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INTRODUCTION: Single-arm studies, particularly single-arm trials (SATs), are increasingly being used in submissions for marketing authorization and health technology assessment. As reviewers of evidence, we sought to better understand the validity of SATs, compared with observational single-arm studies (case series), and how to assess them in our reviews.
METHODS: We conducted a highly pragmatic literature review to create a convenience sample of recent systematic reviews published from January to July 2023 to establish the following: (i) what single-arm study designs are included; (ii) what quality assessment tools are used; and (iii) whether there is a difference in effect size and variability among different study designs. A single reviewer identified reviews of interventions that included single-arm studies and extracted information on the numbers of included SATs and case series, and the quality assessment tools used. Any misclassifications by review authors were identified. For meta-analyses, outcome data were extracted and a subgroup analysis comparing SATs and case series was conducted.
RESULTS: Work is still underway to complete this investigation. So far, it appears that a large proportion of systematic reviews misclassify SATs and case series studies and few use appropriate quality assessment tools. There is not yet any evidence of a systematic difference between SATs and case series in terms of effect size.
CONCLUSIONS: Findings suggest that there is poor understanding of SATs in the review community. There are limited specific quality assessment tools for SATs and review authors frequently use inappropriate tools to assess them. More research is likely to be needed to investigate the relative validity of SATs and single-arm observational studies.
INTRODUCTION: As health technology assessment (HTA) bodies introduce more rigorous requirements, the submission process is becoming increasingly diverse between countries. This study assesses the HTA submission processes and requirements in Australia, Canada, England, France and Germany. This allows the identification of where efficiencies can be made in the global market access strategy, such as when to submit HTA dossiers.
METHODS: A pragmatic review and desk-based research were conducted in November 2023. Published articles, HTA guidelines, process documents, conference abstracts, and white papers were reviewed to identify country-specific processes with implications for market access strategy. Where available, information was extracted about the general submission process and stakeholders involved (including regulatory, HTA and pricing authorities), clinical evidence requirements, and pharmacoeconomic evidence requirements for HTA submission. Comparisons of the median time from marketing authorization to HTA decision within each country allowed the identification of efficiencies in individual HTA submission processes. A narrative summary of the key findings and between-country differences will be presented.
RESULTS: The review identified several areas with implications for market access strategy. The median HTA review time was shortest in Australia (125 days) and longest in England (266 days). Australia and Canada have both sequential and parallel regulatory/HTA processes. The median time taken from regulatory approval to HTA recommendation was faster than the sequential process in both countries. All countries require comparative clinical evidence within the indication. The weight placed on pharmacoeconomic evidence varies between countries. In Germany, economic evaluation is yet to play a real role. Requirements for additional information after HTA submission occurred within all HTA bodies.
CONCLUSIONS: HTA processes in Canada, Australia, England, France, and Germany differ from one another. This will likely affect the market access strategy for health technology developers. Similar requirements allow efficiencies in the preparation of submission documentation. Future research should investigate the impact of the EU HTA Regulation on market access and how this could affect strategic decision making.
INTRODUCTION: Early health technology assessment (eHTA) can help to explore the potential value of a technology in the early stages of development. Care pathway analysis (CPA) is a method to identify and map clinical decisions in the current and new care pathways (including the new intervention). This work provides examples of applying CPA within the context of eHTA for medical interventions.
METHODS: CPA usually involves a pragmatic review to identify and synthesize national/international guidelines that describe the care pathway for the condition of interest. This is typically followed by a qualitative evaluation that can include semi-structured interviews with thematic analysis. Interviews with experts are undertaken to understand where (and why) real-world practices differ from published guidance and to validate the care pathway. They also help to evaluate the strengths/weaknesses of the new technology, potential population and role in the pathway, and barriers/facilitators to adoption. The CPA forms the basis of economic modelling that helps assess the monetary value of the new technology.
RESULTS: The application of CPA from two recent projects will be presented: an innovative diagnostic test for respiratory tract infections and a medical device for treating cataracts. Additionally, the value of CPA in eHTA will be described from the technology developers' perspective. In both projects, CPA was used to inform the potential value propositions of the new technology and its positioning in the care pathway. It also helped to optimize the structure of the early economic model and to identify evidence generation needs. The early model identified the pathway that was more likely to be cost effective in the future.
CONCLUSIONS: CPA is a valuable method within the context of eHTA. Alongside identifying the potential role and positioning of the new technology, test developers found the assessment useful for informing internal strategy decisions and discussions with potential external investors. The developers were able to demonstrate the clinical perspective around the value of the test, elicited through an independent and rigorous methodology.
INTRODUCTION: Conducting a systematic review (SR) of clinical trials is labor-intensive and expensive. However, existing open-source content can be used to develop custom machine learning tools suited to the workflow of individual organizations. This case study details the potential of a bespoke tool developed by York Health Economics Consortium (YHEC) for reducing the time and cost involved in producing an SR.
METHODS: RESbot is a flexible, stand-alone machine learning tool created using an extensively tested open-source dataset developed by Cochrane. The tool identifies randomized controlled trials (RCTs) from a large corpus of records. It has a user interface and inputs/outputs to fit into the company's existing workflow at any stage. RESbot has two settings. The "sensitive" setting identifies a higher number of possible RCTs with a lower risk of missing eligible studies, while the "precise" setting is more focused. For both settings, we estimated the reduction in resources required for record screening in two examples of RCT-only reviews.
RESULTS: Scoping searches in MEDLINE were conducted for SRs of RCTs in femoropopliteal artery diseases (FAD) and postpartum depression (PD). The results were run through RESbot. For the FAD SR, 1,444 references were retrieved, with the sensitive and precise RESbot settings reducing the record set by 38 percent and 64 percent, respectively. For the PD SR, a record set of 2,153 records was reduced by 25 percent and 41 percent, respectively. Resource savings offered by RESbot vary depending on subject but may reduce the time taken to screen records by up to 64 percent, with a subsequent reduction in cost to the organization commissioning the SR.
CONCLUSIONS: The use of bespoke machine learning tools in SR production has the potential to reduce the time and staff costs involved in producing a review. This case study tested the effect on a small number of records, but for larger reviews retrieving tens of thousands of records, reductions in time and costs can be very significant.
INTRODUCTION: Quick and equitable market access to vaccines is a global priority. However, market access routes for vaccines are complex and differ to those for pharmaceuticals. Furthermore, there is variation in decision making between countries due to local requirements. This work aims to increase awareness of the key elements of these pathways and the stakeholders involved in EU and non-EU countries.
METHODS: Pragmatic desk-based research was undertaken in November 2023 to explore key elements of the market access pathways for vaccines and how these differ between countries. Specifically, the countries of interest were England, France, Germany, Italy, Spain, United States (US), and Canada. Where available, information was extracted about the key stages and stakeholders involved in the decision-making pathway as well as details about any post-licensing monitoring, the value assessment framework used, vaccine pricing and the procurement process. In addition, examples of barriers to vaccine access were extracted. A narrative summary of the key findings and between-country differences will be presented.
RESULTS: National Immunization Technical Advisory Groups (NITAGs) are key stakeholders in all countries explored, with varying roles. The evidence requirements differ among countries, such as Germany's requirement for economic and epidemiological modelling. The Vaccine Monitoring Platform coordinates studies for post-authorization monitoring of vaccines across EU countries. However, England is not part of this network and uses a national agency instead. Vaccine procurement and pricing also differ (e.g. France uses individual reimbursement, England uses national tendering, and Canada uses regional tendering). There is variation within the US on vaccine pricing, depending on the healthcare provider. Barriers to vaccine access are well reported.
CONCLUSIONS: These results can influence the market access strategy of vaccine developers to ensure rapid and equitable vaccine access across countries. Several between-country differences in vaccine market access routes are identified; for example, the role of NITAGs, evidence requirements, and post-licensing monitoring processes. Barriers to vaccine access have been reported in the literature, with some organizations providing recommendations to overcome these.
INTRODUCTION: While systematic reviews (SRs) are regarded as the gold standard in healthcare evidence reviewing (and a requirement of many health technology assessments [(HTAs)]), other types of review also play an important role throughout a product's lifecycle. Drawing on more than thirty years' experience in conducting reviews, we present key points to consider when deciding which review type might be required.
METHODS: SRs are recommended when a comprehensive search and synthesis approach is required, for example HTAs. They have highly structured methods, emphasizing bias minimization, transparency, and replicability. "Rapid," "pragmatic," or "targeted" reviews are increasingly popular due to their accelerated timelines and reduced costs, with methodological shortcuts possible at various stages. Scoping reviews explore what is known about a topic and typically have a broad research question. "Reviews of reviews" or "overviews" identify existing SRs on an established topic. Finally, "living reviews" follow the same process as an SR or rapid review but incorporate new evidence on a continual or regular basis.
RESULTS: Rapid reviews may be appropriate when flexibility exists regarding the scope and review methods. Any limitations due to methodological shortcuts must be acknowledged in a transparent manner. Scoping reviews are useful for pioneering research ahead of an SR, or early in a product's development phase, when an overall understanding of the evidence base is required. Reviews of reviews are particularly useful when the size of the primary study literature means that a review of primary studies would be unfeasible. Living reviews are best suited to topics where the evidence base is changing rapidly, or the best information is needed quickly.
CONCLUSIONS:
When considering conducting or commissioning a review, organizations should consider the intended audience for the review, the resources, time, and budget available, and the size of the existing literature. Although SRs remain the gold standard, a rapid review, scoping review, or review of reviews may offer a more suitable way to approach a given research question.
BACKGROUND: "Kooth" is a web-based mental health platform commissioned by the National Health Service (NHS), local authorities, charities, and businesses in the UK. The platform gives children and young people (CYP) access to an online community of peers and a team of counsellors. This study reports an early economic evaluation of the potential benefits of Kooth in the UK.
METHODS: An early evidence cost calculator was built to estimate the potential costs and savings of implementing Kooth from a UK NHS and crime sector perspective. A decision tree structure was used to track the progress of CYP with emerging mental health needs (EMHN), comparing CYP with access to Kooth to CYP without access to Kooth. The model implemented a 12-month time horizon and followed a typical Kooth contract in relation to costing, engagement, and CYP demographics.
RESULTS: The base case results followed a cohort of 2160 CYP. The results of the cost calculator estimated that engagement with Kooth is associated with a cost saving of £469,237 to the NHS across a 12-month time horizon, or £236.15 per CYP with an EMHN. From a combined NHS and UK crime sector perspective, the cost savings increased to £489,897, or £246.54 per CYP with an EMHN. The largest cost savings were provided by an estimated reduction of 5346 GP appointments and 298 antidepressant prescriptions. For this cohort, the model predicted that engagement with Kooth averted 6 hospitalisations due to suicidal ideation and 13 hospitalisations due to self-harm. Furthermore, the number of smokers and binge drinkers was reduced by 20 and 24, respectively. When a crime sector perspective was taken, 3 crimes were averted.
DISCUSSION: This early model demonstrates that Kooth has the potential to be a cost-saving intervention from both an NHS and a combined NHS and UK crime sector perspective. Cost savings were provided through aversion in clinical and social outcomes. The model used a conservative approach to balance the uncertainty around assumptions of the intermediate outcomes (GP and medication use). However, it is limited by a paucity of costing data and published evidence relating to the impact of digital mental health platforms.
