Abstract

BACKGROUND: Sickle cell disease (SCD) and all associated comorbidities were estimated to be the 12th most common cause of mortality in children younger than 5 years in 2021 (Thomson et al. The Lancet Haematology, 2023). Regular automated red blood cell exchange (aRBCX) improves management of SCD compared with manual red blood cell exchange (mRBCX) (Tsitsikas et al. Journal of Clinical Medicine, 2021). This study compared the expected clinical event frequency and economic impact of aRBCX with mRBCX in children with SCD requiring regular disease modifying transfusion treatments (DMTs). The study focussed on children at high risk of clinical events and ineligible for, refractory to, or unwilling to take disease modifying pharmacological treatments (e.g. hydroxyurea).

METHODS: A global individual patient-level simulation model was developed to estimate lifetime clinical events and costs of regular aRBCX compared with mRBCX in a heterogenous population of children aged 2 with no history of chronic events. The UK cost perspective was investigated. People received a DMT per cycle as per local recommendations. Monte Carlo methods determined the presence of iron overload. Chelation therapy treats iron overload. Monte Carlo methods determined clinical event occurrence. Clinical events are not mutually exclusive in practice. Thus, a person's clinical event history, in particular vaso-occlusive crises (VOCs), impacted subsequent clinical event and mortality rates. Clinical events impacted costs and health-related quality of life (HRQoL).

Findings from a pragmatic review informed efficacy, mortality, HRQoL and cost parameters. Where data were sparce, clinical experts were consulted to inform inputs and assumptions. Costs were sourced from national databases and literature and inflated to 2022/23 if necessary. Costs and HRQoL were discounted in line with local guidelines. A preliminary model run with 250 lifetime simulations of 250 children varied parameters probabilistically on their statistical distribution when appropriate.

RESULTS: Total acute clinical events were 19% lower with aRBCX compared with mRBCX. VOCs reduced by 20% from 117 (115 to 119) for mRBCX to 94 (91 to 96) for aRBCX. aRBCX also caused a reduction of 9% for ACS and 2% for strokes.
aRBCX is more resource intensive and costly per administration than mRBCX, but, aRBCX required 49% fewer DMT administrations than mRBCX (44% fewer when considering DMTs and emergency transfusions). People receiving mRBCX were anticipated to spend approximately 13% of their life on chelation therapy, totalling 6.4 (6.3 to 6.5) years. Only people with iron overload at baseline had chelation therapy with aRBCX, totalling 5.5 (5.4 to 5.5) months.

aRBCX was cost saving compared to mRBCX. Regular aRBCX was expected to save £109,964 (£107,275 to £112,653) per lifetime compared with mRBCX. This conclusion was consistent for 100% of the 250 probabilistic model runs and for scenarios where children received DMTs until adulthood and the lifetime of children at high risk of stroke.

DISCUSSION: aRBCX allows for increased success in achieving clinical targets leading to improved control of SCD, fewer transfusions, clinical events and time on chelation therapy. There is potential for large cost savings, allowing funds, hospital beds, and staff time to be redistributed.
The global model can be easily adapted to other healthcare settings where SCD prevalence and mortality are high. Research into the life-altering and cost-saving potential of aRBCX in these settings is essential to achieve the World Health Organisation's (WHO) goal of achieving universal health coverage by integrating SCD treatments into existing healthcare programmes in an equitable and cost-effective manner (WHO, Sickle strategic guidance framework, 2024).

Abstract

OBJECTIVES: Increasing uptake and completion of Pulmonary Rehabilitation in people with COPD has the potential to deliver health benefit and reduce health inequalities. We have quantified the cost-effectiveness of enhancing PR access and completion by reviewing the cost-effectiveness literature for PR in COPD.

METHODS: A literature review identified studies that provided cost-effectiveness evidence for PR compared to no PR. The key metrics of interest were healthcare resource use and cost savings, and quality adjusted life year (QALY) gains. Healthcare resource use data were valued using the UK NHS National Tariff 2022/23. From the literature search we identified the QALY gain resulting from completion of PR. The value of the QALY gain resulting from PR completion was calculated using the standard willingness-to-pay threshold of £20,000 considered by the UK National Institute for Health and care Excellence (NICE).

RESULTS: We estimated a QALY gain resulting from completion of PR of 0.065 and value of the QALY gain was therefore calculated to be £1300 per person completing PR. We estimated the 12 month reduction in hospitalisation following completion of PR to be 8.2% giving a total cost reduction per patient of £245. We therefore calculated that up to £1545 could be spent per person with COPD to deliver PR cost-effectively.

CONCLUSION: Our analysis provides commissioners with the information they need to make informed decisions about planning and provision of PR. The data allows estimation of additional resources that could be deployed in addressing inequitable access to PR among disadvantaged and underserved populations whilst retaining cost effectiveness of the intervention.

Abstract

OBJECTIVES: Health technology assessment (HTA) processes are applied throughout Europe to evaluate the comparative clinical and economic value of a novel intervention to inform resource allocation decision-making. Various economic evaluation frameworks are employed in European HTA submissions, including - predominantly - cost-effectiveness and cost-utility analyses and this research explores the clarity and standardisation (or lack thereof) of these evaluations in a European context.

METHODS: A pragmatic literature review was performed on all relevant European HTAs which covered the United Kingdom, Scandinavia, Western Europe, Central and Southern Europe. It is clear there is substantial amount of information generated by economic evaluations and systematic literature reviews, checklists such as CHEERs and PRISMA which are available to inform the standards and minimum amount of information for reporting, ensuring consistency and transparency. However, similar consideration is not given to the reporting of pharmacoeconomic guidelines, and between-country variation in the format, content and standard of reporting limits the comparability and transferability between guidelines.

RESULTS: Guidelines for agencies such as the TLV, SUKL and AIFA are also not universally available in additional languages. EU HTA Regulation, published in January 2022, aims to standardise clinical assessment of pharmaceutical interventions to enable a central assessment across the 27 EU markets. Joint Clinical Assessment is reportedly beginning implementation in January 2025, signalling increased cross-country collaboration in HTA. There is an opportunity for further standardisation in evidentiary requirement reporting.

CONCLUSIONS: By providing a standardised, validated template for reporting pharmacoeconomic guideline requirements would aid companies when planning clinical trials, ensuring the necessary patient outcomes are collected. Clearer reporting surrounding preferred methods, evidence sources (e.g. value sets, population norm data) may contribute to higher evidence standards. Consensus across EU HTA agencies may also inform standards for less established agencies, such as AIFA, aiding development of HTA procedures in their respective regions.

Abstract

OBJECTIVES: Healthcare systems are increasingly using 'precision medicine' to ensure that patients receive the most appropriate treatment. Whilst the benefits of precision medicine are widely discussed, there is less discussion around the circumstances where precision medicine is most likely to reap benefits, and even less discussion around the potential downsides of precision medicine. This study aims to address these points.

METHODS: A hypothetical case study was developed that with two available treatments: T1 (with an effectiveness rate of 90%) and T2 (effectiveness = 60%). Different scenarios are run, where the individual patients who would benefit from T2 are (i) entirely 'within' the 90% that would also benefit from T1, (ii) covering the 10% who would not benefit from T1 but also including some would benefit from T1, and (iii) an 'overlapping' case in-between. For each scenario, two options were assessed: 'With precision medicine' (i.e. the decision maker can identify which patients will benefit from each treatment) and 'no precision medicine'.

RESULTS: In all scenarios, total population health increased when precision medicine would be applied. Costs were reduced in all scenarios, although this did not include the cost of implementing the precision medicine approach itself. Decision making was shown to be more complex, because precision medicine would introduce multiple layers of decisions. Data requirements were greatly increased with precision medicine, and decision uncertainty was also greater (due to smaller sample sizes within smaller subgroups). In a health system that uses value-based pricing, value was shown not to increase, since the price of treatments would likely increase in line with the improved effectiveness due to precision medicine methods.

CONCLUSIONS: In the case study presented, precision medicine methods delivered increase population health, but the value for money varied considerably between scenarios. Better understanding of disease areas in which precision medicine will benefit patients is essential.

Abstract

Health technology assessment (HTA) evaluates the benefits of medical technologies and helps determine the value of a diagnostic or medical intervention and whether it should be made available in a health system. Real World Evidence (RWE) provides insights on how technologies are used and perform in a real world setting and is becoming increasingly important for reimbursement and regulatory decision making.
HTA submissions typically use generic frameworks for assessing medical innovations, which are not specific for diagnostics or medical devices, and may hinder how their value is measured and evaluated. Additionally, these frameworks may not include RWE, which is important to enable a complete evaluation of evidence, particularly for medical devices.

This forum aims to highlight opportunities for improvements to HTA frameworks to more fully capture the value of diagnostics and medical devices. Case studies will be used to illustrate uses of RWE and the importance of including a tailored evidence evaluation framework for diagnostics and medical devices. The forum will also include a state of the art discussion on the methods to evaluate diagnostic tests (Dr. Lavinia Ferrante), a presentation on the current challenges experienced by HTAs for the assessment on these technologies (Mr. David Tamblyn), and a discussion with two medical device companies (representatives: Lindsay Bockstedt and Chiara Capobianco) presenting their approaches in using RWE, and sharing how evidence standards may evolve as RWE becomes more widely accepted. The panel will conclude with questions from the moderator and the audience.

Abstract

OBJECTIVES: Healthcare's supply chain contributes 62% of the 25 million tonnes of CO2e emissions generated by the UK National Health Services per annum. Changing from single use equipment to reusable equivalent can reduce CO2e up to 56%. The SHTG recognized the need to evaluate the environmental credentials of single use equipment through a parallel assessment alongside a health economic analysis. This novel research is the first UK parallel assessment published the Scottish Health Technologies Group (SHTG). An innovative hybrid approach utilized multidisciplinary methods to overcome data challenges. The findings of the report are in line with research and provides important methods for HTA sustainability globally.

METHODS: Applying environmental management frameworks, a carbon footprint of single use rhinolaryngoscopes was compared with a reusable equivalent. Data collection techniques included questionnaires, interviews and the use of guidance for technological representativeness were used to quantify national GHG emissions and waste volumes. The technologies were categorized using thresholds based on the functional unit, to strengthen support for the HTA decision making process. Sensitivity analyses were performed.

RESULTS: The carbon emissions of a single use flexible rhinolaryngoscope compared to its reusable equivalent was 6.03kgCO2e and 3.26kgCO2e respectively. Data extrapolation reveals the annual environmental impact of this technology, throughout NHS Scotland, to be 13,652kgCO2e and 7,381kgCO2e, for the single use and reusable devices, respectively. Raw material acquisition, the use of personal protective equipment and transportation were carbon hotspots. Use of the single use devices generates 12.58 tonnes of waste per year further burdening healthcare resources. This pilot study recommends the use a reusable equivalent in this setting.

CONCLUSIONS: Aligned with NHS net zero targets, these findings confirm the need to perform a parallel environmental assessment of technologies alongside a health economic analysis. Data constraints can be overcome using hybrid methodologies. This work support policy development in HTA sustainability framework development.

Abstract

BACKGROUND: Three recent randomized controlled trials demonstrated that, in patients with symptomatic paroxysmal atrial fibrillation (PAF), first-line pulmonary vein isolation with cryoballoon catheter ablation reduces atrial arrhythmia recurrence compared to initial antiarrhythmic drug (AAD) therapy. This study aimed to evaluate the cost-effectiveness of first-line cryoablation compared to first-line AADs from a German healthcare payer perspective.

METHODS: Individual patient-level data from 703 participants with untreated PAF enrolled into three randomized clinical trials (Cryo-FIRST, STOP AF First and EARLY-AF) were used to derive parameters for the cost-effectiveness model (CEM).

The CEM structure consisted of a hybrid decision tree and Markov model. The decision tree (one-year time horizon) informed initial health state allocation in the first cycle of the Markov model (40-year time horizon; three-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Cost inputs were sourced from German diagnosis-related groups and the Institute for the Hospital Remuneration System (InEK). Costs and benefits were discounted at 3% per annum.

RESULTS: Cryoablation was cost-effective, incurring ~ €200 per patient while offering an increase in QALYs (~ 0.18) over a lifetime. This produced an average incremental cost-effectiveness ratio of ~ €1,000 per QALY gained. Individuals were expected to receive ~ 1.2 ablations over a lifetime, regardless of initial treatment. However, those initially treated with cryoablation as opposed to AADs experience 0.9 fewer re-ablations and a 45% reduction in time spent in AF health states.

CONCLUSION: Initial rhythm control with cryoballoon ablation in symptomatic PAF is a cost-effective treatment option in a German healthcare setting.