Wales has ambitious health, wealth, and innovation policies and a clear goal to use the economic muscle of the Welsh National Health Service (NHS) to support its strong life sciences sector. Health Technology Wales (HTW) has a clear remit to appraise technologies over the span of their lifecycle from innovation to obsolescence. HTW is collaborating with the Bevan Commission through their national Health Technology Exemplars (HTEs), which partners NHS and industry stakeholders to strengthen innovation within the Welsh health system.

Health technology assessment (HTA) methods were used to produce topic exploration reports for assessing the evidence underpinning applicant innovations. A “Dragons’ Den” expert panel was convened to select the successful HTEs.

Fourteen Bevan HTEs were awarded funds, which were matched by industry partners. Application of HTA methods resulted in more critical consideration of technology value propositions, including: developing pull models of innovation focused on delivering health technology solutions for current problems facing NHS Wales; supporting early dialogue between the NHS and industry partners around demonstrating evidence of improved patient outcomes; and focusing on transformative rather than incremental innovation. The most promising innovations will progress to rapid HTA, where the evidence generated will be used to develop guidance for NHS Wales.

HTA methods were productively deployed at the innovation phase of the technology lifecycle to support evidence-informed allocation of scarce innovation resources. In this way, HTW is working with key stakeholders to identify and offer early support to the most promising innovations, with the aim of expediting their adoption and realizing health benefits for patients as quickly as possible. The Bevan Commission has partnered with HTW to routinely build in HTA and evidence considerations in its future innovation calls and competitions. Thus, HTW has established a “feeder” pipeline for assessing bottom-up service-led innovations and encouraging evidence consideration throughout the lifecycle of innovative technologies.

Wearable Digital Health Technologies (WDHTs) can support and enhance self-management by giving individuals with chronic conditions more control over their health, safety and wellbeing. Involving patients early on in the design of these technologies facilitates the development of person-centered products. It may increase the potential uptake of (and adherence to) any intervention they are designed to deliver. This research aims to elicit chronic kidney disease (CKD) patients’ preferences for WDHTs that may help patients manage their conditions.

We used discrete choice experiments (DCE) to elicit preferences for WDHTs characterized by their generalizable characteristics. The study design was informed by a multi-stage mixed-method approach (MSMMA). This included a review of the published literature, focus group interviews and one-to-one interactions with CKD patients to identify relevant characteristics (that is, attributes and levels) associated with wearable DHTs. We collected the data from 113 patients (age ≥18 years) with stage 3 or above CKD. The analysis started with a conventional multinomial logit model and was extended by investigating heterogeneity in preferences via latent class models.

Our MSMMA yielded ten potential attributes for consideration in a choice task. The final list included five attributes, cross-checked and validated by the research team, and patient representatives. The most preferred attributes of WDHTs were device appearance, format and type of information provided, and mode of engagement with patients. Respondents preferred a discreet device, which offered options that individuals could choose from and provided medical information.

We show how to use MSMMA to elicit user preferences in (and to inform the) early stages of the development of WDHTs. Individuals with CKD preferred specific characteristics that would make them more likely to engage with the self-management support WDHT. Our results provide valuable insights that can be used to inform the development of different WDHTs for different segments of the CKD patients population, moving away from a one-size-fits-all provision and resulting in population health gains.

The objective of the present policy analysis was to understand how a disinvestment approach to the process of health technology assessment (HTA), applied to the field of medical devices, might help Italian policymakers to properly spend the resources in healthcare.

Previous international and national experiences in disinvestment for medical devices were reviewed. Precious insights for the rational expenditure of the resources were derived by assessing the evidence available.

The disinvestment of ineffective or inappropriate technologies or interventions with an inadequate value-for-money ratio has become a growing priority for National Health Systems. Different international disinvestment experiences of medical devices were identified and described through a rapid review. Although most of them have a strong theoretical framework, their practical application remains difficult. In Italy, there are no examples of large and complex HTA-based disinvestment practices, but their importance is becoming increasingly acknowledged, especially given the need to prioritize the funds provided by Recovery and Resilience Plan.

Anchoring decisions on health technologies without reassessing the current technological landscape through a robust HTA model might expose to the risk of not ensuring the best employment of the resources available. Thus, it is necessary to develop a strong HTA ecosystem in Italy through adequate consultation with stakeholders to enable a data-driven and evidence-based prioritization of resources toward choices characterized by high value for both patients and society as a whole.

Both patient composition and medical care received in clinical trials may not be representative of clinical practice, yet health technology assessments (HTAs) commonly use extrapolation results from trials to estimate incremental benefit. Due to data limitations, external validation of trial extrapolations are uncommon. With the goal of better estimating the benefit of new therapies in practice, we compared long-term survival estimated from real-world patients who received therapy similar to the comparator arm of the OAK trial, a phase III study of patients with advanced non-small cell lung cancer (aNSCLC) who progressed following initial chemotherapy, to standard estimation approaches.

We estimated long-term survival from: (i) direct extrapolation of trial survival curves; and (ii) aNSCLC patients from the United States Flatiron Health Electronic Health Record ()-derived de-identified database diagnosed between January 2011 and August 2019 who received docetaxel monotherapy after platinum-doublet and had adequate organ function as well as functional status. Patients with unknown organ function and functional status were also included. Standard parametric extrapolations were applied and selected based on visual inspection and goodness-of-fit tests for each cohort.

Using a log-logistic model to extrapolate the trial comparator arm (N = 425), estimated lifetime mean overall survival was 19.2 months (95% confidence interval [95% CI]: 16.5–22.6), and 14.4 months (95% CI: 12.4–17.0) for the real-world cohort (N = 415). Estimated 5-year overall survival rates were 5.4 percent (95% CI: 3.9–7.3) for the trial patients, compared to 3.7 percent (95% CI: 2.6–5.0) among real-world cohort patients.

Our results suggest that directly extrapolating observed survival for trial patients may overestimate the long-term survival compared to the experience of patients treated in routine practice. Our findings have implications for those wishing to estimate the incremental benefit for novel versus established treatments. We plan to compare our results to a generic patient cohort from national cancer registry. Further EHR-based studies utilizing real world data are needed to confirm our findings and to extend beyond this use case for other cancer types and anti-neoplastic therapies.

High-intensity focused ultrasound (HIFU) is a non-invasive ablative technique to treat breast fibroadenomas and benign thyroid nodules. A rapid Health Technology Assessment (HTA) was commissioned to inform the Changi General Hospital's decision on procuring a HIFU system.

A systematic literature search was conducted for systematic reviews, HTA reports and clinical practice guidelines on the clinical effectiveness of HIFU systems with the following PICO elements:

Patients = patients with benign breast fibroadenomas or thyroid nodules

Intervention = HIFU

Comparator = conventional treatment

Outcomes = clinical outcomes

Retrieved studies were summarized in a narrative synthesis.

A few small case series showed reduction in volume of fibroadenomas/nodules in the short term and side effects were minor. Additionally, in HIFU for benign thyroid nodules, conference abstracts described a small open-label, randomized controlled trial where patients receiving HIFU had nodule volume reduction of over 30 percent compared to no reduction in the observation group, at 6 months; and a small non-randomized controlled study where volume reduction was about 70 percent in patients receiving HIFU compared to active observation.

Recent clinical guidelines do not mention HIFU as a therapeutic option for fibroadenomas/nodules.

Major United States health insurers do not cover HIFU and consider it experimental, investigational or unproven. In Germany, HIFU for breast fibroadenomas and benign thyroid nodules are covered by some insurers under special integrated care contracts.

HIFU for fibroadenomas/nodules is a technology still developing its evidence base. The peer-reviewed literature comprises a few small case series and two controlled trials showing fibroadenoma/nodule reduction in the short term (up to 12 months) but no long term outcomes. Professional opinion from current guidelines does not mention HIFU as an option.

It may be prudent to await stronger evidence on long-term patient-important outcomes before offering the treatment as a hospital service. HIFU may be suitable for further clinical research.

Extracorporeal circulatory membrane oxygenation (ECMO) is a technology that allows recovery of adults in cardiorespiratory failure with encouraging results, but is not available in the Brazilian universal public health system (SUS) due to high implementation costs. Time-driven activity based costing (TDABC) is applied to measure processes in an economic perspective by identifying opportunities to make processes more efficient through the reduction of resources used in each activity. The literature has explored the use of TDABC to measure costs related with clinical procedures and technologies in microcosting studies, identifying opportunities to improve the process by making it more efficient. This research measures the real costs to implement ECMO in Brazil to compare with the current public reimbursement system.

This study applied TDABC using data from 6 patients to measure costs of ECMO intervention considering the public perspective in Brazil. In sequence, standard price payed by SUS was used to estimate the current reimbursement amount received by the hospital for ECMO procedure. Cost variable analysis was conducted to understand when and how patients receiving ECMO are using hospital resources. Cost data were collected from an academic public hospital using an average of 18 months (2016–2017) for the department costs.

The real average cost was USD 128,923. Most significant resource costs was medical staff, particularly for the three survivor patients, and the ECMO equipment presented the second highest cost. ECMO activities were separated into: before implantation of ECMO, period using ECMO, intensive care post-ECMO and rehabilitation, being the period where ECMO is the most expensive, particularly in nurse and physician costs. The SUS average was USD 31,437, which shows a difference of USD 97,485 between the real ECMO cost and the public reimbursement in Brazil.

A critical element of the propagation of ECMO in Brazil and its reimbursement by public health system is the high cost and out-of-date standard payments by the Ministry of Health. Effort to implement a trustworthy method to guide decisions of SUS for the adoption and financing new technologies is essential to contribute to the optimization of public health policies in a country with a universal health system and limited resources dedicated to health sectors.

The European Health Technology Assessment Network (EUnetHTA) Work Package 5B1, is focused on testing the levels of cross-border collaboration on real world data for supporting reimbursement/pricing decision-making. Within this Work Package, we are conducting a pilot on Left Ventricular Assist Device on destination therapy in collaboration with the National Institute for Health and Care Excellence (NICE, UK), the Belgian Health Care Knowledge Centre (KCE, Belgium) and the Italian National Agency for Regional Health Services (AGENAS, Italy). This pilot aims to define the minimum data set for gathering and sharing high quality registry data on key uncertainties found at the time of the health technology assessment (HTA). Furthermore, the pilot will assess the feasibility of carrying out a common analysis or reusing this data for National or Joint Reassessments.

Evidence gaps were based on the four national assessments. Collaborating partners were responsible for agreeing on the key outcomes and proposing the minimum dataset to be registered. European clinical experts and patients rated and prioritized the dataset using a two round Delphi technique (not relevant, important but not critical; critical). The dataset will confirm the basis for the Spanish LVAD registry, implemented at the national health service level to inform inclusion into the healthcare portfolio.

The key outcomes agreed upon by agencies relate to safety, effectiveness, satisfaction and acceptability of the patient and cost-effectiveness, budget impact and organizational impact. Expert cardiologists and cardiac surgeons representing the European and Spanish Society, among others, participated in the prioritization of basic data. The final dataset is expected by December 2020.

The variation in the quality and definition of outcome measures for measuring key evidence gaps reduces the utility of registries for HTA, making it difficult to compare, link, and aggregate data across countries. The EUnetHTA pilot is intended to offer a model for cross-border collaboration on real world data for supporting the decision-making process for pricing and reimbursement.

Multi-stakeholder interactions have evolved at product and policy levels. There is a need to assess the current and future landscape of interactions between companies, and regulatory and HTA agencies to address challenges and identify areas for improvement.

The aims of this study were to review the current interactions within and across regulatory and HTA agencies, and companies’ experiences in engaging in these activities; to assess the added value of interactions as well as limitations; to explore the future ecosystem for stakeholder interactions.

Three separate questionnaires were developed for companies, regulators and HTA agencies, respectively, to assess their experiences and perceptions. The responses were analyzed using descriptive statistics and discussed at a multi-stakeholder workshop. Key outcomes from the surveys and workshop discussion were reported.

All seven regulators and seven HTA agencies in the survey indicated that they had stakeholder interactions. More formal collaboration occurred with regulators compared with HTA agencies. All nine companies have taken early advice but indicated the need for future prioritization. Success indicators can be built at the product and therapy levels, with the added value of faster patient access. Four principles were proposed for the future ecosystem: separate remit and functions between regulators and HTA; align processes; converge evidence requirements where possible; increase transparency.

This research brought together regulators, HTA agencies, companies to examine how they interact with one another. We propose measures of value and make recommendations on future evolution to enable better evidence generation and improve regulatory and HTA decision-making.

Poor nutrition links to chronic diseases, emphasizing the need for optimized diets. The EU-funded project PREVENTOMICS, introduced personalized nutrition to address this. This study aims to perform a health technology assessment (HTA) comparing personalized nutrition interventions developed through this project, with non-personalized nutrition interventions (control) for people with normal weight, overweight, or obesity. The goal is to support decisions about further development and implementation of personalized nutrition.

The PREVENTOMICS interventions were evaluated using the European Network for HTA Core Model, which includes a methodological framework that encompasses different domains for value assessment. Information was gathered via [1] different statistical analyses and modeling studies, [2] questions asked of project partners and, [3] other (un)published materials.

Clinical trials of PREVENTOMICS interventions demonstrated different body mass index changes compared to control; differences ranged from −0.80 to 0.20 kg/m2. Long-term outcome predictions showed generally improved health outcomes for the interventions; some appeared cost-effective (e.g., interventions in UK). Ethical concerns around health inequality and the lack of specific legal regulations for personalized nutrition interventions were identified. Choice modeling studies indicated openness to personalized nutrition interventions; decisions were primarily affected by intervention’s price.

PREVENTOMICS clinical trials have shown promising effectiveness with no major safety concerns, although uncertainties about effectiveness exist due to small samples (n=60–264) and short follow-ups (10–16 weeks). Larger, longer trials are needed for robust evidence before implementation could be considered. Among other considerations, developers should explore financing options and collaborate with policymakers to prevent exclusion of specific groups due to information shortages.

The hazard ratio (HR) is a commonly used summary statistic when comparing time to event (TTE) data between trial arms, but assumes the presence of proportional hazards (PH). Non-proportional hazards (NPH) are increasingly common in NICE technology appraisals (TAs) due to an abundance of novel cancer treatments, which have differing mechanisms of action compared with traditional chemotherapies. The goal of this study is to understand how pharmaceutical companies, evidence review groups (ERGs) and appraisal committees (ACs) test for PH and report clinical effectiveness in the context of NPH.

A thematic analysis of NICE TAs concerning novel cancer treatments published between 1 January 2020 and 31 December 2021 was undertaken. Data on PH testing and clinical effectiveness reporting for overall survival (OS) and progression-free survival (PFS) were obtained from company submissions, ERG reports, and final appraisal determinations (FADs).

NPH were present for OS or PFS in 28/40 appraisals, with log-cumulative hazard plots the most common testing methodology (40/40), supplemented by Schoenfeld residuals (20/40) and/or other statistical methods (6/40). In the context of NPH, the HR was ubiquitously reported by companies, inconsistently critiqued by ERGs (10/28), and commonly reported in FADs (23/28).

There is inconsistency in PH testing methodology used in TAs. ERGs are inconsistent in critiquing use of the HR in the context of NPH, and even when critiqued it remains a commonly reported outcome measure in FADs. Other measures of clinical effectiveness should be considered, along with guidance on clinical effectiveness reporting when NPH are present.

Aiming for hepatitis C elimination by 2030, Taiwan has set up a mid-term goal of “over 50 percent of patients treated by 2025.” Among various aspects of evidence that are needed, the target number to be treated is difficult to estimate with certainty due to great geographical heterogeneity of hepatitis C prevalence, and the absence of a nation-wide large scale prevalence survey.

A broad estimate of the number of patients to be treated with high uncertainty was calculated, and reimbursement criteria were set for year 2017 given limited data and treatment budget. In the meanwhile, various sources and approaches to estimate the target number to be treated, and to identify the high prevalence areas, were collected and synthesized for future planning through a systematic review of published data and consulting experts for unpublished data. An expert panel was consulted for the level of confidence and completeness of the evidence. A plan for using real-world data to reduce the uncertainty after initial actions of national program was also in place.

Eight thousand patients who fulfilled the reimbursement criteria were treated in 2017 as planned. Strategic steps were identified based on the collected data, and the treatment target, namely 200,000 patients to be treated during 2018 to 2025, was then set for appropriate action plans. National registry infrastructure is planned for supporting future policy modification.

Hepatitis C elimination is an important public health task and it requires immediate actions. The expected expenses are high, yet the number of patients is difficult to estimate with precision. How to deal with this uncertainty (financially and in care program design) will be the most challenging part. An adaptive approach (“evidence”-”action”-”more evidence”-”modified action”) could be the pragmatic way to move forward without sacrificing the quality of decision-making.

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.

Registration of trial protocols has become increasingly important in recent years. In the context of systematic reviews, published trial protocols facilitate the identification of studies. Data recorded in trials registers requires standardization to assist with ease of identification, and availability of the most current protocol version. Searching sources of trial protocols, for example trials registers, has issues relating to currency, coverage, functionality and indexing. An empirical study was conducted in the context of a funded systematic review, to establish; the proportion of trial protocols retrievable, the most effective retrieval methods, barriers to retrieving protocols, and whether the most easily retrieved protocol copy remains the document of record.

In a systematic review of primary care interventions for medically unexplained symptoms, seventy-four trials were identified as potential included studies. To search for the seventy-four trial protocols, multiple sources and methods were utilized to identify the the differential coverage of sources and the relative efficiency of retrieval methods. Retrieval methods included searching trials registers and bibliographic databases, internet searching, checking journal websites and contacting authors.

Results included; (i) number of trial protocols that were referenced in the corresponding study publication(s), (ii) percentage of protocols indexed in each checked source, including MEDLINE and various trials registers, (iii) number of authors that responded to email contact, (iv) number of authors that provided a reference to, or copy of, the protocol. Information on when the trial protocol was published, funding sources, and trial registration, was also recorded.

Conclusions are made regarding the coverage of different sources of trial protocols. This will enable Information Specialists to prioritize retrieval methods for identifying trial protocols to inform future search methods guidance. The main barriers to retrieving protocols are discussed together with recommendations for future empirical studies.

To estimate the minimum percent change in failed extubation to make a tool designed to reduce extubation failure (Extubation Advisor [EA]) economically viable.

We conducted an early return on investment (ROI) analysis using data from intubated intensive care unit (ICU) patients at a large Canadian tertiary care hospital. We obtained input parameters from the hospital database and published literature. We ran generalized linear models to estimate the attributable length of stay, total hospital cost, and time to subsequent extubation attempt following failure. We developed a Markov model to estimate the expected ROI and performed probabilistic sensitivity analyses to assess the robustness of findings. Costs were presented in 2020 Canadian dollars (C$).

The model estimated a 1 percent reduction in failed extubation could save the hospital C$289 per intubated patient (95 percent CI: 197, 459). A large center seeing 2,500 intubated ICU patients per year could save C$723,124/year/percent reduction in failed extubation. At the current annual price of C$164,221, the EA tool must reduce extubation failure by at least 0.24 percent (95 percent CI: .14, .41) to make the tool cost-effective at our site.

Clinical decision-support tools like the EA may play an important role in reducing healthcare costs by reducing the rate of extubation failure, a costly event in the ICU.