In 2019, the German government established a new evaluation procedure for digital health applications (DiGAs) to facilitate their reimbursement by statutory health insurance. The procedure involves the assessment of a DiGA’s “positive healthcare effect”, which is defined as a medical benefit and/or “a patient-relevant improvement of structure and processes”. If the available clinical evidence is insufficient to prove the manufacturer’s claim on the positive healthcare effect, but the claim seems plausible, the DiGA is provisionally reimbursed, and further clinical evidence within twelve months must be generated. DiGAs eligible for provisional or permanent reimbursement are publicly listed in the DiGA directory.

In contrast to the usual pathways for reimbursement of healthcare technologies which involve IQWiG as the national HTA agency and the G-BA (Federal Joint Committee) as the decision-making body, the DiGA procedure is currently carried out by the national competent authority (BfArM) and thus outside the joint self-government. Furthermore, legal evidence requirements for DiGAs are comparatively low.

This work analyzed the suitability of clinical studies that intended to prove a DiGA’s medical benefit. For this purpose, the key elements for clinical studies published in the DiGA directory and clinical trial registries were extracted and compared with the usual evidence requirements in the reimbursement context.

As of October 2020, 20 DiGAs have successfully undergone the application procedure. Fourteen DiGAs (70%) were provisionally accepted. A randomized controlled study (RCT) design was chosen for all clinical studies to be conducted for further evidence generation. However, in four cases (28%), it is questionable whether the clinical study is suitable to demonstrate a medical benefit mainly due to the choice or operationalization of the primary endpoint (n=2), the timing of the endpoint survey (n=2) and/or the choice of the control intervention (n=1).

Even though all currently ongoing or planned clinical studies with DiGAs are RCTs, not all of them are adequate to demonstrate a medical benefit according to the usual evidence requirements.

The use of mobile applications in the treatment of health issues is more frequently becoming common practice. Apps are fast, versatile, and manageable tools that allow the empowerment of patients and professionals, and can reduce the possible stigmatization suffered by some patients, mainly in mental health. There are more than 325,000 health apps on the market, but their impact remains unclear. There are several initiatives to define how health applications should be assessed, however, all of them address only partial aspects of the evaluation. The theoretical frameworks existing to date highlight the need to develop new tools and methodologies to assess mobile applications whose objective is the management of specific pathologies.

The primary goal of the EvalDepApps project is to develop and pilot an assessment tool for mobile applications whose main objectives are the treatment, monitoring or social support of people suffering from depression. The project is inspired by the results and lessons learnt from a previous project, EVALAPPS, whose central aim was to develop a tool to assess health apps targeted toward the management of overweight and obesity. The first steps of the EvalDepApps project are: (i) to explore and characterize the current landscape of mobile applications available in the market to treat depression through a systematic appraisal, and (ii) to review the existing evidence about the effectiveness and safety of these applications through systematic research of the existing evidence.

Preliminary results show that all the depression management studies were by design based on cognitive-behavioral therapy (CBT) interventions (n=17) and the main management tools included in the services (web or apps) are psychoeducation and coaching (14), together with self-monitoring and feedback messaging (13).

Moreover, although health apps seem to be an interesting strategy to treat depression, there are very few apps available on the markets (30) and the supporting evidence is very limited. This result uncovers a need for further systematic and clinically oriented validation and testing of such apps.

In the context of the COVID-19 pandemic, which required urgent responses from health systems, and ongoing decision making in a context of limited and evolving evidence, modeling played a significant role in supporting public policy making. Nonetheless, particularly in low and middle-income countries, modeling groups are scarce, and usually not routinely involved in supporting public health policy making. We aimed to appraise COVID-19 modeling work in Brazil during the pandemic.

We performed a scoping review following PRISMA guidelines to identify groups conducting COVID-19 modeling to support health decision-making in Brazil. Search strategies were applied to MEDLINE, LILACS, Embase, ArXiv, and also included National data repositories and gray literature. We excluded reports of models without modeling results. Titles, abstracts, data repository descriptions and full-text articles identified were read and selected by two reviewers. Data extracted included modeling questions, model characteristics (structure, type, and programming), epidemiologic data sources, main outcomes reported, and parameters. To further identify modeling groups that might have not yet published results, snowball sampling was performed, and a short survey was sent electronically. Investigators and policymakers were invited to an online interview, to obtain further information on how they interacted, communicated, and used modeling results.

We retrieved 1,061 references. After removing duplicates (127), 1,016 abstracts and titles were screened. From an initial selection of 142 abstracts, 133 research groups were identified, of which 67 didn’t meet the eligibility criteria. Of these, 66 groups were invited for an interview, of which 24 were available, including 18 modeling groups from academic institutions, and four groups from State Health departments. Most models assessed the impact of mitigation measures in cases/hospitalization/deaths and healthcare service demand. Interaction and communication with decision-makers were not well established in most groups.

Despite a large number of modeling groups in Brazil, we observed a significant gap in modeling demand and communicating its results to support the decision-making process during the COVID-19 pandemic.

Scottish Medicine Consortium (SMC) meetings were suspended in March 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. This led to a high number of submissions awaiting appraisal, prompting interim process changes to ensure minimal disadvantages to patient access. We expanded the eligibility criteria for the shorter (abbreviated) submissions process and expedited advice for submissions the New Drugs Committee (NDC) intended to accept. This study aimed to evaluate the impact of the COVID-19 pandemic and these interim process changes on the characteristics of submissions received, acceptance rates, and time to advice publication.

Data for all submissions received between January 2015 and November 2021 (n=720) were extracted from an organizational database. Characteristics of and acceptance rates for submissions received before and after the start of the pandemic were compared using chi-squared and one-proportion Z-tests, respectively. Additional analyses explored the number of submissions received per month and the time from receipt of submission to NDC and SMC decision.

The numbers of full and abbreviated submissions increased from March 2020 (6% in each case), with a corresponding decrease in the number of medicine-indication pairs (e.g., pembrolizumab for breast cancer) for which companies did not submit (8%; p=0.01). An increase in the SMC acceptance rate was also observed (62 to 72%; p=0.03). Fewer submissions were received in 2020 (n=65), compared with the pre-pandemic average (mean=79.6), whereas the total in 2021 to date was higher than average (n=92). Time series analysis suggested an increasing trend in monthly submissions (from approximately 6 to 9), which is the likely reason for the increase in average time to decision (146 versus 170 days).

Process changes in response to the pandemic have been effective in expediting advice for submissions with sufficiently robust evidence. This demonstrates agility and efficiencies for submitting companies and patient groups, with no perceived impact on process rigor. The average number of submissions has increased since March 2020, and further work is warranted to understand the influence of process improvements on reducing time to advice.

Health Technology Assessment (HTA) Process assists decision-making in health policies. The COVID-19 pandemic caused a high demand on protocol or guideline updates and incorporation of new drugs or therapies, overwhelming local agencies. A recent study reported that major HTA bodies in England, Scotland, Germany, and Canada reduced their number of drug recommendations in 2020, due to reprioritization of resources and COVID-related challenges. The present study aimed to evaluate the impact of the COVID-19 pandemic at the Brazilian National Committee for Health Technology Incorporation (Conitec) recommendation process.

This descriptive study evaluated all official recommendation reports available on the Government website in 2020 and 2021, extracting the data of disease category, technology type, the aim of the report, Public Involvement, and final result for the recommendation. The results were presented in tabular and graphical form using the machine learning, through the software R studio and excel.

A total of 168 documents were evaluated, including guidelines and recommendation reports, with no reduction in the number of evaluations considering 2019. In 2020, there was a more significant evaluation of guidelines, and in 2021, a report on the non-incorporation of technologies. There were four specific documents about COVID 19, including vaccines and hospital care guidelines. The most incorporated and non-incorporated technologies were medication, targeting rare and highly prevalent diseases in balance. The Brazilian government was the main proposer. These results are part of the study “A Survey about the core methods of the recommendation reports for Brazilian Ministry of Health carried out by Brazilian Health Technology Assessment Centers”, which will characterize and analyze the core methods of the recommendation reports conducted by the Brazilian HTA Centers.

The pandemic had a low impact on demands in the routine of the Conitec. Establish indicators and technological norms applicable to health services, contribute to the identification of possible new practices, methods or criteria.

Diabetic Macular Edema (DME) is an important complication of Diabetic Retinopathy (DR). Intravitreal steroids in slow-release systems represent a safe and effective therapeutic option for the management of DME, capable of improving patients’ quality of life by reducing the number of injections thus increasing the therapeutic adherence and the effectiveness of the treatment. This study aims to determine the economic impact of DME and the consequences, in terms of both expenditure and organizational impact, associated with a greater use of the intravitreal dexamethasone implant.

The analysis entailed the comparison between two scenarios: a first scenario based on the current use of therapeutic alternatives available in the Italian healthcare setting (as is) and an alternative scenario based on the assumption of an increased use of intravitreal dexamethasone implant (to be). The results of the analysis are expressed in terms of resource absorption associated with the two scenarios as well as in terms of the cost differential given by their comparison.

Despite an increase in expenditure in terms of acquisition costs of pharmacological alternatives (EUR 898,362) and interventions provided (EUR 22,093,160), the greater use of prolonged-release dexamethasone allows for significant savings in terms of healthcare professionals’ time, follow-up and productivity losses incurred by patient/caregiver. These reductions in healthcare costs resulted in a saving of EUR 1,987,678 over a 5-year period. Such a reduction would allow, considering a total annual management cost of EUR 6,115 for the intravitreal dexamethasone, to treat 325 more patients at the same cost of the as is scenario based on the current rate of use of dexamethasone.

In a context characterized by the need to increase the allocative efficiency of economic resources, the recourse to therapeutic alternatives, such as prolonged release dexamethasone, allowing the reduction of costs for the management of a given pathology is crucial to generate more value for patients and the entire society.

In many low- and middle-income countries scarcity of local data on health outcomes and health-related quality of life (HRQoL) is a hindrance to conducting cost-effectiveness analyses. The Tunisian National Authority for Accreditation and Assessment in Healthcare (INEAS) developed a set of methodological guidelines to support pharmaceutical companies in the submission of health technology assessment (HTA) dossiers. The guidelines include INEAS’ methodological choices for pharmacoeconomic analysis, which take into consideration the specificities and constraints of the Tunisian context. We aimed to present the principal recommendations of the Tunisian guidelines for pharmacoeconomic studies, with a focus on patient-reported outcome and HRQoL measurement.

The INEAS pharmacoeconomic analysis guidelines were reviewed and the recommendations regarding outcome measurement and HRQoL were retrieved and reported.

To populate the economic model, INEAS recommends using the best available evidence. Health outcomes should be measured in terms of life-years gained and quality-adjusted life-years (QALYs); disability-adjusted life-years can be used but are not the preferred method. To estimate QALYs, INEAS favors the indirect measure of patient preferences with a validated measurement instrument. Alternatively, other measures of utility may be used, including those identified through a systematic review of the scientific literature and the publications of other HTA agencies. Justification and details of the source of the data must be provided. The utility values selected should be recent and representative of the Tunisian population, as far as possible. The guidelines refer to a set of generic preference-based HRQoL instruments, including the EuroQol five-dimensions (EQ5D), the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3), and the Short-Form Six-Dimension (SF-6D), but do not provide any explicit recommendations on their use.

The INEAS pharmacoeconomic analysis guidelines adhere to international best practices but provide more flexibility for overcoming the lack of local data. The INEAS economic guidelines constitutes a further milestone in the process of implementing HTA in Tunisia and in the Middle Eastern and African regions.

Patients treated with immunotherapy are divided into two subgroups: (i) long-term survivors (LTS) and (ii) moderate survivors. Nevertheless, clinical trials (RCTs) report only average treatment effects such as hazard rate (HRs). Health economic-models often only input average treatment effects, even though it has been shown that accounting for the LTS subgroup is crucial for accurate projection of long-term survival under immunotherapy. We investigated the incorporation of a statistical mixture cure model (MCM) in a health-economic model for lung cancer as a way to account for LTS while incorporating reported average RCT-based treatment effects.

We developed a microsimulation model describing disease progression under three treatment lines in advanced lung cancer using Dutch real-world data of chemotherapies treated patients. Here we focus on first-line treatment, for which we used gompertz distribution to simulate time-to-progression. To simulate the impact of immunotherapy, we adjusted base-model assuming MCM for first-line treatment, where the LTS subgroup was not at risk to progress, but instead die from background mortality. The subgroup of moderate survivors on the other hand are at risk to progress with adjusted progression-free HR (PF-HR). We simulated the model with size of LTS (prop_LTS) ranging from 14-34 percent (keynote-001 five-year overall survival [OS], 95% confidence interval) while fixing average RCT PF-HR at 0.5. Model predictions under the different prop_LTS were compared to real-world Dutch OS as well as the long-term RCT five-year OS.

With respect to observed short-term survival outcomes, model predictions were insensitive to assumptions regarding the size of the LTS subgroup. However, to match the five-year RCT OS rate reported (32%), the prop_LTS had to be equal to 34 percent. Under this latter setting for the prop_LTS, the progression HR in the subgroup of moderate survivors was calibrated to be 1.1.

The use of a mixture cure model improves long-term model-based projections with the implicit assumption that moderate survivors have little or no treatment benefit.

Circulating tumor DNA (ctDNA) is a promising new biomarker with multiple potential applications in cancer care. As part of the “ctDNA on the way to implementation in the Netherlands (COIN)” project, an early, comprehensive Health Technology Assessment (HTA) is ongoing. Information about the costs of ctDNA testing is essential for implementation. Estimating the total cost associated with ctDNA-testing is challenging due to variation in the workflow, wide range in purchase and operational costs of the platforms, and the highly dynamic field. As a first step in the HTA, the aim of this study was to develop a flexible micro-costing framework and open-access model for consistent cost calculation of ctDNA-testing.

First, the complete diagnostic workflow of ctDNA-testing was mapped based on expert discussions. This step-wise workflow was used as the foundation of the framework. Second, the activity-based costing method was used and included costs for personnel, materials, equipment, overhead, housing, and test failures. Third, the framework was validated by experts and by applying the cost calculation model to six case studies.

The diagnostic workflow was mapped from blood sample collection to reporting the diagnostic findings. The framework was developed from a Dutch perspective and takes into account the testing volume. The total cost per sample for the case studies with different workflows and testing volumes ranged from EUR 168 to EUR 7,638.

The developed micro-costing framework can be used to calculate the costs for ctDNA-testing for different workflows. The results from the case studies show the wide range of costs for ctDNA-testing and that the costs are determined by the choice of platform, setting, and testing volume. The open access model allows users to adapt and specify parameters in the diagnostic workflow matching their setting and can be used to support investment decisions and future cost-effectiveness studies.

It is estimated that prostate cancer will reach 66 thousand by the triennium 2020-2022 according to the National Cancer Institute (INCA). After initial diagnosis and staging the patient may undergo radical prostatectomy and/or curative radiotherapy. In patients with biochemical relapse (PSA >0.2 ng/ml) initially treated with radical prostatectomy, salvage external radiotherapy is indicated. The [68Ga] Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography (PSMA PET-CT) scan is mainly used for localization of prostate cancer in the setting of first biochemical recurrence and can significantly influence the clinical management of the patient.

The overall objective of this work is to perform a treatment cost analysis for patients in first biochemical recurrence of prostate cancer after curative radical prostatectomy and after performing [68Ga] PSMA PET-CT from the perspective of the Brazilian Health System (SUS). A decision tree was constructed through consultation with experts to outline the patient’s entire treatment. Values per modelled therapeutic procedure were surveyed in two different scenarios, with and without [68Ga] PSMA PET-CT. The average treatment in scenario 1 was stereotaxic radiation therapy (SBRT), and rescue radiotherapy and androgen deprivation therapy (ADT). In scenario 2, it was salvage radiotherapy and ADT. The reimbursement table was prepared from data collected by SUS system. Variations were analyzed using a sensitivity study. Total average values included: individual procedure, according to medical management (up to 3 years) and population percentage with and without [68Ga] PSMA PET-CT.

Values were calculated in Brazilian currency (BRL) for each procedure. The total amount calculated for scenario 1 was BRL 264,965,465.00 (USD 55,642,747.65) and for scenario 2 was BRL 123,585,612.72 (USD 26,162,978.67).

The reimbursement of line of care adopted after [68Ga] PSMA PET-CT is an important information to expand access to the Brazilian population. It shows an increased cost with [68Ga] PSMA PET-CT adoption. A prospective study should be considered with high follow up.

Migraine, the second leading cause of disability worldwide, remains underdiagnosed and undertreated. Considering the high burden of migraine, we analyzed the strengths and limitations of existing migraine management guidelines.

A targeted literature review was conducted using MEDLINE on 24 March 2021 to identify current migraine management guidelines (including policies and position statements) published in the English language from France, Germany, Italy, Spain, the United Kingdom, and the USA. This was supplemented by a gray literature search. Disease state or pharmacological management guidelines for adults with migraine comprising any of the following perspectives were included: health economics; payer; health technology assessment; treatment access; and impact of guideline implementation on economic or disease burden. Guidelines were analyzed using the Centers for Disease Control and Prevention (CDC) policy analytical framework, which comprises three domains: problem identification, policy analysis, and strategy or policy development, with ranking criteria for each.

Of 39 selected guidelines, 25 adequately identified problems related to migraine, 35 sufficiently reviewed the literature on migraine treatment, three failed to cite literature, and one lacked sufficient content. Twenty-three guidelines targeted healthcare professionals. Almost all guidelines lacked a stepwise migraine treatment approach; only the American Academy of Family Physicians guideline offered first- and second-line treatment options. Four guidelines mentioned current political forces, and coverage of economic or budgetary impact aspects was limited. Numerous guidelines described the substantial economic burden of migraine and were categorized as ‘high’ for benefits. Public health impact was categorized as ‘high’ for 28 guidelines and budgetary impact was rated as ‘more favorable’ for 27 guidelines. Thirteen guidelines defined a strategy for the intended purpose. Only the United States Department of Health and Human Services pain management guideline met all of the CDC criteria.

Future policies on migraine management may benefit from the inclusion of information on economic data, political feasibility, and public health impact. Furthermore, migraine management guidelines could potentially be improved by considering a comprehensive treatment approach and guideline implementation, as well as addressing knowledge gaps in disease state, public health, and economic aspects.

Long-term cocaine use is associated with a wide range of cognitive deficits and neuropsychiatric pathologies. Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapeutic strategy that stimulates the prefrontal cortex and may improve cognitive inhibitory control and decision-making. This systematic review aimed to evaluate and synthesize evidence on the safety, effectiveness, and cost effectiveness of rTMS for the treatment of cocaine addiction.

A systematic review of the literature was carried out. The following electronic databases were searched to identify relevant studies published from inception to October 2020: MEDLINE, Embase, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials (RCTs), non-randomized controlled trials (nRCTs), case series studies, and full economic evaluations were included.

A total of 12 relevant studies were identified, which included five RCTs, one nRCTs, and six case series studies. None of the studies reported data on cost effectiveness. The results indicated that rTMS reduces cocaine cravings and the number of doses consumed. No serious adverse effects were observed.

The ability to modulate the craving for cocaine in a specific way with non-invasive brain stimulation techniques, such as rTMS, could be a new adjunct to the behavioral treatment of addiction, especially for cocaine use where there is currently no approved pharmacological treatment. Despite the low quality of the included studies, preliminary results indicate that rTMS may reduce cocaine use and cravings. In any case, since this effect is considered moderate, future studies with larger sample sizes and longer follow up are required.

The assessment of current technologies needs a more holistic approach to obtain accurate recommendations for decision-making. The VALues In Doing Assessments of health TEchnologies (VALIDATE) methodology considers that facts and values from all stakeholders need to be included in the scoping of an assessment to gather the comprehensive information needed for unbiased decision-making. This report aimed to explore how to properly assess the integrated care of patients with aortic valve stenosis (AVS) using the VALIDATE approach.

A literature review was conducted, and 11 semi-structured interviews were performed with various hospital-based healthcare professionals (cardiac surgeon, clinical cardiologist, interventional cardiologist, anesthetist, process coordinator nurse, and others) and patients. Content analysis was used for data analysis and integration.

The literature review showed that the cardiology and cardiac surgery perspectives were dominant in 90 percent of the articles and present in the remaining ten percent. The perspectives of other specialties (anesthesiology, primary care, and psychology) were included in three percent of the articles and patient perspectives were included in nine percent. Interviewing and considering the perspectives of the different stakeholders involved in the care pathway identified the following indicators that should be included in the assessment care for patients with AVS: difficulties associated with late diagnosis of AVS; the need to incorporate a multidisciplinary approach in patient risk assessment; the importance of geriatric evaluations; considering patient (and family and caregiver) preferences for type of treatment; the importance of following up pharmaceutical treatment and palliative care; use of telemonitoring; and digital exclusion of patients with respect to the use of apps for prehabilitation and rehabilitation.

The stakeholders interviewed were involved in different steps of the care pathway and had differing needs, some of which were not found in the literature. The indicators suggested for inclusion in the assessment differed according to type of stakeholder and their involvement in the care pathway. Therefore, this case study exemplifies the VALIDATE method and endorses the need for multistakeholder involvement in eliciting values when scoping the assessment of a complex technology.

The reverse transcription polymerase chain reaction (RT-PCR) test is the gold standard for detecting coronavirus disease 2019 (COVID-19), but recent studies have reported false negative results for RT-PCR. Consequently, several countries are looking at chest computed tomography (CT) for the diagnostic workup of patients with suspected or probable COVID-19 to inform clinical management. Therefore, this rapid review provides the best available evidence on the use of chest CT for detecting COVID-19 pneumonia.

Literature searches were conducted in the PubMed, Cochrane Library, JBI Library, Epistemonikos, and Evidence Aid databases for relevant papers published from 1 December 2019 to 12 June 2020. The search strategy was based on the identified population, concept, and context with respect to the objective of the review. The methodological quality of the seven systematic reviews identified was appraised using the AMSTAR checklist.

The use of CT as a first-line screening tool for COVID-19 is not beneficial. Nevertheless, for patients with suspected COVID-19 pneumonia who had a false-negative RT-PCR results, cross-checking with CT and a repeated RT-PCR test is essential to avoid misdiagnosis. Chest CT offered high sensitivity for detecting COVID-19 pneumonia among symptomatic individuals, especially in those with severe disease. It was also useful for evaluating the potential complications, disease severity, and progression of COVID-19 pneumonia. The features of CT images differed at the early, intermediate, and late stages of COVID-19 pneumonia, but the most common imaging findings were patchy and ground glass opacities. It was also found that diagnosing COVID-19 in children using CT is challenging.

Even though chest CT is not useful for primary screening of COVID-19, it is useful for detecting later stage disease and for evaluating patients with COVID-19 pneumonia. For patients with suspected COVID-19 pneumonia and a false negative RT-PCR result, cross-checking with a chest CT and a repeat RT-PCR test is essential to avoid misdiagnosis.

The COVID-19 pandemic has had a dramatic impact on the health and social care landscape, both in terms of service provision and citizen need. Responsive, evidence-based research is essential to develop and implement appropriate policies and practices that manage both the pandemic itself, and the impact COVID-19 has on other health and social care issues.

To address this, the Wales COVID-19 Evidence Centre (WCEC) was launched in 2021 with the aim of providing the best available, up-to-date, and relevant evidence to inform health and care decision making across Wales.

Funded by the Welsh Government, the WCEC comprises of a core team and several collaborating partner organizations, including Health Technology Wales, Wales Centre for Evidence-Based Care, Specialist Unit for Review Evidence Centre, SAIL Databank, Public Health Wales, Bangor Institute for Health & Medical Research in conjunction with Health and Care Economics Cymru, and the Public Health Wales Observatory. Over the last year, WCEC has developed its rapid review processes and methodology informed by best international practice and aims to provide around 50 reviews each year. WCEC works alongside various stakeholder groups from health and social care across Wales, and they form an integral part of the review process, from scoping to knowledge mobilization.

To date, the WCEC has produced reviews on a diverse range of COVID-19 topics, including transmission, vaccination uptake (barriers, facilitators and interventions), mental health and wellbeing, as well as face coverings and other preventative interventions. The topics have also covered a wide range of populations, from general public, to healthcare workers, to children. These reviews have been used to inform policy and decision-making, including the Welsh Government’s Chief Medical Officer 21-day COVID-19 reviews.

The WCEC has brought together multiple specialist centers with a diverse range of skills to produce timely reviews of the most up-to-date research to support decision makers across health and social care. These reviews have informed policy and decision-making across Wales.

Since the vaccine roll out, research has focused on vaccine safety and efficacy, with large clinical trials confirming that vaccines are generally effective against symptomatic COVID-19 infection. However, breakthrough infections can still occur, and the effectiveness of vaccines against transmission from infected vaccinated people to susceptible contacts is unclear.

Health Technology Wales (HTW) collaborated with the Wales COVID-19 Evidence Centre to identify and examine evidence on the transmission risk of SARS-CoV-2 from vaccinated people to unvaccinated or vaccinated people.

We conducted a systematic literature search for evidence on vaccinated people exposed to SARS-CoV-2 in any setting. Outcome measures included transmission rate, cycle threshold (Ct) values and viral load. We identified a rapid review by the University of Calgary that was the main source of our outcome data. Nine studies published following the rapid review were also identified and included.

In total, 35 studies were included in this review: one randomized controlled trial (RCT), one post-hoc analysis of an RCT, 13 prospective cohort studies, 16 retrospective cohort studies and four case control studies.

All studies reported a reduction in transmission of the B.1.1.7 (Alpha) variant from partial and fully vaccinated individuals. More recent evidence is uncertain on the effects of vaccination on transmission of the B.1.617.2 (Delta) variant. Overall, vaccine effectiveness in reducing transmission appears to increase with full vaccination, compared with partial vaccination. Most of the direct evidence is limited to transmission in household settings therefore, there is a gap in the evidence on risk of transmission in other settings. One UK study found protection against onward transmission waned within 3 months post second vaccination.

Early findings that focused on the alpha variant, showed a reduction in transmission from vaccinated people. There is limited evidence on the effectiveness of vaccination on transmission of the Delta variant, therefore alternative preventative measures to reduce transmission may still be required.

Treatments for coronary heart disease patients have had major developments in recent decades, both in the pharmacological and interventional fields, and this has helped to prolong the survival of these patients. However, the growing number of patients who show persistent and disabling symptoms of angina proves that at the same time their quality of life has not been equally improved.

We conducted a multidimensional assessment coherent with health technology assessment methodology on the Coronary Sinus Reducer System (CSRS). CSRS is the latest line of therapy for patients with coronary artery disease who are ineligible for revascularization, demonstrate reversible ischemia, and have refractory angina pectoris (AP) despite optimal standard medical therapy. We performed a literature review in order to gather evidence on efficacy and safety of the device and on the economic and organizational impact of the procedure. In the economic domain we developed a cost-utility model based on a decision tree and a five-year time horizon budget impact model.

Several studies in the literature have shown that this therapy is related to an increase in quality of life and an improvement in symptoms of refractory angina. The economic evaluations conducted show how the therapy, despite an increase in the resources absorbed in the first years of implementation, reaches a cost saving profile in the medium term due to positive outcomes, while leading to an increase in the quality of life in patients suffering from refractory angina.

The treatment of refractory angina remains a challenge for today’s medicine. Patients suffering from this condition are often described as “no option” patients. Thus, despite there is a need of further evidence to establish even more robustly the economic sustainability of the device, especially on its effectiveness in the medium-long term, the device should be taking into account in those patients who could benefit from it in terms of relieving the symptoms of angina and improving their quality of life.

Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) fetuses increases the neonatal survival rate. However, FETO also increases the number of preterm prelabour rupture of membranes (PPROM) and preterm deliveries (PTDs) as fetal membrane defects after fetoscopy do not spontaneously heal. To solve this issue, an advanced sealing plug is being developed. Through early-stage health economic modelling, we estimated the potential value of this innovative plug in terms of costs and effects and determined the properties for it to become cost-effective.

We applied early-stage health economic modelling to the case of performing FETO in singleton pregnant women whose fetus is prenatally diagnosed with CDH. We simulated a cohort of women using a state-transition model over a 45-year time horizon. In our best-case scenario analysis, we compared the current care strategy to a perfect plug strategy, which reduces PPROM and PTDs by 100 percent, to determine the maximum quality-adjusted life years (QALYs) gained and costs saved. Using threshold analysis, we determined the minimum percentage of reduction in PPROM and PTDs for the plug to be considered cost-effective. Model parameters’ impact on outcomes was investigated in a sensitivity analysis.

Our model indicated that a perfect plug strategy would yield an additional 1.94 QALYs at a cost decrease of EUR 2,554 per patient per year. These values were strongly influenced by the percentage of very preterm deliveries. Threshold analysis showed that, for EUR 500 per plug, the plug strategy needs a minimum relative reduction of 1.83 percent in PPROM and PTDs (i.e., PPROM: 47.50 to 46.63 %, PTDs: 71.50 to 70.19 %) to be cost-effective.

Our model-based approach showed clear potential for the plug strategy when applied in the context of FETO for CDH fetuses, as only a small reduction in PPROM and PTDs is needed for the plug to be cost-effective. Its value is expected to be even higher when used in conditions suffering from more very preterm deliveries. Continuation of investment in the innovation’s research and development seems to provide value for money.

Guidance on appropriate methods to obtain a comparator arm for the cost-effectiveness analysis of tumor-agnostic drugs is needed. In recent years, multiple tumor-agnostic drugs have been submitted to health technology assessment (HTA) bodies based on data from single-arm basket trials. These target a specific genetic mutation, as opposed to targeting a specific tumor type. Since HTA bodies are interested in the comparative effectiveness of a treatment, manufacturers have used several methods to obtain a synthetic control arm in their submissions. This study provides an overview of the recommendations by HTA bodies on the methodology to obtain comparator efficacy.

A targeted literature review will be conducted focusing on the methodology used to obtain a comparator arm in the context of tumor-agnostic drugs. The search will cover key HTA organizations; including the National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS) and the Canadian Agency for Drugs & Technologies in Health (CADTH). Methodologies used in entrectinib and larotrectinib submissions will be extracted. Particular focus will be given on the impact of the applied methodology to the reimbursement decision, as well as key critiques by the HTA bodies. Key search terms will include the following: ‘tumor-agnostic’, ‘histology independent’, ‘HIT’, ‘entrectinib’, ‘larotrectinib’.

An overview of the results will be presented. These will include the applied methodology for obtaining a comparator arm, critiques and recommendations from HTA bodies, and the impact these methodologies had on the overall reimbursement decision. This will enable comparison of HTA decision-making across regions, and key evidence gaps that need to be further explored.

The results of this study could be useful in the future assessment of tumor-agnostic drug submissions, focusing on the methodology used to obtain comparator efficacy.

Chemotherapy-induced alopecia (CIA), although reversible, is one of the most common and distressing side effects of cancer therapy, affecting approximately 65 percent of all patients and influencing treatment decisions in some of them. Scalp cooling (SC) is a method aiming to prevent CIA. Our study aims to evaluate the real value of SC devices.

A systematic review of the available scientific literature on the safety, effectiveness and cost-effectiveness of the use of SC compared with no intervention was performed. Overall effect size was estimated through a meta-analysis. An economic analysis in the Spanish context from the Spanish National Healthcare System (NHS) and social perspectives was performed.

Thirteen randomized controlled trials (n = 832) were included but only nine contributed to the meta-analysis. A large effect in favor of SC reducing hair loss was found (RR=0.57; 95% CI: 0.46-0.69). No differences were observed according to the type of cancer, although there was a small positive effect for breast cancer. A higher effect was found in patients treated with a combination anthracyclines/taxanes treatment compared to those treated only with anthracyclines. The only economic evaluation found in the literature was conducted in The Netherlands and concluded that Paxman system was less costly than usual care from societal perspective and no differences in quality adjusted life years (QALYs) were observed. The de novo economic analysis showed that the strategies including SC devices generated more costs and QALYs (given some assumed utility values) than usual care (not SC), presenting incremental cost-effectiveness ratios below the threshold calculated for Spain (EUR 25,000 /QALY), from both perspectives.

The results suggest that SC are effective for the prevention of CIA. Furthermore, assuming the utility values used in the model, SC devices are cost-effective compared to usual care (not SC).