New Vaccine Platforms-Novel Dimensions of Economic and Societal Value and Their Measurement.

The COVID-19 pandemic's dramatic impact has been a vivid reminder that vaccines-especially in the context of infectious respiratory viruses-provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.

Paediatric MOG-antibody disease presenting with intracranial hypertension and unilateral vision loss without radiological evidence of optic neuritis.

Intracranial hypertension (IH) is poorly described in paediatric myelin oligodendrocyte glycoprotein antibody disease (MOGAD). We describe a unique case of seropositive MOGAD in an obese 13-year-old boy who presented with an isolated IH, bilateral optic disc swelling and sudden-onset complete vision loss in one eye without radiological evidence of optic nerve involvement. Treatment with intravenous methylprednisolone combined with an emergency shunt fully restored vision and resolved the optic disc swelling. This report adds to the growing body of evidence suggesting that obese children presenting with isolated IH should be investigated for MOGAD, and the importance of managing IH during MOGAD.

Estimates of the Global Burden of COVID-19 and the Value of Broad and Equitable Access to COVID-19 Vaccines.

The objectives of this research were to produce a macro-level overview of the global COVID-19 burden and estimate the value of access to COVID-19 vaccines. A targeted literature review collated evidence of the burden. Linear modelling and data analysis estimated the health and economic effects of COVID-19 vaccines delivered in 2021, and whether additional value could have been achieved with broader and more equitable access. By 1 December 2020, there had been an estimated 17 million excess deaths due to COVID-19. Low-income countries allocated more than 30% of their healthcare budgets to COVID-19, compared to 8% in high-income countries. All country income groups experienced gross domestic product (GDP) growth lower than predicted in 2020. If all 92 countries eligible for COVAX Advance Market Committee (AMC), access had reached 40% vaccination coverage in 2021, 120% more excess deaths would have been averted, equivalent to USD 5 billion (109) in savings to healthcare systems. Every USD spent by advanced economies on vaccinations for less advanced economies averted USD 28 of economic losses in advanced economies and USD 29 in less advanced economies. The cost to high-income countries when not all countries are vaccinated far outweighs the cost of manufacturing and distributing vaccines globally.

Cost-effectiveness of high dose versus adjuvanted trivalent influenza vaccines in England and Wales.

AIMS: High dose trivalent influenza vaccine (HD TIV) and adjuvant TIV (aTIV) have been developed specifically for adults aged 65 and older (65+) who are at high risk of life-threatening complications. However, there is a scarcity of evidence comparing the clinical and cost-effectiveness of HD TIV and aTIV. The aim of this study was to determine the cost-effectiveness of HD TIV versus aTIV in the England and Wales 65+ population. METHODS: A cost-utility analysis was conducted using a decision tree with two influenza related outcomes: Laboratory confirmed cases that could result in GP consultation, and hospitalizations that may result in premature mortality. Due to a lack of comparative evidence, the effectiveness of HD TIV versus aTIV was calculated indirectly, based on relative effectiveness estimates for each vaccine versus a common comparator, standard dose (SD) TIV. The primary analysis included hospitalizations explicitly due to influenza/pneumonia. Cost-effectiveness was established for three scenarios applying differing relative effectiveness estimates for aTIV versus SD TIV. Uncertainty was analysed in one-way deterministic sensitivity analyses. A secondary analysis included hospitalizations due to any respiratory illness. RESULTS: The minimum population impact of vaccination with HD TIV rather than aTIV was 13,092 fewer influenza cases, 1,109 fewer influenza related deaths, 4,673 fewer hospitalizations, and 3,245 fewer GP appointments. HD TIV was cost-effective versus aTIV for all three effectiveness scenarios, with incremental cost-effectiveness ratios (ICER) equal to £1,932, £4,181, and £8,767 per quality adjusted life year. Results were consistent across the secondary analysis and deterministic sensitivity analyses. LIMITATIONS: The analysis was limited by a lack of robust and consistent effectiveness data for aTIV. CONCLUSION: HD TIV is cost-effective versus aTIV in people aged 65+ in England and Wales. Use of HD TIV over aTIV could increase clinical benefits and reduce the public health and economic burden of influenza.

Burden of selected infectious diseases covered by UK childhood vaccinations: systematic literature review.

Aim: An overview of recent epidemiology and disease burden, independent of patient age, of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hemophilus influenzae invasive disease in the UK. Materials & methods: A systematic review was undertaken. Outcomes included incidence, prevalence, risk factors and cost burden. Results: 39 publications were included. Hepatitis B prevalence is high among certain risk groups. A small pertussis risk remains in pregnancy and for infants, which led to the introduction of maternal vaccination. H. influenzae invasive disease cases are limited to rare serotypes. Polio, tetanus and diphtheria are well controlled. Conclusion: The evaluated diseases are currently well controlled, thanks to a comprehensive vaccination program, with a generally low clinical and cost burden.

Quantifying the direct secondary health care cost of seasonal influenza in England.

BACKGROUND: The winter pressure often experienced by NHS hospitals in England is considerably contributed to by severe cases of seasonal influenza resulting in hospitalisation. The prevention planning and commissioning of the influenza vaccination programme in the UK does not always involve those who control the hospital budget. The objective of this study was to describe the direct medical costs of secondary care influenza-related hospital admissions across different age groups in England during two consecutive influenza seasons. METHODS: The number of hospital admissions, length of stay, and associated costs were quantified as well as determining the primary costs of influenza-related hospitalisations. Data were extracted from the Hospital Episode Statistics (HES) database between September 2017 to March 2018 and September 2018 to March 2019 in order to incorporate the annual influenza seasons. The use of international classification of disease (ICD)-10 codes were used to identify relevant influenza hospitalisations. Healthcare Resource Group (HRG) codes were used to determine the costs of influenza-related hospitalisations. RESULTS: During the 2017/18 and 2018/19 seasons there were 46,215 and 39,670 influenza-related hospital admissions respectively. This resulted in a hospital cost of £128,153,810 and £99,565,310 across both seasons. Results showed that those in the 65+ year group were associated with the highest hospitalisation costs and proportion of in-hospital deaths. In both influenza seasons, the HRG code WJ06 (Sepsis without Interventions) was found to be associated with the longest average length of stay and cost per admission, whereas PD14 (Paediatric Lower Respiratory Tract Disorders without Acute Bronchiolitis) had the shortest length of stay. CONCLUSION: This study has shown that influenza-related hospital admissions had a considerable impact on the secondary healthcare system during the 2017/18 and 2018/19 influenza seasons, before taking into account its impact on primary health care.

Cicatricial ectropion surgery: a prospective study of long-term symptom control, patient satisfaction and anatomical success.

IMPORTANCE: Cicatricial ectropion repair is effective and has a low complication rate. BACKGROUND: To evaluate the effectiveness and long-term functional outcomes of surgical repair of lower lid cicatricial ectropion. DESIGN: Prospective consecutive case series. PARTICIPANTS: Forty-four consecutive operations for cicatricial ectropion repair. METHODS: Consecutive cases of cicatricial ectropion repair completed during 2007-2011 in Waikato Hospital and Hamilton Eye Clinic, New Zealand, were enrolled in the study following formal ethics approval. Ectropion repair was completed using inferior retractor repositioning, horizontal lid tightening and full-thickness skin grafting. MAIN OUTCOME MEASURES: Patient-reported symptoms and satisfaction, ectropion recurrence and punctal ectropion. RESULTS: Forty-four eyes of 40 patients (30 males and 10 female) were included in the study. The average age at surgery was 75 years. Watering and poor appearance were the most common presenting symptoms. Postoperative follow-up was 1-6 years (mean = 4 years). There were no major perioperative complications, one patient developed trichiasis postoperatively. There were five reoperations (11%) during the study period. Two patients underwent medial spindle procedures for symptomatic medial ectropion and three patients required additional horizontal lid tightening. Seventy percent of patients reported satisfaction with their long-term results despite the partial recurrence of symptoms in 45%. Ectropion recurrence in <1 year occurred in three patients. CONCLUSION AND RELEVANCE: In this series, satisfactory appearance and symptom control were reported by 68% of patients at long-term follow-up. Preoperative marked ectropion with marked lid laxity is associated with early treatment failure and may be regarded as a relative contraindication to surgical correction with this technique. Punctal ectropion is an unreliable indicator of functional success.

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis.

AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland. METHODS: A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. RESULTS: Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44 mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20 mg. Results were most sensitive to variations in each DMT's efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. LIMITATIONS: The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators. Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.

Sources and Characteristics of Utility Weights for Economic Evaluation of Pediatric Vaccines: A Systematic Review.

BACKGROUND: Cost-effectiveness analysis of pediatric vaccines for infectious diseases often requires quality-of-life (utility) weights. OBJECTIVE: To investigate how utility weights have been elicited and used in this context. METHODS: A systematic review was conducted of studies published between January 1990 and July 2013 that elicited or used utility weights in cost-effectiveness analyses of vaccines for pediatric populations. The review focused on vaccines for 17 infectious diseases and is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. RESULTS: A total of 6410 titles and abstracts and 225 full-text articles were reviewed. Of those selected for inclusion (n = 101), 15 articles described the elicitation of utility weights and 86 described economic modeling studies using utilities. Various methods were used to generate utilities, including time trade-off, contingent valuation, and willingness to pay, as well as a preference-based measure with associated value sets, such as the EuroQol five-dimensional questionnaire or the Health Utilities Index. In modeling studies, the source of utilities used was often unclear, poorly reported, or based on weak underlying evidence. We found no articles that reported on the elicitation or use of utilities in diphtheria, polio, or tetanus. CONCLUSIONS: The scarcity of appropriate utility weights for vaccine-preventable infectious diseases in children and a lack of standardization in their use in economic assessments limit the ability to accurately assess the benefits associated with interventions to prevent infectious diseases. This is an issue that should be of concern to those making decisions regarding the prevention and treatment of infectious childhood illnesses.

Assessing Patient-Reported Outcomes in Pediatric Populations With Vaccine-Preventable Infectious Diseases: A Systematic Review of the Literature (the PROCHID Study).

OBJECTIVE: To investigate the use of patient-reported outcomes (PROs) in pediatric populations with vaccine-preventable infectious diseases in high-income Western countries. METHODS: Systematic review of PRO use in populations younger than 18 years with any of 17 infectious diseases for which vaccines are available or in development. The search was limited to studies performed in Europe, North America, Australia, and New Zealand and published between January 1, 1990, and July 31, 2013. Searches were conducted in Scopus and PsycINFO, and reference lists were manually searched. Results are reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 6410 titles and abstracts and 174 full-text articles reviewed, 17 full-text articles were included for data extraction. The largest number of PRO studies was carried out in patients with anogenital warts and rotavirus gastroenteritis. No PRO studies were identified for nine conditions. A total of 24 PRO measures (12 generic and 12 disease-specific) were used in the studies reviewed. Most of the instruments used were of high quality. Proxy responses were occasionally obtained when self-report would have been feasible. No validated disease-specific instruments for children with any of the conditions studied were found. CONCLUSIONS: The paucity of studies and PRO instruments to assess pediatric health status in vaccine-preventable infectious diseases, and the lack of a standardized approach to measurement, makes it difficult to capture the impact of disease and the benefit of vaccination and could potentially hinder decision making. Guidelines from relevant bodies to steer research in this area would be useful.

Penile cancer treatment costs in England.

BACKGROUND: Penile cancer is a rare malignancy in Western countries, with an incidence rate of around 1 per 100,000. Due to its rarity, most treatment recommendations are based on small trials and case series reports. Furthermore, data on the resource implications are scarce. The objective of this study was to estimate the annual economic burden of treating penile cancer in England between 2006 and 2011 and the cost of treating a single case based on a modified version of the European Association of Urology penile cancer treatment guidelines. METHODS: A retrospective (non-comparative) case series was performed using data extracted from Hospital Episode Statistics. Patient admission data for invasive penile cancer or carcinoma in situ of the penis was extracted by ICD-10 code and matched to data from the 2010/11 National Tariff to calculate the mean number of patients and associated annual cost. A mathematical model was simultaneously developed to estimate mean treatment costs per patient based on interventions and their associated outcomes, advised under a modified version of the European Association of Urologists Treatment Guidelines. RESULTS: Approximately 640 patients per year received some form of inpatient care between 2006 and 2011, amounting to an average of 1,292 spells of care; with an average of 48 patients being treated in an outpatient setting. Mean annual costs per invasive penile cancer inpatient and outpatient were £3,737 and £1,051 respectively, with total mean annual costs amounting to £2,442,020 (excluding high cost drugs). The mean cost per case, including follow-up, was estimated to be £7,421 to £8,063. Results were sensitive to the setting in which care was delivered. CONCLUSIONS: The treatment of penile cancer consumes similar levels of resource to other urological cancers. This should be factored in to decisions concerning new treatment modalities as well as choices around resource allocation in specialist treatment centres and the value of preventative measures.

Vaccination: short- to long-term benefits from investment.

In the context of current economic difficulties across Europe, accurate budgeting and resource allocation have become increasingly important. Vaccination programmes can respond to the needs of governments to budget with confidence. It may be more reliable and accurate to forecast budget and resource allocation for a vaccination programme than for unpredictable seasonal disease peaks of infections such as rotavirus gastroenteritis, influenza, and pneumonia. In addition, prevention through vaccination involves low levels of investment relative to the substantial benefits that may be obtained. In France, total lifelong vaccination costs, per fully compliant individual, ranged from €865 to €3,313, covering 12 to 16 diseases, which is comparable to, or lower than, costs of other preventive measures. In addition, effectively implemented vaccination programmes have the potential to generate substantial savings both in the short and in the long term. For example, vaccination programmes for rotavirus, meningitis C, human papillomavirus, influenza, and pneumonia have all been shown to significantly reduce the disease burden, and thus the associated costs, in the first years following vaccination implementation. These programmes demonstrate the potential for health authorities to obtain early, and often substantial, return on investment.

The societal role of lifelong vaccination.

The full economic and societal value of vaccination is complex to assess. Although direct protection is the immediate goal of vaccination programmes, it is rare that 100% uptake is attained. An important facet of vaccines value comes from the indirect (or herd) protection they provide. The evolving dynamics of our society, including the increase in the proportion of older individuals enhances the value of indirect protection in reducing disease transmission within the family setting and the society as a whole. For example, grandparents are increasingly involved in childcare, putting them at risk of disease transmission if they or the children are not vaccinated. Preventing disease in children can also reduce absenteeism for parents who otherwise would take days off work to care for their sick children, leading to a substantial societal burden. Preventing disease in working adults reduces absenteeism and presenteeism, enhancing productivity and contributing in turn to economic growth. Quality of life is essential at all ages. It is fundamental in children for their life chances, educational achievements, and healthy wellbeing. Additionally, preventing common diseases in adults and the elderly also contributes to their quality of life and helps to assure healthy ageing for growing ageing populations. These wider economic and societal values, although difficult to measure, should be taken into consideration in assessments of the economic value and cost-effectiveness of vaccination programmes.

The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.

Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n = 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPV-associated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine.

Prevalence of human papillomavirus in head and neck cancers in European populations: a meta-analysis.

BACKGROUND: Infection with human papillomavirus (HPV) is necessary for the development of cervical carcinoma. By contrast, the role of HPV in the pathogenesis of other malignancies, such as head and neck cancers, is less well characterised. This study aimed to address key information gaps by conducting a systematic review and meta-analysis of the prevalence of HPV infection in head and neck cancers, focusing on data for European populations. METHODS: MEDLINE, Embase and grey literature sources were systematically searched for primary studies that were published in English between July 2002 and July 2012, and which reported on the prevalence of HPV infection in head and neck cancers in European populations. Studies on non-European populations, those not published in English, and those assessing patients co-infected with human immunodeficiency virus were excluded. Eligible studies were combined in a meta-analysis. In addition, the potential statistical association between the head and neck cancers and certain HPV types was investigated. RESULTS: Thirty-nine publications met the inclusion criteria. The prevalence of HPV of any type in 3,649 patients with head and neck cancers was 40.0% (95% confidence interval, 34.6% to 45.5%), and was highest in tonsillar cancer (66.4%) and lowest in pharyngeal (15.3%) and tongue (25.7%) cancers. There were no statistically significant associations between the HPV types analysed and the geographical setting, type of sample analysed or type of primer used to analyse samples in head and neck cancers. CONCLUSIONS: The prevalence of HPV infection in European patients with head and neck cancers is high but varies between the different anatomical sites of these malignancies. There appears to be no association between HPV type and geographical setting, type of samples analysed or type of primer used to analyse samples in such cancers.

The cost of anal cancer in England: retrospective hospital data analysis and Markov model.

BACKGROUND: Anal cancer requires a multidisciplinary approach to treatment with often complex interventions. Little is known regarding the associated costs and resource use. METHODS: Patient records were extracted from a national hospital database to estimate the number of patients treated for anal cancer in England. Identified resource use was linked to published UK cost estimates to quantify the reimbursement of treatment through the Payment by Results system. A mathematical model was developed simultaneously to validate findings and to calculate the average 10-year cost of treating a squamous cell anal carcinoma case from diagnosis. The model utilised data from the Association of Coloproctology of Great Britain and Ireland's anal cancer position statement. RESULTS: On average, 1,564 patients were admitted to hospital and 389 attended an outpatient facility per year. The average annual cost per inpatient and outpatient ranged from £4,562-£5,230 and £1,146-£1,335, respectively. Based on the model estimates, the inflated cost per case was between £16,470-£16,652. Results were most sensitive to the mode of admission for primary treatment and the costs of staging/diagnosis (inflated range: £14,309-£23,264). CONCLUSIONS: Despite limitations in the available data, these results indicate that the cost of treating anal cancer is significant. Further observational work is required in order to verify these findings.

Cost-effectiveness of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

OBJECTIVE: The introduction of routine childhood vaccination with pneumococcal conjugate vaccines (PCVs) has led to a decrease in the overall incidence of pneumococcal disease in all ages and a change in the serotype distribution of the remaining disease. This study assessed the cost-effectiveness of vaccinating ≥65 years and at risk adults with either the 23-valent pneumococcal polysaccharide vaccine (PPV23) or the 13-valent conjugate vaccine (PCV13) in the UK, accounting for epidemiological changes. METHODS: A population-based Markov model was used to track one UK-based cohort of individuals assuming PPV23, PCV13 or no vaccination until death. RESULTS: The ICER was estimated at £8413 when PPV23 was compared to no vaccination. PPV23 dominated PCV13. CONCLUSION: This model suggests that vaccinating with PPV23 is cost-effective when compared to both PCV13 and no vaccination. As PPV23 covers 80-90% in the UK of all serotypes causing invasive pneumococcal diseases, it remains cost-effective despite recent reductions in invasive pneumococcal diseases incidence in adults.

A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

OBJECTIVE: Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. METHODS: The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. RESULTS: Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). CONCLUSION: PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.