Long-term Cost-effectiveness of Case Finding and Mass Screening for Celiac Disease in Children.

BACKGROUND & AIMS: Celiac disease (CD) is a common yet underdiagnosed autoimmune disease with substantial long-term consequences. High-accuracy point-of-care tests for CD antibodies conducted at youth primary health care centers may enable earlier identification of CD, but evidence about the cost-effectiveness of such strategies is lacking. We estimated the long-term cost-effectiveness of active case finding and mass screening compared with clinical detection in the Netherlands. METHODS: A decision tree and Markov model were used to simulate a cohort of 3-year-old children with CD according to each strategy, taking into account their impact on long-term costs (from a societal perspective) and quality-adjusted life-years (QALYs). Model parameters incorporated data from the GLUTENSCREEN project, the Dutch Celiac Society, the Dutch Pediatric Surveillance Unit, and published sources. The primary outcome was the incremental cost-effectiveness ratio (ICER) between strategies. RESULTS: Mass-screening produced 7.46 more QALYs and was €28,635 more costly compared with current care (ICER: €3841 per QALY), and case finding produced 4.33 more QALYs and was €15,585 more costly compared with current care (ICER: €3603 per QALY). At a willingness to pay of €20,000 per QALY, both strategies were highly cost-effective compared with current care. Scenario analyses indicated that mass screening is likely the optimal strategy, unless no benefit in detecting asymptomatic cases is assumed. CONCLUSIONS: An earlier identification of CD through screening or case finding in children using a point-of-care tests leads to improved health outcomes and is cost-effective in the long-term compared with current care. If the feasibility and acceptability of the proposed strategies are successful, implementation in Dutch regular care is needed.

Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

OBJECTIVES: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. METHODS: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. RESULTS: Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. CONCLUSIONS: For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Systematic Review of Cost-Effectiveness Models in Prostate Cancer: Exploring New Developments in Testing and Diagnosis.

OBJECTIVES: Recent innovations in prostate cancer diagnosis include new biomarkers and more accurate biopsy methods. This study assesses the evidence base on cost-effectiveness of these developments (eg, Prostate Health Index and magnetic resonance imaging [MRI]-guided biopsy) and identifies areas of improvement for future cost-effectiveness models. METHODS: A systematic review using the National Health Service Economic Evaluation Database, MEDLINE, Embase, Health Technology Assessment databases, National Institute for Health and Care Excellence guidelines, and United Kingdom National Screening Committee guidance was performed, between 2009 and 2021. Relevant data were extracted on study type, model inputs, modeling methods and cost-effectiveness conclusions, and results narratively synthesized. RESULTS: A total of 22 model-based economic evaluations were included. A total of 11 compared the cost-effectiveness of new biomarkers to prostate-specific antigen testing alone and all found biomarkers to be cost saving. A total of 8 compared MRI-guided biopsy methods to transrectal ultrasound-guided methods and found MRI-guided methods to be most cost-effective. Newer detection methods showed a reduction in unnecessary biopsies and overtreatment. The most cost-effective follow-up strategy in men with a negative initial biopsy was uncertain. Many studies did not model for stage or grade of cancer, cancer progression, or the entire testing and treatment pathway. Few fully accounted for uncertainty. CONCLUSIONS: This review brings together the cost-effectiveness literature for novel diagnostic methods in prostate cancer, showing that most studies have found new methods to be more cost-effective than standard of care. Several limitations of the models were identified, however, limiting the reliability of the results. Areas for further development include accurately modeling the impact of early diagnostic tests on long-term outcomes of prostate cancer and fully accounting for uncertainty.

Efficacy and safety of first-line therapies in EGFR-mutated advanced non-small-cell lung cancer: a network meta-analysis.

Aim: To evaluate the comparative efficacy and safety of identified first-line therapies for patients with EGFR mutation-positive (EGFRm+) advanced non-small-cell lung cancer (NSCLC), with a focus on ramucirumab + erlotinib. Methods: In the absence of head-to-head studies, a Bayesian network meta-analysis was conducted using randomized clinical trial data to evaluate first-line systemic therapies with erlotinib/gefitinib as the reference treatment. Results: For progression-free survival, ramucirumab + erlotinib was comparable to osimertinib and dacomitinib in the primary analysis. Conclusion: The analysis showed ramucirumab + erlotinib efficacy to be comparable to best-in-class treatment options for previously untreated patients with EGFRm+ advanced NSCLC. Registration information: PROSPERO ID: CRD42020136247.

A clinical tool to identify older women with back pain at high risk of osteoporotic vertebral fractures (Vfrac): a population-based cohort study with exploratory economic evaluation.

BACKGROUND: osteoporotic vertebral fractures (OVFs) identify people at high risk of future fractures, but despite this, less than a third come to clinical attention. The objective of this study was to develop a clinical tool to aid health care professionals decide which older women with back pain should have a spinal radiograph. METHODS: a population-based cohort of 1,635 women aged 65+ years with self-reported back pain in the previous 4 months were recruited from primary care. Exposure data were collected through self-completion questionnaires and physical examination, including descriptions of back pain and traditional risk factors for osteoporosis. Outcome was the presence/absence of OVFs on spinal radiographs. Logistic regression models identified independent predictors of OVFs, with the area under the (receiver operating) curve calculated for the final model, and a cut-point was identified. RESULTS: mean age was 73.9 years and 209 (12.8%) had OVFs. The final Vfrac model comprised 15 predictors of OVF, with an AUC of 0.802 (95% CI: 0.764-0.840). Sensitivity was 72.4% and specificity was 72.9%. Vfrac identified 93% of those with more than one OVF and two-thirds of those with one OVF. Performance was enhanced by inclusion of self-reported back pain descriptors, removal of which reduced AUC to 0.742 (95% CI: 0.696-0.788) and sensitivity to 66.5%. Health economic modelling to support a future trial was favourable. CONCLUSIONS: the Vfrac clinical tool appears to be valid and is improved by the addition of self-reported back pain symptoms. The tool now requires testing to establish real-world clinical and cost-effectiveness.

Exploratory comparison of Healthcare costs and benefits of the UK's Covid-19 response with four European countries.

BACKGROUND: In responding to Covid-19, governments have tried to balance protecting health while minimizing gross domestic product (GDP) losses. We compare health-related net benefit (HRNB) and GDP losses associated with government responses of the UK, Ireland, Germany, Spain and Sweden from UK healthcare payer perspective. METHODS: We compared observed cases, hospitalizations and deaths under 'mitigation' to modelled events under 'no mitigation' to 20 July 2020. We thus calculated healthcare costs, quality adjusted life years (QALYs), and HRNB at £20,000/QALY saved by each country. On per population (i.e. per capita) basis, we compared HRNB with forecast reductions in 2020 GDP growth (overall or compared with Sweden as minimal mitigation country) and qualitatively and quantitatively described government responses. RESULTS: The UK saved 3.17 (0.32-3.65) million QALYs, £33 (8-38) billion healthcare costs and £1416 (220-1637) HRNB per capita at £20,000/QALY. Per capita, this is comparable to £1455 GDP loss using Sweden as comparator and offsets 46.1 (7.1-53.2)% of total £3075 GDP loss. Germany, Spain, and Sweden had greater HRNB per capita. These also offset a greater percentage of total GDP losses per capita. Ireland fared worst on both measures. Countries with more mask wearing, testing, and population susceptibility had better outcomes. Highest stringency responses did not appear to have best outcomes. CONCLUSIONS: Our exploratory analysis indicates the benefit of government Covid-19 responses may outweigh their economic costs. The extent that HRNB offset economic losses appears to relate to population characteristics, testing levels, and mask wearing, rather than response stringency.

Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: Clinical outcome and cost-effectiveness analyses.

BACKGROUND: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT). METHODS AND FINDINGS: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change. CONCLUSIONS: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

Computing the Expected Value of Sample Information Efficiently: Practical Guidance and Recommendations for Four Model-Based Methods.

Value of information (VOI) analyses can help policy makers make informed decisions about whether to conduct and how to design future studies. Historically a computationally expensive method to compute the expected value of sample information (EVSI) restricted the use of VOI to simple decision models and study designs. Recently, 4 EVSI approximation methods have made such analyses more feasible and accessible. Members of the Collaborative Network for Value of Information (ConVOI) compared the inputs, the analyst's expertise and skills, and the software required for the 4 recently developed EVSI approximation methods. Our report provides practical guidance and recommendations to help inform the choice between the 4 efficient EVSI estimation methods. More specifically, this report provides: (1) a step-by-step guide to the methods' use, (2) the expertise and skills required to implement the methods, and (3) method recommendations based on the features of decision-analytic problems.

Incorporating single-arm evidence into a network meta-analysis using aggregate level matching: Assessing the impact.

Increasingly, single-armed evidence is included in health technology assessment submissions when companies are seeking reimbursement for new drugs. While it is recognized that randomized controlled trials provide a higher standard of evidence, these are not available for many new agents that have been granted licenses in recent years. Therefore, it is important to examine whether alternative strategies for assessing this evidence may be used. In this work, we examine approaches to incorporating single-armed evidence formally in the evaluation process. We consider matching aggregate level covariates to comparator arms or trials and including this evidence in a network meta-analysis. We consider two methods of matching: (i) we include the chosen matched arm in the data set itself as a comparator for the single-arm trial; (ii) we use the baseline odds of an event in a chosen matched trial to use as a plug-in estimator for the single-arm trial. We illustrate that the synthesis of evidence resulting from such a setup is sensitive to the between-study variability, formulation of the prior for the between-design effect, weight given to the single-arm evidence, and extent of the bias in single-armed evidence. We provide a flowchart for the process involved in such a synthesis and highlight additional sensitivity analyses that should be carried out. This work was motivated by a hepatitis C data set, where many agents have only been examined in single-arm studies. We present the results of our methods applied to this data set.

R You Still Using Excel? The Advantages of Modern Software Tools for Health Technology Assessment.

Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of healthcare resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research.

Choice of Prosthetic Implant Combinations in Total Hip Replacement: Cost-Effectiveness Analysis Using UK and Swedish Hip Joint Registries Data.

BACKGROUND: Prosthetic implants used in total hip replacements (THR) have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, and metal-on-metal), head sizes (small [<36 mm in diameter] and large [≥36 mm in diameter]), and fixation techniques (cemented, uncemented, hybrid, and reverse hybrid). These can influence prosthesis survival, patients' quality of life, and healthcare costs. OBJECTIVES: To compare the lifetime cost-effectiveness of implants for patients of different age and sex profiles. METHODS: We developed a Markov model to compare the cost-effectiveness of various implants against small-head cemented metal-on-polyethylene implants. The probability that patients required 1 or more revision surgeries was estimated from analyses of more than 1 million patients in the UK and Swedish hip joint registries, for men and women younger than 55, 55 to 64, 65 to 74, 75 to 84, and 85 years and older. Implant and healthcare costs were estimated from local procurement prices, national tariffs, and the literature. Quality-adjusted life-years were calculated using published utility estimates for patients undergoing THR in the United Kingdom. RESULTS: Small-head cemented metal-on-polyethylene implants were the most cost-effective for men and women older than 65 years. These findings were robust to sensitivity analyses. Small-head cemented ceramic-on-polyethylene implants were most cost-effective in men and women younger than 65 years, but these results were more uncertain. CONCLUSIONS: The older the patient group, the more likely that the cheapest implants, small-head cemented metal-on-polyethylene implants, were cost-effective. We found no evidence that uncemented, hybrid, or reverse hybrid implants were the most cost-effective option for any patient group. Our findings can influence clinical practice and procurement decisions for healthcare payers worldwide.

State selection in Markov models for panel data with application to psoriatic arthritis.

Markov multistate models in continuous-time are commonly used to understand the progression over time of disease or the effect of treatments and covariates on patient outcomes. The states in multistate models are related to categorisations of the disease status, but there is often uncertainty about the number of categories to use and how to define them. Many categorisations, and therefore multistate models with different states, may be possible. Different multistate models can show differences in the effects of covariates or in the time to events, such as death, hospitalisation, or disease progression. Furthermore, different categorisations contain different quantities of information, so that the corresponding likelihoods are on different scales, and standard, likelihood-based model comparison is not applicable. We adapt a recently developed modification of Akaike's criterion, and a cross-validatory criterion, to compare the predictive ability of multistate models on the information which they share. All the models we consider are fitted to data consisting of observations of the process at arbitrary times, often called 'panel' data. We develop an implementation of these criteria through Hidden Markov models and apply them to the comparison of multistate models for the Health Assessment Questionnaire score in psoriatic arthritis. This procedure is straightforward to implement in the R package 'msm'.

Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension.

BACKGROUND: Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening direct comparisons of two or more treatments for the management of disease by combining evidence from multiple studies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted to randomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to include single-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate the method with an indirect comparison of treatments for pulmonary arterial hypertension (PAH). METHODS: Our method uses a random effects model for placebo improvements to include single-arm observational studies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjusted continuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-arm RCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAH combining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs and single-arm observational studies, both identified by a systematic review. RESULTS: Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-on therapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCT evidence available. However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice. CONCLUSIONS: Our method for the inclusion of single-arm observational studies allows the performance of indirect comparisons that had previously not been possible due to incomplete networks composed solely of available RCTs. We also built on many recent innovations to enable researchers to use both aggregate data and IPD. This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

Indirect comparisons of ranibizumab and dexamethasone in macular oedema secondary to retinal vein occlusion.

BACKGROUND: Two treatments, ranibizumab and dexamethasone implant, for visual impairment due to macular oedema (ME) secondary to retinal vein occlusion (RVO) have recently been studied in clinical trials. There have been no head to head comparisons of the two treatments, and improvement measured as gain in Best Corrected Visual Acuity (BCVA) was reported using different outcomes thresholds between trials. To overcome these limitations, and inform an economic model, we developed a combination of a multinomial model and an indirect Bayesian comparison model for multinomial outcomes. METHODS: Outcomes of change from baseline in BCVA for dexamethasone compatible with those available for ranibizumab, reported by 4 randomised controlled trials, were estimated by fitting a multinomial distribution model to the probability of a patient achieving outcomes in a range of changes from baseline in BCVA (numbers of letters) at month 1. A Bayesian indirect comparison multinomial model was then developed to compare treatments in the Branch RVO (BRVO) and Central RVO (CRVO) populations. RESULTS: The multinomial model had excellent fit to the observed results. With the Bayesian indirect comparison, the probabilities of achieving ≥20 letters, with 95% credible intervals, at month 1 in patients with BRVO were 0.191 (0.130, 0.261) with ranibizumab and 0.093 (0.027, 0.213) with dexamethasone. In patients with CRVO, probabilities were 0.133 (0.082, 0.195) (ranibizumab) and 0.063 (0.016, 0.153) (dexamethasone). Probabilities of a gain in ≥10 letters in BRVO patients were 0.500 (0.365, 0.650) v 0.459 (0.248, 0.724) and in CRVO patients 0.459 (0.332, 0.602) v 0.498 (0.263, 0.791) for ranibizumab and dexamethasone treatments respectively. The comparisons also favoured ranibizumab at month 6 although changes to therapies after month 3 may have introduced bias. CONCLUSION: The newly developed combination of multinomial and indirect Bayesian comparison models indicated a trend for ranibizumab association with a greater percentage of ME patients achieving visual gains than dexamethasone at months 1 and 6 in a common clinical context, although results were not classically significant. The method was a useful tool for comparisons of probability distributions between clinical trials that reported events on different categorical scales and estimates can be used to inform economic models.

Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.

INTRODUCTION: A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. METHODS: Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). RESULTS: At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. CONCLUSIONS: Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

The cost-effectiveness of a bimekizumab versus IL-17A inhibitors treatment-pathway in patients with active axial spondyloarthritis in Scotland.

OBJECTIVE: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective. METHODS: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost. LIMITATIONS: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce. CONCLUSIONS: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

Clinical effectiveness of point of care tests for diagnosing urinary tract infection: a systematic review.

BACKGROUND: Point of care tests (POCTs) have the potential to improve the urinary tract infection (UTI) diagnostic pathway, as they can provide a diagnosis quickly in near-patient settings, and some also identify causative pathogens/antimicrobial sensitivity. OBJECTIVES: To assess the clinical impact, accuracy, and technical characteristics of POCT for diagnosing UTI. METHODS OF DATA SYNTHESIS: Narrative summary and bivariate random effects meta-analyses to estimate summary sensitivity and specificity. DATA SOURCES: Five electronic databases, two clinical trial registries, study reports and review reference lists, and websites. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials/non-randomized studies and diagnostic test accuracy studies published since 2000. PARTICIPANTS: People with suspected UTI. TESTS: Rapid tests (results <40 minutes): Astrego PA-100 system, Lodestar DX, Uriscreen, UTRiPLEX. Culture tests (results <24 hours): Flexicult Human, ID Flexicult, Diaslide, Dipstreak, Chromostreak, Uricult, Uricult Trio, Uricult Plus. REFERENCE STANDARD: Any. ASSESSMENT OF RISK OF BIAS: Risk of Bias-2, Quality Assessment of Diagnostic Accuracy Studies-2, Quality Assessment of Diagnostic Accuracy Studies-C. RESULTS: Two randomized controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). No difference was reported in antibiotic use concordant with culture results (OR 0.84 95% CI 0.58-1.20) or appropriate antibiotic prescribing (OR 1.44 95% CI 1.03-1.99). Initial antibiotic prescribing was lower with Flexicult than standard care (OR 0.56 95% CI 0.35-0.88). No difference for other measures of antibiotic use, symptom duration, patient enablement, or resource use. Fifteen studies reported accuracy data. Limited data were available, with most POCT evaluated in single studies or not evaluated at all. Uriscreen (four studies), Uricult Trio (three studies), Flexicult Human (four studies), and ID Flexicult (two studies) had modest sensitivity and specificity. POCTs were easier to use and interpret than standard culture. CONCLUSIONS: There is currently insufficient evidence to support the use of POCTs in UTI diagnosis. Due to the rapid development of POCT, this review should be updated regularly.

Cost-Effectiveness of Routine Monitoring of Long-Term Conditions in Primary Care: Informing Decision Modelling with a Systematic Review in Hypertension, Type 2 Diabetes and Chronic Kidney Disease.

BACKGROUND: Long-term conditions (LTCs) are major public health problems with a considerable health-related and economic burden. Modelling is key in assessing costs and benefits of different disease management strategies, including routine monitoring, in the conditions of hypertension, type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in primary care. OBJECTIVE: This review aimed to identify published model-based cost-effectiveness studies of routine laboratory testing strategies in these LTCs to inform a model evaluating the cost effectiveness of testing strategies in the UK. METHODS: We searched the Medline and Embase databases from inception to July 2023; the National Institute for Health and Care Institute (NICE) website was also searched. Studies were included if they were model-based economic evaluations, evaluated testing strategies, assessed regular testing, and considered adults aged >16 years. Studies identified were summarised by testing strategies, model type, structure, inputs, assessment of uncertainty, and conclusions drawn. RESULTS: Five studies were included in the review, i.e. Markov (n = 3) and microsimulation (n = 2) models. Models were applied within T2DM (n = 2), hypertension (n = 1), T2DM/hypertension (n = 1) and CKD (n = 1). Comorbidity between all three LTCs was modelled to varying extents. All studies used a lifetime horizon, except for a 10-year horizon T2DM model, and all used quality-adjusted life-years as the effectiveness outcome, except a TD2M model that used glycaemic control. No studies explicitly provided a rationale for their selected modelling approach. UK models were available for diabetes and CKD, but these compared only a limited set of routine monitoring tests and frequencies. CONCLUSIONS: There were few studies comparing routine testing strategies in the UK, indicating a need to develop a novel model in all three LTCs. Justification for the modelling technique of the identified studies was lacking. Markov and microsimulation models, with and without comorbidities, were used; however, the findings of this review can provide data sources and inform modelling approaches for evaluating the cost effectiveness of testing strategies in all three LTCs.

Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer.

Introduction: In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was conducted to compare the relative efficacy of these treatments. Materials & methods: A systematic literature review of randomized controlled trials evaluating first-line-to-progression and second-line treatments for advanced NsqNSCLC informed Bayesian NMAs for overall survival (OS) and progression-free survival (PFS) end points. Results: Among first-line-to-progression treatments, pembrolizumab + pemetrexed + platinum showed the greatest OS benefit versus other regimens and a PFS benefit versus all but three regimens. Among second-line treatments, an OS benefit was seen for atezolizumab, nivolumab and pembrolizumab versus docetaxel. Conclusion: Pembrolizumab + pemetrexed + platinum showed the maximum OS benefit in the first-line setting. In the second-line setting, anti-PD-1/anti-PD-L1 monotherapies were better than docetaxel.