Quality-adjusted Life-year Threshold Research Articles

Staff training in positive behaviour support for behaviour that challenges in people with intellectual disability: cost-utility analysis of a cluster randomised controlled trial.

Behaviour that challenges in people with intellectual disability is associated with higher healthcare, social care and societal costs. Although behavioural therapies are widely used, there is limited evidence regarding the cost and quality-adjusted life-years (QALYs). We aimed to assess the incremental cost per QALY gained of therapist training in positive behaviour support (PBS) and treatment as usual (TAU) compared with TAU using data from a cluster randomised controlled trial (Clinical Trials.gov registration: NCT01680276). We conducted a cost-utility analysis (cost per QALY gained) of 23 teams randomised to PBS or TAU, with a total of 246 participants followed up over 36 months. The primary analysis was from a healthcare cost perspective with a secondary analysis from a societal cost perspective. Over 36 months the intervention resulted in an additional 0.175 QALYs (discounted and adjusted 95% CI -0.068 to 0.418). The total cost of training in and delivery of PBS is £1598 per participant plus an additional cost of healthcare of £399 (discounted and adjusted 95% CI -603 to 1724). From a healthcare cost perspective there is an 85% probability that the intervention is cost-effective compared with TAU at a £30 000 willingness to pay for a QALY threshold. There was a high probability that training in PBS is cost-effective as the cost of training and delivery of PBS is balanced out by modest improvements in quality of life. However, staff training in PBS is not supported given we found no evidence for clinical effectiveness.

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France.

Midostaurin (MIDO) combined with standard chemotherapy was approved by the European Medicines Agency in 2017 for the treatment of adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) based on results from the RATIFY trial. A cost-effectiveness model was developed to compare MIDO and standard-of-care (SOC) to SOC alone in France. Per Haute Autorité de Santé (HAS) guidelines, a partitioned survival model with eight health states was used: diagnosis/induction, complete remission, relapse, hematopoietic stem cell transplantation (HSCT), HSCT recovery, post-HSCT recovery (stabilized after HSCT recovery), post-HSCT relapse, and mortality. A lifetime horizon was used beginning at diagnosis with a "cure model,", which assumed natural mortality after trial cut-off. Utility values were obtained from a systematic literature review and included disutilities. Resource utilization was based on HAS clinical guidelines and a survey of French physicians and included drugs and administration, adverse events, routine medical care, HSCT, and end-of-life care costs. In RATIFY and after extrapolation, MIDO improved survival compared to SOC, translating into MIDO-treated patients gaining 1.12 life years (LYs) and 1.23 quality-adjusted life years (QALYs) versus SOC. The incremental cost-effectiveness ratio (ICER) for MIDO versus SOC was €68,781 per LY and €62,305 per QALY. Sensitivity analyses showed consistency with base case findings. MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment.

Cost-effectiveness of offering an area-level financial incentive on breast feeding: a within-cluster randomised controlled trial analysis

ObjectiveTo provide the first estimate of the cost-effectiveness of financial incentive for breastfeeding intervention compared with usual care.DesignWithin-cluster (‘ward’-level) randomised controlled trial cost-effectiveness analysis (trial registration number ISRCTN44898617).SettingFive local authority...

Cost-effectiveness analysis of pembrolizumab compared to standard of care as first line treatment for patients with advanced melanoma in Hong Kong

BackgroundPembrolizumab has been shown to improve overall survival (OS) and progression free survival (PFS) compared to ipilimumab in patients with ipilimumab-naïve advanced melanoma; however, there are no published data on the cost-effectiveness for pembrolizumab compared to standard-of-care treatments currently used in Hong Kong for advanced melanoma.MethodsA partitioned-survival model based on data from a recent randomized phase 3 study (KEYNOTE-006) and meta-analysis was used to derive time in PFS, OS, and post-progression survival for pembrolizumab and chemotherapy, such as dacarbazine (DTIC), temozolomide (TMZ), and the paclitaxel-carboplatin combination (PC). A combination of clinical trial data, published data, results of meta-analysis, and melanoma registry data was used to extrapolate PFS and OS curves. The base-case time horizon for the model was 30 years with costs and health outcomes discounted at a rate of 5% per year. Individual patient level data on utilities and frequencies of adverse events were obtained from the final analysis of KEYNOTE-006 (cut-off date: 3-Dec-15) for pembrolizumab. Cost data included drug acquisition, treatment administration, adverse event management, and clinical management of advanced melanoma. The distribution of patient weight from the Hong Kong population was applied to calculate the drug costs. Analyses were performed from a payer’s perspective. The incremental cost effectiveness ratio (ICER) expressed as cost in US Dollars (USD) per quality-adjusted life years (QALYs) was the main outcome.ResultsIn base-case scenario, the ICER for pembrolizumab as a first-line treatment for advanced melanoma was USD49,232 compared to DTIC, with the ICER values lower than cost-effectiveness threshold in Hong Kong. Results comparing pembrolizumab to TMZ and to PC were similar to that when compared to DTIC. Probability sensitivity analyses showed that 99% of the simulated ICERs were below three times the Gross Domestic Product (GDP) per capita for Hong Kong (currently at $119,274//QALY threshold). In a scenario analysis comparing pembrolizumab with ipilimumab, the estimated ICER was USD8,904.ConclusionsPembrolizumab is cost-effective relative to chemotherapy (DTIC, TMZ and PC), and highly-cost-effective compared to ipilimumab, for the first-line treatment of advanced melanoma in Hong Kong.

Formal Implementation of Cost-Effectiveness Evaluations in Japan: A Unique Health Technology Assessment System

In April 2019, Japan formally introduced health technology assessment (HTA) and, more specifically, a cost-effectiveness analysis, to inform healthcare decision making, mainly when it comes to the pricing of new technologies. This article provides an overview of this new policy, which was implemented formally after a pilot program. In the fiscal year (FY) 2012, discussions on cost-effectiveness assessments were initiated in Japan. After 7 years of deliberations, a cost-effectiveness assessment was implemented formally in April 2019. In Japan, the cost-effectiveness analysis has been used to inform price adjustments of healthcare technologies, although it has not yet been used for decision making on insurance coverage. Selection criteria were established because not all drugs and medical devices could be evaluated owing to a shortage of experts. Exclusion criteria have also been applied to prevent access restriction. The scope of the evaluation’s price adjustment target is limited to part of the product price. If the cost per quality-adjusted life-year (QALY) threshold falls below ¥5 million per QALY, the price adjustment rate changes stepwise according to the cost per QALY. In addition to price reduction, a price-raising scheme has also been implemented for scenarios where products are evaluated to be highly cost-effective and innovative. This article describes the first formally implemented HTA system in Japan. Although it is too early to make any conclusions about its effect, the Japan-specific context makes this system unique. To fully understand the opportunities and challenges of the new system, it is vital that Japan accumulates experience with this system and develops human resources in health economic evaluation.

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation.

Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%. Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. This study is registered as PROSPERO CRD42017058688. The National Institute for Health Research Health Technology Assessment programme.

Understanding Payer Perspectives on Value in the Use of Pharmaceuticals in the United States.

In recent years, value assessment frameworks have been introduced to inform discussions about how to define and assess value in the U.S. health care system. However, there is uncertainty as to how value assessment frameworks and other approaches to achieve value such as outcomes-based contracting are perceived and used in coverage decisions. To understand how U.S. payers determine value in the use of pharmaceuticals and how it differs from payers outside the United States. Qualitative in-depth phone interviews with 13 executive-level public and private U.S. managed care representatives and 6 health technology assessment advisors outside the United States were conducted from September to November 2017. Despite various mechanisms used by U.S. payers to assess value, no consistent definitions of value were provided, and U.S. payers felt limited in what they can do to achieve value in pharmaceutical decision making. Value assessment frameworks are not formally considered in formulary and reimbursement decisions but are used as a reference as they become available by most or all U.S. health plans. U.S. payers expressed concerns, including limited control over pharmaceutical pricing and budget caps, and limited ability to use incremental cost per quality-adjusted life-year thresholds. Outcomes-based contracting could have some utility in specific cases where the treatment has a particularly high cost and a clear outcomes measure, but payers indicated that outcomes-based contracts can be difficult to operationalize, and determination of savings was uncertain. Payers outside the United States-who are enabled by government health care bodies, policy tools, and analytical frameworks that have no counterpart in the United States-have a wider array of instruments at their disposal. U.S. payers were largely open to learning from other health care systems outside the United States, particularly the German health care system, where patient-relevant benefit compared with a predetermined treatment comparator is the primary determinant for price negotiations. Although there is interest in including value assessment frameworks during the decision-making process in the United States, there are significant challenges to operationalizing them. The current environment in the United States restricts payers' ability to make favorable contracts with manufacturers, and changes to the U.S. health system design are needed to facilitate this effort. Adoption of a value assessment framework in Medicare or Medicaid would accelerate adoption of these tools by private payers in the United States. This study was conducted by RTI Health Solutions under the direction of The Pew Charitable Trusts and was funded by The Pew Charitable Trusts. Vekaria is employed by RTI Health Solutions. Reynolds and Coukell are employed by The Pew Charitable Trusts. Brogan and Hogue have nothing to disclose.

Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia.

Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.

PRS14 COST-EFECTIVENESS ANALYSIS OF AN INTERVENTION TO REDUCE THE CRITICAL HANDLING ERRORS OF FIXED-DOSE ICS/LABA COMBINATIONS IN ASTHMA PATIENTS IN SPAIN

This study explores the cost-effectiveness of an error-targeted intervention, in asthma patients treated with fixed-dose inhaled corticosteroid/long-acting beta-2 agonist (ICS/LABA) devices, consisting in the use of the new breath-activated inhaler (K-Haler®) in comparison with the most used ICS/LABA combination devices: Fluticasone/Saltemerol pMDI (FS-MDI), Fluticasone/Salmeterol Accuhaler® (ACCU), Budesonide/Formoterol Turbuhaler® (TURBU). A probabilistic Markov cost-utility model was developed, based on the CRITIKAL study findings (Price et al. 2017). Patients with moderate-severe asthma, according to Global Initiative for Asthma (GINA) criteria, transitioned between controlled and uncontrolled health states, on weekly cycles over a 5-year period. Estimated asthma exacerbations were also included in the model. Spanish costs and resources were accounted, based on literature review and an expert panel opinion. Effectiveness outcome measure were Quality-Adjusted Life Years (QALYs). Model analysis was carried out, primary, from the perspective of the Spanish National Health System (SNHS) and, secondarily, from the societal perspective. A 3% discount rate, was reckoned, affecting costs (€2019) and effects. The intervention (K-Haler® device) dominated pMDI as well as the two DPI devices compared over 5 years. Direct cost savings of €207.44/€421.68/€957.12 vs FS-MDI, ACCU and TURBU respectively, alongside additional 0.03/0.05/0.02 QALY gains. Furthermore, it showed the highest probability of being cost-effective at a €30,000/QALY threshold. Key factors driving variance were weekly utilities per state and RR of moving to an uncontrolled state, and its impact on exacerbations. The robustness of the model was validated with both deterministic and probabilistic sensitivity analysis. Handling error minimization due to K-Haler® device utilization resulted in an improved asthma control, improving treatment effectiveness as quality of life of patients. K-Haler® is a dominant therapeutic alternative in comparison with the other inhaler devices analyzed from the SNHS perspective. Study funded by Mundipharma Pharmaceuticals, S.L.

PCN179 TREOSULFAN-BASED CONDITIONING VS BUSULFAN-BASED CONDITIONING FOR ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH AML OR MDS — A UK COST-UTILITY ANALYSIS

Cost-utility analyses comparing alternative conditioning regimens for patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) have not previously been conducted. A cost-utility analysis was developed to compare a treosulfan and fludarabine conditioning regimen (Tr-Fl) versus busulfan with fludarabine based conditioning (Bu-Fl) prior to alloHSCT, for patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) considered ineligible to receive standard conditioning regimens. A partitioned survival model was developed to compare Tr-Fl with Bu-Fl from a UK National Health Service and Personal Social Services perspective. Patients started in the induction/alloHSCT health state, before transitioning to alloHSCT recovery (remission), relapse/progression and death after the first model cycle. Data on patient characteristics, overall survival (OS), event-free survival (EFS) and adverse events were collected from a head to head phase III clinical trial. OS and EFS were extrapolated beyond the trial duration using parametric survival models. A functional cure assumption was applied at 5 years based on clinical expert opinion, with subsequent mortality defined using a hazard ratio for long-term post-HSCT patients applied to UK life table data. Utilities and mapping algorithms were identified through systematic and targeted literature review and were adjusted for age and sex using a published model for general population utility. Costs of treatment, adverse events, inpatient/outpatient care, and mortality were included in the analysis. Tr-Fl dominated Bu-Fl, with incremental quality-adjusted life-years (QALYs) and costs of 0.78 and -£17,689, respectively. Probabilistic sensitivity analysis indicated that Tr-FL had an 94.1% probability of cost-effectiveness at a £30,000 per QALY threshold. Tr-Fl also dominated Bu-Fl for each indication subgroup, with incremental QALYs of 0.71 and 1.03 and incremental costs of -£24,138 and -£2,570 for AML and MDS, respectively. Tr-Fl is a highly cost-effective conditioning treatment for alloHSCT patients with AML or MDS ineligible for standard conditioning regimens, compared with Bu-Fl.

PSY18 COST-EFFECTIVENESS OF TOFACITINIB IN ACTIVE PSORIATIC ARTHRITIS AFTER ANTI-TUMOUR NECROSIS FACTOR (ANTI-TNF) FAILURE OR INTOLERANCE IN SPAIN

To evaluate the cost-effectiveness of initiating treatment for psoriatic arthritis (PsA) with tofacitinib in comparison to interleukin IL-23/IL-12 and IL-17A antagonists, after failure or intolerance to a first line of anti-TNF biologic disease-modifying antirheumatic drugs (bDMARD population), from the Spanish National Health System perspective. A lifetime Markov model was developed. A panel of experts defined two sets of therapeutic sequences consisting on six lines of treatment, where only the first line was modified in order to compare tofacitinib versus ustekinumab, secukinumab and ixekizumab in bDMARD population. After six months of no response, patients switched to next treatment line. Response was evaluated using both 20% and 50% improvement in American College of Rheumatology criteria (ACR20 and ACR50, respectively) as the efficacy measures. Comparative efficacy data were inferred from a network meta-analysis and utilities were obtained from a post-hoc analysis of tofacitinib OPAL-BROADEN clinical trial. Direct medical resources and local unitary costs (€, 2018) were considered. Costs and outcomes were discounted at 3% and a 25.000€/quality-adjusted life-years (QALY) threshold value was used. Probabilistic sensitivity analysis were conducted. Tofacitinib versus ustekinumab was associated with comparable QALYs gain (-0.04 and -0.006 for ACR20 and ACR50, respectively) with a cost reduction of 5,784.34€ and 3,140.65€. Similarly, secukinumab 300mg and ixekizumab generated a small QALYs gain while tofacitinib was associated in both cases with substantial incremental costs-savings (versus secukinumab: 18,104.33€ and 9,068.56€ for ACR20 & ACR50, respectively; versus ixekizumab: 6,622.14€ and 15,159.59€ for ACR20 & ACR50, respectively). Sensitivity analysis confirmed tofacitinib's probability of being cost-effective is over 90% for all comparisons. Yielding similar QALYs gain, tofacitinib is the most cost-saving therapeutic option for PsA treatment after failure or intolerance to anti-TNF biologics in comparison to IL-23/IL-12 antagonist ustekinumab, or IL-17A antagonist secukinumab and ixekizumab, with a probability of being cost-effective over 90%.

Influence of Modeling Choices on Value of Information Analysis: An Empirical Analysis from a Real-World Experiment.

Value of information (VOI) analysis often requires modeling to characterize and propagate uncertainty. In collaboration with a cancer clinical trial group, we integrated a VOI approach to assessing trial proposals. This paper aims to explore the impact of modeling choices on VOI results and to share lessons learned from the experience. After selecting two proposals (A: phase III, breast cancer; B: phase II, pancreatic cancer) for in-depth evaluations, we categorized key modeling choices relevant to trial decision makers (characterizing uncertainty of efficacy, evidence thresholds to change clinical practice, and sample size) and modelers (cycle length, survival distribution, simulation runs, and other choices). Using a $150,000 per quality-adjusted life-year (QALY) threshold, we calculated the patient-level expected value of sample information (EVSI) for each proposal and examined whether each modeling choice led to relative change of more than 10% from the averaged base-case estimate. We separately analyzed the impact of the effective time horizon. The base-case EVSI was $118,300 for Proposal A and $22,200 for Proposal B per patient. Characterizing uncertainty of efficacy was the most important choice in both proposals (e.g. Proposal A: $118,300 using historical data vs. $348,300 using expert survey), followed by the sample size and the choice of survival distribution. The assumed effective time horizon also had a substantial impact on the population-level EVSI. Modeling choices can have a substantial impact on VOI. Therefore, it is important for groups working to incorporate VOI into research prioritization to adhere to best practices, be clear in their reporting and justification for modeling choices, and to work closely with the relevant decision makers, with particular attention to modeling choices.

A Simplified Cost-Utility Analysis of Inpatient Flap Monitoring after Microsurgical Breast Reconstruction and Implications for Hospital Length of Stay.

The number of free flap take-backs and successful salvages following microsurgical breast reconstruction decreases as time from surgery increases. As a result, the cost of extended inpatient monitoring to achieve a successful flap salvage rises rapidly with each postoperative day. This study introduces a simplified cost-utility model of inpatient flap monitoring and identifies when cost-utility exceeds the thresholds established for other medical treatments. A retrospective review of a prospectively maintained database was performed of patients who underwent microsurgical breast reconstruction to identify flap take-back and salvage rates by postoperative day. The number of patients and flaps that needed to be kept on an inpatient basis each day for monitoring to salvage a single failing flap was determined. Quality-of-life measures and incremental cost-effectiveness ratios for inpatient flap monitoring following microsurgical breast reconstruction were calculated and plotted against a $100,000/quality-adjusted life-year threshold. A total of 1813 patients (2847 flaps) were included. Overall flap take-back and salvage rates were 2.4 percent and 52.3 percent, respectively. Of the flaps taken back, the daily take-back and salvage rates were 56.8 and 60.0 percent (postoperative day 0 to 1), 13.6 and 83.3 percent (postoperative day 2), 11.4 and 40.0 percent (postoperative day 3), 9.1 and 25.0 percent (postoperative day 4), and 9.1 and 0.0 percent (>postoperative day 4), respectively. To salvage a single failing flap each day, the number of flaps that needed to be monitored were 121 (postoperative day 0 to 1), 363 (postoperative day 2), 907 (postoperative day 3), 1813 (postoperative day 4), and innumerable for days beyond postoperative day 4. The incremental cost-effectiveness ratio of inpatient flap monitoring begins to exceed a willingness-to-pay threshold of $100,000/quality-adjusted life-year by postoperative day 2. The health care cost associated with inpatient flap monitoring following microsurgical breast reconstruction begins to rise rapidly after postoperative day 2.

Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily for 6 months, then extended prevention with 10 mg once daily) or apixaban (10 mg twice daily for 1 week, followed by 5 mg twice daily for 6 months, then extended prevention with 2.5 mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6 months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.

Cost Effectiveness of Advanced Pharmacy Services Provided in the Community and Primary Care Settings: A Systematic Review.

Pharmacists working in community and primary care are increasingly developing advanced skills to provide enhanced services, particularly in dealing with minor acute illness. These services can potentially free-up primary care physicians' time; however, it is not clear whether they are sufficiently cost effective to be recommended for wider provision in the UK. The aim of this study was to review published economic evaluations of enhanced pharmacy services in the community and primary care settings. We undertook a systematic review of economic evaluations of enhanced pharmacy services to inform NICE guidelines for emergency and acute care. The review protocol was developed and agreed with the guideline committee. The National Health Service Economic Evaluation Database, Health Technology Assessment Database, Health Economic Evaluations Database, MEDLINE and EMBASE were searched in December 2016 and the search was updated in March 2018. Studies were assessed for applicability and methodological quality using the NICE Economic Evaluation Checklist. Of 3124 records, 13 studies published in 14 papers were included. The studies were conducted in the UK, Spain, The Netherlands, Australia, Italy and Canada. Settings included community pharmacies, primary care/general practice surgeries and patients' homes. Most of the studies were assessed as partially applicable with potentially serious limitations. Services provided in community and primary care settings were found to be either dominant or cost effective, at a £20,000 per quality-adjusted life-year threshold, compared with usual care. Those delivered in the patient's home were not found to be cost effective. Advanced pharmacy services appear to be cost effective when delivered in community and primary care settings, but not in domiciliary settings. Expansion in the provision of these services in community and primary care can be recommended for wider implementation.

Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma.

Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness. We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty. In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS. At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.

Cost-effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma.

7561 Background: Two anti-CD19 chimeric antigen receptor T-cell therapies are approved for large B-cell lymphoma (DLBCL): axicabtagene ciloleucel (axi-cel) and tisagenlecleucel. Each costs $373,000 (wholesale acquisition). We evaluated each therapy’s cost-effectiveness. Methods: A decision analytic Markov model evaluated axi-cel and tisagenlecleucel in multiply relapsed/refractory adult DLBCL from a US health-payer perspective over a lifetime horizon. The model was informed by recent multi-center, single-arm clinical trials. Under a range of plausible long-term effectiveness assumptions, axi-cel and tisagenlecleucel were each compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were un-discounted life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Sensitivity analyses explored uncertainty. Results: In an optimistic scenario, assuming 40% five-year progression-free survival (PFS), axi-cel increased life-expectancy by 8.15 years at $129,000/QALY (95% UI: $90,000-215,000/QALY) gained. At 30% five-year PFS, improvements in life-expectancy were more modest (6.4 years) and expensive ($159,000/QALY [$107,000-281,000/QALY] gained). In an optimistic scenario, assuming 35% five-year PFS, tisagenlecleucel increased life-expectancy by 4.6 years at $168,000/QALY ($104,000-453,000/QALY) gained. At 25% five-year PFS, improvements in life-expectancies were more modest (3.4 years) and expensive ($224,000/QALY [$124,000-1,190,000/QALY] gained). Administering CAR-T to all indicated patients would increase US healthcare costs by $10 billion over 5 years. Price reductions to $250,000 or payment only for initial CR or 90-day CR/PR (at current prices) would allow both therapies to cost < $150,000/QALY down to 25% PFS. Conclusions: At current prices, it is possible that each CAR-T therapy may meet a < $150,000/QALY threshold; this is dependent on long-term benefit compared with chemoimmunotherapy and SCT, which is uncertain. Widespread adoption would increase non-Hodgkin lymphoma healthcare costs substantially. Price reductions or payment for initial CR or 90-day CR/PR would favorably influence cost-effectiveness even if long-term outcomes are modest.

Cost-effectiveness of integrating buprenorphine-naloxone treatment for opioid use disorder into clinical care for persons with HIV/hepatitis C co-infection who inject opioids

BackgroundUntreated opioid use disorder (OUD) affects the care of HIV/HCV co-infected people who inject opioids. Despite active injection opioid use, there is evidence of increasing engagement in HIV care and adherence to HIV medications among HIV/HCV co-infected persons. However, less than one-half of this population is offered HCV treatment onsite. Treatment for OUD is also rare and largely occurs offsite. Integrating buprenorphine-naloxone (BUP-NX) into onsite care for HIV/HCV co-infected persons may improve outcomes, but the clinical impact and costs are unknown. We evaluated the clinical impact, costs, and cost-effectiveness of integrating (BUP-NX) into onsite HIV/HCV treatment compared with the status quo of offsite referral for medications for OUD. MethodsWe used a Monte Carlo microsimulation of HCV to compare two strategies for people who inject opioids: 1) standard HIV care with onsite HCV treatment and referral to offsite OUD care (status quo) and 2) standard HIV care with onsite HCV and BUP-NX treatment (integrated care). Both strategies assume that all individuals are already in HIV care. Data from national databases, clinical trials, and cohorts informed model inputs. Outcomes included mortality, HCV reinfection, quality-adjusted life years (QALYs), costs (2017 US dollars), and incremental cost-effectiveness ratios. ResultsIntegrated care reduced HCV reinfections by 7%, cases of cirrhosis by 1%, and liver-related deaths by 3%. Compared to the status quo, this strategy also resulted in an estimated 11/1,000 fewer non-liver attributable deaths at one year and 28/1,000 fewer of these deaths at five years, at a cost-effectiveness ratio of $57,100/QALY. Integrated care remained cost-effective in sensitivity analyses that varied the proportion of the population actively injecting opioids, availability of BUP-NX, and quality of life weights. ConclusionsIntegrating BUP-NX for OUD into treatment for HIV/HCV co-infected adults who inject opioids increases life expectancy and is cost-effective at a $100,000/QALY threshold.

PRO24 COST-EFFECTIVENESS OF LANADELUMAB AND C1-INHIBITORS FOR PROPHYLAXIS AGAINST ACUTE ATTACKS OF HEREDITARY ANGIOEDEMA

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent episodes of body tissue swelling. We evaluated the cost-effectiveness of lanadelumab and the C1-inhibitors, Cinryze and Haegarda, for long-term prophylaxis against acute HAE attacks versus no prophylaxis in adult patients with HAE type 1/2 from a US health system perspective. We developed a Markov model with two health states: alive with HAE and dead with monthly cycles over a life-time horizon. Baseline characteristics were: mean age of 39.6 years, 68.4% female, mean weights of 88.8kg (male) and 76.4 kg (female), and a baseline attack rate of 3.39 per month. We tracked number of attacks, time attack free, survival, quality-of-life, and costs. Parameters were obtained from publicly available databases, published literature, and expert opinion. Outcomes included discounted (3% per year) quality-adjusted life-years (QALYs) and costs (2018 US$), and incremental cost per QALY gained (ICER). We conducted univariate and probabilistic sensitivity analyses, and scenario analyses. Expected QALYs were 17.47 for no prophylaxis, and ranged from 18.21 (Cinryze) to 18.66 (lanadelumab) for patients receiving prophylaxis. Expected costs were $9,953,000 for no prophylaxis and ranged from $10,343,000 (Haegarda) to $14,396,000 (Cinryze) yielding ICERs ranging from $328,000 (Haegarda) to $5,954,000 (Cinryze). ICERs were extremely sensitive to drug acquisition costs, the baseline attack rate and treatment effects. The probability that Haegarda and lanadelumab were cost-effective at a $150,000/QALY threshold was 36% and 5%, respectively. A scenario analysis showed that 75% of patients would need to be switched to every four-week dosing for lanadelumab to be cost-effective at a $150,000/QALY threshold. In the base case, drugs for prophylaxis against acute attacks of HAE were likely to exceed the cost-effectiveness threshold of $150,000/QALY. However, the model outcomes were highly sensitive to changes in model inputs and assumptions and should be interpreted with caution.

PMU9 DO NICE APPRAISAL PROCESSES REWARD INNOVATIVE AND CURATIVE THERAPIES? AN ASSESSMENT OF CURRENT AND POTENTIAL FUTURE TECHNOLOGY APPRAISALS FOR RARE DISEASES

To assess NICE processes for rare diseases: Highly Specialised Technologies (HST) committee appraisal, weightings of quality-adjusted life years (QALY), and differential discounting. We assessed current and proposed HST and Single Technology Assessment (STA) evaluated technologies for adherence to the HST qualification criteria, eligible patient population/prevalence, undiscounted survival benefit and application of the QALY weighting. We also assessed a targeted selection of pipeline therapies with the potential for substantial survival and quality of life gain. Using published literature, we identified which therapies might qualify for the HST evaluation and, of those, which qualify for the QALY weighting and/or differential discounting. We simulated the impact of these processes on a hypothetical drug with a large survival benefit in a rare disease. To date, eight therapies have been recommended out of 20 referred to the NICE HST committee. Of those recommended, only one qualified for QALY weighting. For the others, the expected QALY benefit did not exceed the 10 QALY threshold. Of 11 selected pipeline therapies, only three (27%) would be expected to meet HST criteria and zero would meet thresholds for QALY weighting. In a hypothetical scenario where a drug for a rare condition improved survival by 20 years with an average utility score of 0.6, failure to qualify for QALY weighting/HST process would reduce the cost-effective price by more than £1M. NICE HST approaches are intended to make allowance for rare, debilitating conditions where treatments may not meet traditional cost-effectiveness thresholds. In practice, however, these allowances are ambiguous and evaluated technologies rarely qualify. Future innovative therapies may deliver substantial benefits, however, access may be limited if traditional thresholds are applied. Over time, this may signal to industry that without extreme survival benefit, treatments for rare disease are unattractive investments.