What methods are currently available for incorporating implementation considerations within the economic evaluation of health technologies? A scoping review.

BACKGROUND: When clinically effective, cost-effective health interventions are not fully implemented in clinical practice, population health suffers. Economic factors are among the most commonly cited reasons for suboptimal implementation. Despite this, implementation and economic evaluation are not routinely performed in conjunction with one another. This review sought to identify and describe what methods are available for researchers to incorporate implementation within economic evaluation, how these methods differ, when they should be used, and where gaps remain. METHODS: We conducted a scoping review using systematic methods. A pearl-growing approach was used to identify studies. References and citations were identified using Web of Science and Scopus. We included for review any study that contained terms relating to economic evaluation and a series of implementation-related terms in the title or abstract. The search was conducted and validated using two independent researchers. RESULTS: Our review identified 42 unique studies that included a methodology for combining implementation and economic evaluation. The methods identified could be categorized into four broad themes: (i) policy cost-effectiveness approach (11 studies), (ii) value of information and value of implementation approach (16 studies), (iii) mixed methods approach (6 studies), and (iv) costing approach (9 studies). We identified a trend over time from methods that adopted the policy cost-effectiveness approach to methods that considered the trade-off between the value of information and value of implementation. More recently, mixed methods approaches to incorporate economic evaluation and implementation have been developed, alongside methods to define, measure and cost individual components of the implementation process for use in economic evaluation. CONCLUSION: Our review identified a range of methods currently available for researchers considering implementation alongside economic evaluation. There is no single method or tool that can incorporate all the relevant issues to fully incorporate implementation within an economic evaluation. Instead, there are a suite of tools available, each of which can be used to answer a specific question relating to implementation. Researchers, reimbursement agencies and national and local decision-makers need to consider how best to utilize these tools to improve implementation.

A Model-Based Economic Evaluation of Hypothetical Treatments for Amyotrophic Lateral Sclerosis in the UK: Implications for Pricing of New and Emerging Health Technologies.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon. OBJECTIVES: The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective. METHODS: We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness. RESULTS: Starting from King's stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness. CONCLUSIONS: Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care.

Incorporating Real Option Value in Valuing Innovation: A Way Forward.

BACKGROUND: Considerable progress has been made in defining and measuring the real option value (ROV) of medical technologies. However, questions remain on how to estimate (1) ROV outside of life-extending oncology interventions; (2) the impact of ROV on costs and cost effectiveness; and (3) potential interactions between ROV and other elements of value. METHODS: We developed a 'minimal modeling' approach for estimating the size of ROV that does not require constructing a full, formal cost-effectiveness model. We proposed a qualitative approach to assessing the level of uncertainty in the ROV estimate. We examined the potential impact of ROV on the incremental cost-effectiveness ratio as well as on the potential interactions between ROV and other elements of value. Lastly, we developed and presented a 15-item checklist for reporting ROV in value assessment. RESULTS: The minimal modeling approach uses estimates on the efficacy of current treatment and potential future innovation, as well as success rate and length of new treatment development, and can be applied to all types of ROV across disease areas. ROV may interact with the conventional value, value of hope, productivity effects, and insurance value. The impact of ROV on cost effectiveness can be evaluated via threshold analysis. CONCLUSION: The minimal modeling approach and the checklist developed in this paper simplifies and standardizes the estimation and reporting of ROV in value assessment. Systematically including and reporting ROV in value assessment will minimize bias and improve transparency, which will help improve the credibility of ROV research and acceptance by stakeholders.

The role of budget impact and its relationship with cost-effectiveness in reimbursement decisions on health technologies in the Netherlands.

Health authorities using cost-effectiveness analysis (CEA) for informing reimbursement decisions on health technologies increasingly require economic evaluations encompassing both CEA and budget impact analysis (BIA). Good Research Practices advocate that the economic and clinical assumptions underlying these analyses are aligned and consistently applied. Nonetheless, CEAs and BIAs often are stand-alone analyses used in different stages of the decision-making process. This article used policy reports and Ministerial correspondence to discuss and elucidate the role of budget impact and its relationship with cost-effectiveness in reimbursement decisions in the Netherlands. The results indicate that CEAs and BIAs are both considered important for informing these decisions. While the requirements regarding CEAs-and application of the associated decision rule-are consistent across the different stages, the same does not hold for BIAs. Importantly, the definition of and evidence on budget impact differs between stages. Some important aspects (e.g. substitution and saving effects) typically are considered in the assessment and appraisal stages but are seemingly not considered in price negotiations and the final reimbursement decision. Further research is warranted to better understand why BIAs are not aligned with CEAs (e.g. in terms of underlying assumptions), vary in form and importance between stages, and do not have a clear relationship with the results of CEAs in the decision-making framework. Improving the understanding of the circumstances under which decision-makers attach a relatively larger or smaller weight to (different aspects of) budget impact may contribute to increasing the transparency, consistency, and optimality of reimbursement decisions in the Netherlands.

Exploring the approach to parameter uncertainty in early economic evaluations of surgical technology - a systematic review.

INTRODUCTION: The role of early economic evaluation (EEE) in the development of medical technology has been increasingly recognized; however, data on the use of EEE in surgical technology are sparse. The objective of this review was to explore the use of EEE in the development of surgical technologies, with emphasis on how uncertainty has been addressed. AREAS COVERED: A systematic review was conducted, and original articles employing any form of EEE of surgical technology were selected for review, with 10 studies included in the analysis. These studies demonstrated significant variation in the approach to managing parameter uncertainty, specifically regarding the type of analysis used and the inclusion of effectiveness parameters in sensitivity analysis. The conclusions drawn did not appear to factor in uncertainty in the models. EXPERT OPINION: Approaches to handling parameter uncertainty in previous EEEs of surgical technology have been limited, with some studies failing to address parameter uncertainty. In addition, EEEs do not appear to follow established guidelines with respect to the use of sensitivity analyses. It is important that EEEs of surgical technology address parameter uncertainty in order to draw more robust conclusions from the analysis and allow investors to consider this uncertainty when making investment decisions.

Surface Modification of Bacterial Cellulose for Biomedical Applications.

Bacterial cellulose is a naturally occurring polysaccharide with numerous biomedical applications that range from drug delivery platforms to tissue engineering strategies. BC possesses remarkable biocompatibility, microstructure, and mechanical properties that resemble native human tissues, making it suitable for the replacement of damaged or injured tissues. In this review, we will discuss the structure and mechanical properties of the BC and summarize the techniques used to characterize these properties. We will also discuss the functionalization of BC to yield nanocomposites and the surface modification of BC by plasma and irradiation-based methods to fabricate materials with improved functionalities such as bactericidal capabilities.

Societal Perspectives and Real-World Cost-Effectiveness: Expanding the Scope of Health Economics Inquiry.

Economic evaluations of health technologies for cancer are frequently seen in the literature, but not all economic perspectives have the same frequency [...].

Costing methodologies in European economic evaluation guidelines: commonalities and divergences.

From both the methodological point of view and standardization of methodology, little attention has been paid to the estimation of direct costs in evaluation of healthcare technologies. The objective is to revise the recommendations on direct costs provided in European economic evaluation guidelines and to identify the commonalities and divergences among them. To achieve this, a comprehensive search through several online databases was performed resulting in 41 documents from 26 European countries, be they economic evaluation guidelines or costing guidelines. The results show a large disparity in methodologies used in estimation of direct costs to be included in economic evaluations of health technologies recommended by European countries. A lack of standardization of cost estimation methodologies influences arbitrariness in selecting costs of resources included in economic evaluations of medicinal products or any other technologies and, therefore, in decision making process necessary to introduce new technology. In addition, this heterogeneity poses a major challenge for identifying factors that could affect the variability of unit costs across countries.

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909 patients; follow-up <12 months) that compared web-based interventions, mobile applications, and different telemedicine platforms with SoC (clinic-based encounters). Although overall disease activity and risk of relapse were comparable between digital health technologies and SoC (very low certainty of evidence), digital health interventions were associated with lower rate of health care utilization and health care costs (low certainty of evidence). Digital health interventions did not significantly improve patients' QoL and treatment adherence compared with SoC (very low certainty of evidence). Trials may have intrinsic selection bias due to nature of digital interventions. DISCUSSION: Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Bringing Your Idea to the Market: A Primer for Plastic Surgeons.

SUMMARY: The progress of biotechnology, medical instruments, and applied sciences contributes to a rapidly expanding space for the advancement of the medical field. Surgeons experience first-hand the limitations of current medical devices and thus have unique insight into problems that could be solved with new products. The process of turning an idea into a product capable of success in the marketplace, however, is often unfamiliar to surgeons. The authors seek to illuminate this process and provide an ordered list of tasks that can make bringing ideas to market more achievable for surgeons. The first step in this process is the generation and protection of a new idea. Next, the process of making an idea into a product is outlined. This phase involves team assembly, business planning, and product development. Market research and valuation are key to understanding how a product can be applied in the market, and meticulous research during this phase allows for informed decision-making that will help secure funding down the road. Finally, various options for financing are discussed and compared to help surgeon-entrepreneurs find an option that best fits their project, and steps to maximize leverage are described. The development of new products can be a complicated process for surgeons. Organized into four phases, with ordered instructional steps to advance through each phase, the process of bringing an idea to the market is clarified. Facilitating this process will possibly contribute to the continual improvement of medical and surgical abilities through the introduction of new devices and technologies.

Virtual and augmented reality for biomedical applications.

3D visualization technologies such as virtual reality (VR), augmented reality (AR), and mixed reality (MR) have gained popularity in the recent decade. Digital extended reality (XR) technologies have been adopted in various domains ranging from entertainment to education because of their accessibility and affordability. XR modalities create an immersive experience, enabling 3D visualization of the content without a conventional 2D display constraint. Here, we provide a perspective on XR in current biomedical applications and demonstrate case studies using cell biology concepts, multiplexed proteomics images, surgical data for heart operations, and cardiac 3D models. Emerging challenges associated with XR technologies in the context of adverse health effects and a cost comparison of distinct platforms are discussed. The presented XR platforms will be useful for biomedical education, medical training, surgical guidance, and molecular data visualization to enhance trainees' and students' learning, medical operation accuracy, and the comprehensibility of complex biological systems.

Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies.

The development of reprogramming technology to generate human induced pluripotent stem cells (iPSCs) has tremendously influenced the field of regenerative medicine and clinical therapeutics where curative cell replacement therapies can be used in the treatment of devastating diseases such as Parkinson's disease (PD) and diabetes. In order to commercialize these therapies to treat a large number of individuals, it is important to demonstrate the safety and efficacy of these therapies and ensure that the manufacturing process for iPSC-derived functional cells can be industrialized at an affordable cost. However, there are a number of manufacturing obstacles that need to be addressed in order to meet this vision. It is important to note that the manufacturing process for generation of iPSC-derived specialized cells is relatively long and fairly complex and requires differentiation of high-quality iPSCs into specialized cells in a controlled manner. In this chapter, we have summarized our efforts to address the main challenges present in the industrialization of iPSC-derived cell therapy products with focus on the development of a current Good Manufacturing Practice (cGMP)-compliant iPSC manufacturing process, a comprehensive iPSC characterization platform, long-term stability of cGMP compliant iPSCs, and innovative technologies to address some of the scale-up challenges in establishment of iPSC processing in 3D computer-controlled bioreactors.

Medicare Accountable Care Organizations and the Adoption of New Surgical Technology.

BACKGROUND: Dissemination of new surgical technology is a major contributor to healthcare spending growth. Accountable care organization (ACO) policy aims to control spending while maintaining quality. As a result, ACOs provide incentive for hospitals to selectively adopt newer procedures with high value. STUDY DESIGN: We conducted a retrospective cohort study using a 20% sample of national Medicare claims from 2010 to 2015. We identified hospitals that performed 1 of 6 sets of procedures: abdominal aortic aneurysm repair, aortic valve replacement, carotid endarterectomy or stent, lung lobectomy, colectomy, and prostatectomy. We identified hospitals participating in a Medicare Shared Savings Program ACO and a set of matched non-ACO control hospitals. We used a difference-in-differences approach to compare rate of surgical treatment and use of newer surgical technology for each set of procedures in ACO and non-ACO hospitals. RESULTS: We included 707 ACO-hospitals and 1,770 control hospitals. ACO hospitals performed surgery for carotid stenosis at a lower rate than non-ACO hospitals. There was no difference in the rate of surgical treatment for all other procedure sets. ACO hospitals were less likely to use an endovascular approach for abdominal aortic aneurysm repair (85.2% vs 88.2%, p < 0.001) and more likely to use a minimally invasive approach for lung lobectomy (42.2% vs 34.7%, p = 0.004) than non-ACO hospitals. In difference-in-differences analysis, ACO participation was not associated with any significant difference in use of surgical care for any of the 6 procedure sets, nor with any significant difference in use of newer surgical technology. CONCLUSIONS: Despite ACO policy incentives to selectively adopt newer surgical technology, ACO participation was not associated with differences in rate of surgery or use of newer surgical technology for 6 major surgical procedures.

Polyhydroxyalkanoates: Next generation natural biomolecules and a solution for the world's future economy.

Petrochemical plastics have become a cause of pollution for decades and finding alternative plastics that are environmental friendly. Polyhydroxyalkanoate (PHA), a biopolyester produced by microbial cells, has characteristics (biocompatible, biodegradable, non-toxic) that make it appropriate as a biodegradable plastic substance. The different forms of PHA make it suitable to a wide choice of products, from packaging materials to biomedical applications. The major challenge in commercialization of PHA is the cost of manufacturing. There are a lot of factors that could affect the efficiency of a development method. The development of new strategic parameters for better synthesis, including consumption of low cost carbon substrates, genetic modification of PHA-producing strains, and fermentational strategies are discussed. Recently, many efforts have been made to develop a method for the cost-effective production of PHAs. The isolation, analysis as well as characterization of PHAs are significant factors for any developmental process. Due to the biodegradable and biocompatible properties of PHAs, they are majorly used in biomedical applications such as vascular grafting, heart tissue engineering, skin tissue repairing, liver tissue engineering, nerve tissue engineering, bone tissue engineering, cartilage tissue engineering and therapeutic carrier. The emerging and interesting area of research is the development of self-healing biopolymer that could significantly broaden the operational life and protection of the polymeric materials for a broad range of uses. Biodegradable and biocompatible polymers are considered as the green materials in place of petroleum-based plastics in the future.

Diplomacia da saúde e COVID-19: reflexões a meio caminho / Health diplomacy and COVID-19: reflections halfway

Organizada por Paulo Marchiori Buss e Luiz Eduardo Fonseca, coordenadores do Centro de Relações Internacionais em Saúde da Fiocruz, esta obra reúne as análises produzidas sobre as respostas do multilateralismo ao novo coronavírus. Dividida em três partes, a coletânea viabiliza o acesso do público a um panorama de ações internacionais promovidas para o enfrentamento da crise sanitária. A publicação engloba renomados pesquisadores das mais diversas áreas de saúde, diplomacia e relações internacionais, examinando as ações de órgãos e agências, como OMS, ONU e OCDE, além de iniciativas multilaterais, como G20 e países do BRICS. Os capítulos abordam ainda as respostas de diferentes países e regiões do mundo, incluindo Brasil, China, Estados Unidos, África, Oriente Médio, Europa, América Latina e Caribe, além de instituições financeiras internacionais,como FMI e Banco Mundial. Primeiro livro da série "Informação para Ação na Covid-19", que tem como objetivo reunir o conjunto de respostas, pesquisas e ações técnicas produzidas pela Fiocruz durante a pandemia causada pelo novo coronavírus. Publicada em coedição por Observatório Covid-19 Fiocruz e Editora Fiocruz, com apoio da Rede SciELO Livros, a série estará disponível exclusivamente em formato digital e acesso aberto.

The use of real-world evidence in ICER's scoping process and clinical evidence assessments.

BACKGROUND: There has been growing interest in using real-world evidence (RWE) for health technology assessment (HTA) in the United States. The Institute for Clinical and Economic Review (ICER) is an independent U.S.-based HTA organization that focuses primarily on pharmaceuticals. RWE is used to inform ICER's scoping and comparative clinical effectiveness (CCE) assessments, but the extent to which it is used has not been quantified. OBJECTIVE: To systematically evaluate use of RWE in the scoping and CCE assessment sections of the ICER HTA reports on pharmaceuticals. METHODS: We reviewed all ICER reports of pharmaceuticals published between January 2014 and June 2019. We examined the average number of instances and the proportion of RWE use in the scoping documents to inform the population, intervention, comparator, outcome, setting, or timing (PICOTS) elements of the appraisal. We also examined the average number of instances and the proportion of RWE use in the CCE assessments to inform effectiveness, safety, or treatment patterns. Finally, we evaluated use of RWE in clinical guidelines that were cited in the CCE assessments. RESULTS: In ICER scoping documents, the mean (SD) number of instances of RWE use was 3.8 (3.7) per document (55% for outcomes, 20% for population, 14% for comparator, 11% for intervention, and 0% for timing and setting). In ICER CCE assessments, the mean (SD) number of instances per assessment was 0.7 (0.5) per drug (53% for effectiveness, 44% for safety, and 3% for treatment patterns). In clinical guidelines used in ICER reports, the mean (SD) number of instances of RWE use was 1.6 (2.3) per drug per guideline (41% for effectiveness, 30% for safety, and 29% for treatment patterns). CONCLUSIONS: RWE was frequently used in the ICER scoping process, particularly to inform selection of outcomes. RWE was used infrequently in ICER CCE assessments, while more often used to inform effectiveness, safety, and treatment patterns in relevant clinical guidelines. There are opportunities to increase the use of RWE in U.S. HTA processes. DISCLOSURES: This study was supported by the Health Tech Fund, University of Washington School of Pharmacy, which was created through unrestricted support from several health care industry companies. Veenstra and Carlson report grant support from the Institute for Clinical and Economic Review outside the submitted work. Carlson reports personal fees from Bayer, Allergan, and Galderma outside the submitted work. Jiao, Lee, and Devine report no support outside the submitted work.