Abstract

LAY SUMMARY: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) and accounts for significant morbidity and mortality, particularly in older adults. This modelling study evaluated the public health benefits and cost-effectiveness of mRNA-1345, an RSV vaccine, in preventing RSV-related outcomes in people aged =60 years in the UK. The analysis found that mRNA-1345 vaccination reduced RSV-related case numbers, hospitalisations and deaths. mRNA-1345 is cost-effective for preventing RSV-related disease in older adults.

INTRODUCTION: RSV is an important cause of LRTD in older adults. In September 2024, NHS England will introduce its first RSV vaccination campaign, which includes adults aged 75-80 years and those turning 75 years. Countries such as Australia, Canada, the US and France recommend an RSV vaccine for subgroups of people =60 years. This modelling study explored the cost-effectiveness and public health impact of a novel RSV vaccine (mRNA-1345) using clinical trial data for UK adults aged =60 and =65 years.

METHODS: The cost-effectiveness model was built from a UK NHS perspective and used a decision-analytic structure over three years. Based on phase 2/3 clinical trial data (18.8-months median follow-up), mRNA-1345 was presumed to prevent RSV-acute respiratory disease (ARD),RSV-LRTD, and RSV-LRTD hospitalisations amongst those developing infections. To address the known issue of under detection of RSV, the sourced RSV hospitalisation rates were adjusted using a published multiplier of 1.5. Calibration techniques were performed to ensure external validation. Costs, quality-adjusted life-years (QALYs) and population-related parameters were sourced from publicly available sources.

RESULTS: Vaccination of adults =60 years with a single dose of mRNA-1345 results in a 23.8% and 35.1% reduction in RSV-ARD and RSV-LRTD cases over three years, compared with no vaccine, respectively. For a population of 16,814,195 adults =60 years, without RSV vaccination, the annual number of RSV hospitalisations is projected to be 36,696. The annual number of hospitalisations aligns with published literature when adjusted for the under detection of RSV. A single dose of mRNA-1345 is estimated to save 40,558 (38.9%) hospitalisations over three years. The NNV to prevent one RSV-LRTD case, hospitalisation and death is 44, 293 and 527, respectively. There are 39.8% less RSV-related deaths and, consequently, 161,947 life years are gained over three years. Incurred costs from mRNA-1345 implementation are offset by 123,824 QALYs gained to produce an ICER of £14,557 per QALY gained.
The direction of the results for adults =65 years remained consistent. The ICER fell to £12,425 per QALY gained. mRNA-1345 vaccination was estimated to save 38,581 (40.1%) RSV-LRTD hospitalisations over a three-year time horizon in a population of 12,736,451 adults. It was associated with a 25.9% and 37.7% reduction in RSV-ARD and RSV-LRTD cases, respectively.

CONCLUSION: Vaccination with mRNA-1345 could have a substantial impact on reducing RSV-related morbidity and mortality in UK adults aged =60 years. The vaccine could contribute to reducing ongoing winter pressures for the NHS. The ICER for mRNA-1345 is substantially lower than the UK willingness-to-pay threshold of £20,000 per QALY gained, suggesting that RSV vaccination with mRNA-1345 is highly cost effective.

Abstract

BACKGROUND: Community-acquired pneumonia (CAP) remains a leading cause of hospital admissions and mortality. A novel host-response test, MeMed BV (MMBV), has been developed for discriminating between bacterial and viral infection that could improve the clinical management of CAP.

OBJECTIVES: To evaluate the cost-effectiveness of using MMBV to guide antibiotic decisions in the clinical management of CAP in the UK.

METHODS: An economic model was developed to understand the incremental cost per person associated with the implementation of MMBV from the UK NHS perspective. A qualitative care pathway analysis was performed to inform the standard of care (SOC) and SOC plus MMBV (SOC + MMBV) clinical pathways captured in the model.

RESULTS: In the base case analysis, the SOC + MMBV strategy for a hypothetical cohort of 1000 patients (adults and children modelled independently) presenting to the emergency department with suspected CAP was estimated to provide total cost savings of £134 018 and £105 750 for adults and children, respectively. Cost savings were associated with reductions in total antibiotic treatment, the number of patients receiving additional diagnostic tests, and hospital admissions. Deterministic sensitivity analysis revealed that the specificity of SOC + MMBV and sensitivity of the SOC were primary drivers of the cost model for adults, whereas the specificity of SOC and SOC + MMBV were primary drivers for paediatrics.

CONCLUSIONS: Overall, the model predicts that the introduction of SOC + MMBV has the potential to be cost-saving and promote antimicrobial stewardship for both adult and paediatric CAP patients.

Abstract

BACKGROUND: Degenerative disc disease (DDD) is associated with chronic lower back pain that may have impacts on individual's quality of life and functional ability. Lumbar interbody fusion can be carried out with a variety of bone grafting products, the choice depends on several factors including the patient, site, procedure, cost and indication. This systematic review (SR) intends to validate and consolidate the existing evidence base supporting bone graft materials related to lumbar interbody fusion procedures for DDD, specifically anterior lumbar interbody fusion (ALIF) and oblique lumbar interbody fusion (OLIF).

METHODS: An SR was conducted in February 2023. Clinical and economic studies of adults with DDD in regions L2 to S1 undergoing lumbar interbody fusion with Infuse™, allograft, synthetic bone grafts, demineralized bone matrices or cell-based matrices were eligible for inclusion.

RESULTS: Twenty-one studies (reported in 25 publications) were included in the review. Eighteen studies (reported in 22 publications) reported clinical outcomes, while 4 studies reported economic outcomes. Nine studies (in 5 publications) investigated Infuse™, including 3 randomized controlled trials (RCTs), one cohort study and 4 case series. Ten studies investigated allograft bone, bone harvested from the vertebral spur combined with apacerum powder, or tricalcium phosphate soaked in autologous bone marrow aspirate, including one RCT, 2 cohort studies, and 7 case series.

CONCLUSIONS: The SR shows that Infuse™ offers comparable results to iliac crest bone graft with the benefit of not requiring harvested bone and offers significant benefits in surgical time and blood loss. There is a lack of comparative evidence for any other bone grafts identified in this SR, highlighting the need for further well-designed studies to be conducted in this area.

Abstract

INTRODUCTION: Interventional single-arm trials (SATs) are increasingly being used as evidence, despite a lack of agreement on their validity and where they should sit in the hierarchy of evidence. We conducted a meta-epidemiological study to investigate whether there are systematic differences in outcomes and levels of between-study heterogeneity for SATs compared with their observational counterpart, single-arm cohort studies.

METHODS: We identified systematic reviews (SRs) of pharmacological interventions, published in 2023, that included both interventional and observational single-arm studies. For each SR, subgroup meta-analysis of dichotomous outcomes was conducted for included SATs and single-arm cohort studies to assess effect sizes, levels of heterogeneity and between group differences. In a sensitivity analysis, clinically heterogeneous primary studies were removed and analyses re-run.

RESULTS: 66 SRs contained single-arm studies, of which 13 reported meta-analyses of dichotomous efficacy outcomes. There was no overall risk difference for SATs compared with single-arm cohort studies (risk difference: -0.020, 95% CI: -0.092 to 0.052, p = 0.59). In the sensitivity analysis, there was a tendency to higher effect for single-arm cohort studies, but no significant difference (risk difference: -0.071, 95% CI: -0.161, 0.019, p = 0.12). There were high levels of between-study heterogeneity within both SATs (median; range I2: 54.8; 11.3-91.0) and single-arm cohorts (median; range I2: 77.2; 0-94.7) and heterogeneity remained high in the sensitivity analysis.

CONCLUSION: There do not appear to be systematic differences in outcome between SATs and single-arm cohort studies, but further research is recommended to confirm this finding. Levels of heterogeneity are high within both designs, even after attempts to reduce clinical heterogeneity. Because clinical heterogeneity had potentially been removed, remaining statistical heterogeneity may have been due to bias related to study conduct. Future work should utilize larger samples and additional methods to further clarify the relative validity of single-arm designs.

Abstract

BACKGROUND: In 2021, there were an estimated 7.74 million people living with sickle cell disease (SCD) globally: a 41% increase from 2001 (Thomson et al. The Lancet Haematology, 2023). Regular automated red blood cell exchange (aRBCX) has been shown to improve control and 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 adults with SCD requiring regular disease-modifying transfusion treatments (DMTs). The study focussed on adults 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 a heterogenous population of adults with SCD (aged over 18) requiring regular DMTs. A UK perspective was used in the base case. Adults received a DMT per cycle as per local recommendations. Monte Carlo methods were employed to determine the presence of iron overload at baseline and after mRBCX. Chelation therapy treats iron overload. Monte Carlo methods determined clinical event occurrence. Clinical events are not mutually exclusive in practice. Thus, an adult'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 were inflated to 2022/23 if necessary. Costs and HRQoL were discounted in line with local guidelines. 250 lifetime simulations of 250 adults were run, with parameters varied probabilistically on their statistical distribution when appropriate.

RESULTS: The total number of lifetime acute clinical events reduced by 18% with aRBCX compared with mRBCX. VOC reduction comprised 96% of the total acute clinical event change. The total number of lifetime VOCs reduced from 66.04 (64.7 to 67.39) with mRBCX to 52.86 (51.25 to 54.47) with aRBCX.

aRBCX is more resource intensive and costly per administration than mRBCX. However, aRBCX required 49% fewer DMT administrations than mRBCX (43% fewer when considering DMTs and emergency transfusions). Adults receiving mRBCX spent on average 41.93 (41.09 to 42.76) months (14% of their adult life) on chelation therapy compared with 5.45 (5.43 to 5.48) months for those receiving aRBCX with iron overload at baseline.
Over a lifetime, aRBCX was expected to save £52,097 (£49,957 to £54,238) per person compared with mRBCX. Key drivers of this cost saving were the reduction in VOCs, DMTs and time on chelation therapy. aRBCX was cost saving compared with mRBCX in 99% of the probabilistic model runs.

DISCUSSION: aRBCX allows for increased success in achieving clinical targets, leading to improved control of SCD, fewer transfusions, fewer clinical events, and less 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 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).