Terms Of Quality-adjusted Life Years Research Articles

Optimal Surveillance Strategies for Early-Stage Cutaneous Melanoma Post Primary Tumor Excision: An Economic Evaluation.

Background. Consensus on standardized active surveillance or follow-up care by clinicians is lacking leading to considerable variation in practice across countries. An important structural modelling consideration is that self-examination by patients and their partners can detect melanoma recurrence outside of active surveillance regimes. Objectives. To identify candidate melanoma surveillance strategies for American Joint Committee on Cancer (AJCC) stage I disease and compare them with the current recommended practice in a cost-utility analysis framework. Methods. In consultation with UK clinical experts, a microsimulation model was built in TreeAge Pro 2019 R1.0 (Williamstown, MA, USA) to evaluate surveillance strategies for AJCC stage IA and IB melanoma patients separately. The model incorporated patient behaviors such as self-detection and emergency visits to examine suspicious lesions. A National Health Service (NHS) perspective was taken. Model input parameters were taken from the literature and where data were not available, local expert opinion was sought. Probabilistic sensitivity analysis, one-way sensitivity analysis on pertinent parameters and value of information was performed. Results. In the base-case probabilistic sensitivity analysis, less intensive surveillance strategies for AJCC stage IA and IB had lower total lifetime costs than the current National Institute for Health and Care Excellence (NICE) recommended strategy with similar effectiveness in terms of quality-adjusted life years and thereby likely to be cost-effective. Many strategies had similar effectiveness due to the relatively low chance of recurrence and the high rate of self-detection. Sensitivity and scenario analyses did not change these findings. Conclusions. Our model findings suggest that less resource intensive surveillance may be cost-effective compared with the current NICE surveillance guidelines. However, to advocate convincingly for changes, better evidence is required.

POSC76 Cost-Utility Analysis of Pegaspargase for the Treatment of Acute Lymphoblastic Leukemia in Greece

To assess the cost-utility of pegaspargase versus L- asparaginase, both followed by Erwinase in the therapy sequence, as treatment option for pediatric, adolescents and adult patients with acute lymphoblastic leukemia (ALL) in Greece. A published cost-utility model comprised a decision tree (DT) and a state-transition Markov model was adapted from public payer perspective to compare a treatment sequence with pegaspargase to a sequence with L-asparaginase. The DT model included treatment regimen cycles and potential hypersensitivity to asparaginase. As patients experience a survival outcome during and after treatment, a Markov model was also incorporated in parallel to extrapolate over a life-time horizon. Efficacy and safety data, as well as utility values, were extracted from published literature. Direct costs pertaining to drug acquisition, administration, and management of hypersensitivity were considered in the analysis (€,2020). Resource consumption associated with each treatment was based on experts’ advice. Model outcomes were patient quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICER) per QALY gained. All future outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to explore the impact in changing input data. The analysis showed that pegaspargase sequence was estimated to produce 0.05 additional QALYs (18.12 versus 18.07) and lower cost of -€1,698 compared to L-asparaginase, indicating that sequence with pegaspargase was a dominant treatment strategy (improve outcomes with reduced costs) compared to L-asparaginase. Deterministic sensitivity analysis confirmed pegaspargase cost-effective profile. At the defined willingness-to-pay threshold of €54,000/QALY gained, probabilistic sensitivity analysis showed that pegaspargase had a 100% probability of being cost-effective relative to asparaginase sequence. Pegaspargase sequence was found to be less costly and more effective (in terms of QALYs) in relation to asparaginase sequence, representing a dominant strategic option for Greek public payer in ALL.

Cost-effectiveness analysis in patients with an unruptured cerebral aneurysm treated with observation or surgery.

The main goal of preventive treatment of unruptured intracranial aneurysms (UIAs) is to avoid the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage. A comparison between the conservative approach and the surgical approach combining endovascular treatment and microsurgical clipping is currently lacking. This study aimed to conduct an updated evaluation of cost-effectiveness comparing the two approaches in patients with UIA. A decision tree with a Markov model was developed. Quality-adjusted life-years (QALYs) associated with living with UIA before and after treatment were prospectively collected from a cohort of patients with UIA at a tertiary center. Other inputs were obtained from published literature. Using Monte Carlo simulation for patients aged 55, 65, and 75 years, the authors modeled the conservative management in comparison with preventive treatment. Different proportions of endovascular and microsurgical treatment were modeled to reflect existing practice variations between treatment centers. Outcomes were assessed in terms of QALYs. Sensitivity analyses to assess the model's robustness and completed threshold analyses to examine the influence of input parameters were performed. Preventive treatment of UIAs consistently led to higher utility. Models using a higher proportion of endovascular therapy were more cost-effective. Models with older cohorts were less cost-effective than those with younger cohorts. Treatment was cost-effective (willingness to pay < 100,000 USD/QALY) if the annual rupture risk exceeded a threshold between 0.8% and 1.9% in various models based on the proportion of endovascular treatment and cohort age. A higher proportion of endovascular treatments and younger age lowered this threshold, making the treatment of aneurysms with a lower risk of rupture more cost-effective. Preventive treatment of aneurysms led to higher utility compared with conservative management. Models with a higher proportion of endovascular treatment and younger patient age were most cost-effective.

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease.

Background: “On-demand” treatments approved in the United States (US) for “OFF” episodes in Parkinson’s disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301.Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing “OFF” episodes from a US payer perspective.Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments’ pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without “OFF” episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per “OFF” hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted.Results: In the base case, APL had the lowest total “on-demand” treatment costs ($42,095) compared with SC-APO ($276,320; difference: –$234,225) and CVT-301 ($69,577; difference: –$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per “OFF” hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results.Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and adverse event–related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and substantially higher efficacy.Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of “OFF” episodes in patients with PD.

Cost-effectiveness analysis of the first‐line EGFR‐TKIs in patients with advanced EGFR-mutated non-small-cell lung cancer

ABSTRACT Aim To evaluate the cost-effectiveness of first-line treatments, such as erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib, for patients diagnosed with stage IIIB/IV NSCLC harboring EGFR mutations. Materials & methods A partitioned survival model was developed to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) from the perspective of the Spanish National Health System. Two Bayesian NMAs were performed independently, by using the polynomial fraction method to fit Kaplan–Meier curves for overall survival and progression-free survival. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. Results The ICER was calculated for the four first-line treatments by comparing them with gefitinib, and the ratios obtained were as follows: €166,416/QALY for osimertinib, €183,682/QALY for dacomitinib, €167,554/QALY for afatinib, €36,196/QALY for erlotinib. It was seen that patients who received osimertinib presented higher QALYs (0.49), followed by dacomitinib (0.33), afatinib (0.32), erlotinib (0.31), and gefitinib (0.28). Conclusions Gefitinib is the most cost-effective treatment. In terms of QALYs gained, Osimertinib was more effective than all other TKIs. Nevertheless, with a Spanish threshold of €24,000/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 70%, to obtain a cost-effectiveness alternative.

PD25-10 COST-UTILITY ANALYSIS IN UROLOGY

You have accessJournal of UrologyHealth Services Research: Value of Care: Cost and Outcomes Measures II (PD25)1 Sep 2021PD25-10 COST-UTILITY ANALYSIS IN UROLOGY Katherine Fero, Vidit Sharma, Patrick Lec, Christopher Saigal, and Karim Chamie Katherine FeroKatherine Fero More articles by this author , Vidit SharmaVidit Sharma More articles by this author , Patrick LecPatrick Lec More articles by this author , Christopher SaigalChristopher Saigal More articles by this author , and Karim ChamieKarim Chamie More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002018.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cost-effectiveness analysis (CEA) defines value in healthcare by quantifying the benefit of an intervention for a given dollar expense. Cost-utility analysis (CUA) is a type of CEA that quantifies an intervention’s health benefits in terms of quality-adjusted life years (QALY’s). Understanding the CUA supporting an intervention is valuable in defining its best use. Here we characterize the state of cost-utility research in urology by evaluating the quality of published studies and reporting adherence to methodological guidelines. METHODS: We performed an analysis of all CUAs in the Cost-Effectiveness Analysis Registry (CEAR) published between 1976 and 2019. Studies on topics related to urology were screened by diagnosis code and then by title review. Studies were assigned to a urologic subspecialty by abstract review. Intervention studied, perspective, and quality score (1-7) are reported per CEAR abstraction processes. Associations between study characteristics and quality scores were evaluated using the Pearson product moment correlation coefficient. Mean quality scores between subspecialties were compared with ANOVA. RESULTS: 9080 articles were screened; 254 (2.8%) were pertinent to urology and were included in this analysis. There was an increase in studies published over the study period with a peak in 2013 (Figure 1a). Figure 1b shows the distribution of studies published by subspecialty. There were more CUA of pharmaceuticals than surgeries (38% vs 26%). Few modeled a reference case from the societal perspective (15%), most were from a payer perspective (62.6%). There was no change in proportion of studies reporting reference case from a societal perspective after the publication of guidelines recommending its use (p=0.38). A more recent publication year was associated with a higher study quality score (correlation co-efficient 0.18; p=0.004). No differences in quality were found by subspecialty (p=0.2), or between urology and non-urology CUA (mean score 4.7 vs 4.7). CONCLUSIONS: CUAs in urology make up a small fraction of published CEA research. More numerous and higher quality analyses have been published in recent years. Surgical interventions are understudied in urology and should be an area of focus for future analysis. Attention should be paid to methodological rigor, including use of recommended reference case perspective, when CEAs are considered for publication. Source of Funding: KEF Supported by H&H Lee Surgical Scholars (UCLA) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e435-e436 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katherine Fero More articles by this author Vidit Sharma More articles by this author Patrick Lec More articles by this author Christopher Saigal More articles by this author Karim Chamie More articles by this author Expand All Advertisement Loading ...

Cost-Effective Analysis of Dual-Energy Computed Tomography for the Diagnosis of Occult Hip Fractures Among Older Adults

ObjectiveEarly and accurate diagnosis of hip fractures minimizes morbidity and mortality. Although current guidelines favor magnetic resonance imaging (MRI) for the diagnosis of occult hip fractures, a new technology called dual-energy computed tomography (DECT) seems an effective alternative. This article investigates a potentially cost-effective strategy for the diagnosis of occult hip fractures in older adults in Singapore. MethodsA decision tree model was developed to compare costs from a payer’s perspective and outcomes in terms of quality-adjusted life-years (QALYs) of different imaging strategies for diagnosing occult hip fracture, comparing MRI with DECT supplementing single-energy computed tomography (SECT) and SECT alone. Model inputs were obtained from local sources where available. Sensitivity analyses are performed to test the robustness of the results. ResultsThe MRI strategy was dominated by the DECT strategy, whereas DECT supplementing SECT provided 0.30 more QALYs at an incremental cost of SGD106.41 with an incremental cost-effectiveness ratio of SGD352.52 per QALY relative to SECT alone. DECT seemed a cost-effective strategy at a willingness-to-pay threshold of SGD50 000 per QALY. ConclusionDECT supplementing SECT is a cost-effective imaging strategy to diagnose occult hip fractures among older adults in Singapore and should be included in clinical pathways to expedite timely treatment and considered for reimbursement schemes.

The Epidemiology of Meniscus Injury.

Meniscus surgery is one of the most commonly performed orthopedic procedures worldwide. Modifiable risk factors for meniscus injury include body mass index, participation in athletics and occupation. Nonmodifiable risk factors include age, sex, lower extremity alignment, discoid meniscus, ligamentous laxity, and biconcave tibial plateau. Conditions commonly associated with meniscal injury are osteoarthritis, anterior cruciate ligament injury, and tibial plateau fractures. Tear type and location vary by patient age and functional status. Surgical management of meniscus injury is typically cost-effective in terms of quality-adjusted life years. The purpose of this review is to provide an overview of meniscal injury epidemiology by summarizing tear types and locations, associated conditions, and factors that increase the risk for meniscal injury. The economic burden of meniscus injury and strategies to prevent injury to the meniscus are also reviewed.

Cost-effectiveness analysis of a community-based colorectal cancer screening program in Shanghai, China.

This study investigated the cost-effectiveness of a community-based colorectal cancer-screening program (C-CRCSP) in Shanghai, China, among the residents in the urban, suburban and rural areas. A Markov model was constructed to evaluate the cost-effectiveness of a 25-year annual C-CRCSP including 100 000 populations. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER); referring to either life-years gained, or quality-adjusted life-years (QALYs) gained. The threshold was gross domestic product per capita. Univariate and multivariate sensitivity analyses were performed to investigate the influence of compliance, prevalence, technological performance, medical cost and annual cost discount rate (3.5%) on ICER. A probabilistic sensitivity analysis evaluated the probability of the cost-effectiveness of C-CRCSP at different maximum acceptable ceiling ratios. Compared with no screening, the C-CRCSP resulted in total gains of 7840 QALYs and 2210 life-years (LY), at a total cost of CNY 58.54 million; that is, the ICER were CNY 7460/QALYs and CNY 26650/LY. Stratifying by residency, the cumulative gains in QALYs and LY were estimated to be the lowest in the urban populations compared with the rural and suburban populations. The cost for the urban population was 3-fold and 6-fold that of the suburban and rural populations. The ICER for QALYs ranged from 2180 (rural) to 16 840 (urban). The cost-effectiveness of a C-CRCSP in Shanghai was most favorable for the rural population, while the urban population benefits less in terms of QALYs. ICER could be enhanced by measures that increase compliance.

Cost-effectiveness analysis of a multiple health behaviour change intervention in people aged between 45 and 75\u2009years: a cluster randomized controlled trial in primary care (EIRA study)

BackgroundMultiple health behaviour change (MHBC) interventions that promote healthy lifestyles may be an efficient approach in the prevention or treatment of chronic diseases in primary care. This study aims to evaluate the cost-utility and cost-effectiveness of the health promotion EIRA intervention in terms of MHBC and cardiovascular reduction.MethodsAn economic evaluation alongside a 12-month cluster-randomised (1:1) controlled trial conducted between 2017 and 2018 in 25 primary healthcare centres from seven Spanish regions. The study took societal and healthcare provider perspectives. Patients included were between 45 and 75 years old and had any two of these three behaviours: smoking, insufficient physical activity or low adherence to Mediterranean dietary pattern. Intervention duration was 12 months and combined three action levels (individual, group and community). MHBC, defined as a change in at least two health risk behaviours, and cardiovascular risk (expressed in % points) were the outcomes used to calculate incremental cost-effectiveness ratios (ICER). Quality-adjusted life-years (QALYs) were estimated and used to calculate incremental cost-utility ratios (ICUR). Missing data was imputed and bootstrapping with 1000 replications was used to handle uncertainty in the modelling results.ResultsThe study included 3062 participants. Intervention costs were €295 higher than usual care costs. Five per-cent additional patients in the intervention group did a MHBC compared to usual care patients. Differences in QALYS or cardiovascular risk between-group were close to 0 (− 0.01 and 0.04 respectively). The ICER was €5598 per extra health behaviour change in one patient and €6926 per one-point reduction in cardiovascular risk from a societal perspective. The cost-utility analysis showed that the intervention increased costs and has no effect, in terms of QALYs, compared to usual care from a societal perspective. Cost-utility planes showed high uncertainty surrounding the ICUR. Sensitivity analysis showed results in line with the main analysis.ConclusionThe efficiency of EIRA intervention cannot be fully established and its recommendation should be conditioned by results on medium-long term effects.Trial registrationClinicaltrials.gov NCT03136211. Registered 02 May 2017 – Retrospectively registered

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study

BackgroundOpen radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. ObjectiveTo assess the cost-effectiveness of RARC compared to ORC in bladder cancer. Design, setting, and participantsThis economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. Outcome measurements and statistical analysisOver 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. Results and limitationsThe mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791–€18 720) for ORC and €21 266 (95% CI €19 163–€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431–€22 642) for ORC and €24 896 (95% CI €21 925–€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74–0.85) compared to 0.81 QALYs (95% CI 0.77–0.85) for ORC patients, resulting in a mean QALY difference of −0.02 (95% CI −0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. ConclusionsRARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. Patient summaryThis study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive.This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).

Preoperative comprehensive geriatric assessment and optimisation prior to elective arterial vascular surgery: a health economic analysis.

increasing numbers of older people are undergoing vascular surgery. Preoperative comprehensive geriatric assessment and optimisation (CGA) reduces postoperative complications and length of hospital stay. Establishing CGA-based perioperative services requires health economic evaluation prior to implementation. Through a modelling-based economic evaluation, using data from a single site clinical trial, this study evaluates whether CGA is a cost-effective alternative to standard preoperative assessment for older patients undergoing elective arterial surgery. an economic evaluation, using decision-analytic modelling, comparing preoperative CGA and optimisation with standard preoperative care, was undertaken in older patients undergoing elective arterial surgery. The incremental net health benefit of CGA, expressed in terms of quality-adjusted life-years (QALYs), was used to evaluate cost-effectiveness. CGA is a cost-effective substitute for standard preoperative care in elective arterial surgery across a range of cost-effectiveness threshold values. An incremental net benefit of 0.58 QALYs at a cost-effectiveness threshold of £30k, 0.60 QALYs at a threshold of £20k and 0.63 QALYs at a threshold of £13k was observed. Mean total pre- and postoperative health care utilisation costs were estimated to be £1,165 lower for CGA patients largely accounted for by reduced postoperative bed day utilisation. this study demonstrates a likely health economic benefit in addition to the previously described clinical benefit of employing CGA methodology in the preoperative setting in older patients undergoing arterial surgery. Further evaluation should examine whether CGA-based perioperative services can be effectively implemented and achieve the same clinical and health economic outcomes at scale.

Economic Evaluation of Adding Bevacizumab to Chemotherapy for Metastatic Colorectal Cancer (mCRC) Patients in Indonesia.

Objective:Since 2016, bevacizumab has been widely used to treat metastatic colorectal cancer (mCRC) in Indonesia. Nevertheless, the high cost of bevacizumab has raised the question of whether the therapy is considered cost-effective and should be included in the national health insurance system. This study aimed to assess the cost-effectiveness of bevacizumab plus chemotherapy versus chemotherapy alone for the treatment of mCRC patients.Methods:A Markov model was applied using the perspective of the Indonesian healthcare system to assess cost-effectiveness. The health outcomes were expressed in terms of quality-adjusted life years (QALY) using the validated EuroQoL-5D-5L instrument. Data for medical costs were collected from hospital billings in four hospitals located in three different cities in Indonesia. Meanwhile, data for utility were obtained from interviewing 90 patients who came to the hospital. We compared those mCRC patients who received chemotherapy alone either with FOLFOX or FOLFIRI, versus patients who received the addition of bevacizumab. Results:With the perspective of societal, the incremental cost-effectiveness ratio (ICER) of adding bevacizumab was USD 49,312 per QALY gained using secondary data and USD 28,446 per QALY using real world data. Conclusion:Using either a healthcare or societal perspective, the addition of bevacizumab for mCRC treatment was considered not cost-effective.

PNS82 The Methods for Incorporating Carer HRQoL Should be More Clearly Defined By NICE

The broader societal benefits offered by new technologies in terms of quality-adjusted life-years (QALYs) accrued by carers (e.g., a partner, parent, or family member) are accepted for inclusion in the Reference Case for National Institute for Health and Care Excellence (NICE) technology appraisals (TAs) and highly specialised technology (HST) guidance. The research presented here reviews all published TAs and HST assessments to identify those that considered the impact of an intervention on QALYs for carers and how these have incorporated carer health-related quality of life (HRQoL). We reviewed all TAs and HST assessments published between April 2013, when the current NICE methods guidance was issued, and July 2020. Manufacturers included carer HRQoL in their economic models in 5% (17/331) of NICE TAs and HST assessments. Most of these (9/17) concerned neurological conditions; 7/9 were for multiple sclerosis, 6 of which used utility decrements for carers of patients with Alzheimer’s disease. In 2/17 submissions, carer disutilities were derived using vignettes valued through the EuroQol five-dimension questionnaire (EQ-5D) visual analogue scale (VAS). One submission included the QALY loss to a family due to the premature death of a child. The remaining studies used disutilities from the literature. Of the 17 submissions, 9 included carer HRQoL in the base case only, and 2 in the base case and scenario analyses. NICE accepted inclusion of disutilities for carers in all of these. Six included carer HRQoL only in a scenario analysis. NICE rejected 4 of them. Carer HRQoL benefits/analyses are not routinely submitted for NICE decision-making. In the cases where NICE accepted it, various methodologies were applied besides EQ-5D to derive utility decrements. NICE should provide further guidance and evidence to support a consistent approach to including carer/family health outcomes in appraisals.

P535 Optimising vedolizumab in treatment sequences for Crohn’s disease: Results from a simulation model using real-world evidence

Abstract Background With the availability of biologic therapies for treating Crohn’s disease (CD) there are limited data to inform optimal treatment decisions. Vedolizumab (VDZ), an anti-integrin antibody that selectively targets lymphocyte migration to the gut, was approved in 2014 for the treatment of moderate-to-severe CD. We developed a model based on real-world evidence (RWE) to examine the effect of different positioning for VDZ in CD treatment sequences on clinical outcomes. Methods A Markov sequential model was developed to identify the optimal position of VDZ within a sequence of CD therapies that included corticosteroids (CS), 2 biologics and best supportive care. Three sequences were compared: VDZ as first biologic (first position), second and last biologic among anti-TNFs and ustekinumab as alternate biologic treatments. To test the behaviour of the model, VDZ was also positioned before CS (Position 0, off label). Model inputs were informed using published RWE. At each position in the treatment sequence, patients achieving clinical response or remission during induction continued on maintenance; patients on maintenance could lose clinical response or remission; patients who did not achieve response during induction or lost response during maintenance (including after dose escalation) moved to the next position of the sequence after a treatment-free interval. Surgery, development of intestinal malignancy/lymphoma, and discontinuation of treatment due to serious adverse events or death could occur at each sequence position. VDZ sequences were compared and ranked based on quality-adjusted life years (QALYs), patient-reported outcomes (PRO2/3) derived from CDAI scores, or proportion of patients undergoing surgery by the end of the 10-year time horizon for model simulation. Probabilistic sensitivity analysis (PSA) evaluated the impact of model inputs uncertainty on the outcomes. Results For QALYs, PRO2/3, and rates of surgery, VDZ early in the treatment sequence was the optimal positioning strategy (Table). Using QALYs as the ranking criterion, VDZ before CS was the optimal sequence yielding 5.19 QALYs and incremental QALYs of 0.7, 0.20, and 0.20 versus the second-, third- and fourth-line strategy, respectively. The ranking of VDZ in treatment sequences was preserved when PRO2/3 or surgery were used as ranking criteria. In 1,780/2,000 PSA iterations (89%), VDZ before CS or as first biologic yielded the highest QALYs vs. other sequence positions. Conclusion The results of this simulation model using real-world evidence clearly indicate that positioning VDZ earlier in the treatment sequence may yield better patient outcomes in terms of QALYs, PROs and rates of surgery.

Medicare's Hospital Value-Based Purchasing Program Values Quality over QALYs.

Medicare's Hospital Value-Based Purchasing Program (HVBP) is the first national pay-for-performance program to combine measures of quality of care with a measure of episode spending. We estimated the implicit tradeoffs between mortality reduction and spending reduction. To earn points in HVBP, a hospital can either lower mortality or reduce spending, creating a tradeoff between the 2 measures. We analyzed the quality performance and earned points of 2814 hospitals using publicly available data. We then quantified the tradeoffs between spending and mortality in terms of quality-adjusted life-years (QALYs). If incentives in the program were balanced, then the tradeoff between spending and QALYs should be comparable with those of high-value health interventions, roughly $50,000 to $200,000 per QALY. Instead, the tradeoff in HVBP was about $1.2 million per QALY. HVBP overvalues improvements in quality of care relative to spending reductions. We propose 2 possible policy adjustments that could improve incentives for hospitals to deliver high-value care.

Optimising AVATAR therapy for people who hear distressing voices: study protocol for the AVATAR2 multi-centre randomised controlled trial

BackgroundAVATAR therapy is a novel intervention targeting distressing auditory verbal hallucinations (henceforth ‘voices’). A digital simulation (avatar) of the voice is created and used in a three-way dialogue between participant, avatar and therapist. To date, therapy has been delivered over 6 sessions, comprising an initial phase, focusing on standing up to a hostile avatar, and a second phase in which the avatar concedes and focus shifts to individualised treatment targets, including beliefs about voices. The first fully powered randomised trial found AVATAR therapy resulted in a rapid and substantial fall in voice frequency and associated distress that was superior to supportive counselling at 12 weeks. The main objective of this AVATAR2 trial is to test the efficacy of two forms of AVATAR therapy in reducing voice-related distress: AVATAR-brief (standardised focus on exposure, assertiveness and self-esteem) and AVATAR-extended (phase 1 mirroring AVATAR-brief augmented by a formulation-driven phase 2). Secondary objectives include the examination of additional voice, wellbeing and mood outcomes, the exploration of mediators and moderators of therapy response, and examining cost-effectiveness of both forms of therapy compared with usual treatment (TAU).MethodsThis multi-site parallel group randomised controlled trial will independently randomise 345 individuals to receive AVATAR-brief (6 sessions) plus TAU or AVATAR-extended (12 sessions) plus TAU or TAU alone (1:1:1 allocation). Participants will be people with a diagnosis of schizophrenia spectrum and other psychotic disorders who have heard distressing voices for more than 6 months. The primary outcome is the PSYRATS Auditory Hallucinations Distress dimension score at 16 and 28 weeks, conducted by blinded assessors. Statistical analysis will follow the intention-to-treat principle and data will be analysed using linear mixed models. Mediation and moderation analyses using contemporary causal inference methods will be conducted as secondary analyses. Service costs will be calculated, and cost-effectiveness assessed in terms of quality-adjusted life years accrued.DiscussionThis study will clarify optimal therapy delivery, test efficacy in a multi-site study and enable the testing of the AVATAR software platform, therapy training and provision in NHS settings.Trial registrationISRCTN registry ISRCTN55682735. Registered on 22 January 2020. The trial is funded by the Wellcome Trust (WT).

Guided Internet-Based Cognitive Behavioral Therapy for Insomnia: Health-Economic Evaluation From the Societal and Public Health Care Perspective Alongside a Randomized Controlled Trial.

BackgroundThe evidence base for internet-based cognitive behavioral therapy for insomnia (iCBT-I) is firm; however, little is known about iCBT-I’s health-economic effects.ObjectiveThis study aimed to evaluate the cost-effectiveness and cost–utility of iCBT-I in reducing insomnia among schoolteachers.MethodsSchoolteachers (N=128) with clinically significant insomnia symptoms and work-related rumination were randomized to guided iCBT-I or a wait list control group, both with unrestricted access to treatment as usual. Health care use, patient and family expenditures, and productivity losses were self-assessed and used for costing from a societal and a public health care perspective. Costs were related to symptom-free status (score <8 on the insomnia severity index) and quality-adjusted life years (QALYs) gained. Sampling error was handled using nonparametric bootstrapping.ResultsStatistically significant differences favoring the intervention group were found for both health outcomes (symptom-free status yes or no: β=.30; 95% CI 0.16-0.43; QALYs: β=.019, 95% CI 0.01-0.03). From a societal perspective, iCBT-I had a 94% probability of dominating the wait list control for both health outcomes. From a public health care perspective, iCBT-I was more effective but also more expensive than the wait list control, resulting in an incremental cost-effectiveness ratio of €650 per symptom-free individual. In terms of QALYs, the incremental cost-effectiveness ratio was €11,285. At a willingness-to-pay threshold of €20,000 per QALY gained, the intervention’s probability of being cost-effective was 89%.ConclusionsOur trial indicates that iCBT could be considered as a good value-for-money intervention for insomnia.Trial RegistrationGerman Clinical Trial Registry: DRKS00004700; https://tinyurl.com/2nnk57jmInternational Registered Report Identifier (IRRID)RR2-10.1186/1745-6215-14-169

How to Value Orphan Drugs? A Review of European Value Assessment Frameworks.

Background: Decision-makers have implemented a variety of value assessment frameworks (VAFs) for orphan drugs in European jurisdictions, which has contributed to variations in access for rare disease patients. This review provides an overview of the strengths and limitations of VAFs for the reimbursement of orphan drugs in Europe, and may serve as a guide for decision-makers. Methods: A narrative literature review was conducted using the databases Pubmed, Scopus and Web of Science. Only publications in English were included. Publications known to the authors were added, as well as conference or research papers, or information published on the website of reimbursement and health technology assessment (HTA) agencies. Additionally, publications were included through snowballing or focused searches. Results: Although a VAF that applies a standard economic evaluation treats both orphan drugs and non-orphan drugs equally, its focus on cost-effectiveness discards the impact of disease rarity on data uncertainty, which influences an accurate estimation of an orphan drug’s health benefit in terms of quality-adjusted life-years (QALYs). A VAF that weighs QALYs or applies a variable incremental cost-effectiveness (ICER) threshold, allows the inclusion of value factors beyond the QALY, although their methodologies are flawed. Multi-criteria decision analysis (MCDA) incorporates a flexible set of value factors and involves multiple stakeholders’ perspectives. Nevertheless, its successful implementation relies on decision-makers’ openness toward transparency and a pragmatic approach, while allowing the flexibility for continuous improvement. Conclusion: The frameworks listed above each have multiple strengths and weaknesses. We advocate that decision-makers apply the concept of accountability for reasonableness (A4R) to justify their choice for a specific VAF for orphan drugs and to strive for maximum transparency concerning the decision-making process. Also, in order to manage uncertainty and feasibility of funding, decision-makers may consider using managed-entry agreements rather than implementing a separate VAF for orphan drugs.

Cost-Effectiveness of Pulmonary Rehabilitation in Patients With Bronchial Asthma: An Analysis of the EPRA Randomized Controlled Trial

ObjectivesAt 3 months after the intervention, this study evaluates the cost-effectiveness of a 3-week inpatient pulmonary rehabilitation (PR) in patients with asthma compared with usual care alongside the single-center randomized controlled trial—Effectiveness of Pulmonary Rehabilitation in Patients With Asthma. MethodsAdopting a societal perspective, direct medical costs and productivity loss were assessed using the Questionnaire for Health-Related Resource Use-Lung, a modification of the FIM in an Elderly Population. The effect side was operationalized as minimal important differences (MIDs) of the Asthma Control Test (ACT) and the Asthma Quality of Life Questionnaire (AQLQ) and through quality-adjusted life-years (QALYs) gained. Adjusted mean differences in costs (gamma-distributed model) and each effect parameter (Gaussian-distributed model) were simultaneously calculated within 1000 bootstrap replications to determine incremental cost-effectiveness ratios (ICERs) and to subsequently delineate cost-effectiveness acceptability curves. ResultsPR caused mean costs per capita of €3544. Three months after PR, we observed higher mean costs (Δ€3673; 95% confidence interval (CI) €2854-€4783) and improved mean effects (ACT Δ1.59 MIDs, 95% CI 1.37-1.81; AQLQ Δ1.76 MIDs, 95% CI 1.46-2.08; QALYs gained Δ0.01, 95% CI 0.01-0.02) in the intervention group. The ICER was €2278 (95% CI €1653-€3181) per ACT-MID, €1983 (95% CI €1430-€2830) per AQLQ-MID, and €312 401 (95% CI €209 206-€504 562) per QALY gained. ConclusionsContrasting of PR expenditures with ICERs suggests that the intervention, which achieves clinically relevant changes in asthma-relevant parameters, has a high probability to be already cost-effective in the short term. However, in terms of QALYs, extended follow-up periods are likely required to comprehensively judge the added value of a one-time initial investment in PR.