a device are recommended by expert guidelines and international regulators. The current study sought to estimate the budget impact of a screening trial of SCS and the costs or savings of discontinuing the use of a screening trial. A budget impact analysis was performed considering a study population that reflects the size and characteristics of a patient population with neuropathic pain in England eligible for SCS. The perspective adopted was that of the NHS with a 5-year time horizon. The base case analysis indicate that a no screening trial strategy would result in cost-savings to the NHS England of £400,000-£500,000 per year. Sensitivity analyses were conducted to evaluate different scenarios. If ≥5% of the eligible neuropathic pain population received a SCS device, cost-savings would be >£2.5 million/year. In contrast, at the lowest assumed cost of a screening trial (£1,950/patient), a screening trial prior to SCS implantation would be cost-saving. The proportion of patients having an unsuccessful screening trial would have to be ≥14.4% for current practice of a screening trial to be cost-saving. The findings from this budget impact analysis support the results of a recent UK multicenter randomized controlled trial (TRIAL-STIM) of a policy for the discontinuation of compulsory SCS screening trials, namely that such a policy would result in considerable cost-savings to healthcare systems.

Can Beta-D-Glucan testing as part of the diagnostic pathway for invasive fungal infection reduce anti-fungal treatment costs?

We performed a cost comparison of the current diagnostic and treatment pathway for invasive fungal infection (IFI) versus a proposed pathway that incorporates Beta-D-Glucan (BDG) testing from the NHS perspective. A fungal pathogen was identified in 58/107 (54.2%) patients treated with systemic anti-fungals in the Critical Care Department. Mean therapy duration was 23 days (standard deviation [SD] = 22 days), and cost was £5590 (SD = £7410) per patient. Implementation of BDG tests in the diagnostic and treatment pathway of patients with suspected IFI could result in a mean saving of £1643 per patient should a result be returned within 2 days. LAY SUMMARY: Invasive fungal infection increases the risk of death in very sick people. So, treatment is started before test results are known. Beta-D-Glucan (BDG) test is faster than standard blood culture tests. We estimate that using BDG tests in how patients are diagnosed could save about £1643 per patient.

A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.

INTRODUCTION: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?' METHODS AND ANALYSIS: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years. ETHICS AND DISSEMINATION: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN85731188.

A systematic review of health state utility values for thyroid cancer.

PURPOSE: Health state utility values are commonly used to inform economic evaluations and determine the cost-effectiveness of an intervention. The aim of this systematic review is to summarise the utility values available to represent the health-related quality of life (HRQoL) of patients with thyroid cancer. METHODS: Eight electronic databases were searched from January 1999 to April 2019 for studies which included assessment of HRQoL for patients with thyroid cancer. Utility estimates derived from multiple sources (EuroQol questionnaire 5-dimension (EQ-5D), time trade-off [TTO] and standard gamble [SG] methods) were extracted. In addition, utility estimates were generated by mapping from SF-36 and EORTC QLQ-30 to the EQ-5D-3L UK value set using published mapping algorithms. RESULTS: Searches identified 33 eligible studies. Twenty-six studies reported HRQoL for patients with differentiated thyroid cancer and seven studies for patients with general thyroid cancer. We identified studies which used different methods and tools to quantify the HRQoL in patients with thyroid cancer, such as the EQ-5D-3L, SF-36, EORTC QLQ-30 and SG and TTO techniques to estimate utility values. Utility estimates range from 0.205 (patients with low-risk differentiated thyroid cancer) to utility values approximate to the average UK population (following successful thyroidectomy surgery and radioiodine treatment). Utility estimates for different health states, across thyroid cancer sub-types and interventions are presented. CONCLUSION: A catalogue of utility values is provided for use when carrying out economic modelling of thyroid cancer; by including mapped values, this approach broadens the scope of health states that can be considered within cost-effectiveness modelling.

The Unmet Need for Intrathecal Drug Delivery Pumps for the Treatment of Cancer Pain in England: An Assessment of the Hospital Episode Statistics Database.

OBJECTIVES: Intrathecal drug delivery (ITDD) devices have been shown to be a clinically effective and cost-effective option for the management of cancer pain and recommended for use in England. The aim of this study is to assess the impact of the 2015 NHS England Clinical Commissioning Policy on the uptake of ITDD pumps for the management of cancer pain or if there is an ongoing unmet need for this intervention in England. MATERIALS AND METHODS: Hospital Episode Statistics (HES) were obtained for all patients undergoing ITDD for the management of cancer pain between 2014 and January 2020. In addition, HES were utilized to estimate the number of patients with cancer potentially eligible for ITDD pump during the same period. RESULTS: The number of patients with cancer and those potentially suitable to receive an ITDD for the management of cancer pain have increased year on year since 2014. This increase has not been matched by an uptake in the provision of ITDD. Conservative estimates suggest that at least 8000 people with cancer pain would be eligible for ITDD; 458 patients received an intervention for pain management between April 2018 and March 2019 and only 30 ITDD pumps were implanted in that same period. CONCLUSIONS: We observed a substantial gap between the need and provision of ITDD for patients with refractory cancer pain in England despite the recommendation for the use of ITDD for this patient population. In addition, we present suggestions for improvement of access to and provision of ITDD in England.

Does a screening trial for spinal cord stimulation in patients with chronic pain of neuropathic origin have clinical utility and cost-effectiveness (TRIAL-STIM)? A randomised controlled trial.

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at 3 centres in the United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG). Treatment was open label, but outcome assessors were masked. The primary outcome measure was numerical rating scale (NRS) pain at 6-month follow-up. Between June 2017 and September 2018, 105 participants were enrolled and randomised (TG = 54, NTG = 51). Mean numerical rating scale pain decreased from 7.47 at baseline (before SCS implantation) to 4.28 at 6 months in TG and from 7.54 to 4.49 in NTG (mean group difference: 0.2, 95% confidence interval [CI]: -1.2 to 0.9, P = 0.89). We found no difference between TG and NTG in the proportion of pain responders or other secondary outcomes. Spinal cord stimulation screening trial had a sensitivity of 100% (95% CI: 78-100) and specificity of 8% (95% CI: 1-25). The mean incremental cost-effectiveness ratio of TG vs NTG was £78,895 per additional quality-adjusted life-year gained. In conclusion, although the SCS screening trial may have some diagnostic utility, there was no evidence that an SCS screening TG provides superior patient outcomes or is cost-effective compared to a no trial screening approach.

Assessing the turbulent kinetic energy budget in an energetic tidal flow from measurements of coupled ADCPs.

Two coupled four-beam acoustic Doppler current profilers were used to provide simultaneous and independent measurements of the turbulent kinetic energy (TKE) dissipation rate ε and the TKE production rate [Formula: see text] over a 36 h long period at a highly energetic tidal energy site in the Alderney Race. The eight-beam arrangement enabled the evaluation of the six components of the Reynolds stress tensor which allows for an improved estimation of the TKE production rate. Depth-time series of ε, [Formula: see text] and the Reynolds stresses are provided. The comparison between ε and [Formula: see text] was performed by calculating individual ratios of ε corresponding to [Formula: see text]. The depth-averaged ratio [Formula: see text] averaged over whole flood and ebb tide were found to be 2.2 and 2.8 respectively, indicating that TKE dissipation exceeds TKE production. It is shown that the term of diffusive transport of TKE is significant. As a result, non-local transport is important to the TKE budget and the common assumption of a local balance, i.e. a balance between production and dissipation, is not valid at the measurement site. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.

A Systematic Review of Economic Evaluations Reporting the Cost-Effectiveness of Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) is a recognized treatment for chronic pain. This systematic review aims to assess economic evaluations of SCS for the management of all chronic pain conditions, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research. METHODS: Economic evaluations were identified by searching general medical and economic databases complemented with screening of reference lists of identified studies. No restrictions on language or treatment comparators were applied. Relevant data were extracted. The quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Fourteen studies met the inclusion criteria and were judged to be of acceptable quality. Economic evaluations assessed SCS for the management of refractory angina pectoris, failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), diabetic peripheral neuropathy (DPN), and peripheral arterial disease. Model-based studies typically applied a 2-stage model, i.e. decision tree followed by Markov model. Time horizon varied from 1 year to lifetime. Cost-effectiveness ranged widely from dominant (SCS cost-saving and more effective) to incremental cost-effectiveness ratio of >£100,000 per quality-adjusted life-year. Cost-effectiveness appeared to depend on the time horizon, choice of comparator, and indication. Ten of the studies indicated SCS as cost-saving or cost-effective compared with the alternative strategies. CONCLUSION: The results consistently suggest that SCS is cost-effective when considering a long-term time horizon, particularly for the management of FBSS and CRPS. Further studies are needed to assess the cost-effectiveness of SCS for ischemic pain and DPN.

Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation.

BACKGROUND: Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). OBJECTIVES: We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. DATA SOURCES: EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. REVIEW METHODS: We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. RESULTS: Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. LIMITATIONS: We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. CONCLUSIONS: Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017055516. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

WHAT WAS THE PROBLEM?: Differentiated thyroid cancer is a common type of thyroid cancer. For many patients, radioactive iodine is an effective treatment; however, for some patients, the treatment stops working or becomes unsafe. Two new drugs, lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany), may be new treatment options. WHAT DID WE DO?: We reviewed the clinical evidence of lenvatinib and sorafenib. We also estimated the costs and benefits of treatment. WHAT DID WE FIND?: Compared with no treatment, treatment with lenvatinib or sorafenib may increase the time that people live with thyroid cancer before their disease gets worse; however, both drugs are expensive and may have unpleasant side effects. WHAT DOES THIS MEAN?: At their published (undiscounted) prices, lenvatinib or sorafenib may not be considered to provide good value for money to the NHS.

Multicentre, double-blind, randomised, sham-controlled trial of 10 khz high-frequency spinal cord stimulation for chronic neuropathic low back pain (MODULATE-LBP): a trial protocol.

INTRODUCTION: Chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population. METHODS: This is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient. DISCUSSION: The outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018. DISCLAIMER: The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication. ROLES AND RESPONSIBILITIES: AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.

Lead-I ECG for detecting atrial fibrillation in patients with an irregular pulse using single time point testing: a systematic review and economic evaluation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with an increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can be used to detect AF at a single time point in people who present with relevant signs or symptoms. OBJECTIVE: To assess the diagnostic test accuracy, clinical impact and cost-effectiveness of using single time point lead-I ECG devices for the detection of AF in people presenting to primary care with relevant signs or symptoms, and who have an irregular pulse compared with using manual pulse palpation (MPP) followed by a 12-lead ECG in primary or secondary care. DATA SOURCES: MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PubMed, Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database. METHODS: The systematic review methods followed published guidance. Two reviewers screened the search results (database inception to April 2018), extracted data and assessed the quality of the included studies. Summary estimates of diagnostic accuracy were calculated using bivariate models. An economic model consisting of a decision tree and two cohort Markov models was developed to evaluate the cost-effectiveness of lead-I ECG devices. RESULTS: No studies were identified that evaluated the use of lead-I ECG devices for patients with signs or symptoms of AF. Therefore, the diagnostic accuracy and clinical impact results presented are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% [95% confidence interval (CI) 86.2% to 97.4%] and summary specificity was 96.5% (95% CI 90.4% to 98.8%). One study reported limited clinical outcome data. Acceptability of lead-I ECG devices was reported in four studies, with generally positive views. The de novo economic model yielded incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generated ICERs per QALY gained below the £20,000-30,000 threshold. Kardia Mobile (AliveCor Ltd, Mountain View, CA, USA) is the most cost-effective option in a full incremental analysis. LIMITATIONS: No published data evaluating the diagnostic accuracy, clinical impact or cost-effectiveness of lead-I ECG devices for the population of interest are available. CONCLUSIONS: Single time point lead-I ECG devices for the detection of AF in people with signs or symptoms of AF and an irregular pulse appear to be a cost-effective use of NHS resources compared with MPP followed by a 12-lead ECG in primary or secondary care, given the assumptions used in the base-case model. FUTURE WORK: Studies assessing how the use of lead-I ECG devices in this population affects the number of people diagnosed with AF when compared with current practice would be useful. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018090375. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Atrial fibrillation (AF) is the most common type of abnormal heart rhythm. People with AF are more likely to have a serious stroke or die than people without the condition. Many people go to their general practitioner (GP) with the signs or symptoms commonly linked to AF, such as feeling dizzy, being short of breath, feeling tired and having heart palpitations. GPs check for AF by taking the patient's pulse by hand. If the GP thinks that the patient might have AF, a 12-lead electrocardiogram (ECG) test is arranged. Lead-I (i.e. one lead) ECGs are handheld electronic devices that could detect AF more accurately than a manual pulse check. If GPs were to routinely use lead-I ECG devices, people with suspected AF could receive treatment while waiting for the AF diagnosis to be confirmed by a 12-lead ECG. This study aimed to assess whether or not the use of lead-I ECGs in GP surgeries could benefit these patients and offer good value for money to the NHS. All studies that examined how well lead-I ECGs identified people with AF were reviewed, and the economic value of using these devices was assessed. No evidence was found that examined the use of lead-I ECGs for people with signs or symptoms of AF. As an alternative, evidence for the use of lead-I ECGs for people with no symptoms of AF was searched for and these data were used to assess value for money. The study found that using a manual pulse check followed by a lead-I ECG offers value for money when compared with a manual pulse check followed by a 12-lead ECG. This is mostly because patients with AF can begin treatment earlier when a GP has access to a lead-I ECG device.

Lead-I ECG for detecting atrial fibrillation in patients attending primary care with an irregular pulse using single-time point testing: A systematic review and economic evaluation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can detect AF at a single-time point. PURPOSE: To assess the diagnostic test accuracy, clinical impact and cost effectiveness of single-time point lead-I ECG devices compared with manual pulse palpation (MPP) followed by a 12-lead ECG for the detection of AF in symptomatic primary care patients with an irregular pulse. METHODS: Electronic databases (MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process, EMBASE, PubMed and Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database) were searched to March 2018. Two reviewers screened the search results, extracted data and assessed study quality. Summary estimates of diagnostic accuracy were calculated using bivariate models. Cost-effectiveness was evaluated using an economic model consisting of a decision tree and two cohort Markov models. RESULTS: Diagnostic accuracy The diagnostic accuracy (13 publications reporting on nine studies) and clinical impact (24 publications reporting on 19 studies) results are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% (95% confidence interval [CI]: 86.2% to 97.4%) and summary specificity was 96.5% (95% CI: 90.4% to 98.8%). Cost effectiveness The de novo economic model yielded incremental cost effectiveness ratios (ICERs) per quality adjusted life year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generate ICERs per QALY gained below the £20,000-£30,000 threshold. Kardia Mobile is the most cost effective option in a full incremental analysis. Lead-I ECG tests may identify more AF cases than the standard diagnostic pathway. This comes at a higher cost but with greater patient benefit in terms of mortality and quality of life. LIMITATIONS: No published data evaluating the diagnostic accuracy, clinical impact or cost effectiveness of lead-I ECG devices for the target population are available. CONCLUSIONS: The use of single-time point lead-I ECG devices in primary care for the detection of AF in people with signs or symptoms of AF and an irregular pulse appears to be a cost effective use of NHS resources compared with MPP followed by a 12-lead ECG, given the assumptions used in the base case model. REGISTRATION: The protocol for this review is registered on PROSPERO as CRD42018090375.

Correction to: Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial.

Following publication of the original article [1], we have been notified that the final specification of randomisation implemented in the study is slightly different to that stated in the protocol and needs to be corrected as follows.