The evolution of breast cancer (BC) treatments has resulted in tailored therapies for the different types and stages of BC. Each treatment has a profile of benefits and adverse effects which are taken into consideration when planning a treatment pathway. This study examines whether patients’ preferences are in line with what is considered important from decision makers viewpoint.

An online discrete choice experiment was conducted in six European countries (France, Germany, Ireland, Poland, Spain, UK) with BC patients. Six attributes were included: overall survival (OS), hyperglycemia, rash, pain, functional well-being (FWB), and out-of-pocket payment (OOP). Sixteen choice sets with two hypothetical treatments and a “No treatment” option were presented. Data were analyzed with the use of heteroscedastic conditional, mixed logistic, and latent class models. Marginal rate of substitution (MRS) were estimated for OOP versus the rest of attributes to establish the ranking of preferences for each attribute.

Two hundred and forty-seven patients with advanced or metastatic BC and 314 with early-stage BC responded. Forty-nine percent of patients were < 44 years old and 65 percent had completed university education. The MRS of the analysis demonstrated that “severe pain” is the highest dis-preferred attribute level, followed by “severe impairment in FWB” and OS. Four classes of patients as “decision makers” were identified.

This study suggests that there is heterogeneity in treatment preferences of BC patients depending on their sociodemographic and disease-related characteristics. In combination with clinical guidelines, patient preferences can support the selection and tailoring of treatment options.

The COVID-19 pandemic significantly affected healthcare systems. The most immediate effect was the increased demand for healthcare resources. This study aimed to conduct a case-mix analysis at one of the teaching hospitals in Malaysia to understand the economic implications of the pandemic.

Admissions related to COVID-19, either as a primary or secondary diagnosis, were extracted and given ICD-10 codes for diagnosis and ICD9-CM codes for procedures. The combined ICD-10 and ICD9-CM codes were imported into a case-mix grouper to generate the case-mix codes. The codes used for COVID-19 were A-4-13-I, A-4-13-II, and A-4-13-III for mild, moderate, and severe disease, respectively. Clinical pathways were collected and healthcare resource utilization was estimated by combining top-down and bottom-up costing approaches. Discounting and inflation were based on guidelines and official rates. The cost data were reported in US dollars (price year 2021).

A total of 4,889 patients with a COVID-19 diagnosis were admitted to the hospital in 2021. Of these, 4,813 patients (98%) had a primary diagnosis of COVID-19. The remaining 76 patients (2%) were admitted for other medical reasons but were found to be positive for SARS-Cov-2 during admission. Therefore, for these patients, infection with the virus was considered a secondary diagnosis during the treatment episode.

Among the 4,813 patients, 3,909 (81%) were admitted with mild COVID-19 (A-4-13-I), 630 (13%) had moderate COVID-19 (A-4-13-II), and 274 (6%) had severe disease (A-4-13-III). More than half (56%) of the patients with a secondary diagnosis of COVID-19 were admitted for elective procedures. The average length of hospital stay (LOS) for mild disease was 9 days, with cumulative hospital costs of USD1,543. The average LOS for both moderate and severe disease was 21 days, and the cumulative hospital costs were USD23,527 and USD26,731 respectively. The total costs incurred for COVID-19 were estimated at USD19,259,153.

COVID-19 has considerable economic implications. This study provided information as part of a health technology assessment in the hospital to inform evidence-based healthcare decisions.

Systematic reviews (SRs) are usually conducted by a highly specialized group of researchers. The routine involvement of methodological experts is a core methodological recommendation. The present commentary describes the qualifications required for information specialists and statisticians involved in SRs, as well as their tasks, the methodological challenges they face, and potential future areas of involvement.

Information specialists select the information sources, develop search strategies, conduct the searches, and report the results. Statisticians select the methods for evidence synthesis, assess the risk of bias, and interpret the results. The minimum requirements for their involvement in SRs are a suitable university degree (e.g., in statistics or librarian/information science or an equivalent degree), methodological and content expertise, and several years of experience.

The complexity of conducting SRs has greatly increased due to a massive rise in the amount of available evidence and the number and complexity of SR methods, largely statistical and information retrieval methods. Additional challenges exist in the actual conduct of an SR, such as judging how complex the research question could become and what hurdles could arise during the course of the project.

SRs are becoming more and more complex to conduct and information specialists and statisticians should routinely be involved right from the start of the SR. This increases the trustworthiness of SRs as the basis for reliable, unbiased and reproducible health policy, and clinical decision making.

Gaucher disease is a lysosomal storage disease of autosomal recessive inheritance that is caused by a deficiency of the enzyme glucocerebrosidase. This deficiency results in accumulation of the enzyme’s main substrate in the lysosomes of macrophages, mainly in the spleen, liver, and bone marrow. In more severe cases it can affect the lung, kidneys, and central nervous system. There are two main treatments available for patients with Gaucher disease: enzyme replacement therapy and inhibition of substrate synthesis. The main enzyme replacement therapy used in Brazil is imiglucerase, an analog of the human β-glucocerebrosidase enzyme. Imiglucerase is produced by recombinant DNA technology using a cell culture derived from the Chinese hamster ovary. It has 497 amino acids and differs from the endogenous enzyme by an amino acid at position 495, where histidine is replaced by arginine. The objective of the study was to analyze the survival of patients treated for Gaucher disease with imiglucerase in Brazil from 2000 to 2015.

We constructed a retrospective cohort study of patients with Gaucher disease who received imiglucerase through the Brazilian National Health System from 2000 to 2015 using a national database created from the linkage of administrative databases.

A total of 1,241 patients who received imiglucerase were included. The overall survival rates at one, ten, and 15 years were 98.7 percent (95% confidence interval [CI]: 98.1, 99.4), 92.3 percent (95% CI: 90.2, 94.4), and 89.4 percent (95% CI: 85.6, 93.3), respectively.

Our findings advance the understanding of the profile, survival, and risk factors of people with Gaucher disease, adding new data to the discussion regarding pharmaceutical therapies and patient care, and providing data for the development of new public health policies for the use of advanced, high-cost drugs for rare diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that can affect the skin, joints, and nails. The treatment of the disease is offered by the Brazilian Public Health System (SUS) in accordance with the guidelines of the Ministry of Health. The aim of this study was to analyze real-world data (RWD) on the implementation and use of monoclonal antibodies (mAbs) for the treatment of psoriasis in the SUS.

This is a descriptive study that used national administrative data on drug dispensing from the Open Room for Health Intelligence Situation (SABEIS-SUS) from October 2019 to December 2021. Adult individuals (≥18 years) with vulgar (L40.0), generalized pustular (L40.1), gutata (L40.4) and other (L40.8) psoriasis who used the mAbs adalimumab, etanercept, risankizumab, secukinumab and ustekinumab were included.

The year of implementation of mAbs for the treatment of psoriasis in the SUS was October 2019 (adalimumab, etanercept and secukinumab) and May 2020 (ustekinumab). Risankizumab was implemented in April 2022. The number of individuals using mAb grew from 366 in 2019 to 10,146 in 2021. In 2019, 2020 and 2021, the proportion of individuals using each mAbs was 62.3 percent, 46.2 percent and 35.4 percent (adalimumab), 7.9 percent, 3.3 percent and 2.7 percent (etanercept), 29.8 percent, 33.8 percent and 30.5 percent (secukinumab), 0 percent, 16.7 percent and 31.4 percent (ustekinumab), respectively.

The number of mAbs users has greatly increased from 2019 to 2021, which may indicate a successful implementation of the psoriasis treatment in SUS. Most individuals used adalimumab in the year of the first implementation. However, the proportion of users of this mAb has greatly decreased after the implementation of ustekinumab. This reduction should not be so expressive since adalimumab and ustekinumab are recommended in different lines of treatment. The low proportion of etanercept use may be due the fact the medication is indicated for individuals up 18 years of age. This study provides important real-word evidence for monitoring the implementation of mAbs for psoriasis treatment in Brazil.

To develop best-practice guidance for health technology assessment (HTA) agencies when appraising diagnostic tests for SARS-CoV-2 and treatments for COVID-19.

We used a policy sandbox approach to develop best-practice guidance for HTA agencies to approach known challenges associated with assessing tests and treatments for COVID-19. The guidance was developed by a multi-stakeholder workshop of twenty-one participants representing HTA agencies, clinical and patient experts, academia, industry, and a payer, from across Europe and North America. The workshop was supported by extensive background work to identify the key challenges, including: targeted reviews of existing COVID-related methods guidance for assessing interventions and clinical guidelines, engagement with clinical experts, a survey and workshop of HTA agencies, a systematic review of published economic evaluations, and a workshop of health economic modelers.

We suggest HTA agencies should consider using other types of evidence (e.g., real world) where high-quality randomized controlled trials may be lacking and healthcare systems would value timely HTA outputs. A “living” HTA approach may be useful, given the context of an evolving disease, scientific understanding and evidence base, allowing for decisions to be efficiently revisited in response to new information; particularly, if supported by a common “disease model” for COVID-19. Innovative ways of engaging with the public and clinicians, and early engagement with regulators and payers, are recommended.

HTA agencies should consider the elements of this guidance that are most suited to their existing processes to enable them to assess the effectiveness and value of interventions for COVID-19.

During COVID-19 pandemic Follow-up Centers were established by Turkish Ministry of Health (MoH) to detect possible complications in recovered COVID-19 patients at an early stage and make necessary interventions on time. It was aimed to reveal the short, medium and long-term effects of the disease by monitoring regularly. The Follow-up Center algorithms were designed by 10 clinicians of different branches with the support from United Nations Development Programme (UNDP). The follow-ups were made for one year in two pilot centers by using the health information systems infrastructure. In the dissemination process, Follow-Up centers were established initially in 24 and subsequently in 81 provinces.

In this study, the establishment, dissemination, operation and patient follow-up process of the COVID-19 Follow-up Centers were examined. The one-year (between 1 December 2021 and 1 December 2022) data obtained were analyzed. The patient follow-up;

• • was made at 0, 1, 3, 6 and 12 months for the first year,

• • planned to be made twice in the second year and the following years if needed.

In the first year, people who received 3 follow-ups by using the forms and scales in the integrated information system modules were assumed to be followed up regularly.

Among the one-year data obtained from the COVID-19 follow-up centers, the total number of follow-ups, the distribution of follow-ups by date, gender and age groups and symptoms according to time were examined. In the first year; 11,288 people were included in the follow-ups and 18,328 follow-ups were made; 2,462 people were followed-up regularly. The followed up people consisted of 51.8% women; 48.3% of them were men. The incidence of symptoms decreased from 1,198 people in the first follow-up and to 180 people in the third follow-up.

The establishment of Follow-up Centers is considered to be an important initiative to generate systematic data on the long-term effects of COVID-19. It was concluded that conducting studies using two-year data obtained from the follow-up centers, especially for complications, would be beneficial for management of the COVID-19 pandemic and in preparation for similar pandemics.

Remote patient monitoring (RPM) has emerged as a viable and valuable care delivery method to improve chronic disease management. In light of the high prevalence and substantial economic burden of cardiovascular disease (CVD), this systematic review examines the cost and cost-effectiveness of using RPM to manage CVD in the United States.

We systematically searched databases to identify potentially relevant research. Findings were synthesized for cost and cost-effectiveness by economic study type with consideration of study perspective, intervention, clinical outcome, and time horizon. The methodological quality was assessed using the Joanna Briggs Institute Checklist for Economic Evaluations.

Thirteen articles with fourteen studies published between 2011 and 2021 were included in the final review. Studies from the provider perspective with a narrow scope of cost components identified higher costs and similar effectiveness for the RPM group relative to the usual care group. However, studies from payer and healthcare sector perspectives indicate better clinical effectiveness of RPM relative to usual care, with two cost-utility analysis studies suggesting that RPM relative to usual care is a cost-effective tool for CVD management even at the conservative $50,000 per Quality-Adjusted Life-Year threshold. Additionally, all model-based studies revealed that RPM is cost-effective in the long run.

Full economic evaluations identified RPM as a potentially cost-effective tool, particularly for long-term CVD management. In addition to the current literature, rigorous economic analysis with a broader perspective is needed in evaluating the value and economic sustainability of RPM.

Assessing, funding, and implementing cell and gene therapies are usually based on limited evidence. This requires health technology assessment (HTA) agencies to develop new methodologies; payers to accept risk-based funding; industry to consider the right evidence and price; hospitals to consider if they have the necessary requirements; patients to consider their risk appetite for gene therapies; and health departments to consider all the above. Ensuring timely patient access to these therapies is challenging in Australia’s federated health system. To ensure stakeholders are aligned, all must come to the table and share their respective insights, experiences, and expertise to support planning, decision-making, funding, and commissioning of these therapies. It is time to develop a new consultative and decision-making paradigm to expedite HTAs, funding, commissioning, and timely patient access for cell and gene therapies.

Australian federal, state, and territory government representatives agreed to develop a framework that clarifies processes around information sharing, HTA, funding, commissioning, and monitoring of highly specialized therapies and services (including cell and gene therapies). A draft national framework was developed that addresses assessment, funding, and implementation of high cost, highly specialized therapies and services (e.g., bone marrow transplants). However, it is unclear whether non-government stakeholders have been consulted.

The framework for assessing, funding, and implementing high cost, highly specialized therapies and services across Australia’s public hospital system is pending endorsement by each of the jurisdictional governments. High-level in nature, the framework’s primary audiences are industry and public hospitals. While not all processes are in place, the framework is forward-looking. A detailed implementation plan is warranted to better inform the roles and requirements of each stakeholder.

The framework allows stakeholders to better understand government processes regarding assessment, funding, and implementation of high-cost therapies and services, thereby fostering a collaborative environment that supports timely patient access. Articulating process details in a follow-up implementation plan is essential to gain the trust of, and input from, industry, clinicians, and patient representatives.

Outcome-based commissioning – a set of arrangements to define and pay for a service based on pre-agreed outcomes – has been operationalized in some regional care settings (e.g., adult social care). However, it remains largely aspirational due to operational considerations and challenges. Outcomes-based commissioning shares a common goal with economic evaluation alongside health technology appraisal (HTA): to achieve value for money for outcomes from a finite budget.

We explored the considerations, implications, and challenges regarding the practical role of relevant outcomes in economic evaluation, relative to care commissioning, using England as a case study. Our exploration bridges a gap between economic evaluation evidence and practical resource allocation decision-making, focusing on conceptual (e.g., what are ‘relevant’ outcomes), practical considerations (e.g., quantifying and using relevant endpoints or surrogate outcomes alongside costs), and pertinent issues when linking these to commissioning based payment mechanisms.

Firstly, there is a disconnect between existing economic evaluation approaches and commissioning processes. For example, using a single quality-adjusted life-year (QALY) maximum and limited consideration of affordability relative to cost effectiveness. Secondly, service-focused outcomes (e.g., seeing a specialist team) rather than person-focused outcomes (e.g., QALYs) are often desirable from a practical commissioning and service provider perspective as they make it easier to measure key performance indicators. Thirdly, both person- and service-focused payment structures could lead to market inefficiencies when activity is focused on only people for whom a prespecified outcome can be achieved or service delivered; these approaches require additional efficiency-equity tradeoff considerations (e.g., using distributional cost-effectiveness analyses).

We highlight payment structures as a major and complex consideration for commissioning, for which economic evaluation provides little to no consideration. Service-related outcomes and payments can be used as surrogate outcomes within economic modeling frameworks, while monitoring and evaluation can still be based on economic outcomes (e.g., QALYs and aggregated costs). Accounting for and explaining direct links from payment structures to economic outcomes is a major step to bridging a gap between economic evaluation evidence and practical resource allocation.

Despite increasing emphasis on the inclusion of patient input in health technology assessment (HTA) in Europe in particular, questions remain as to the integration of patient insight alongside other HTA inputs. This paper aims to explore how HTA processes, while ensuring the scientific quality of assessments, “make do” with patient knowledge elicited through patients’ involvement mechanisms.

The qualitative study analyzed institutional HTA and patient involvement in four European country contexts. We combined documentary analysis with interviews with HTA professionals, patient organizations, and health technology industry representatives, complemented with observational findings made during a research stay at an HTA agency.

We present three vignettes which showcase how different parameters of assessment become reframed upon the positioning of patient knowledge alongside other forms of evidence and expertise. Each vignette explores patients’ involvement during an assessment of a different type of technology and at a different stage of the HTA process. First, cost-effectiveness considerations were reframed during an appraisal of a rare disease medicine based on patient and clinician input regarding its treatment pathway; in the second vignette reframing amounted to what counts as a meaningful outcome measure for a glucose monitoring device; in the third, evaluating pediatric transplantation services involved reframing an option’s appropriateness from a question of moral to one of legal acceptability.

Making do with patient knowledge in HTA involves reframing of what is being assessed. Conceptualizing patients’ involvement in this way helps us to consider the inclusion of patient knowledge not as complementary to, but as something that can transform the assessment process.

Gender medicine responds to the need for a reassessment of the medical-scientific approach in a gender perspective, to increase knowledge of the different aspects underlying gender differences and the appropriateness/ effectiveness of health interventions.

A policy review of documents prepared by the Italian Ministry of Health on gender medicine was carried out, to investigate the possible areas of intervention of health technology assessment in the development of this interdisciplinary dimension. The areas of highest priority for action have been identified.

In Italy, the Ministry of Health, with the support of the National Institute of Health, issued a Plan for Application and Dissemination of Gender Medicine in June 2019. Our review shows that for the development of research on the mechanisms of pathogenesis the Italian Plan gives indications on the identification of diagnostic markers, prognostic and predictive response in a gender perspective, but there are no formalized rules that constitute a constraint or an obligation to do so. In Horizon Europe calls, for example, “Pragmatic trials on minimally invasive diagnostics” (HORIZON-MISS-2023-CANCER-01-03) on the other hand, it is required that gender and gender issues should be taken into account in all projects and all data should be disaggregated by gender, socio-economic status and ethnicity. Separating subjects into two groups in the analysis leads to greater complexity. This is even more true when considering the different types of gender. The total number of subjects to be included must likely increase to maintain statistical power in evaluating effects in subgroups. This increase leads to an increase in time and cost, if one needs to provide separate data by sex and even more so by gender. Different statistical tests to be used, according to the type of variables of the primary endpoint, should be considered in the study protocols.

It seems appropriate to suggest reviewing upcoming health technology assessments with an eye to gender medicine. Gender medicine should become a strategic goal of prevention in public health and will strengthen the concept of the patient centrality until the personalization of therapies is achieved.

During public health crises such as the COVID-19 pandemic, decision-makers have relied on infectious disease models to predict and estimate the impact of various health technologies. The difficulties associated with capturing and representing uncertainty using infectious disease models leads to a high risk of making decisions that are misaligned to policy objectives. Even when uncertainty is adequately captured in the analysis, the tools for communicating the risks and harms of making wrong decisions have proved inadequate, which can lead to the suboptimal adoption of critical health technologies including vaccines and antivirals. We aim to adapt and extend health economic methods for the characterization, estimation, and communication of uncertainty to infectious disease modeling.

Economic and infectious disease models share many features, including the comparison of policy alternatives on outcomes important to decision-makers (such as hospital census, total infections), but each takes a different approach to analysis of uncertainty. We extend best practices from health economics to infectious disease modeling and develop a suite of tools and visualization techniques which represent parameter uncertainty and the risk these unknowns present to decision-makers.

In consultation with decision-makers and infectious disease modeling experts we developed the ‘Decision Uncertainty Toolkit’ of model outputs and visuals. Visual tools for uncertainty are developed to: (i) accurately capture uncertainty in key infectious disease model outputs, and (ii) support intuitive and direct interpretation by infectious disease modelers and decision-makers. We also developed quantitative measures for the downside risk of policy alternatives, specified to capture both the probability and magnitude of losses relative to policy targets for a range of infectious disease model outputs. Together, these outputs can support decision-making by quantifying outcome uncertainty and the risks associated with policy alternatives.

We developed the toolkit visuals and risk measures alongside infectious disease modelers and decision makers. The toolkit is designed to improve decision-maker understanding of decision risk in order to improve outcomes during future public health crises.

This study aimed to assess whether there have been changes in the quality of clinical evidence submitted for government subsidy decisions on cancer medicines over the past 15 years.

We reviewed public summary documents (PSDs) reporting on subsidy decisions made by the Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to July 2020. Information was extracted on the study design, directness of comparison, sample size, and risk of bias (RoB). Changes in the quality of evidence were assessed using regression analysis.

Overall, 214 PSDs were included in the analysis. Thirty-seven percent lacked direct comparative evidence. Thirteen percent presented observational or single-arm studies as the basis for decisions. Among PSDs presenting indirect comparisons, 78 percent reported transitivity issues. Nearly half (41 percent) of PSDs reporting on medicines supported by head-to-head studies noted there was a moderate/high/unclear RoB. PSDs reporting concerns with RoB increased by a third over the past 7 years, even after adjusting for disease rarity and trial data maturity (OR 1.30, 95% CI: 0.99, 1.70). No time trends were observed regarding the directness of clinical evidence, study design, transitivity issues, or sample size during any of the analyzed periods.

Our findings indicate that the clinical evidence supplied to inform funding decisions for cancer medicines is often of poor quality and has been deteriorating over time. This is concerning as it introduces greater uncertainty in decision making. This is particularly important as the evidence supplied to the PBAC is often the same as that supplied to other global decision-making bodies.

The aim of this study was to deliver insights from multiple stakeholders into actual and future collaboration for health technology assessment (HTA) in general and in oncology in particular.

Eighteen semi-structured interviews were conducted with experts from European HTA bodies (HTAbs), former board members of the European Network for Health Technology Assessment (EUnetHTA), and representatives from the pharmaceutical industry, a regulatory agency, academia, and patient organizations. The stakeholders were asked about their support of the EUnetHTA’s intent, about the general strengths and challenges of the EUnetHTA and its Joint Action 3 (JA 3), the strengths and challenges of the clinically oriented HTA collaboration in oncology during JA 3 across the technology life cycle, about future challenges to HTA in oncology with consequences for collaboration, and about collaboration in the economic domains of HTA. The transcribed interviews were analyzed qualitatively.

The participants perceived the intention and work quality of the EUnetHTA as positive. The experts described methodological, procedural, and capacity challenges in early dialogues (EDs) and rapid relative effectiveness assessments (REAs) meant to analyze clinical effectiveness in oncology. The majority attached increasing importance to collaboration in the future to cope with the uncertainty of HTA. Several stakeholders also proposed the incorporation of joint postlaunch evidence generation (PLEG) activities. Some gave sporadic suggestions for voluntary nonclinical collaboration as well.

Stakeholders’ continued readiness to discuss the remaining challenges to and sufficient resources for implementing HTA regulation, as well as further cooperative expansion along the technology life cycle, are necessary for improved HTA collaboration in Europe.

Decision makers often use value-based decision rules to determine whether technologies offer good value for money and should therefore be adopted, comparing cost-effectiveness analysis results with a threshold value. This assumes that decision makers are indifferent to interventions with the same expected value but different levels of underlying uncertainty. Such indifference is unlikely to hold in practice. We propose a risk-based price and accompanying decision rules to address this limitation.

We characterized risk using the per-patient expected value of perfect independent information (EVPII), a modification of a standard output from value of information analysis. The EVPII estimates the expected value of net benefit losses caused by uncertainty related to a technology, independent of the uncertainty related to alternative treatments. ‘Payer risk tolerance’ is then defined as the maximum per-patient risk of making wrong decisions that payers are willing to accept, expressed in monetary terms. The risk-based price is the price at which the EVPII is equal to the payer risk tolerance.

The risk-based pricing decision rules are as follows: (i) a technology is acceptable for adoption at the submitted price if the incremental net benefit of the technology is greater than or equal to zero and the EVPII is less than or equal to the payer risk tolerance; and (ii) the optimal technology has the greatest expected net benefit at the lowest of the sponsor submitted, value-based, or risk-based price at a given cost-effectiveness threshold value.

The risk-based price incorporates uncertainty and risk attitudes into decision-making. We demonstrate that both risk-averse and risk-neutral payers prefer the outcomes of risk-based pricing. Risk-based decision rules incentivize sponsors to develop evidence. Implementation of the risk-based price improves outcomes for patients by increasing health system net benefits under constrained resources, with better alignment to decision maker risk attitudes.

Value-based agreements (VBAs) link access, reimbursement, or price to the real-world usage and impact of a medicine, thereby enabling patient access while reducing clinical or financial uncertainty for the payer. VBAs have the potential to support improved patient outcomes, given the value-oriented approach to care, and lead to overall savings, while enabling payers to share risk and reduce uncertainty.

This commentary outlines the key challenges, enablers, and a framework for successful implementation by comparing the experience of two VBAs for AstraZeneca medicines, aiming to increase confidence in their future use.

Engagement by payers, manufacturers, physicians, and provider institutions, and robust data collection systems that are accessible, simple to use, and add little burden to physicians were key to successfully negotiating a VBA that worked for all stakeholders. In both country systems, a legal/policy framework enabled innovative contracting.

These examples demonstrate proof of concept for VBA implementation in different settings, and may inform future VBAs.

In health technology assessment (HTA), economic evaluations assessing biologic drugs for rheumatoid arthritis (RA) involve modeling patients’ responses to multiple treatments given sequentially over a lifetime horizon. When data from randomized controlled trials (RCTs) are scarce, data from non-randomized studies (e.g., single-arm trials [SATs] and disease registries) can be used to supplement the evidence base. This research aimed to demonstrate meta-analytic methods for combining effectiveness data from randomized and non-randomized studies and their corresponding impact on cost-effectiveness estimates.

Data comparing patients receiving second-line rituximab with continued background non-biologic treatment were extracted from one RCT and six SATs identified in an HTA assessing second-line rituximab for RA, and from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis, by applying a target trial emulation approach. A binomial meta-analysis model was used to estimate the probabilities of achieving the European League against Rheumatism (EULAR) response criteria by pooling data from the RCT, SATs, and the registry. The probabilities were entered into a decision model from a previous HTA to derive incremental cost-effectiveness ratio (ICER) estimates for treatment strategies with and without biologic drugs.

Compared with the original analysis, the estimated probability of at least a moderate EULAR response on rituximab from combined sources was substantially lower. For example, the probability obtained from an RCT was 0.68 (95% credible interval [CrI]: 0.345, 0.907), but only 0.29 (95% [CrI]: 0.242, 0.333) when using RCT plus registry data and 0.29 (95% CrI: 0.244, 0.336) for combined RCT, registry, and SAT data. In the cost-effectiveness analysis, the median ICERs were higher when including real-world data.

Synthesis of all relevant data, including RWD, provides additional information regarding the variability in cost-effectiveness estimates and can be considered in sensitivity analyses for HTA decision-making.