Trial-based Cost-effectiveness Analysis Research Articles

An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (eADVICE) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent (ECA). A trial-based cost-effectiveness analysis was performed from the perspective of the healthcare funder as a sub-study of eADVICE, a multicenter waitlist-controlled randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars ($). The use of eADVICE was found to be cost-saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (RD 0.13; 95%CI 0.02-0.23, P = .03) and mean healthcare costs reduced by $188 (95%CI $61-$315) per participant. An individualized, evidence-informed web-based program delivered by an ECA is likely cost-saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial and may be transferable to outpatient clinic settings for other chronic health conditions.

A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children

BackgroundAntibiotic prescription for respiratory tract infections (RTIs) in children attending primary care centres is almost double that predicted according to bacterial prevalence. Delayed antibiotic prescription (DAP) is designed to deploy a more rational use of antibiotics. While studies have evaluated DAP efficacy and safety for children with RTIs, little research has been conducted on the economic implications.MethodsOur trial compared cost-effectiveness for DAP, immediate antibiotic prescription (IAP), and no antibiotic prescription (NAP) for children aged 2–14 years with acute uncomplicated RTIs attended to in 39 primary care centres in Spain. The main outcome was the incremental cost-effectiveness ratio (ICER), measured in euros per gained quality-adjusted life days (QALDs). Net monetary benefit (NMB) was also calculated as a tool for decision making. The analysis was performed from a societal perspective for a time horizon of 30 days, and included healthcare direct costs, non-healthcare direct and indirect costs, and the antimicrobial resistance (AMR) cost.ResultsDAP was the most cost-effective strategy, even when the cost of AMR was included. QALD values for the three strategies were very similar. IAP compared to DAP was more costly (109.68 vs 100.90 euros) and similarly effective (27.88 vs 27.94 QALDs). DAP compared to NAP was more costly (100.90 vs 97.48 euros) and more effective (27.94 vs. 27.82 QALDs). The ICER for DAP compared to NAP was 28.84 euros per QALD. The deterministic sensitivity analysis indicated that non-healthcare indirect costs had the greatest impact on the ICER. The cost-effectiveness acceptability curve showed that DAP was the preferred option in approximately 81.75% of Monte Carlo iterations, assuming a willingness-to-pay value of 82.2 euros per gained QALD.ConclusionsWhen clinicians are in doubt about whether an antibiotic is needed for children with RTIs attending PC centres, those treated with the DAP strategy will have slightly better efficiency outcomes than those treated with IAP because its costs are lower than those of IAP. DAP is also the most cost-effective strategy over a time horizon of 30 days if AMR is considered, despite higher short-term costs than NAP. However, if in the long term the costs of AMR are larger than estimated, NAP could also be an alternative strategy.Trial registrationThis trial has been registered at www.clinicaltrials.gov (identifier NCT01800747; Date: 28/02/2013 (retrospectively registered).

Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter.

You have accessJournal of UrologyLetters to the Editor1 Apr 2023Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter. Ashish Ranjan, Ankit Misra, Sanjoy Kumar Sureka, and Uday Pratap Singh Ashish RanjanAshish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Ankit MisraAnkit Misra * E-mail Address: [email protected] Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Sanjoy Kumar SurekaSanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , and Uday Pratap SinghUday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003363AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail J Urol. 2023;209(1):131-139. To the Editor: We read with great interest the study investigating the novel role of intravesical mitomycin-C (MMC) in nonmuscle-invasive bladder cancer (NMIBC) in a neoadjuvant setting.1 Single, immediate, post-transurethral resection of bladder tumor (TURBT) instillation of MMC is the standard protocol in NMIBC.2 It primarily reduces the recurrence risk by eliminating viable residual tumors and preventing reseeding of the free-floating cancer cells.3 However, fear of extravasation and its associated serious complications has led to its low practical compliance worldwide.4 This study has demonstrated the use of neoadjuvant intravesical MMC for NMIBC with promising therapeutic efficacy, better tolerability, and low significant adverse effects. Although the dose and schedule of neoadjuvant MCC followed in the study were convenient for the patient, we would like to know the scientific basis for using 2 doses at a specific interval. The writers mention a preliminary study for deciding on 2 doses of neoadjuvant MMC, but no reference has been given. Do the authors feel that the control group should have received a single immediate post-TURBT MMC per the standard? Were any morphological or radiological criteria considered before administering the neoadjuvant therapy? The rationale of giving MMC post-TURBT is only to give it to patients with superficial disease on resection. Would it not be an overtreatment and waste of resources on those that eventually come out as muscle invasive? MMC concentration in tumor and normal tissue was measured to know about uptake, but is there any standard concentration in the postoperative instillation setting to which it was matched? Moreover, it would be interesting to know the method used to detect the concentration of MMC in the tissue. Would continuous saline irrigation used during the TURBT have diluted the effect of MMC on the tissue? Multifocal tumors were more in the control arm (24, 63%) than in the intervention arm (15, 46%). Was this difference statistically significant? This could have a bearing on better recurrence-free survival in the intervention arm and more progression in control. Lastly, we appreciate the authors' focus on an important area in NMIBC treatment. REFERENCES 1. . Clinical efficacy of neoadjuvant intravesical mitomycin-C therapy immediately before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer: preliminary results of a prospective, randomized phase II study. J Urol. 2023; 209(1):131-139. Link, Google Scholar 2. . Trial-based cost-effectiveness analysis of an immediate postoperative mitomycin C instillation in patients with non–muscle-invasive bladder cancer. Eur Urol Open Sci. 2022; 37:7-13. Crossref, Medline, Google Scholar 3. . Continuous saline bladder irrigation in reducing recurrence and progression when compared to immediate mitomycin-C instillation post-resection of bladder tumor: a short communication. Asian Pac J Cancer Prev. 2022; 23(1):171-175. Crossref, Medline, Google Scholar 4. . Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa-pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation?Eur Urol. 2016; 69(2):231-244. Crossref, Medline, Google Scholar Submitted December 19, 2022; accepted February 2, 2023; published 000. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue 4April 2023Page: 677-678 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Ankit Misra Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India * E-mail Address: [email protected] More articles by this author Sanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Uday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Expand All Submitted December 19, 2022; accepted February 2, 2023; published 000. 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Cemiplimab combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer: an updated EMPOWER-Lung 3 trial-based cost-effectiveness analysis.

Cemiplimab combined with chemotherapy has emerged as a promising treatment option for advanced non-small cell lung cancer (NSCLC). Accordingly, this study has been conducted to evaluate the cost-effectiveness of this combination therapy in comparison to chemotherapy alone from the perspective of the United States healthcare system. The present study is based on a partitioned survival model developed from clinical data obtained during the 2-year follow-up of the phase III EMPOWER-Lung 3 part 2 trial. The purpose of this investigation is to estimate the 10-year life expectancy and total healthcare costs of patients with advanced NSCLC by leveraging primary outcomes that evaluated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).To establish the willingness-to-pay (WTP) threshold for the analysis, a value of $150,000/QALY was adopted. Sensitivity analysis was performed to determine the impact of varying levels of uncertainty on the results of this study. When compared to chemotherapy alone, the addition of cemiplimab to chemotherapy has been demonstrated to result in an incremental gain of 1.593 QALY at an additional cost of $109351.298. This equates to an incremental cost-effectiveness ratio (ICER) of $68644.883/QALY. One-way sensitivity analyses were conducted on the model, which acknowledged the influence of several parameters, such as subsequent costs, the utility of progressive disease, the cost of best supportive care, the cost of cemiplimab per mg, and the utility of progression-free survival on the outcomes. Nonetheless, none of these parameters yielded an ICER lower than the WTP threshold. From the perspective of the United States healthcare system, the utilization of cemiplimab in combination with chemotherapy as a first-line treatment option for NSCLC appears to be a cost-effective approach as compared to using chemotherapy as a standalone therapy.

Osimertinib versus platinum-pemetrexed in patients with previously treated EGFR T790M advanced non-small cell lung cancer: An updated AURA3 trial-based cost-effectiveness analysis.

A recently overall survival (OS) analysis from the AURA3 trial indicated that osimertinib improves median OS versus platinum-pemetrexed for patients with previously treated epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC). Here, we assessed the cost-effectiveness of second-line osimertinib versus platinum-pemetrexed, from the perspectives of the United States payer and the Chinese health care system. A Markov model was constructed to compare the costs and health outcomes of osimertinib versus platinum-pemetrexed in second-line treatment of EGFR T790M advanced NSCLC. Life years (LYs), quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were calculated. One-way and probabilistic sensitivity analyses assessed the robustness of the model. Cost-effectiveness was examined in the intention-to-treat (ITT) population and central nervous system (CNS) metastases population. In the United States, compared with platinum-pemetrexed, osimertinib yielded additional effectiveness of 0.43 QALYs and -0.12 QALYs, with incremental costs of $67,588 and $16,465 in the ITT population and CNS metastases population, respectively. The ICERs of osimertinib over platinum-pemetrexed were $159,126/QALY and $-130,830/QALY, respectively. The probability of osimertinib being cost-effective was 37% and 5.76%, respectively, at the willingness-to-pay (WTP) threshold of $150,000/QALY. In China, osimertinib showed incremental effectiveness of 0.34 QALYs and -0.14 QALYs, with incremental costs of $1,663 and $-505, resulting in ICERs of $4,950/QALY and $3,754/QALY in the ITT population and CNS metastases population, respectively. At the WTP threshold of $37,489/QALY, there was a 100% and 26% likelihood that osimertinib was cost-effective in the ITT population and CNS metastases population. In the United States, second-line osimertinib treatment for EGFR T790M advanced NSCLC is not cost-effective compared to platinum-pemetrexed under the current WTP threshold. When the osimertinib price reduces, the economic outcome may become favorable. In China, assuming a WTP threshold of $37,489/QALY, osimertinib is the dominant treatment strategy compared with platinum-pemetrexed in the ITT population and provides cost savings for CNS metastases patients.

MSR15 A Bayesian Approach for Handling Missing Items in Trial-Based Cost-Effectiveness Analysis with Multi-Item Questionnaires

Cost-effectiveness analyses (CEAs) alongside longitudinal randomised controlled trials (RCTs) often use multi-item questionnaires to collect data at multiple follow-ups, and are generally characterised by non-negligible proportions of incomplete outcome data. As routine trial-based CEAs typically aggregate costs and effects data into cross-sectional measures, researchers are motivated to apply standard missing data methods (e.g. multiple imputation) at the most aggregated level (i.e. total costs or QALYs) rather than the disaggregated level (i.e.

Economic evaluation of prevention of cystoid macular edema after cataract surgery in diabetic patients: ESCRS PREMED study report 6.

To investigate the cost-effectiveness of prophylactic treatments against cystoid macular edema after cataract surgery in diabetic patients. 7 ophthalmology clinics in the Netherlands and Belgium. Prospective trial-based cost-effectiveness analysis using data from a European multicenter randomized clinical trial. Diabetic patients (n = 163) undergoing uneventful cataract surgery were randomized to perioperative subconjunctival triamcinolone acetonide (n = 36), perioperative intravitreal bevacizumab (n = 36), combination treatment (n = 45), or no additional treatment (control group, n = 46). The cost analysis was performed from a healthcare perspective within a 12-week postoperative time horizon. The main effectiveness outcome was quality-adjusted life years (QALYs). The main cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER; cost per QALY). The mean total healthcare costs and QALYs were as follows: triamcinolone group €1827 (U.S. dollars [$] 2295)/0.166; bevacizumab group €2050 ($2575)/0.144; combination group €2027 ($2546)/0.166; and control group €2041 ($2564)/0.156. Bevacizumab and control treatment were most costly and least effective. The ICER was €321 984 ($404 503) per QALY for the combination group compared with that of the triamcinolone group. Assuming the willingness-to-pay as €20 000 ($25 126) per QALY, the cost-effectiveness probability was 70% and 23% in the triamcinolone and combination groups, respectively. No patient who received triamcinolone developed clinically significant macular edema (CSME). A secondary cost-effectiveness analysis based on this outcome showed a clear preference for triamcinolone. In diabetic patients, subconjunctival triamcinolone was effective in preventing CSME after cataract surgery. The cost-effectiveness analysis showed that triamcinolone is also cost-effective.

Immune checkpoint inhibition in first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A CAPTAIN-1st and JUPITER-02 trial-based cost-effectiveness analysis

ObjectivesThis study was aimed to evaluate the cost-effectiveness of the recently approved first-line treatments, toripalimab or camrelizumab combined with gemcitabine plus cisplatin22GP, gemcitabine plus cisplatin. (GP) and GP alone for patients with recurrent or metastatic nasopharyngeal carcinoma33RM-NPC, recurrent or metastatic nasopharyngeal carcinoma. (RM-NPC) from the Chinese payers’ perspective. Materials and MethodsWe established a Markov model to estimate the cost and effectiveness of currently first-line therapies for RM-NPC. Survival data were derived from the CAPTAIN-1st and JUPITER-02 trials. Direct medical costs and utilities were collected from the published literature and standard fee database. Main outcomes were total costs, quality-adjusted life-year44QALY, quality-adjusted life-year. (QALY), and incremental cost-effectiveness ratios (ICER) at a willingness-to-pay55WTP, willingness-to-pay. (WTP) of $34 066/QALY. The robustness of the model was assessed by performing one-way and probability sensitivity analyses. ResultsCompared with the GP chemotherapy, toripalimab or camrelizumab plus GP chemotherapy as first-line therapy for RM-NPC provided an incremental cost of $6 026 and $43 138 with additional 0.90 QALYs and 0.78 QALYs, respectively, resulting in an ICER of 6 696 $/QALY and 55 305 $/QALY. In the pairwise comparison between the two immunotherapy-related groups, toripalimab plus GP was the dominant strategy with lower costs and higher efficiency than the camrelizumab plus GP group. ConclusionIn our analysis, compared with GP chemotherapy alone, toripalimab plus GP was more cost-effective, while camrelizumab plus GP chemotherapy was not cost-effective. In the pairwise comparison between the two immunotherapy-related groups, toripalimab plus GP would be more cost-effective than camrelizumab plus GP chemotherapy.

Linear mixed models to handle missing at random data in trial-based economic evaluations.

Trial‐based cost‐effectiveness analyses (CEAs) are an important source of evidence in the assessment of health interventions. In these studies, cost and effectiveness outcomes are commonly measured at multiple time points, but some observations may be missing. Restricting the analysis to the participants with complete data can lead to biased and inefficient estimates. Methods, such as multiple imputation, have been recommended as they make better use of the data available and are valid under less restrictive Missing At Random (MAR) assumption. Linear mixed effects models (LMMs) offer a simple alternative to handle missing data under MAR without requiring imputations, and have not been very well explored in the CEA context. In this manuscript, we aim to familiarize readers with LMMs and demonstrate their implementation in CEA. We illustrate the approach on a randomized trial of antidepressants, and provide the implementation code in R and Stata. We hope that the more familiar statistical framework associated with LMMs, compared to other missing data approaches, will encourage their implementation and move practitioners away from inadequate methods.

Prevention of violence against women and girls: A cost-effectiveness study across 6 low- and middle-income countries.

BackgroundViolence against women and girls (VAWG) is a human rights violation with social, economic, and health consequences for survivors, perpetrators, and society. Robust evidence on economic, social, and health impact, plus the cost of delivery of VAWG prevention, is critical to making the case for investment, particularly in low- and middle-income countries (LMICs) where health sector resources are highly constrained. We report on the costs and health impact of VAWG prevention in 6 countries.Methods and findingsWe conducted a trial-based cost-effectiveness analysis of VAWG prevention interventions using primary data from 5 randomised controlled trials (RCTs) in sub-Saharan Africa and 1 in South Asia. We evaluated 2 school-based interventions aimed at adolescents (11 to 14 years old) and 2 workshop-based (small group or one to one) interventions, 1 community-based intervention, and 1 combined small group and community-based programme all aimed at adult men and women (18+ years old). All interventions were delivered between 2015 and 2018 and were compared to a do-nothing scenario, except for one of the school-based interventions (government-mandated programme) and for the combined intervention (access to financial services in small groups). We computed the health burden from VAWG with disability-adjusted life year (DALY). We estimated per capita DALYs averted using statistical models that reflect each trial’s design and any baseline imbalances. We report cost-effectiveness as cost per DALY averted and characterise uncertainty in the estimates with probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs), which show the probability of cost-effectiveness at different thresholds. We report a subgroup analysis of the small group component of the combined intervention and no other subgroup analysis. We also report an impact inventory to illustrate interventions’ socioeconomic impact beyond health. We use a 3% discount rate for investment costs and a 1-year time horizon, assuming no effects post the intervention period. From a health sector perspective, the cost per DALY averted varies between US$222 (2018), for an established gender attitudes and harmful social norms change community-based intervention in Ghana, to US$17,548 (2018) for a livelihoods intervention in South Africa. Taking a societal perspective and including wider economic impact improves the cost-effectiveness of some interventions but reduces others. For example, interventions with positive economic impacts, often those with explicit economic goals, offset implementation costs and achieve more favourable cost-effectiveness ratios. Results are robust to sensitivity analyses. Our DALYs include a subset of the health consequences of VAWG exposure; we assume no mortality impact from any of the health consequences included in the DALYs calculations. In both cases, we may be underestimating overall health impact. We also do not report on participants’ health costs.ConclusionsWe demonstrate that investment in established community-based VAWG prevention interventions can improve population health in LMICs, even within highly constrained health budgets. However, several VAWG prevention interventions require further modification to achieve affordability and cost-effectiveness at scale. Broadening the range of social, health, and economic outcomes captured in future cost-effectiveness assessments remains critical to justifying the investment urgently required to prevent VAWG globally.

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a trial-based and model-based cost-effectiveness analysis from a stepped wedge, cluster-randomised trial

BackgroundThe AFFIRM intervention aimed to reduce stillbirth and neonatal deaths by increasing awareness of reduced fetal movements (RFM) and implementing a care pathway when women present with RFM. Although there is uncertainty regarding the clinical effectiveness of the intervention, the aim of this analysis was to evaluate the cost-effectiveness.MethodsA stepped-wedge, cluster-randomised trial was conducted in thirty-three hospitals in the United Kingdom (UK) and Ireland. All women giving birth at the study sites during the analysis period were included in the study. The costs associated with implementing the intervention were estimated from audits of RFM attendances and electronic healthcare records. Trial data were used to estimate a cost per stillbirth prevented was for AFFIRM versus standard care. A decision analytic model was used to estimate the costs and number of perinatal deaths (stillbirths + early neonatal deaths) prevented if AFFIRM were rolled out across Great Britain for one year. Key assumptions were explored in sensitivity analyses.ResultsDirect costs to implement AFFIRM were an estimated £95,126 per 1,000 births. Compared to standard care, the cost per stillbirth prevented was estimated to be between £86,478 and being dominated (higher costs, no benefit). The estimated healthcare budget impact of implementing AFFIRM across Great Britain was a cost increase of £61,851,400/year.ConclusionsPerinatal deaths are relatively rare events in the UK which can increase uncertainty in economic evaluations. This evaluation estimated a plausible range of costs to prevent baby deaths which can inform policy decisions in maternity services.Trial registrationThe trial was registered with www.ClinicalTrials.gov, number NCT01777022.

Trial-based Cost-effectiveness Analysis of an Immediate Postoperative Mitomycin C Instillation in Patients with Non–muscle-invasive Bladder Cancer

BackgroundBladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens. ObjectiveTo assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient’s risk group. Design, setting, and participantsThis economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period. Outcome measurements and statistical analysisThe treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves. Results and limitationsTime to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58–2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06–0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22959) than for delayed MMC instillation (€24624), with an adjusted mean difference of −€1350 (95% CI −€1799 to −€900). The study is limited by the retrospective estimation of costs. ConclusionsThis trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation. Patient summaryWe assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non–muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non–muscle-invasive bladder cancer.

Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy

Aims Proliferating hematopoietic stem and progenitor cells (HSPCs) are susceptible to chemotherapy-induced damage, resulting in myelosuppressive adverse events (AEs) such as neutropenia, anemia, and thrombocytopenia that are associated with high health care costs and decreased quality of life (QoL). In this study, a trial-based cost-effectiveness analysis was performed to help assess the economic impact of administering trilaciclib, a myeloprotective therapy that protects multilineage HSPCs from chemotherapy-induced damage, prior to standard first-line chemotherapy, using data from a pivotal Phase II study of trilaciclib in the setting of extensive-stage small cell lung cancer (ES-SCLC, NCT03041311). Method The aim of this study was to assess the cost-effectiveness of administering trilaciclib prior to chemotherapy versus chemotherapy alone among patients with ES-SCLC from a United States payer perspective. Data on the rate and frequency of myelosuppressive AEs and health utility were derived from the pivotal study of trilaciclib. Costs of managing myelosuppressive AEs and costs of chemotherapy treatment were sourced from published literature. Outcomes included the number of myelosuppressive AEs, costs (in 2021 US dollars), quality-adjusted life-years (QALYs), incremental cost, incremental QALY, and an incremental cost-effectiveness ratio. Results Administering trilaciclib prior to chemotherapy was associated with a reduction in neutropenia (82%), febrile neutropenia (75%), anemia (43%), and thrombocytopenia (96%) compared with chemotherapy alone. Additionally, trilaciclib prior to chemotherapy was cost-saving compared with chemotherapy alone ($99,919 vs $118,759, respectively) and associated with QALY improvement (0.150 vs 0.145, respectively). Probabilistic sensitivity analyses showed 58% of iterations projecting cost savings and QALY improvement with trilaciclib. Conclusions The findings suggest that the use of trilaciclib prior to first-line chemotherapy in patients with ES-SCLC can be cost-beneficial owing to fewer myelosuppressive AEs and lower costs, together with a favorable QoL profile.

Intravitreal ranibizumab versus aflibercept versus bevacizumab for macular oedema due to central retinal vein occlusion: the LEAVO non-inferiority three-arm RCT.

Licensed ranibizumab (0.5 mg/0.05 ml Lucentis®; Novartis International AG, Basel, Switzerland) and aflibercept (2 mg/0.05 ml Eylea®; Bayer AG, Leverkusen, Germany) and unlicensed bevacizumab (1.25 mg/0.05 ml Avastin®; F. Hoffmann-La Roche AG, Basel, Switzerland) are used to treat macula oedema due to central retinal vein occlusion, but their relative clinical effectiveness, cost-effectiveness and impact on the UK NHS and Personal Social Services have never been directly compared over the typical disease treatment period. The objective was to compare the clinical effectiveness and cost-effectiveness of three intravitreal antivascular endothelial growth factor agents for the management of macula oedema due to central retinal vein occlusion. This was a three-arm, double-masked, randomised controlled non-inferiority trial. The trial was set in 44 UK NHS ophthalmology departments, between 2014 and 2018. A total of 463 patients with visual impairment due to macula oedema secondary to central retinal vein occlusion were included in the trial. The participants were treated with repeated intravitreal injections of ranibizumab (n = 155), aflibercept (n = 154) or bevacizumab (n = 154). The primary outcome was an increase in the best corrected visual acuity letter score from baseline to 100 weeks in the trial eye. The null hypothesis that aflibercept and bevacizumab are each inferior to ranibizumab was tested with a non-inferiority margin of -5 visual acuity letters over 100 weeks. Secondary outcomes included additional visual acuity, and imaging outcomes, Visual Function Questionnaire-25, EuroQol-5 Dimensions with and without a vision bolt-on, and drug side effects. Cost-effectiveness was estimated using treatment costs and Visual Function Questionnaire-Utility Index to measure quality-adjusted life-years. The adjusted mean changes at 100 weeks in the best corrected visual acuity letter scores were as follows - ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). Aflibercept was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval -2.17 to 6.63 letters; p = 0.0006), but not superior. The study was unable to demonstrate that bevacizumab was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference -1.73 letters, 95% confidence interval -6.12 to 2.67 letters; p = 0.071). A post hoc analysis was unable to demonstrate that bevacizumab was non-inferior to aflibercept in the intention-to-treat population (adjusted mean best corrected visual acuity difference was -3.96 letters, 95% confidence interval -8.34 to 0.42 letters; p = 0.32). All per-protocol population results were the same. Fewer injections were required with aflibercept (10.0) than with ranibizumab (11.8) (difference in means -1.8, 95% confidence interval -2.9 to -0.8). A post hoc analysis showed that more bevacizumab than aflibercept injections were required (difference in means 1.6, 95% confidence interval 0.5 to 2.7). There were no new safety concerns. The model- and trial-based cost-effectiveness analyses estimated that bevacizumab was the most cost-effective treatment at a threshold of £20,000-30,000 per quality-adjusted life-year. The comparison of aflibercept and bevacizumab was a post hoc analysis. The study showed aflibercept to be non-inferior to ranibizumab. However, the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out. Bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered. To obtain extensive patient feedback and discuss with all stakeholders future bevacizumab NHS use. Current Controlled Trials ISRCTN13623634. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 38. See the NIHR Journals Library website for further project information.

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers: a research programme including the REACH-HF RCT

BackgroundRates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation.ObjectivesTo develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers.DesignIntervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction).SettingFour centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial.ParticipantsAdults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction < 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50).InterventionA self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone.Main outcome measuresThe primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations.ResultsThe main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51;p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted life-year gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with > 85% retention at follow-up.LimitationsKey limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities.ConclusionsEvaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes.Future workSystematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial.Trial registrationCurrent Controlled Trials ISRCTN86234930 and ISRCTN78539530.Funding detailsThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 9, No. 1. See the NIHR Journals Library website for further project information.

Cost-effectiveness of a lifestyle intervention in high-risk individuals for diabetes in a low- and middle-income setting: Trial-based analysis of the Kerala Diabetes Prevention Program

BackgroundData on the cost-effectiveness of lifestyle-based diabetes prevention programs are mostly from high-income countries, which cannot be extrapolated to low- and middle-income countries. We performed a trial-based cost-effectiveness analysis of a lifestyle intervention targeted at preventing diabetes in India.MethodsThe Kerala Diabetes Prevention Program was a cluster-randomized controlled trial of 1007 individuals conducted in 60 polling areas (electoral divisions) in Kerala state. Participants (30–60 years) were those with a high diabetes risk score and without diabetes on an oral glucose tolerance test. The intervention group received a 12-month peer-support lifestyle intervention involving 15 group sessions delivered in community settings by trained lay peer leaders. There were also linked community activities to sustain behavior change. The control group received a booklet on lifestyle change. Costs were estimated from the health system and societal perspectives, with 2018 as the reference year. Effectiveness was measured in terms of the number of diabetes cases prevented and quality-adjusted life years (QALYs). Three times India’s gross domestic product per capita (US$6108) was used as the cost-effectiveness threshold. The analyses were conducted with a 2-year time horizon. Costs and effects were discounted at 3% per annum. One-way and multi-way sensitivity analyses were performed.ResultsBaseline characteristics were similar in the two study groups. Over 2 years, the intervention resulted in an incremental health system cost of US$2.0 (intervention group: US$303.6; control group: US$301.6), incremental societal cost of US$6.2 (intervention group: US$367.8; control group: US$361.5), absolute risk reduction of 2.1%, and incremental QALYs of 0.04 per person. From a health system perspective, the cost per diabetes case prevented was US$95.2, and the cost per QALY gained was US$50.0. From a societal perspective, the corresponding figures were US$295.1 and US$155.0. For the number of diabetes cases prevented, the probability for the intervention to be cost-effective was 84.0% and 83.1% from the health system and societal perspectives, respectively. The corresponding figures for QALY gained were 99.1% and 97.8%. The results were robust to discounting and sensitivity analyses.ConclusionsA community-based peer-support lifestyle intervention was cost-effective in individuals at high risk of developing diabetes in India over 2 years.Trial registrationThe trial was registered with Australia and New Zealand Clinical Trials Registry (ACTRN12611000262909). Registered 10 March 2011.

Cost-utility and cost-effectiveness analysis of a clinical medication review focused on personal goals in older persons with polypharmacy compared to usual care: Economic evaluation of the DREAMeR study.

The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost-effectiveness analysis from a societal perspective of a patient-centred CMR. A trial-based cost-utility and cost-effectiveness analysis was performed as part of the DREAMeR study, a pragmatic controlled trial that randomised patients aged ≥70 years using at least seven drugs to either CMR or usual care. Over six months, healthcare consumption and drug use were collected to estimate costs, and effects were collected in terms of quality-adjusted life years (QALYs) measured with EQ-5D-5 L and EQ-VAS and as reduced health-related complaints with impact on patients' daily lives. The total mean costs per patient (n = 588) over six months were €4,189 ± 6,596 for the control group (n = 294) and €4,008 ± 6,678 for the intervention group (n = 294), including estimated intervention costs of €199 ± 67, which resulted in a mean incremental total cost savings of €181 for the intervention group compared to the control group. Compared to the control group, for the intervention group, the mean incremental QALYs over six months were: -0.00217 measured with EQ-5D and 0.003 measured with EQ-VAS. The incremental effect of reduced health-related complaints with impact was -0.34. There was a likelihood of >90% that the intervention was cost-saving. The benefits of a patient-centred CMR were inconsistent with no benefits on HR-QoL measured with EQ-5D-5 L and small benefits on HR-QoL measured with EQ-VAS and health-related complaints with impact on patients' daily lives. Additionally, a CMR could potentially be cost saving from a societal perspective.

Durvalumab vs placebo consolidation therapy after chemoradiotherapy in stage III non-small-cell lung cancer: An updated PACIFIC trial-based cost-effectiveness analysis

IntroductionRecently updated three-year survival data from the PACIFIC trial showed that durvalumab consolidation therapy improved OS rates versus placebo for patients with unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy. Considering the impact of the high cost of durvalumab, its cost-effectiveness should be updated to see if its cost-effectiveness has changed from the US payers’ perspective. MethodsA comprehensive Markov model was used to evaluate mean lifetime costs and effectiveness of first-line durvalumab consolidation therapy versus placebo for patients with unresectable stage III NSCLC imputing updated survival and quality-of-life data from the PACIFIC trial. The main endpoints include total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way, two-way, and probabilistic sensitivity analyses were conducted to access the uncertainty in the variables. We also considered durvalumab cost-effectiveness in the subgroups. ResultsDurvalumab consolidation therapy resulted in additional 1.34 LYs and 1.01 QALYs, resulting in an ICER of $138,920 per QALY versus the placebo treatment. One-way sensitivity analysis revealed that the utility values of two treatments, body weight, and unit cost of durvalumab have the greatest influence on the result. Subgroup analyses demonstrated that durvalumab was more cost effective for patients with non-squamous-cell lung cancer, followed by 25% or greater PD-L1 expression. Probabilistic sensitivity analysis showed that the probability of durvalumab being cost-effective versus the placebo is 62.6% at a willingness-to-pay (WTP) of $150,000 per QALY ConclusionOur analyses demonstrated that receiving durvalumab consolidation therapy was more cost-effective than placebo at a WTP threshold of $150,000. These results can be of use to US practitioners in the application of durvalumab and for durvalumab prescription and reimbursement policies.

Cost-effectiveness and cost-utility analysis of a work-place smoking cessation intervention with and without financial incentives.

AimsTo perform an economic evaluation of a work‐place smoking cessation group training programme with incentives compared with a training programme without incentives.DesignA trial‐based cost‐effectiveness analysis (CEA) and cost–utility analysis (CUA) from a societal perspective and an employer's perspective.SettingSixty‐one companies in the Netherlands.ParticipantsA total of 604 tobacco‐smoking employees.Intervention and comparatorA 7‐week work‐place smoking cessation group training programme. The intervention group earned gift vouchers of €350 for 12 months’ continuous abstinence. The comparator group received no incentives.MeasurementsOnline questionnaires were administered to assess quality of life (EQ‐5D‐5 L) and resource use during the 14‐month follow‐up period (2‐month training period plus 12‐month abstinence period). For the CEA the primary outcome measure was carbon monoxide (CO)‐validated continuous abstinence; for the CUA the primary outcome was quality‐adjusted life years (QALY). Bootstrapping and sensitivity analyses were performed to account for uncertainty. Incremental cost‐effectiveness ratio (ICER) tables were used to determine cost‐effectiveness from a life‐time perspective.FindingsOf the participants in the intervention group, 41.1% had quit smoking compared with 26.4% in the control group. From a societal perspective with a 14‐month follow‐up period, the ICER per quitter for an intervention with financial incentives compared with no incentives was €11 546. From an employer's perspective, the ICER was €5686. There was no significant difference in QALYs between the intervention and control group within the 14‐month follow‐up period. The intervention was dominated by the comparator in the primary analysis at a threshold of €20 000 per QALY. In the sensitivity analysis, these results were uncertain. A life‐time perspective showed an ICER of €1249 (95% confidence interval = €850–2387) per QALY.ConclusionsFinancial incentives may be cost‐effective in increasing quitting smoking, particularly from a life‐time perspective.

SUcceSS, SUrgery for Spinal Stenosis: protocol of a randomised, placebo-controlled trial

IntroductionCentral lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal...