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.

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.

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.

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.

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.

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 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.

Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or older: findings from the Zoster Quality of Life (ZQOL) study.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster (shingles). As a chronic condition, PHN can have a substantial adverse impact on patients' lives. However, UK-specific data concerning the burden of PHN on individual patients, healthcare systems and wider society, are lacking. As the first UK-wide cross-sectional study of its kind, The Zoster Quality of Life (ZQOL) study was designed to address these concerns. METHODS: Patients (n = 152) with a confirmed diagnosis of PHN (defined as pain persisting ≥ 3 months following rash onset) and aged ≥50 years were recruited from primary and secondary/tertiary care centres throughout the UK. All patients completed validated questionnaires, including the Zoster Brief Pain Inventory (ZBPI), the Medical Outcomes Study Short-Form 36 (SF-36), the EuroQol-5 Dimensions (EQ-5D) and the Treatment Satisfaction with Medication (TSQM) questionnaire. Where available, mean patient population scores on these questionnaires were compared to scores derived from age-matched normative samples to quantify the burden associated with PHN. RESULTS: Despite numerous consultations with healthcare professionals and receiving multiple medications for the management of their PHN, the majority of patients reported being in pain 'most of the time' or 'all of the time'. A total of 59.9% (n = 91) of all PHN patients reported pain in the preceding 24 hours to assessment at levels (ZBPI worst pain ≥ 5) typically considered to have a significant impact on Health Related Quality of Life (HRQoL). Accordingly, scores for SF-36 and EQ-5D indicated significant deficits in HRQoL among PHN patients compared to age-matched norms (p < 0.05) and patients reported being dissatisfied with the perceived efficacy of therapies received for the management of PHN. Increased pain severity was observed among older participants and higher levels of pain severity were associated with greater HRQoL deficits. CONCLUSIONS: The inadequate relief provided by PHN therapies available in the UK is associated with a significant burden among PHN patients in terms of pain severity and deficits in HRQoL which may persist for years. Therefore, alternative means such as prevention of shingles and PHN, are essential for reducing the impact on individual patients, healthcare systems and society as a whole.

Challenges in quantifying the patient-reported burden of herpes zoster and post-herpetic neuralgia in the UK: learnings from the Zoster Quality of Life (ZQOL) study.

BACKGROUND: Acute presentation of herpes zoster (HZ) and the subsequent development of post-herpetic neuralgia (PHN) can have a significant impact on patients' lives. To date, evidence regarding the human and economic burden of HZ and PHN in the UK is limited. To address this knowledge gap a national, multicentre, large-scale real-world study was conducted to inform the scientific community and healthcare decision-makers. This paper outlines difficulties encountered and challenges to conducting real-world studies in the UK, methods used to overcome these hurdles and strategies that can be employed to promote and facilitate the conduct of future studies. FINDINGS: The Zoster Quality of Life (ZQOL) study is the first UK-wide and largest observational study investigating patient burden associated with HZ and PHN. A total of 383 patients (229 HZ; 154 PHN) over the age of 50 years were recruited from 42 primary and secondary/tertiary care centres. Patient-reported outcome (PRO) assessments of pain, quality of life and treatment satisfaction were completed by all participants and supplemented by clinical information from participating physicians.Key challenges encountered during the conduct of this study can be broadly categorised as follows: 1) identification of centres willing/able to participate in the study: lack of resources and limited research experience were major barriers to recruitment of centres for participation in the study; 2) obtaining local research & development (R&D) approval: lack of clearly defined processes and requirements specific to real-world studies and limited degree of standardisation between R&D departments in approval procedures led to significant variability in submission requirements and lead times for obtaining approval; 3) recruitment of study participants: rates of recruitment were slower than anticipated, meaning it was necessary to extend the study recruitment period and increase the number of participating centres. DISCUSSION: Initiatives designed to promote and facilitate the conduct of research in the UK are important for real-world studies. The ZQOL study shows that opportunities exist for real-word research. However, streamlining the R&D approval process where possible and further incentivising the participation of primary care centres in such studies would help to further facilitate the generation of real-world evidence to inform healthcare decisions.

A comparison of healthcare resource use for rotavirus and RSV between vulnerable children with co-morbidities and healthy children: a case control study.

OBJECTIVE: To quantify the differences in hospital length of stay (LOS) and cost between healthy and vulnerable children with cystic fibrosis (CF), insulin-dependent diabetes mellitus (IDDM), cancer, and epilepsy who contract rotavirus (RVGE) or respiratory syncytial virus (RSV). METHODS: Hospital Episode Statistics (HES) data were collected for England, for children <5 years old, admitted between April 2001 and March 2008, using ICD-10 codes for RVGE and RSV. Cases were identified as having RVGE and/or RSV plus CF, IDDM, cancer, or epilepsy. Healthy controls had RVGE and/or RSV only, additional controls had eczema only. Cost, hospital LOS, and demographics were collected. RESULTS: Four hundred and eighty-six (0.5%) cases and 101,784 (99.5%) healthy controls were admitted with RVGE or RSV, with 17,420 eczema controls. RVGE was present in 153 (31.5%) cases and 7532 (7.4%) healthy controls, and RSV in 333 (68.5%) cases and 94,252 (92.6%) healthy controls. Cases were older (1.1 years, SD = 1.3 years), had greater LOS (9.9 days, SD = 19.9), and cost more (£3477, SD = £7765) than healthy controls (age = 0.2, SD = 0.5, p < 0.001; LOS = 1.9 days, SD = 3.1, p < 0.001; cost = £595, SD = £727, p < 0.001). Cost for cases was 6-times greater than healthy controls (p < 0.001). Controls had a 0.3 day greater LOS (p < 0.001) with RSV, but a £17 (p = 0.085) lower mean cost than RVGE. CONCLUSION: RVGE and RSV are more serious diseases in vulnerable children, requiring more intense resource use. The importance of preventing infection in vulnerable children is underlined by hygiene and appropriate isolation and vaccination strategies. When universal vaccination is under consideration, as for rotavirus vaccines, evaluation of a vaccination programme should consider the potentially positive impact on vulnerable children. LIMITATIONS: Limitations of the study include a dependency on accurate coding, an expectation that patients are identified through laboratory testing, and the possibility of unidentified underlying conditions affecting the burden.

Rotavirus, respiratory syncytial virus and non-rotaviral gastroenteritis analysis of hospital readmissions in England and Wales.

AIM: To quantify readmissions with infectious diseases and differences in readmission patterns. METHODS: Using the CHKS database, children <5 years admitted to hospital in England and Wales, between 2000 and 2008, with rotavirus (RV), respiratory syncytial virus (RSV) or non-rotaviral gastroenteritis (NRV) were identified. All admissions within a 30-day prior period were similarly identified, and the proportion of readmissions was calculated. RESULTS: There were 365,693 admissions for RV, RSV and NRV; 17.2% were readmissions. In 36% of cases, the cause of the prior admission was also RV, RSV or NRV, with 64% having a different prior diagnosis. The majority of readmissions were within 5 days of their prior admission, the majority of those with RV (n = 2,566/58.7%) within 3 days, NRV (n = 11 326/53.5%) within 4 days and RSV (n = 18 811/50.2%) within 9 days of prior discharge. Readmission for RV was associated with greater LOS than RSV (p < 0.001) and NRV (p < 0.001), while cost per admission was greater for RV compared to RSV (p < 0.001) and NRV (p < 0.001). CONCLUSIONS: Thirty-six percent of readmissions indicated discharge without resolution from the first admission; nosocomial infection needs to be considered as a cause in the other. Although RSV represented the largest readmission group, higher costs and longer LOS were associated with RV.

The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales.

Rotavirus vaccines have shown great potential for reducing the disease burden of the major cause of severe childhood gastroenteritis. The decision regarding whether rotavirus vaccination will be introduced into the national immunization program is currently being reviewed. The conclusions of previous evaluations of rotavirus vaccination cost-effectiveness contradict each other. This is the first analysis to incorporate a dynamic transmission model to assess the cost-effectiveness of rotavirus vaccination in England and Wales. Most previously reported models do not include herd protection, and thus may underestimate the cost-effectiveness of vaccination against rotavirus. We incorporate a dynamic model of rotavirus transmission in England and Wales into a cost-effectiveness analysis to determine the probability that the pentavalent rotavirus vaccination will be cost-effective over a range of full-course vaccine prices. This novel approach allows the cost-effectiveness analysis to include a feasible level of herd protection provided by a vaccination program. Our base case model predicts that pentavalent rotavirus vaccination is likely to be cost-effective in England and Wales at £ 60 per course. In some scenarios the vaccination is predicted to be not only cost-effective but also cost-saving. These savings could be generated within ten years after vaccine introduction. Our budget impact analysis demonstrates that for the realistic base case scenarios, 58-96% of the cost outlay for vaccination will be recouped within the first four years of a program. Our results indicate that rotavirus vaccination would be beneficial to public health and could be economically sound. Since rotavirus vaccination is not presently on the immunization schedule for England and Wales but is currently under review, this study can inform policymakers of the cost-effectiveness and budget impact of implementing a mass rotavirus vaccine strategy.

Economic evaluation of sorafenib in unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: A double-blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 months vs 7.9 months, P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost-effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA. METHODS: A Markov model was developed following time-to-progression and survival using phase III trial data. Health effects are expressed as life-years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis-related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%. RESULTS: Results are presented as incremental cost/life-year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life-years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17 vs 1.05 ± 0.10 life-years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40,639 ± $US3052 for sorafenib and $US7, 804 ± $US1349 for best supportive care. The incremental cost-effectiveness ratio was $US62,473/life-year gained. CONCLUSIONS: The economic evaluation indicates that sorafenib is cost-effective compared to best supportive care, with a cost-effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50,000-$US100,000) and significantly lower than alternative thresholds suggested in recent years ($US183,000-$US264,000/life-year gained, or $US300,000/quality-adjusted life-year) in oncology.

Burden on UK secondary care of rotavirus disease and seasonal infections in children.

OBJECTIVE: Rotavirus is a common infection affecting children under 5 years, which leads to a significant disease burden. This burden is potentially exacerbated by the seasonality of rotavirus, particularly in the context of the seasonality of other common childhood infections. The primary study objective was to describe the pattern and burden of seasonal infections amongst children under 5 years of age with particular attention placed on rotavirus and other gastrointestinal infections. METHODS: A retrospective analysis of all routine inpatient data relating to selected seasonal infections in the UK was conducted between 2001/02 and 2007/08 using data from Capse Healthcare Knowledge Systems (CHKS, England, Northern Ireland and Wales) and Information Services Division (ISD, Scotland). Admissions with selected diagnoses were extracted based on International Classification of Diseases (ICD)-10 coding. All episodes were processed using a HRG grouper and costs applied according to the NHS National Tariff. RESULTS: In the financial year 2007/08, the total number of admissions in the UK for children under 5 years for the selected seasonal infections was 64,879 of which 32,126 admissions were associated with gastrointestinal infections including rotavirus gastroenteritis (RVGE). Seasonal peaks of gastrointestinal infections and RVGE occurred in the spring quarter and respiratory syncytial virus (RSV) and influenza in the winter quarter. Admissions for gastrointestinal infection including RVGE accounted for 35 003 bed days with 9922 due to RVGE. The total cost for admissions involving a diagnosis of seasonal infection was £56 million. Of this, it was estimated that infections with an ICD-10 classification of rotavirus represented a cost of £8.6 million. CONCLUSION: Rotavirus contributes to the significant burden that seasonal infections place on inpatient paediatric resources during the winter and spring months. This study may be limited by issues of clinical coding and the infrequency of confirmatory microbiological testing in real-world practice. Vaccination might be considered as a means of reducing this clinical and economic burden particularly where long-term effectiveness and ease of administration are proven.

Is there anything nicer than NICE? A question the Conservative shadow health team is right to ask.

Access to life-saving treatments, and the role played by the National Institute for Health and Clinical Excellence (NICE) in reaching decisions, continues to represent an important part of modern health policy. High profile cases and critical media coverage have sharpened public interest in this issue. In November 2008, the Conservative Party published detailed proposals on NICE outlining policies for improving the systems and processes for making decisions about NHS drug availability. The Conservatives clearly state their support for NICE, but highlight six areas to improve its configuration, structure and efficiency. These areas are consistent with the Conservative commitment to focus on health outcomes rather than central targets. A "NICE Charter" to codify the Institute's roles and responsibilities; scrapping the current system of Ministerial referral; allowing appraisals to commence at the time of drug licensing; and increasing the use of risk-sharing schemes are among the headline pledges. The policy document also makes clear the need for pharmaceutical companies to better demonstrate product clinical value by shifting the burden of proof from NICE to the manufacturer. Improved cooperation between industry and NICE is promised through the creation of a steering committee. Furthermore, a clear commitment to evaluate wider social costs and benefits is provided. The Conservative proposals make clear that there are no easy solutions to tackle the basic health economic problem of how to best allocate finite NHS resources to satisfy all healthcare needs. However, the proposals offer a solid blueprint for focused reform moving forward.

Economic evaluation of sorafenib in the treatment of hepatocellular carcinoma in Canada.

BACKGROUND: A randomized phase III trial of sorafenib vs. placebo in hepatocellular carcinoma (HCC) demonstrated that sorafenib significantly prolonged overall survival (OS) compared to placebo. RESEARCH DESIGN AND METHODS: A Markov model was developed to evaluate the cost-effectiveness of sorafenib vs. best supportive care (BSC) in HCC from the perspective of the Canadian provincial Ministry of Health. The model followed survival and time to progression (TTP) in monthly cycles based on the extrapolation of patient level trial data. Health effects were expressed as life-years gained (LYG). Resource use included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs were gathered from public sources and were expressed in 2007 Canadian Dollars. Costs and effects were evaluated over a lifetime and discounted at 5%. Results were presented as mean +/- standard deviation. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: LYG was longer for sorafenib (1.52 +/- 0.16 vs. 1.03 +/- 0.09 LYG/patient for sorafenib and BSC, respectively). The lifetime total costs were $47,511 +/- 3 656 for sorafenib and $10,376 +/- 1 649 for BSC, resulting in an incremental cost-effectiveness ratio (ICER) of $75,821/LYG, and deterministic ICER of $75,759/LYG. The results were most sensitive to OS, TTP and BSC costs after progression. Sensitivity analyses results showed that the model was robust. CONCLUSIONS: The economic evaluation indicates that sorafenib is cost-effective as compared to BSC in HCC. Limitations include multiple data sources, use of expert opinion for resource use, and the lack of utility data.