Cost-effectiveness of pembrolizumab for previously treated MSI-H/dMMR solid tumours in the UK.

OBJECTIVES: Patients with previously treated microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) tumours have limited chemotherapeutic treatment options. Pembrolizumab received approval from the EMA in 2022 for the treatment of colorectal, endometrial, gastric, small intestine, and biliary MSI-H/dMMR tumour types. This approval was supported by data from the KEYNOTE-164 and KEYNOTE-158 clinical trials. This study evaluated the cost-effectiveness of pembrolizumab compared with standard of care (SoC) for previously treated MSI-H/dMMR solid tumours in line with the approved EMA label from a UK healthcare payer perspective. METHODS: A multi-tumour partitioned survival model was built consisting of pre-progression, progressed disease, and dead health states. Pembrolizumab survival outcomes were extrapolated using Bayesian hierarchical models (BHMs) fitted to pooled data from KEYNOTE-164 and KEYNOTE-158. Comparator outcomes were informed by published sources. Tumour sites were modelled independently and then combined, weighted by tumour site distribution. A SoC comparator was used to formulate the overall cost-effectiveness result with pembrolizumab as the intervention. SoC comprised a weighted average of the comparators by tumour site based on market share. Drug acquisition, administration, adverse events, monitoring, subsequent treatment, end-of-life costs, and testing costs were included. Sensitivity and scenario analyses were performed, including modelling pembrolizumab efficacy using standard parametric survival models. RESULTS: Pembrolizumab, at list price, was associated with £129,469 in total costs, 8.30 LYs, and 3.88 QALYs across the pooled tumour sites. SoC was associated with £28,222 in total costs, 1.14 LYs, and 0.72 QALYs across the pooled tumour sites. This yields an incremental cost-effectiveness ratio (ICER) of £32,085 per QALY. Results were robust to sensitivity and scenario analyses. CONCLUSIONS: This model demonstrates pembrolizumab provides a valuable new alternative therapy for UK patients with MSH-H/dMMR cancer at the cost of £32,085 per QALY, with confidential discounts anticipated to improve cost-effectiveness further.

Recent advances in addressing the market failure of new antimicrobials: Learnings from NICE's subscription-style payment model.

Background: Antimicrobial resistance (AMR) is a growing threat to global health. With pathogenic bacteria inevitably becoming more resistant to existing antimicrobials, mortality and costs due to AMR will significantly increase over the next few decades if adequate action is not taken. A major challenge in addressing AMR is the lack of financial incentives for manufacturers to invest in developing new antimicrobials. This is partly because current approaches in health technology assessment (HTA) and standard modeling methods fail to capture the full value of antimicrobials. Aim: We explore recent reimbursement and payment frameworks, particularly pull incentives, aimed to address the market failures in antimicrobials. We focus on the "subscription-style" payment model recently used in the UK and discuss the learnings for other European countries. Methods: A pragmatic literature review was conducted to identify recent initiatives and frameworks between 2012 and 2021, across seven European markets. The National Institute for Health and Care Excellence (NICE) technology appraisals for cefiderocol and for ceftazidime with avibactam were reviewed to evaluate how the new UK model has been applied in practice and identify the key challenges. Conclusion: The UK and Sweden are the first European countries to pilot the feasibility of implementing pull incentives through fully and partially delinked payment models, respectively. The NICE appraisals highlighted the complexity and large areas of uncertainty of modeling antimicrobials. If HTA and value-based pricing are part of the future in tackling the market failure in AMR, European-level efforts may be needed to overcome some of the key challenges.

The Cost Effectiveness of Levodopa-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson's Disease in England.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disease, which significantly impacts patients' quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson's disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory. OBJECTIVE: We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson's disease in England, using real-world data. METHODS: A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson's disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG. CONCLUSIONS: The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England.

Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI.

BACKGROUND: Clostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI. METHODS: A SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China. RESULTS: Of 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI. Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively. No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase. Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease. Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI. CONCLUSIONS: Despite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.

The cost-effectiveness of dulaglutide versus insulin glargine for the treatment of type 2 diabetes mellitus in Japan.

AIMS: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines. METHODS: The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine. Direct comparative data from the Araki 2015 trial (NCT01584232) was used to inform the analysis. Costs associated with treatment and complications were derived from Japanese sources wherever possible and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European systematic review of diabetes utilities and adjusted for use in a Japanese population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were conducted on all inputs and key modeling assumptions. RESULTS: Dulaglutide 0.75 mg was associated with higher quality-adjusted life years (QALYs), life years (LYs), and total costs, compared to insulin glargine, resulting in an incremental cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with dulaglutide increased the time alive and free from diabetes-related complications by 4 months. OWSA and PSA indicated that results were robust to plausible variations in input parameters and modeling assumptions. LIMITATIONS: Key limitations of this study are similar to other cost-utility analyses of diabetes, including the extrapolation of short-term clinical trial data into lifelong durations. In addition, due to the lack of robust published Japanese data, some values were derived from non-Japanese sources. CONCLUSIONS: This analysis suggests that dulaglutide 0.75 mg may be a cost-effective treatment alternative to insulin glargine for patients with T2DM in Japan.

Cost-Effectiveness Analysis of Regorafenib for Gastrointestinal Stromal Tumour (GIST) in Germany.

BACKGROUND: No study has compared the cost-effectiveness of active treatment options for unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. The aim of this study was to estimate the cost-effectiveness of regorafenib compared to imatinib rechallenge in this setting in Germany. METHODS: Hazard ratios for progression-free (PFS) and overall survival (OS) with regorafenib versus imatinib rechallenge were estimated by indirect comparison. A state distribution model was used to simulate progression, mortality and treatment costs over a lifetime horizon. Drug acquisition costs and utilities were derived from clinical trial data and published literature; non-drug costs were not included. The outcomes measured were treatment costs, life-years (LYs) and quality-adjusted life-years (QALYs). RESULTS: The indirect comparison suggested that median PFS and OS were longer with regorafenib compared to imatinib but results were not statistically significant. Regorafenib versus imatinib rechallenge was estimated to have hazard ratios of 0.58 (95% CI 0.31-1.11) for PFS and 0.77 (95% CI 0.34-1.77) for OS, with substantial uncertainty due to the rarity of the disease and small number of patients within the trials. Regorafenib treatment per patient over a lifetime horizon provided an additional 0.61 LYs and 0.42 QALYs over imatinib rechallenge, with additional direct drug costs of €8,773. The incremental cost-effectiveness ratio was €21,127 per QALY gained. At a cost-effectiveness threshold of €50,000 per QALY, regorafenib had a 67% probability of being cost-effective. CONCLUSION: Based on the currently available clinical data, this analysis suggests that regorafenib is cost-effective compared with imatinib rechallenge in Germany.

Benchmarking the Cost per Person of Mass Treatment for Selected Neglected Tropical Diseases: An Approach Based on Literature Review and Meta-regression with Web-Based Software Application.

BACKGROUND: Advocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US$ 0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering "free" donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked. METHODS: We reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to "predict" country-specific unit cost benchmarks. RESULTS: We reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US$ 0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the "last mile", or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher. DISCUSSION: The available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms.