A Cardiology Evaluation Unit was established in 2004 within Québec’s Institut national d’excellence en santé et en services sociaux (INESSS) with a novel mandate to collect real-world evidence (RWE) to complement literature-based health technology assessment. In 2010 following publication of the seminal PARTNER trial, INESSS was mandated by the health ministry to review the evidence on transcatheter aortic valve intervention (TAVI) for patients with aortic stenosis. Herein we show how RWE was used to evaluate health system performance throughout the technology’s life cycle and inform organizational and clinical decisions.

Various products were diffused by INESSS over the years: a guidance (2012), an updated literature review (2017) and provincial standards (2017), in parallel with RWE reports covering TAVI use from 2013-2015, from 2013-2018, and a 2021 RWE report combined with administrative data covering transcatheter and surgical treatment of aortic stenosis from 2013-2019.

Based on the guidance’s review of evidence, TAVI was initially recommended for patients considered at too high risk for the surgical approach, under the condition of continued evidence generation to address uncertainty. The subsequent literature review update highlighted that the indication for TAVI had been extended to patients at moderate surgical risk. INESSS produced standards in collaboration with clinical experts to optimize and harmonize the use of TAVI in designated centers. Evaluation of structures, processes and outcomes by INESSS continued until 2019, showing a continuous increase in the use of TAVI, improved short-term survival, and careful patient selection via a multidisciplinary process. RWE also highlighted the impact of TAVI on the overall organization of care for patients with aortic stenosis, as selection criteria further expanded to patients at lower surgical risk, raising important issues regarding patient selection processes, wait times, and longer-term outcomes.

TAVI clinical practice is constantly evolving and leads to changes in the management of aortic stenosis. RWE provided essential organizational and clinical input to inform clinical guidance and decision-making by Québec policy-makers, clinicians and patients.

Breast Units (BU) represent an opportunity to adequately manage and improve quality of care for patients with breast cancer. The presence of specific national guidelines should promote safe and good quality, integrated care. In fact, the presence of a multidisciplinary team of specialists whose workflows follow specific guidelines, set to the highest European standards, should ensure that patients in Breast Units receive appropriate care at diagnosis and throughout the course of the disease.

Two surveys were developed and administered to Breast Unit coordinators and patients throughout Italy. The surveys investigated the provision of healthcare services and the implementation of a new organizational model over two time periods: the first wave of the coronavirus disease 2019 (COVID-19) pandemic from March 2020 to August 2020 and the second wave from September 2020 to December 2020. The surveys aimed to assess the continuity of care during the pandemic from the clinician and patient perspective.

Patients observed a reduction in the postponement of care between the first wave of COVID-19 and the second wave. Some services were delayed, particularly in the second wave where a large number of services were not rescheduled. Management of the COVID-19 pandemic resulted in many healthcare professionals being reallocated to other duties and hospital departments. The effect of this was particularly relevant for both patients and clinicians, with few healthcare professionals having the capacity to focus on conditions other than COVID-19. In the first wave of the pandemic 42 percent of professionals were redeployed, compared with 27 percent in the second wave.

This study demonstrates how COVID-19 affected the care of patients with breast cancer in Italy. Patients and coordinators from Breast Units across the country highlighted many important aspects that should be considered when assessing the effects of the COVID-19 pandemic on the entire healthcare system in order to be better prepared for future pandemics.

Qualitative research is being increasingly integrated in heath technology assessments (HTA) within the Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS). Qualitative research methodological guidelines are given in RedETS HTA guidelines and the Patient Involvement Strategy. A specific methodological guideline to systematically review qualitative studies was published in 2007 and is pending its update. The impact of their implementation is unknown. The aim of this work is to analyze the techniques, impact and reporting of qualitative research (primary and secondary) in HTAs.

A manual search of the HTAs published in the last 5 years in RedETS was conducted to locate assessments that include qualitative research. To ensure a complete identification, RedETS agencies and units were consulted to provide information about the assessments that have used qualitative techniques in their development over the past 5 years. A content analysis of the selected assessments was conducted to analyze the techniques, impact and reporting of qualitative research in HTA.

In the past five years, focus groups, semi-structured interviews, evidence synthesis of observational studies including qualitative studies have been used and integrated in HTA in RedETS. Most of them have been linked to patient involvement facilitation or the inclusion of patient perspectives in HTA. Qualitative research has been used to analyze patient’s experiences and values, to elicit and select important outcome measures for patients, to research for barriers-facilitators for technology implementation and to inform evidence to decision frameworks.

Qualitative primary and secondary research is being used in HTA in Spain. It is mainly linked to patient involvement strategies both to elicit patient perspectives directly or to collect patient-based evidence. The impact of qualitative research in HTA is broad and diverse, extending from the scope of the assessments to the drafting of the recommendations.

The outbreak of the COVID-19 global pandemic in 2020 has been a major challenge for the world’s population and governments. The lack of vaccines, the saturation of health systems, and its rapid spread forced governments to take non-pharmacological interventions (NPI) that had a high impact on the population. Assessing the efficacy of these measures is a challenge for health technology assessment bodies.

The main NPIs for which assessment was required were: mobility restrictions, social distancing, cancellation of events or reduction of seating capacity, closure or reduction of seating capacity in non-essential businesses, closure or limitation of seating capacity in educational establishments, and promotion of teleworking in potential jobs. The implementation of these measures at a global level provides a large population for the study of the impact of these measures. However, the challenges for their evaluation are numerous:

• • The joint implementation of these measures makes it difficult to evaluate them in an isolated manner.

• • The heterogeneity between countries and regions of the pandemic situation at the time when these measures are initiated and terminated.

• • The different accuracy in the application of the measures.

• • Heterogeneity in the quality and accessibility of public health services for citizens.

Outcome variables to assess the effectiveness of these measures should include parameters related to:

• • Incidence variables: the number of new or accumulated cases in a given time range, the variation in the number of cases in a given time range and the proportion of positive tests.

• • Transmission variables: the basic reproductive number (R0) and the effective reproductive number (Rt).

• • Severity and mortality variables: the number or variation of hospitalizations, the number or variation of intensive care unit (ICU) hospitalizations and the number or variation of deaths.

The large number of available data, the heterogeneity of the measures, the differences between populations, the numerous outcome variables and the possible inclusion of mathematical modelling studies, are a methodological challenge for the HTA bodies.

The continuous and pressing challenge that the drug regulatory authorities in Italy and in Europe are facing is that of guaranteeing patients’ quick access to new drugs, ensuring the economic sustainability of the system at the same time. In recent years, flexible and diversified approaches have been developed known as Managed Entry Agreements (MEA).

We performed an analysis of the Italian legislative and regulatory aspects in reference to a new Value-based Managed Entry Agreement (VBMEA) pathway. Thus, we tried to investigate the rationale for a new pathway analyzing three main dimensions related to the new medical product (MP): value; time to entry access; and, data quality and registry design. Moreover, we shared the discussion of the proposal with an international experts’ panel.

The proposal for a new pathway of VBMEA from a procedural point of view shows the novelty related to the possibility to organize joint CTS (Technical Scientific Committee) and CPR (Price and Reimbursement Committee) assessment. A 24-month contract with an ex-factory price (PP) equal to X EUR per dose and a transfer price to the National Public Health System (NPHS), following application of a confidential discount for public structures (-X%), of X EUR per dose. After 24-months, an analysis of VBMEA is carried out. The price of the MP is therefore established based on AIFA registries and VBMEA results. The cost value incurred by the NPHS, intended as the difference between the price in market (entry) access phase and the price negotiated (PVB) in the light of the VBMEA results, shall be returned by the pharmaceutical company in the form of a payback.

Currently, MEAs represent one of the main topics of discussion between the European National Payers Authorities. There is very little information on product performance that results from MEAs. This research project could provide advice to policy makers to decrease negotiation time by ensuring earlier access to innovation for patients.

The emergence of advanced therapy medicinal products (ATMPs), a disruptive class of health technologies, is generating important challenges in terms of value assessment, and their high prices introduce critical access and affordability concerns.

The aim of this oral presentation is to expose the challenges of traditional value assessment and pricing and reimbursement methods in the evaluation of ATMPs, and to characterize the current and prospective financing solutions that may ensure patient access to and affordability for these health technologies.

Standard health technology assessment (HTA) is not designed for assessing ATMPs and may delay access to these therapies; thus, a broader concept of value is required. As a result, value-based pricing methodologies have been gaining prominence as a way to cope with the specific challenges of ATMPs. The pricing and reimbursement framework should ensure a balance between encouraging innovation and maximizing value for money for payers through the attribution of a fair price to new health technologies. The provision of early scientific advice to developers by regulatory and HTA bodies is key, as it will help diminish the perspective gap between developers, regulators, and payers.

The high efficacy and high price dynamic of many ATMPs necessitates novel financing models, both in the European Union and in the USA. Managed entry agreements, where financing is conditional upon the submission of additional evidence, linked with leased payments may offer effective strategies to address the uncertainties caused by the evidence gap associated with ATMPs, ensuring affordable and sustained access to these therapies.

The Chinese National Reimbursement Drug List (NRDL) was established in the early 2000’s and includes the drugs both fully and partially covered by National Basic Medicine Insurance. As China’s health system has been reformed over the past decade, it is important for manufacturers to understand the ever-changing reimbursement process and its implications on newly launched drugs. This study provides an updated overview of the process based on research conducted in 2021.

Targeted secondary research was undertaken to evaluate the pricing and reimbursement landscape in China. Primary research was conducted to assess the perspectives of three payers and one policy expert.

National listing remains the most viable and exclusive pathway to get a product reimbursed by public health insurance in China. Since 2017, the NRDL has been updated annually, and revisions are managed by the National Healthcare Security Administration (NHSA). Insights from 2021 suggests that the process of listing a new product on the NRDL lasts five months (July to November). Manufacturers should ensure that submissions are made when the annual NRDL process formally begins, and clinical and health economic evidence is compulsory. If a successful opinion is made by the assessment board, the manufacturer will be invited to negotiate a price with the NHSA. Data from the NHSA indicated that a total of 704 applications were made in 2020. In addition, 138 exclusive drugs were eligible for price negotiation, of which 96 drugs were successful and added to the NRDL. Findings also suggested that the average discount rate increased from 44.0 percent in 2017 to 50.6 percent in 2020.

The national reimbursement process in China has become more transparent overtime. Even so, NRDL listing remains a challenge, with decisions driven by clinical and pharmacoeconomic evidence, and price. Significant price cuts should be considered and anticipated to ensure successful negotiation outcomes.

Patients with spinal deformity require implanted spinal rods to be specifically shaped to their anatomy. Spinal rods which are manually shaped in the operating theatre are prone to fracture and malpositioning. This emphasizes the need for preoperative planning, intraoperative imaging, and accurate shaping of the implant. The application of machine learning (ML) has enabled precision in shaping patient-specific rods, with the potential to reduce adverse events. Our objective is to assess the economic value of this technology, early in its lifecycle, in the context of Health Technology Assessment (HTA) in Australia.

A budget impact analysis was performed to quantify the economic value of patient-specific spinal rods from an Australian payor perspective. Clinical outcomes were sourced from literature review, and cost inputs were obtained from Medicare, Private Health Data Bureau and Hospital Casemix Protocol Data databases.

Preliminary analysis indicates that a reduction in the rate of revision surgery due to decreased instrument failure results in cost-savings to the healthcare system, despite a higher outlay for the patient-specific rods. Adolescents who may have remained sagittally malaligned after the implantation of manually bent rods are expected to derive the greatest benefit from this ML application. The key uncertainty in this analysis is the limited real-world data of this emerging technology. ML is an iterative process of continuous improvement, identifying correlations within the data collected. As additional surgical data are integrated into predictive models, we anticipate ML technology will enhance decision-making support in surgical strategy and enable better implant precision, resulting in further decreased operating time, reduced mechanical complications, and increased healthcare savings.

ML technology is enabling precision in patient-specific implants, which is expected to drive healthcare cost-savings due to a reduction in instrument failure. Fewer replacement surgeries are an important patient-relevant outcome, especially for adolescents with spinal deformity. This preliminary analysis demonstrates the economic value of ML enabled patient-specific rods to Australian payors, early in its lifecycle.

A disruptive technology has been defined as an innovation that completely changes the way things are done. Early identification of potential disruptive health technologies has become a key point in the agenda of decision makers and health technology assessment (HTA) bodies. The PriTec tool is an automatically executable web application that was developed in 2009 by the Galician HTA Agency to facilitate decision-making regarding the selection of technologies for post-launch observation. The tool has been updated to allow scoring and ranking of technologies before their introduction into the healthcare portfolio. The aim of this work was to propose a framework for assessing the usefulness of the PriTec tool in relation to identifying possible disruptive innovations.

To evaluate the applicability of the PriTec tool for distinguishing disruptive from non-disruptive innovations, we selected a few examples from prior acknowledged disruptive and non-disruptive innovations. These technologies were scored against the predefined criteria and the results were compared and analyzed globally and by type of domain. The PriTec tool assesses six domains of technologies: clinical condition, comparative effectiveness and safety, economic impact, implementation consequences, and dissemination speed.

Disruptive technologies (e.g., transcatheter aortic valve implantation or point-of-care tests) had higher weighted global scores than non-disruptive technologies. In the domain analysis, the scores for implementation consequences were higher for disruptive than for non-disruptive technologies. Both types of technologies had similar scores in the other domains.

The PriTec tool seems to be useful for identifying potential disruptive technologies through its implementation domain. Further validation strategies are required to confirm the tool’s applicability and to improve its accuracy in the field of health disruption. The tool could be used by governments, horizon scanning organizations, and HTA organizations to promote the evidence-based detection of disruptive technologies in clinical practice. However, it is advisable that the tool be further tested and validated in other contexts.

The National Institute for Health and Care Research (NIHR) Innovation Observatory (IO) national horizon scanning research centre, has a remit to notify its stakeholders, including the National Institute for Health and Care Excellence (NICE), about innovative interventions; including biosimilar medicines in the pipeline. Biosimilar medicines bypass many developmental steps, making them substantially cheaper to manufacture for providers, which increases market availability and improves treatment access for patients.

Since 2017, the NIHR IO has monitored biosimilars in clinical development that align to the NICE health technology assessment remit. The data set explored was exported from our internal medicines innovation database - MInD.

Data sets were created that included information on the characteristics of biosimilars and their associated clinical trials. Analyses and visualization creation were carried out using Microsoft Excel and Microsoft Power BI.

A total of 100 unique biosimilar medicines in 136 clinical trials were included in the MInD since April 2017. Of these, 44 percent of biosimilars are currently EMA-approved (Nov 2021). Adalimumab was the reference medicine with the most unique biosimilars identified (12%). Seventy-two percent of the biosimilars in MInD were indicated for non-oncology conditions, twenty percent for oncology condition and eight percent for both.

There were 46 biosimilars unapproved, which were in active development. Of these biosimilars 17.4 percent are indicated for an oncology condition, 78.3 percent for non-oncology conditions, and 4.3 percent for biosimilars for both. Aflibercept was the reference product with the most (eight) biosimilars in active development.

There were 56 individual clinical trials in the MInD that list a biosimilar in development. For 26 trials, the primary completion date (PCD) was prior to 2021, whilst 28 trials listed a PCD post-2021, and 2 PCD’s were unavailable

Our analysis identified high levels of active clinical development for biosimilars. The majority of biosimilars being developed are indicated for non-oncology conditions, with many in trials due to readout in the near future. Early identification, monitoring and reporting of biosimilars allows for expedited patient access and benefits, including cost-savings for health services.

This study is funded by the National Institute for Health Research (NIHR) [(HSRIC-2016-10009)/Innovation Observatory].

Since May 2020, reimbursement can be requested for Digital healthcare applications (DIGAs) in Germany. The prerequisite for reimbursement is a listing in the Federal Institute for Drugs and Medical Devices (BfArM) DiGA-directory, granted after successful completion of an assessment process. In June 2021, IQVIA first evaluated the BfArM’s decision-making and identified criteria that may positively impact a directory listing. In November 2021, the research was updated to consider the latest developments.

Published information for each app in the DiGA-directory was qualitatively compared according to pre-specified criteria by two independent reviewers. With no data available for denied apps, only DiGAs with permanent or preliminary listings were compared.

By 26 November 2021, twenty-four apps had received a positive assessment. Permanently listed apps (n=6) focused on health status improvements and/or patients’ health competency. None claimed to improve patients’ quality of life. Results from at least one randomized controlled trial (RCT) showed efficacy with medium or strong significant effect sizes (Cohen’s d > 0.4) versus standard of care (SOC). For preliminarily listed DiGAs (n=18), final results of positive care effects were not yet provided, but applications included study designs for RCTs including definitions of primary endpoints. The BfArM accepted the trial designs to be suitable to measure an app’s positive effects on health care within twelve months after listing. Since the last analysis, no preliminarily listed apps have been granted permanent DiGA-status. Evaluation periods were extended by up to five months for three apps. With none of the trials for preliminary apps being completed, possibilities for assessment remain limited. Claims for either medical benefit and/or patient-relevant structural/procedural improvements do not seem to impact the type of listing.

Updated research confirmed previous findings. For a DiGA-directory listing DiGA, the (planned) provision of RCT data seems to be gold standard. Medium to strong effects on the improvement of health status compared to SOC appear to be important for a permanent listing. Evaluation periods of five preliminarily listed apps are expected to be completed in December 2021, allowing for further analyses in the future.

Autogenic training consists of reaching a state of deep relaxation through mental representations of physical sensations in different parts of the body. It is a promising technique for improving the psychological well-being of people with chronic diseases, but there are no clinical practice guidelines recommending the use of autogenic training in this population. The aim of this work was to identify, critically evaluate, and synthesize the available evidence on the safety and effectiveness of autogenic training in the prevention and treatment of medical conditions.

We conducted a systematic search for systematic reviews and randomized controlled trials (RCTs) in MEDLINE, Embase, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. The selection and assessment of risk of bias of the included studies was carried out independently by two reviewers.

A total of 2,420 references were identified after eliminating duplicates. Of these, 141 were selected for reading the full text, and 13 systematic reviews and 18 RCTs were included. Compared with no intervention or delayed treatment, autogenic training significantly reduced levels of anxiety and depression as well as some physical symptoms (e.g., headaches and atopic dermatitis).

Autogenic training could be useful for improving the psychological well-being and physical symptoms of patients with chronic health conditions and as an additional element in multicomponent intervention programs. However, these conclusions are not definitive due to the low number of studies available for each health condition and their high or unclear risk of bias.

Aromatherapy is the field of herbal medicine that uses essential oils distilled from flowers, roots, and herbs and other plant compounds to promote physical and psychological well-being. Essential oils are absorbed into the body in different ways, with the inhaled and topical routes being the most widely used. The aim of this review was to critically evaluate and synthesize the available scientific evidence on the efficacy and safety of aromatherapy for the management of any therapeutic indication. This report was requested by the Spanish Ministries of Health and Science and Innovation.

An overview of systematic reviews (SRs) was performed. The MEDLINE, Embase, CINAHL, and PsycINFO databases were searched for literature published from January 2006 to August 2021. SRs reporting the efficacy and safety of aromatherapy were included. We applied no restrictions in terms of administration route or essential oil used. Two reviewers independently performed screening and selection, data extraction, and quality assessment.

We included 74 SRs covering a wide variety of populations and settings. The most reported outcome was anxiety, followed by pain, and the most commonly used essential oil was lavender. Fifteen SRs reported mild adverse events with aromatherapy. Only 11 SRs assessed the certainty of evidence using the GRADE approach. Aromatherapy reduced heart rate and likely reduces anxiety and breathing rate in patients with cardiovascular diseases. Aromatherapy probably also reduces pain in women with primary dysmenorrhea. Additionally, it may reduce blood pressure, acute pain, subjective stress, and the need for antiemetic drugs after surgical procedures. However, the evidence was very uncertain regarding the effect of essential oils on anxiety, pain, and quality of life in patients with cancer, anxiety and pain after a caesarean section, and dental anxiety.

Aromatherapy may be useful for managing psychological and physical symptoms in different settings. However, the conclusions of this review are not definitive because of the moderate to high risk of bias in many of the primary studies included in the SRs.

Health technology assessment (HTA) bodies worldwide recognize the importance of real-world evidence (RWE) in addressing uncertainties around the effectiveness of new drugs at the time of launch and as part of resubmissions. We assessed the use and acceptability of RWE by analyzing HTA recommendations.

We analyzed 24,841 HTA reports, including original submissions, resubmissions, extensions of original indications, and renewals, published from January 2011 to October 2021 from more than 100 HTA agencies across 37 countries.

Our analysis showed that 3,820 (15%) reports mentioned RWE. Between 2011 and 2021 there was an eight-fold increase in the use of RWE, from 4 percent in 2011 to 34 percent in 2021. RWE was most commonly included in HTAs in oncology (26%) and endocrine and metabolic diseases (13%). The main areas supported were effectiveness (40%), safety (38%), and epidemiology (35%). RWE supplemented evidence on survival and quality of life as well as resource utilization, proxy comparators, and utility. Based on an analysis of the 1,474 reports that mentioned RWE, effectiveness was mainly supported by cohort (22%) and observational studies (13%), safety was mainly derived from pharmacovigilance data (9%), and epidemiology data were collected from registries (23%). The top five HTA bodies mentioning RWE in their reports were from France, Germany, Poland, and the United Kingdom (n=2). RWE was most accepted when it supported safety and epidemiological considerations, and to a lesser extent when it was used for effectiveness aspects or understanding management pathways.

The inclusion and acceptability of RWE in HTA recommendations varies between HTAs according to their data requirements and assessment methods. While it is not always specified how RWE was considered, there is a clear tendency for its increased use and acceptability, albeit not in all areas. Greater use of and transparency around RWE are likely to continue as multiple RWE initiatives emerge globally.

Health Technology Assessment (HTA) agencies have recognized the importance of real-world evidence (RWE) to inform access decision-making and different HTA agencies establish distinct requirements for their local jurisdictions. The objective of this study is to understand the differences of RWE included in HTA reports and HTA agencies’ perception of RWE.

HTA reports from agencies in France, Germany, Spain, Italy, United Kingdom (UK), Canada, Australia and South Korea from January 2011 to November 2021, including original submissions, resubmissions, extensions of original indications and renewals were analyzed.

Across the eight countries, RWE has been used in nineteen percent of all HTA reports (N=2,960/15,561), with an exponential increase observed between 2019 and 2021. RWE on clinical effectiveness was mostly used in HTA submissions in the UK (twenty-two percent), with twenty-six percent perceived with full acceptance. In contrast, RWE on safety and epidemiology was reported widely in HTA reports in France and Germany (83% and 87%), respectively. Ninety-three percent of RWE received full acceptance in France, followed by forty-four percent in Germany. A mixed picture of the types of RWE included in HTA reports was observed in the other countries, with high variance of acceptance (between 5 to 37%).

France, Germany, and the UK are the top three countries with a large proportion of HTA reports where RWE was mentioned. The type of RWE used is related to a large extent to the local evidence requirements. For example, RWE around epidemiology was included widely in Germany due to the needs of providing local data for budget impact analyses required by the Federal Joint Committee (G-BA); RWE on tolerability as reported in periodic safety update reports (PSURs) needs to be included in French HTA submissions. RWE on clinical effectiveness has been evaluated the most by the UK HTA bodies.

Outpatient Parenteral Antibiotic Therapy (OPAT) is a complex medical treatment used to treat patients with severe infections. OPAT is provisioned outside hospitals. There is wide variation in the use and organization of OPAT in Denmark. OPAT is increasingly used in Danish regions and municipalities, however, there is limited knowledge on the clinical, economic and organizational consequences of this technology. The purpose of the project was to establish an evidence base for decision-making prior to any further prioritization of OPAT as an alternative to intravenous antibiotic treatment in the hospital (IPAT). The HTA was produced at the request of the Health Directors in the Danish Regions to examine the consequences of using OPAT compared with IPAT.

The results were based on a systematic literature review and qualitative interviews with leaders (n=5), administrative employees (n=5) and health professionals (n=13) involved in the delivery of OPAT. Furthermore, a micro-costing analysis based on interviews with clinical experts was conducted.

The use of OPAT led to similar or better clinical results when compared with the use of IPAT. Current evidence supports OPAT as a safe model for intravenous antibiotic treatment. The organization of OPAT varied in Denmark as well as internationally. The selection of suitable patients for the different OPAT models was crucial for a successful treatment. Insight into patients’ understanding of the pros and cons of the technology indicated that most patients preferred treatment at home. In a Danish context the microeconomic analysis showed that different OPAT models generally led to a reduction in costs compared with IPAT.

The project contributes to practice and political decision making by identifying challenges and opportunities associated with OPAT. There is no one-size-fits-all solution. The choice of OPAT model must be based on careful clinical considerations. Coordination and communication across municipalities and hospitals is challenging. Reducing organizational complexity is necessary to achieve a more standardized practice.

Modeling is important for guiding policy during epidemics. The objective of this work was to describe the experience of structuring a multidisciplinary collaborative network in Brazil for modeling coronavirus disease 2019 (COVID-19) to support decision-making throughout the pandemic.

Responding to a national call in June 2020 for proposals on COVID-19 mitigation projects, we established a team of investigators from public universities located in various regions throughout Brazil. The team’s main objective was to model severe acute respiratory syndrome coronavirus 2 transmission dynamics in various demographic and epidemiologic settings in Brazil using different types of models and mitigation interventions. The modeling results aimed to provide information to support policy making. This descriptive study outlines the processes, products, challenges, and lessons learned from this innovative experience.

The network included 18 researchers (epidemiologists, infectious diseases experts, statisticians, and modelers) from various backgrounds, including ecology, geography, physics, and mathematics. The criteria for joining the network were having a communication channel with public health decision-makers and being involved in generating evidence for public policy. During a 24-month period, the following sub-projects were established: (i) development of a susceptible-exposed-infected-recovered-like, individual-based meta-population and Markov chain model; (ii) projection of COVID-19 transmission and impact over time with respect to cases, hospitalizations, and deaths; (iii) assessment of the impact of non-pharmacological interventions for COVID-19; (iv) evaluation of the impact of reopening schools; and (v) determining optimal strategies for COVID-19 vaccination. In addition, we mapped existing COVID-19 modeling groups nationwide and conducted a systematic review of relevant published research literature from Brazil.

Infectious disease modeling for guiding public health policy requires interaction between epidemiologists, public health specialists, and modelers. Communicating modeling results in a non-academic format is an additional challenge, so close interaction with policy makers is essential to ensure that the information is useful. Establishing a network of modeling groups will be useful for future disease outbreaks.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a single-strand ribonucleic acid virus that was first identified in January 2020 in patients with viral pneumonia in Wuhan, China. The virus has since spread rapidly around the world, leading the World Health Organization to declare it a pandemic on 11 March 2020. In Brazil there have been 21.8 million cases of SARS-CoV-2 infection and 608,500 deaths. The objective of this study was to evaluate the cost utility of the Oxford, CoronaVac, and Janssen vaccines from the perspective of the Brazilian public health system.

Three microsimulation models were constructed using individual data. The simulations contained seven transition states related to the natural history of COVID-19. The model with a daily cycle had a time horizon of one year and used data from 289 days of the pandemic. The analysis considered direct medical costs from the Brazilian health system perspective. Outpatient, hospital, and mortality databases were used for the model inputs and patient data were stratified by age. Effective vaccines reduced the likelihood of patients becoming ill. Information on the quality of life of patients receiving treatment in the outpatient or hospital setting and disease sequelae were extracted from the published literature. The main outcome of the analysis was quality-adjusted life-years (QALYs).

The vaccines had incremental cost-utility ratios ranging from USD 4,121 (Oxford) to USD 3,160 per QALY (CoronaVac). The older the population, the lower the incremental cost-utility ratio. Given a willingness-to-pay threshold of BRL 3,129 per QALY, all the vaccines were considered cost effective in the probabilistic sensitivity analysis. The incremental cost-effectiveness ratio stratified by age ranged from USD 6,327 per QALY in patients older than 75 years (Janssen) to USD 20,993 per QALY in patients younger than 59 years (CoronaVac).

The results of this analysis, stratified by patient age, can help in the preparation of a vaccination prioritization plan.

Health technology assessment (HTA) reports are complex technical documents that address multiple aspects of the incorporation of a technology into the health care system applying complicated methodologies coming from different disciplines. The purpose of HTA is to support decision-makers and these should have an adequate level of training to fully understand these assessments. However, most HTA education programs and courses are intended for HTA doers and there is a lack of practical guidance training aimed at preparing health managers or policy makers in HTA. The objective is to describe an HTA training program developed for decision-makers of the three levels (health care administration, hospital management and clinical practice).

Rolling Collaborative Review (RCR) 01 of convalescent plasma was identified and selected because it complied with our Population Intervention Comparator Outcome Design Question. The EUnetHTA HTA adaptation Toolkit was used to check the relevance (about research question); reliability (quality of the report) and transferability (application of information to the target setting). Additional considerations regarding the local context were examined. A panel of four professionals and one patient was formed to rate the importance of the outcomes and to carry out the external review

According to the toolkit, information on RCR01 Convalescent Plasma could be adopted for the safety and effectiveness domains. The technical characteristics and current use domains were adapted and extended. It was considered of interest to include the domains of organization and ethics. The organizational aspects were answered through the information retrieved in a search for systematic reviews and guides, and with the collaboration of experts. The ethics domain was answered through a specific literature search on ethical issues related to COVID-19 and transfusions.

The use of the EUnetHTA Toolkit has been helpful in supporting the adaptation process. The adoption of the effectiveness and safety domains from already developed HTA assessments is an efficient way to provide useful information for the decision-making process. However, contextual elements should be included in the adaptation process to ensure a complete framework for the decision.

Outcomes Based Agreements (OBAs) are financial arrangements that offer the opportunity to align payment to health outcomes in the real-world, and share the financial risk by providing long-term solutions that grant access to medicines, with reimbursement only when performance is achieved. OBAs are most likely to be useful when there is high uncertainty in the clinical data, but they are difficult to design and implement, and other financial options are usually preferred by payers. As a result, OBAs have been more the exception than the norm, and there is not a clear pattern that indicates if an OBA is likely to succeed in practice.

Through a retrospective OBA exercise with NHS Wales (Project IDEATE: Innovation in Data to Evolve Agreements That Enhance patient health outcomes), we have explored the circumstances under which an OBA might be most appealing to payers, and assessed implementation challenges and solutions, to propose a framework to evaluate the feasibility of a medicine for an OBA.

Along with mitigating some of the clinical uncertainties associated with a lack of mature data at the time of launch, an OBA must also consider other factors: the commercial viability of the agreement, the associated administrative burden, and its cost of implementation. Also, the Health System commitment to a Value-Based Healthcare agenda and, most importantly, its willingness to offer long-term sustainable solutions to optimise treatment, are key to support this approach.

Practical considerations include: how the relevant outcomes are going to be selected and tracked in the real-world, how the whole model is going to fit within the current procurement and finance infrastructures, and how industry works in collaboration with the Health System.

Insights from Project IDEATE will be used to explore how our OBA feasibility framework might be applied in the future.