The FLURESP European commission project: cost-effectiveness assessment of ten public health measures against influenza in Italy: is there an interest in COVID-19 pandemic?

BACKGROUND: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. METHODS: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. RESULTS: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. CONCLUSIONS: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

Using electronic health records for clinical research: the case of the EHR4CR project.

OBJECTIVES: To describe the IMI EHR4CR project which is designing and developing, and aims to demonstrate, a scalable, widely acceptable and efficient approach to interoperability between EHR systems and clinical research systems. METHODS: The IMI EHR4CR project is combining and extending several previously isolated state-of-the-art technical components through a new approach to develop a platform for reusing EHR data to support medical research. This will be achieved through multiple but unified initiatives across different major disease areas (e.g. cardiovascular, cancer) and clinical research use cases (protocol feasibility, patient identification and recruitment, clinical trial execution and serious adverse event reporting), with various local and national stakeholders across several countries and therefore under various legal frameworks. RESULTS: An initial instance of the platform has been built, providing communication, security and terminology services to the eleven participating hospitals and ten pharmaceutical companies located in seven European countries. Proof-of-concept demonstrators have been built and evaluated for the protocol feasibility and patient recruitment scenarios. The specifications of the clinical trial execution and the adverse event reporting scenarios have been documented and reviewed. CONCLUSIONS: Through a combination of a consortium that brings collectively many years of experience from previous relevant EU projects and of the global conduct of clinical trials, of an approach to ethics that engages many important stakeholders across Europe to ensure acceptability, of a robust iterative design methodology for the platform services that is anchored on requirements of an underlying Service Oriented Architecture that has been designed to be scalable and adaptable, EHR4CR could be well placed to deliver a sound, useful and well accepted pan-European solution for the reuse of hospital EHR data to support clinical research studies.

Impact of pigmentary disorders on quality of life in Japan: Interest of the BeautyQoL instrument.

Skin pigmentary disorders and uneven skin tone represent common cosmetic concerns in Japan where fairer skin is culturally desirable. As the demographics of Asian countries continue to evolve, there is a need to understand the impact of cosmetic skin concerns on quality of life (QoL). 199 Japanese women self-claiming facial skin pigmentation disorders were asked to complete the BeautyQoL questionnaire, and the results were compared with those of a control group of 200 women. Of the five dimensions of the BeautyQoL questionnaire, the dimension "mood" appeared to be significantly lower in the group presenting facial dark spots, as compared with the control group (p < 0.05). In the group presenting facial dark spots, the five dimensions and the global score showed that subjects concerned had lower scores than subjects less concerned, even if statistical significance was not reached. This study confirms that common pigmentary disorders such as facial black spots may negatively impact QoL. Further comparative studies with a controlled randomized design would be necessary to confirm these findings.

Cost-effectiveness simulation model of biologic strategies for treating to target rheumatoid arthritis in Germany.

OBJECTIVES: The treatment of active rheumatoid arthritis (RA) usually requires different therapeutic options used sequentially in case of an insufficient response (IR) to previous agents. Since there is a lack of clinical trials comparing biologic treatment sequences, simulation models might add to the understanding of optimal treatment sequences and their cost-effectiveness. The objective of this study was to assess the cost-effectiveness of different biologic treatment strategies in patients with an IR to anti-TNF agents, based on levels of disease activity from the German public payer's perspective. METHODS: A cost-effectiveness sequential model was developed in accordance with local RA treatment strategies, using DAS28 scores as dichotomous effectiveness endpoints: achieving remission/no remission (RS/no RS) or a state of low disease activity (LDAS/no LDAS). Costs were estimated using resource utilisation data obtained from a large observational German cohort. Advanced simulations were conducted to assess the cost-effectiveness over 2 years of four sequential biologic strategies composed of up to 3 biologic agents, namely anti-TNF agents, abatacept or rituximab, in patients with moderate-to-severe active RA and an IR to at least one anti-TNF agent. RESULTS: Over two years, the biological sequence including abatacept after an IR to one anti-TNF agent appeared the most effective and cost-effective versus (vs.) use after two anti-TNF agents (€633 vs. €1,067/day in LDAS and €1,222 vs. €3,592/day in remission), and vs a similar sequence using rituximab (€633 vs. €728/day in LDAS and €1,222 vs. €1,812/day in remission). The sequence using a 3rd anti-TNF agent was less effective and cost-effective than the same sequence using abatacept (€2,000 vs. €1,067/day in LDAS and €6,623 vs. €3,592/day in remission). All differences were statistically significant (p<0.01). CONCLUSIONS: The results suggest that in patients with an IR to at least one anti-TNF agent, biologic sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or only cycled anti-TNF agents.

Interest of modelling in rheumatoid arthritis.

Such as prospective studies can provide evidence-based information for clinicians and regulatory agencies, modelling studies provide useful information when experimental studies are to complex, too long, or too expensive to carry out. If modelling has been widely used in pharmacokinetics, it is in the field of pharmacoeconomics that numerous models have been published in recent years, including models relevant to the management of rheumatoid arthritis (RA). The most common modelling techniques published in RA are decision trees and Markov models which are used to perform cost-effectiveness and cost-utility analyses using real or simulated populations. This paper reviews the main types of modelling techniques used in pharmacoeconomic studies with the aim of clarifying their interest and limitations for the clinicians. Generating such evidence is highly relevant to assisting clinical recommendations and reimbursement decisions towards enabling the optimal management of RA and reducing its overall clinical and economic burden, for the benefits of patients and health systems.

Cost-effectiveness modelling of biological treatment sequences in moderate to severe rheumatoid arthritis in France.

OBJECTIVES: Modern treatment of RA includes the use of biologics. Their cost is high and comparison between different treatment strategies is needed. METHOD: Direct medical costs of RA in France were evaluated based on expert opinion. Then, simulation-decision analytical models were developed to assess four biologic treatment sequences over 2 years in patients failing to respond to at least one anti-TNF agent. Effectiveness was expressed in theoretical expected number of days (TEND) in remission or low disease activity [low disease activity score (LDAS)] based on DAS-28 scores. RESULTS: Direct medical costs of RA in France (excluding the cost of biologics) were estimated at euro 905 (s.d. 263) for 6 months and euro 696 (s.d. 240) for each subsequent 6 months (P < 0.001) for patients achieving LDAS and euro 1215 for 6 months (s.d. 405) for patients not achieving LDAS. Based on LDAS criteria, using abatacept after an inadequate response to the first anti-TNF agent (etanercept) appeared significantly (P < 0.01) more efficacious over a 2-year period (102 TEND) compared with using rituximab at a 6-month re-treatment interval (82 TEND). Mean cost-effectiveness ratios showed significantly lower costs (P < 0.01) per TEND with abatacept as second biologic agent (euro 278) compared with rituximab (euro 303). After an inadequate response to two anti-TNF agents, using abatacept also appeared significantly more efficacious than an anti-TNF agent (P < 0.01). All comparisons were confirmed when using remission criteria instead of LDAS. CONCLUSION: Advanced simulation models based on clinical evidence and medical practice appear to be a promising approach for comparing cost-effectiveness of biologic strategies in RA.

[Value of hospital electronic health records for clinical research: contribution of the European project EHR4CR]. / Intérêt des dossiers de santé électroniques hospitaliers pour la recherche clinique - Le projet européen EHR4CR.

Electronic health records in hospitals contribute to improving the quality of care by enabling better management of clinical information. The databases thus constituted facilitate the exchange of health information with healthcare providers and optimize multidisciplinary coordination for better therapeutic results. The EHR4CR (Electronic Health Records for Clinical Research) European project has developed an innovative pilot platform enabling the reuse of this digital information for clinical research. By enhancing and speeding up clinical research procedures, this innovative approach makes it possible to conduct clinical trials more efficiently, faster, and more economically.

Business analysis for a sustainable, multi-stakeholder ecosystem for leveraging the Electronic Health Records for Clinical Research (EHR4CR) platform in Europe.

INTRODUCTION: The Electronic Health Records for Clinical Research (EHR4CR) technological platform has been developed to enable the trustworthy reuse of hospital electronic health records data for clinical research. The EHR4CR platform can enhance and speed up clinical research scenarios: protocol feasibility assessment, patient identification for recruitment in clinical trials, and clinical data exchange, including for reporting serious adverse events. Our objective was to seed a multi-stakeholder ecosystem to enable the scalable exploitation of the EHR4CR platform in Europe, and to assess its economic sustainability. MATERIALS AND METHODS: Market analyses were conducted by a multidisciplinary task force to define an EHR4CR emerging ecosystem and multi-stakeholder value chain. This involved mapping stakeholder groups and defining their unmet needs, incentives, potential barriers for adopting innovative solutions, roles and interdependencies. A comprehensive business model, value propositions, and sustainability strategies were developed accordingly. Using simulation modelling (including Monte Carlo simulations) and a 5-year horizon, the potential financial outcomes of the business model were forecasted from the perspective of an EHR4CR service provider. RESULTS: A business ecosystem was defined to leverage the EHR4CR multi-stakeholder value chain. Value propositions were developed describing the expected benefits of EHR4CR solutions for all stakeholders. From an EHR4CR service provider's viewpoint, the business model simulation estimated that a profitability ratio of up to 1.8 could be achieved at year 1, with potential for growth in subsequent years depending on projected market uptake. CONCLUSIONS: By enhancing and speeding up existing processes, EHR4CR solutions promise to transform the clinical research landscape. The ecosystem defined provides the organisational framework for optimising the value and benefits for all stakeholders involved, in a sustainable manner. Our study suggests that the exploitation of EHR4CR solutions appears profitable and sustainable in Europe, with a growth potential depending on the rates of market and hospital adoption.

Is there an alternative to quality-adjusted life years for supporting healthcare decision making?

INTRODUCTION: Over the years, a number of criticisms have been raised about the robustness of the Quality-Adjusted Life Years (QALY) indicator and its use in cost-utility analyses; however, costs/QALY are still nowadays recommended as reference case by several Health Technology Assessment (HTA) agencies from some Commonwealth countries, such as the National Institute for Health and Care Excellence (NICE) in the UK, claiming that no alternatives exist to allocate health care resources. AREAS COVERED: This review presents a selection of robust alternative methodologies that could be used to support HTA decisions more accurately and more fairly than using the QALYs, including for determining the level of patient access and reimbursement coverage to healthcare interventions. Expert commentary: Because of the scientific complexity of the situations raised by existing and innovative health technologies and interventions, there is currently no single alternative paradigm to propose at this time, but a spectrum of additional analytical techniques which could handle various outcomes including costs and health consequences, and which are not based on a simple multiplicative formula.

Cost-benefit assessment of using electronic health records data for clinical research versus current practices: Contribution of the Electronic Health Records for Clinical Research (EHR4CR) European Project.

INTRODUCTION: The widespread adoption of electronic health records (EHR) provides a new opportunity to improve the efficiency of clinical research. The European EHR4CR (Electronic Health Records for Clinical Research) 4-year project has developed an innovative technological platform to enable the re-use of EHR data for clinical research. The objective of this cost-benefit assessment (CBA) is to assess the value of EHR4CR solutions compared to current practices, from the perspective of sponsors of clinical trials. MATERIALS AND METHODS: A CBA model was developed using an advanced modeling approach. The costs of performing three clinical research scenarios (S) applied to a hypothetical Phase II or III oncology clinical trial workflow (reference case) were estimated under current and EHR4CR conditions, namely protocol feasibility assessment (S1), patient identification for recruitment (S2), and clinical study execution (S3). The potential benefits were calculated considering that the estimated reduction in actual person-time and costs for performing EHR4CR S1, S2, and S3 would accelerate time to market (TTM). Probabilistic sensitivity analyses using Monte Carlo simulations were conducted to manage uncertainty. RESULTS: Should the estimated efficiency gains achieved with the EHR4CR platform translate into faster TTM, the expected benefits for the global pharmaceutical oncology sector were estimated at €161.5m (S1), €45.7m (S2), €204.5m (S1+S2), €1906m (S3), and up to €2121.8m (S1+S2+S3) when the scenarios were used sequentially. CONCLUSIONS: The results suggest that optimizing clinical trial design and execution with the EHR4CR platform would generate substantial added value for pharmaceutical industry, as main sponsors of clinical trials in Europe, and beyond.

Validation of the underlying assumptions of the quality-adjusted life-years outcome: results from the ECHOUTCOME European project.

BACKGROUND: Quality-adjusted life-years (QALYs) have been used since the 1980s as a standard health outcome measure for conducting cost-utility analyses, which are often inadequately labeled as 'cost-effectiveness analyses'. This synthetic outcome, which combines the quantity of life lived with its quality expressed as a preference score, is currently recommended as reference case by some health technology assessment (HTA) agencies. While critics of the QALY approach have expressed concerns about equity and ethical issues, surprisingly, very few have tested the basic methodological assumptions supporting the QALY equation so as to establish its scientific validity. OBJECTIVES: The main objective of the ECHOUTCOME European project was to test the validity of the underlying assumptions of the QALY outcome and its relevance in health decision making. METHODS: An experiment has been conducted with 1,361 subjects from Belgium, France, Italy, and the UK. The subjects were asked to express their preferences regarding various hypothetical health states derived from combining different health states with time durations in order to compare observed utility values of the couples (health state, time) and calculated utility values using the QALY formula. RESULTS: Observed and calculated utility values of the couples (health state, time) were significantly different, confirming that preferences expressed by the respondents were not consistent with the QALY theoretical assumptions. CONCLUSIONS: This European study contributes to establishing that the QALY multiplicative model is an invalid measure. This explains why costs/QALY estimates may vary greatly, leading to inconsistent recommendations relevant to providing access to innovative medicines and health technologies. HTA agencies should consider other more robust methodological approaches to guide reimbursement decisions.

Quality of life assessment in cosmetics: specificity and interest of the international BeautyQol instrument.

The wide use of cosmetics and their perceived benefits upon well-being imply objective descriptions of their effects upon the different dimensions contributing to the quality of life (QoL). Such a goal pleas for using relevant and validated scientific instruments with robust measurement methods. This paper discusses the interest of the new validated questionnaire BeautyQoL specifically designed to assess the effect of cosmetic products on physical appearance and QoL. After conducting a review of skin appearance and QoL, three phases of the international codevelopment have been carried out in the following sequence: semi-directed interviews (Phase 1), acceptability study (Phase 2), and validation study (Phase 3). Data collection and validation process have been carried out in 16 languages. This review confirms that QoL instruments developed in dermatology are not suitable to assess cosmetic products, mainly because of their lack of sensitivity. General acceptability of BeautyQol was very good. Forty-two questions have been structured in five dimensions that explained 76.7% of the total variance: Social Life, Self-confidence, Mood, Vitality, and Attractiveness. Cronbach's alpha coefficients are between 0.932 and 0.978, confirming the good internal consistency of the results. The BeautyQol questionnaire is the first international instrument specific to cosmetic products and physical appearance that has been validated in 16 languages and could be used in a number of clinical trials and descriptive studies to demonstrate the added value of these products on the QoL.

Modelling cost-effectiveness of biologic treatments based on disease activity scores for the management of rheumatoid arthritis in Spain.

Background. The objective of this simulation model was to assess the cost-effectiveness of different biological treatment strategies based on levels of disease activity in Spain, in patients with moderate to severe active RA and an insufficient response to at least one anti-TNF agent. Methods. Clinically meaningful effectiveness criteria were defined using DAS28 scores: remission and Low Disease Activity State (LDAS) thresholds. Monte-Carlo simulations were conducted to assess cost-effectiveness over 2 years of four biological sequential strategies composed of anti-TNF agents (adalimumab, infliximab), abatacept or rituximab, in patients with moderate to severe active RA and an insufficient response to etanercept as first biological agent. Results. The sequential strategy including etanercept, abatacept and adalimumab appeared more efficacious over 2 years (102 days in LDAS) compared to the same sequence including rituximab as second biological option (82 days in LDAS). Cost-effectiveness ratios showed lower costs per day in LDAS with abatacept (427 €) compared to rituximab as second biological option (508 €). All comparisons were confirmed when using remission criteria. Conclusion. Model results suggest that in patients with an insufficient response to anti-TNF agents, the biological sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or cycled anti-TNF agents.

Direct cost-modeling of rheumatoid arthritis according to disease activity categories in France.

OBJECTIVE: The objective of this cost-of-illness study was to assess the use of direct medical resources, excluding drug costs, by patients with rheumatoid arthritis (RA) in France, and to construct cost estimates according to level of disease activity. METHODS: Three categories of RA disease activity were defined according to Disease Activity Score 28-joint count (DAS28) thresholds: remission (DAS28 < 2.6), low disease activity state (LDAS; i.e., DAS28 ≤ 3.2), and moderate to high disease activity (MHDAS; i.e., DAS28 > 3.2). Eight resource utilization items were defined: medical visits, laboratory tests, hospitalization, imaging, physiotherapy, nursing, adaptive aids, and transportation. Resource utilization and unit costs from the national-payer perspective were estimated through expert opinion and simulated using distribution ranges for each item. Cost distributions were computed by Monte-Carlo simulations estimating overall costs per 6 months over a 2-year period. RESULTS: For patients achieving remission, costs were estimated at a mean of €771 (SD 199) for the first 6 months and at €511 (SD 162) for each subsequent 6-month period. For patients achieving LDAS, costs were estimated at €905 (SD 263) for the first 6 months and €696 (SD 240) for each subsequent 6-month period. For patients in MHDAS, costs were estimated at €1215 per 6 months (SD 405). CONCLUSION: This cost-of-illness assessment provided current estimates of direct medical costs for RA according to disease activity in France. The findings suggest that achieving remission or LDAS is associated with substantially lower medical costs for RA versus being in MHDAS.

Cost-effectiveness modeling of abatacept versus other biologic agents in DMARDS and anti-TNF inadequate responders for the management of moderate to severe rheumatoid arthritis.

To assess the cost-effectiveness of abatacept compared to different biologic treatment strategies for moderate to severe rheumatoid arthritis based on current medical practices in Canada. A model was constructed to assess the cost-effectiveness of various biologic treatments over a 2-year time horizon, using two effectiveness endpoints: "low disease activity state" (LDAS) and "remission". Abatacept, as first biologic agent after an inadequate response to DMARDs, provides greater treatment success rate for achieving LDAS (29.4% versus 15.6%) and remission (14.8% versus 5.2%), and appears significantly more cost-effective compared to the sequential use of anti-TNF agents (p<0.001). Abatacept, as second biologic agent after an inadequate response to one anti-TNF agent, provides greater treatment success rate for achieving LDAS (17.1% versus 10.2%) and remission (7.4% versus 3.9%) and appears significantly more cost-effective compared to the sequential use of anti-TNF agents (p<0.001). Abatacept is a cost-effective strategy in patients with an inadequate response to DMARDs or to one anti-TNF agent.