Abstract

BACKGROUND AND OBJECTIVE: Health technology assessment (HTA) of haemato-oncology therapies typically requires extrapolation of long-term survival beyond a trial’s follow-up. Health technology assessment agencies must balance caution around uncertainty in early follow-up trial data whilst aiming to provide timely access. This study qualitatively and quantitatively assessed how eight HTA agencies considered maturing data and external evidence.

METHODS: The eight HTA appraisals were based on ZUMA-7, a phase III trial for axicabtagene ciloleucel (axi-cel) for second-line diffuse large B-cell lymphoma. ZUMA-7 survival data were submitted with either a 25-month (‘Interim’) or 47-month (‘Primary’) follow-up. To inform axi-cel Interim survival extrapolations, external evidence was available from a prior mature single-arm trial for third-line or later diffuse large B-cell lymphoma (ZUMA-1). A qualitative assessment of eight different submissions to HTA agencies was undertaken to determine key discussion points. The value and cost of waiting for evidence to mature between Interim and Primary analyses were quantified using value of information methods to evaluate the impact of waiting for further evidence collection on population health.

RESULTS: Agencies used varied approaches to account for uncertainty in survival extrapolations in both Interim and Primary analyses. No agency considered external evidence fully during Interim submissions; one used it partially to inform clinical plausibility; four did not consider it. Health technology assessment agencies that did not consider the relevance of ZUMA-1 were more inclined to wait for more mature evidence to mitigate uncertainty. When ZUMA-1 aided in determining a plausible range for Interim extrapolations, the less valuable more mature evidence became, with the cost of waiting for Primary analysis results exceeding the value conferred.

CONCLUSIONS: There was limited consideration of external evidence during the included HTA submissions. In the future, it is recommended that external evidence should be considered to a greater degree by both manufacturers and HTA agencies when extrapolating survival to ensure appropriate and timely HTA decisions that minimise the undue burden on healthcare systems.

Abstract

BACKGROUND: The SECURE trial (NCT02596126) demonstrated the efficacy of the cardiovascular polypill ("CV-Polypill" - acetyl salicylic acid, atorvastatin and ramipril) in reducing the risk of recurrent major cardiovascular events compared with standard care when initiated within six months of a myocardial infarction. This analysis aimed to estimate the cost-effectiveness of the CV-Polypill from the Spanish healthcare perspective using SECURE trial data.

METHODS: A decision analytic Markov modelling approach was conducted to compare the CV-Polypill with standard care over a lifetime time horizon. Six parametric distributions were fitted to SECURE trial data on time to reinfarction, stroke or death (cardiovascular or non-cardiovascular). Cost and utility data were sourced from literature. Respective model outputs were discounted at 3%. The model captured direct medical costs associated with treatment acquisition and acute/ongoing cardiovascular events. Probabilistic sensitivity analyses (PSA) and scenario analyses were conducted.

FINDINGS: The CV-Polypill is dominant (improves health outcomes and reduces costs) in 84·8% of PSA iterations (848/1000 iterations), and cost effective in 89·3% of PSA iterations (893/1000 iterations) at a €30,000 threshold. Secondary prevention with the CV-Polypill reduces the recurrence of cardiovascular events and costs over the time horizon, from the Spanish healthcare perspective. A range of scenario analyses were conducted, demonstrating the robustness of the results when different inputs and assumptions were varied.

INTERPRETATION: The CV-Polypill is a dominant strategy in secondary cardiovascular prevention, compared with standard care, from the Spanish healthcare perspective. The CV-Polypill should be considered as a secondary prevention for Spanish patients, like those enrolled in SECURE, at hospital discharge.

Abstract

BACKGROUND & OBJECTIVES: Patients surviving a non-ST-elevation myocardial infarction (NSTEMI) have an elevated risk of future major adverse cardiovascular events (MACE), which can be mitigated through long-term cardiac arrhythmia monitoring. The present study evaluated the cost-effectiveness of continuous remote arrhythmia monitoring using an insertable cardiac monitor (ICM) combined with standard of care (SoC) compared with SoC alone.

METHODS: A cost-effectiveness analysis using a lifetime partitioned survival model was developed for high-risk NSTEMI patients from a UK National Health Service (NHS) perspective. Survival analysis was used to determine the transition of patients from the pre-MACE health state (where patients could experience arrhythmia, major bleeding, or systemic embolism) to the MACE health state (worsening heart failure, stroke, and acute coronary syndrome events). The survival analysis and arrhythmia diagnosis rates were informed by the BIO|GUARD-MI trial. The model captured direct costs associated with each MACE and implantation and removal of the ICM device and treatment costs following arrhythmia detection. The model captured the health implications for an ICM with SoC, compared with SoC alone, in terms of the total quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty on the model results.

RESULTS: The use of ICMs plus SoC for daily remote cardiac arrhythmia monitoring is cost effective, when compared with SoC alone, in high-risk NSTEMI patients over a lifetime horizon, with an incremental cost-effectiveness ratio of £7766 per QALY gained. The ICM was associated with an additional 0.184 QALYs per patient for an additional cost of £1430. The ICM remained cost effective during the deterministic and probabilistic sensitivity analyses.

CONCLUSION: The addition of an ICM to SoC in high-risk NSTEMI patients is cost effective from the perspective of the UK NHS and would, therefore, be a further option for the management of such patients in clinical practice.

Abstract

OBJECTIVE: A pressure ulcer (PU) develops initially at the cellular level, progressing through damage to subepidermal cells and surrounding tissues before it becomes visible on the surface of the skin. Changes in subepidermal moisture (SEM) are a biomarker for the early stages of PU development. The objective of this study was to evaluate the cost-effectiveness of adding measurement of SEM to current standard of care (SoC), with the aim of reducing the incidence of hospital-acquired pressure ulcers (HAPUs).

METHOD: A decision-tree model was developed. Outcomes were the incidence of HAPUs, quality-adjusted life-years (QALYs) and costs to the UK National Health Service (NHS) at 2022/23 prices. The effects of parameter uncertainty were tested in univariate and probabilistic sensitivity analysis.

RESULTS: In a typical NHS acute hospital with 480 beds, the addition of SEM assessment as an adjunct to SoC is expected to reduce the incidence of HAPUs by 32.9% and lead to a cost saving of £26.53 per admission. The probability that adjunctive SEM is cost-effective at a threshold of £30,000 per QALY is 69%.

CONCLUSION: SEM assessments make it possible to implement early and anatomy-specific interventions which can improve the effectiveness of PU prevention and reduce healthcare costs.

Abstract

OBJECTIVES: The objective of this paper is to present the Environmental Sustainability in Health Technology Assessment (ESHTA) Working Group’s (WG’s) opinion on the definition and scope of early Health Technology Assessment (HTA) developed by a WG under HTA International. The aim is to provide suggestions on how early HTA can support the goals of enhancing environmental sustainability in healthcare.

METHODS: The HTAi ESHTA WG presents our opinion on the proposed definition and scope of early HTA. This includes a broad range of perspectives from stakeholder groups including patient experts, a policy maker, a statistician, HTA researchers and a healthcare professional, located across lower to higher resource settings and several jurisdictions. We suggest how early HTA can support the goals of enhancing environmental sustainability in healthcare.

RESULTS: HTA agencies play a crucial role in embedding sustainability into their evaluations and practices. Integrating environmental sustainability into HTA at three critical stages – product conceptualization, reimbursement decisions, and point of care – can optimize resource use and reduce environmental impacts. Developing sustainability metrics, defining environmental impact categories, and identifying suitable methods for assessing health technologies are essential steps. Early engagement is also vital for optimizing trade-offs and increasing acceptance by diverse stakeholders.

CONCLUSIONS: Incorporating environmental sustainability into early HTA can enhance the likelihood of regulatory approval and reimbursement, ultimately benefiting patients and healthcare systems. By integrating sustainability considerations at the design stage, the potential for environmental impact reduction is maximized. Future efforts should focus on developing comprehensive guidelines and methods, ensuring collaboration between early HTA and ESHTA WGs.

Abstract

BACKGROUND: Non-inferiority and clinical equivalence clinical trials can be used to determine whether a health technology is no worse than an existing treatment. This study identified international guidance for conducting non-inferiority and clinical equivalence trials and investigated the current practices in conducting and reporting such trials, especially in the context of Health Technology Assessment (HTA).

METHODS: A pragmatic approach was used to identify international guidelines and published literature reporting approaches for the conduct and reporting of non-inferiority or clinical equivalence studies. Guidelines from both HTA and regulatory bodies were considered, and literature reviews from 2010 to 2023 were identified. The results of the reviews were supplemented by stakeholder interviews and synthesised to form a series of recommendations for the UK National Institute for Health and Care Excellence in the appraisal of non-inferiority and equivalence trials.

RESULTS AND CONCLUSION: The majority of guidelines (13/15) discussed methods to determine the non-inferiority margin and how the analysis should be conducted. Despite this, the quality of reporting in non-inferiority and clinical equivalence trials is consistently poor. Prior to presentation of trial evidence, HTA submissions that claim non-inferiority or equivalence should present the technical, biological and/or pharmacokinetic reasonings that support the claim.

Abstract

The dynamic nature of infectious diseases introduces inherent challenges to the design of vaccine clinical trials, which consequently makes vaccine indirect treatment comparisons (ITCs) and meta-analyses (MAs) more challenging compared with regular pharmaceuticals. However, comparisons of efficacy and safety between vaccines are being frequently required in vaccine decision making due to a low number of head-to-head clinical trials in the vaccine landscape. The introduction of the European Union Health Technology Assessment (HTA) Regulation (EU HTAR) aims to harmonize HTA efforts across Europe. However, the EU HTAR could also escalate existing challenges for conducting vaccine MAs and ITCs. Such challenges include generating efficacy evidence in time for Joint Clinical Assessment (JCA), incorporating high levels of heterogeneity due to infectious disease-specific characteristics, and tackling a high number of PICOs per submission—likely driven by heterogeneity in the available data and differences in national vaccine calendars. Opportunities to tackle these challenges include introducing a stepwise approach to vaccine assessment in JCA, best-practice recommendations for conducting/interpreting vaccine MAs and ITCs, and condensing the number of PICOs to create larger ‘catch-all’ ITC networks. This perspective article explores these challenges and opportunities further.