The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 vaccine.

BACKGROUND: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a monovalent XBB.1.5 variant-adapted Fall 2023 COVID-19 vaccine (modified version: XBB monovalent) for adults aged ≥18 years on these outcomes. METHODS: A previously developed Susceptible-Exposed-Infected-Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19-related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. RESULTS: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial VE against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. CONCLUSIONS: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19-related infections, hospitalizations, and deaths.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany.

OBJECTIVES: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023-August 2024). METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, a number of COVID-19 related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. RESULTS: Compared to no autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalizations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalizations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. CONCLUSIONS: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA fall 2023 vaccines in the United States.

AIMS: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for fall 2023 in adults aged ≥18 years over a 1-year analytic time horizon (September 2023-August 2024). MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 cases in summer 2023. The numbers of symptomatic infections, COVID-19-related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech fall 2023 vaccines were also examined. RESULTS: Base case results suggest that the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to no vaccine, yielding an ICER of $7700 per QALY gained. Using a societal cost perspective, the ICER is $2100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates, and costs drive cost-effectiveness. With a relative vaccine effectiveness of 5.1% for infection and 9.8% for hospitalization for the Moderna vaccine versus the Pfizer-BioNTech vaccine, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3300 more deaths than the Pfizer-BioNTech vaccine. LIMITATIONS AND CONCLUSIONS: As COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. The effectiveness of fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, our model predicts the Moderna Fall Campaign vaccine is highly cost-effective across all sensitivity analyses.

The potential clinical impact of implementing different COVID-19 boosters in fall 2022 in the United States.

OBJECTIVE: Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for fall vaccinations. This study estimated the number of infections and hospitalizations prevented by three potential booster strategies for adults (≥18 years) in the United States: boosting with either Moderna's (1) licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) or (2) candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or (3) Moderna's updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting November 2022 due to longer development time. METHODS: An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate infections over time; the model contains compartments defined by SEIR and vaccination status. A decision tree was used to estimate clinical consequences of infections. Calibration was performed so the model tracks the actual course of the pandemic to present time. RESULTS: Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, and hospitalizations by 42%, 48%, and 25%, respectively, over 6 months compared to no booster. Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning illustrate that boosting with mRNA-1273.214 in September prevented more cases of infection and hospitalization than the other vaccines. LIMITATIONS AND CONCLUSIONS: With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making parameter estimation difficult. Our analysis demonstrated that boosting with mRNA-1273.214 was more effective over 6 months in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a more effective BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

The Cost-Effectiveness of Vaccination of Older Adults with an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Other Available Quadrivalent Vaccines in Germany.

Enhanced quadrivalent influenza vaccines that include an adjuvant (aQIV) or a high dose of antigen (QIV-HD), which stimulate a stronger immune response in older adults than the standard vaccine (QIVe), are now approved. The objective of this research is to compare available vaccines and determine the cost-effectiveness of immunizing persons aged 65 years and above with aQIV compared to QIVe and QIV-HD in Germany. A compartmental transmission model calibrated to outpatient visits for influenza in Germany was used to predict the number of medically attended infections using the three vaccines. The rates of hospitalizations, deaths, and other economic consequences were estimated with a decision tree using German data where available. Based on meta-analysis, the rVE of -2.5% to 8.9% for aQIV versus QIV-HD, the vaccines are similar clinically, but aQIV is cost saving compared to QIV-HD (unit cost of EUR 40.55). All results were most sensitive to changes in vaccine effectiveness. aQIV may be cost-effective compared to QIVe depending on the willingness to pay for additional benefits in Germany. As aQIV and QIV-HD are similar in terms of effectiveness, aQIV is cost saving compared to QIV-HD at current unit prices.

An Economic Comparison of Influenza Vaccines Recommended for Use in Eligible Adults under 65 Years in the United Kingdom.

Background: In the United Kingdom (UK), a cell-based quadrivalent influenza vaccine (QIVc) and a recombinant vaccine (QIVr) are recommended for eligible adults under 65 years. The objective of this analysis was to determine the potential cost-effectiveness of QIVc compared to QIVr for this age group using a range of assumptions about relative vaccine effectiveness (rVE). Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The list price was £12.50 for QIVc and £22.00 for QIVr. The base case effectiveness of QIVc was 63.9%. As there are no data comparing the vaccines in the 18 to 64-year-old age group, rVE was varied. Results: For the base case, the rVE of QIVr compared with QIVc must be at least 25% in order for the cost per quality-adjusted life-year gained to be £20,000 or lower. Sensitivity analysis demonstrated that the rVE required for QIVr to be cost-effective was most dependent on the absolute effectiveness of QIVc. Conclusion: At list prices, our analysis predicts that the rVE for QIVr must be at least 25% compared to QIVc in order to be considered cost-effective.

The cost-effectiveness of an adjuvanted quadrivalent influenza vaccine in the United Kingdom.

In the United Kingdom (UK), both the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose QIV (QIV-HD) are preferred for persons aged 65 years and older but only aQIV is reimbursed by the National Health Service (NHS). The objective was to determine the potential cost-effectiveness of vaccinating adults aged 65 years and above with aQIV compared with QIV-HD in the UK. A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the impact of vaccination in 10 influenza seasons. Vaccine effectiveness was based on a meta-analysis that concluded the vaccines were not significantly different. Vaccine coverage, physician visits, hospitalizations, deaths, utility losses and NHS costs were estimated using published UK sources. The list price of aQIV was £11.88 while a range of prices were tested for QIV-HD. The price of the trivalent high-dose vaccine (TIV-HD) is £20.00 but a list price for QIV-HD is not yet available. The projected differences between the vaccines in terms of clinical cases and influenza treatment costs are minimal. Our analysis demonstrates that in order to be cost-effective, the price of QIV-HD must be similar to that of aQIV and may range from £7.57 to £12.94 depending on the relative effectiveness of the vaccines. The results of the analysis were most sensitive to variation in vaccine effectiveness and the rate of hospitalization due to influenza. Given the evidence, aQIV is cost-saving unless QIV-HD is priced lower than the existing list price of TIV-HD.

The Cost-Effectiveness of Expanding Vaccination with a Cell-Based Influenza Vaccine to Low Risk Adults Aged 50 to 64 Years in the United Kingdom.

BACKGROUND: In response to COVID-19, the UK National Health Service (NHS) extended influenza vaccination in 50- to 64-year-olds from at-risk only to all in this age group for the 2020/21 season. The objective of this research is to determine the cost-effectiveness of continuing to vaccinate all with a quadrivalent cell-based vaccine (QIVc) compared to returning to an at-risk only policy after the pandemic resolves. METHODS: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The base case effectiveness of QIVc was 63.9% and the list price was GBP 9.94. RESULTS: Vaccinating 50% of all 50- to 64-year-olds with QIVc reduced the average annual number of clinical infections (-682,000), hospitalizations (-5800) and deaths (-740) in the UK. The base case incremental cost per quality-adjusted life-year gained (ICER) of all compared to at-risk only was GBP6000 (NHS perspective). When the cost of lost productivity was considered, vaccinating all 50- to 64-year-olds with QIVc became cost-saving. CONCLUSION: Vaccinating all 50- to 64-year-olds with QIVc is likely to be cost-effective. The NHS should consider continuing this policy in future seasons.

The potential public health and economic value of a hypothetical COVID-19 vaccine in the United States: Use of cost-effectiveness modeling to inform vaccination prioritization.

BACKGROUND: Researchers are working at unprecedented speed to develop a SARS-CoV-2 vaccine. We aimed to assess the value of a hypothetical vaccine and its potential public health impact when prioritization is required due to supply constraints. METHODS: A Markov cohort model was used to estimate COVID-19 related direct medical costs and deaths in the United States (US), with and without implementation of a 60% efficacious vaccine. To prioritize the vaccine under constrained supply, the population was divided into tiers based on age; risk and age; and occupation and age; and outcomes were compared across one year under various supply assumptions. The incremental cost per quality-adjusted life-year (QALY) gained versus no vaccine was calculated for the entire adult population and for each tier in the three prioritization schemes. RESULTS: The incremental cost per QALY gained for the US adult population was $8,200 versus no vaccination. For the tiers at highest risk of complications from COVID-19, such as those ages 65 years and older, vaccination was cost-saving compared to no vaccination. The cost per QALY gained increased to over $94,000 for those with a low risk of hospitalization and death following infection. Results were most sensitive to infection incidence, vaccine price, the cost of treating COVID-19, and vaccine efficacy. Under the most optimistic supply scenario, the hypothetical vaccine may prevent 31% of expected deaths. As supply becomes more constrained, only 23% of deaths may be prevented. In lower supply scenarios, prioritization becomes more important to maximize the number of deaths prevented. CONCLUSIONS: A COVID-19 vaccine is predicted to be good value for money (cost per QALY gained <$50,000). The speed at which an effective vaccine can be made available will determine how much morbidity and mortality may be prevented in the US.

A Budget Impact Model of the Addition of Telotristat Ethyl Treatment to the Standard of Care in Patients with Uncontrolled Carcinoid Syndrome.

BACKGROUND: Carcinoid syndrome, a rare condition in patients with neuroendocrine tumours, characterised by flushing and diarrhoea, severely affects patients' quality of life. The current carcinoid syndrome standard of care includes somatostatin analogues, but some patients experience uncontrolled symptoms despite somatostatin analogue therapy. Telotristat ethyl is a novel treatment approved by the European Medicines Agency (EMA) and US FDA that significantly reduces bowel movement frequency in patients with uncontrolled carcinoid syndrome. OBJECTIVE: We developed a model to evaluate the 5-year budget impact of introducing telotristat ethyl to standard care in Swedish patients with uncontrolled carcinoid syndrome. METHODS: Treatment response in the 12-week phase III TELESTAR trial (NCT01677910) informed telotristat ethyl efficacy; subsequently, health states were captured by a Markov model using 4-week cycles. TELESTAR open-label extension data informed telotristat ethyl discontinuation. The number of treatment-eligible patients was estimated from literature reviews reporting the prevalence, incidence and mortality of carcinoid syndrome. A Swedish database study informed real-world costs related to carcinoid syndrome and carcinoid heart disease costs. Telotristat ethyl market share was assumed to increase annually from 24% (year 1) to 70% (year 5). RESULTS: Over the 5-year model horizon, 44 patients were expected to initiate telotristat ethyl treatment. The cumulative net budget impact of adding telotristat ethyl to current standard of care was €172,346; per-year costs decreased from €66,495 (year 1) to €29,818 (year 5). Increased drug costs from adding telotristat ethyl were offset by reduced costs elsewhere. CONCLUSIONS: The expected budget impact of adding telotristat ethyl to the standard of care in Sweden was relatively low, largely because of the rarity of carcinoid syndrome.

Granulocyte colony-stimulating factors in the prevention of febrile neutropenia: review of cost-effectiveness models.

INTRODUCTION: We reviewed the evolution of the methods used in cost-effectiveness analyses of granulocyte colony-stimulating factors (G-CSFs) in the primary and secondary prevention of febrile neutropenia (FN) in patients receiving myelosuppressive cancer chemotherapy. Areas covered: FN is a side effect of myelosuppressive chemotherapy associated with significant morbidity, mortality, and costs. The risk of FN may depend on the drugs used within a chemotherapy regimen, and an FN event may cause chemotherapy dose reductions or delays in subsequent cycles. Expert commentary: More recent pharmacoeconomic models have reflected these clinical observations by modeling sequential chemotherapy regimens to account for FN risk on a per-cycle basis, and by accounting for chemotherapy dose reductions and consequent survival losses.

Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma.

OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. METHODS: A Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted. RESULTS: Base-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the mortality hazard ratio for RDI (<90% vs ≥90% [for NHL]). In the PSAs for stage II breast cancer and NHL, the probabilities that PP with pegfilgrastim was cost effective or dominant versus all other prophylaxis strategies at a €30,000/QALY willingness-to-pay threshold were 52% (other strategies ≤24%) and 58% (other strategies ≤24%), respectively. CONCLUSION: From a Belgian payer perspective, PP with pegfilgrastim appears cost effective compared to other prophylaxis strategies in patients with stage II breast cancer or NHL at a €30,000/QALY threshold.

High-dose inactivated influenza vaccine is associated with cost savings and better outcomes compared to standard-dose inactivated influenza vaccine in Canadian seniors.

Seasonal influenza infects approximately 10-20% of Canadians each year, causing an estimated 12,200 hospitalizations and 3,500 deaths annually, mostly occurring in adults ≥65 years old (seniors). A 32,000-participant, randomized controlled clinical trial (FIM12; Clinicaltrials.gov NCT01427309) showed that high-dose inactivated influenza vaccine (IIV-HD) is superior to standard-dose vaccine (SD) in preventing laboratory-confirmed influenza illness in seniors. In this study, we performed a cost-utility analysis (CUA) of IIV-HD versus SD in FIM12 participants from a Canadian perspective. Healthcare resource utilization data collected in FIM12 included: medications, non-routine/urgent care and emergency room visits, and hospitalizations. Unit costs were applied using standard Canadian cost sources to estimate the mean direct medical and societal costs associated with each vaccine (2014 CAD). Clinical illness data from the trial were mapped to quality-of-life data from the literature to estimate differences in effectiveness between vaccines. Time horizon was one influenza season, however, quality-adjusted life-years (QALYs) lost due to death during the study were captured over a lifetime. A probabilistic sensitivity analysis (PSA) was also performed. Average per-participant medical costs were $47 lower and societal costs $60 lower in the IIV-HD arm. Hospitalizations contributed 91% of the total cost and were less frequent in the IIV-HD arm. IIV-HD provided a gain in QALYs and, due to cost savings, dominated SD in the CUA. The PSA indicated that IIV-HD is 89% likely to be cost saving. In Canada, IIV-HD is expected to be a less costly and more effective alternative to SD, driven by a reduction in hospitalizations.

Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial.

BACKGROUND: Adults aged 65 years and older account for most seasonal influenza-related hospital admissions and deaths. Findings from the randomised controlled FIM12 study showed that high-dose inactivated influenza vaccine is more effective than standard-dose vaccine for prevention of laboratory-confirmed influenza in this age group. We aimed to assess the economic impact of high-dose versus standard-dose influenza vaccine in participants in the FIM12 study population. METHODS: The FIM12 study was a head-to-head randomised controlled trial in which 31,989 participants aged 65 years and older were randomly assigned (1:1) to receive either high-dose or standard-dose trivalent inactivated influenza vaccine over two influenza seasons (2011-12 and 2012-13). Data for health-care resource consumption obtained in the FIM12 study were summarised across vaccine groups. Unit costs obtained from standard US cost sources were applied to each resource item, including to the vaccines (high dose US$31·82, standard dose $12·04). Clinical illness data were mapped to existing quality-of-life data. The time horizon was one influenza season; however, quality-adjusted life-years (QALYs) lost due to death during the study were calculated over a lifetime. We calculated incremental cost-effectiveness ratios (ICERs) for high-dose versus standard-dose vaccine and used QALYs as an outcome in the cost-utility analysis. We undertook a probabilistic sensitivity analysis using bootstrapping to explore the effect of statistical uncertainty on the study results. FINDINGS: Mean per-participant medical costs were lower in the high-dose vaccine group ($1376·72 [SD 6857·59]) than in the standard-dose group ($1492·64 [7447·14]; difference -$115·92 [95% CI -264·18 to 35·48]). Mean societal costs were likewise lower in the high-dose versus the standard-dose group ($1506·48 [SD 7305·19] vs $1634·50 [7952·99]; difference -$128·02 [95% CI -286·89 to 33·30]). Hospital admissions contributed 95% of the total health-care-payer cost and 87% of the total societal costs. The mean per-participant number of hospital admissions was 0·0937 (SD 0·3644) in the high-dose group and 0·1017 (0·3708) in the standard-dose group (difference -0·0080, 95% CI -0·0160 to -0·0003). The high-dose vaccine provided a gain in QALYs (mean 8·1502 QALYs gained per participant [SD 0·5693]) compared with the standard-dose vaccine (8·1499 QALYs [0·5697]) and, due to cost savings, dominated standard-dose vaccine in the cost-utility analysis. The probabilistic sensitivity analysis showed that the high-dose vaccine is 93% likely to be cost saving. INTERPRETATION: High-dose trivalent inactivated influenza vaccine is a less costly and more effective alternative to the standard-dose vaccine, driven by a reduction in the number of hospital admissions. These findings are relevant to US health-care beneficiaries, providers, payers, and recommending bodies, especially those seeking to improve outcomes while containing costs. FUNDING: Sanofi Pasteur.

Despite High Cost, Improved Pneumococcal Vaccine Expected To Return 10-Year Net Savings Of $12 Billion.

In 2010 the US Advisory Committee on Immunization Practices recommended that the seven-valent pneumococcal conjugate vaccine (PCV7) be replaced by the thirteen-valent version (PCV13), which provides protection against six additional serotypes of the bacterium Streptococcus pneumoniae. The higher price of PCV13, compared to PCV7, may be a concern for funding agencies and payers, as has been the case with other new vaccines. This study estimated the budgetary impact on both public and private US insurance payers of the routine use of PCV13 instead of PCV7 from 2010 to 2019. Implementing the PCV13 vaccine is projected to cost public and private payers $3.5 billion and $2.6 billion, respectively, more than PCV7. However, PCV13 is expected to provide net cost savings of $6.1 billion and $4.2 billion, respectively, to those payers during the ten-year period by preventing pneumococcal disease and its associated costs. An additional $1.7 billion in cost savings would be realized for uninsured patients, whose costs ultimately fall on those payers. Despite its higher price, compared to PCV7, this new vaccine is expected to provide payers with substantial net budgetary savings.

Cost-effectiveness of prophylaxis treatment strategies for febrile neutropenia in patients with recurrent ovarian cancer.

OBJECTIVE: Evaluate the cost-effectiveness of primary prophylaxis (PP) or secondary prophylaxis (SP) with pegfilgrastim, filgrastim (6-day and 11-day), or no prophylaxis to reduce the risk of febrile neutropenia (FN) in patients with recurrent ovarian cancer receiving docetaxel or topotecan. METHODS: A Markov model was used to evaluate the cost-effectiveness of PP vs SP from a US payer perspective. Model inputs, including the efficacy of each strategy (relative risk of FN with prophylaxis compared to no prophylaxis) and mortality, costs, and utility values were estimated from public sources and peer-reviewed publications. Incremental cost-effectiveness was evaluated in terms of net cost per FN event avoided, incremental cost per life-year saved (LYS), and incremental cost per quality-adjusted life-year (QALY) gained over a lifetime horizon. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. RESULTS: For patients receiving docetaxel, the incremental cost-effectiveness ratio (ICER) for PP vs SP with pegfilgrastim was $7900 per QALY gained, and PP with pegfilgrastim dominated all other comparators. For patients receiving topotecan, PP with pegfilgrastim dominated all comparators. Model results were most sensitive to baseline FN risk. PP vs SP with pegfilgrastim was cost effective in 68% and 83% of simulations for docetaxel and in >99% of simulations for topotecan at willingness-to-pay thresholds of $50,000 and $100,000 per QALY. CONCLUSIONS: PP with pegfilgrastim should be considered cost effective compared to other prophylaxis strategies in patients with recurrent ovarian cancer receiving docetaxel or topotecan with a high risk of FN.

Economic analysis of bevacizumab, cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC).

OBJECTIVE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients. METHODS: A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources. RESULTS: Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab + FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab + FBC, panitumumab + FBC is dominated and cetuximab + FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab + FBC had ∼100%, ∼100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively. CONCLUSION: For first-line treatment of KRAS-WT mCRC, bevacizumab + FBC is associated with substantially lower costs as compared to panitumumab + FBC or cetuximab + FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.

Resource utilization and cost of treatment with anidulafungin or fluconazole for candidaemia and other forms of invasive candidiasis: focus on critically ill patients.

BACKGROUND: Candidaemia and other forms of invasive candidiasis (C/IC) are serious and costly events for hospitalized patients, particularly those in the ICU. Both fluconazole and the echinocandins are recommended as first-line therapy for C/IC. Resource use and cost considerations are important in selecting appropriate treatment but little information is available on the economic implications of using echinocandins in this setting. OBJECTIVE: To compare resource utilization and treatment costs (in $US) associated with the echinocandin anidulafungin (200 mg intravenously on day 1, then 100 mg intravenously daily) versus those of fluconazole (800 mg intravenously on day 1, then 400 mg intravenously daily) as first-line treatment for C/IC. METHODS: Available charts from patients enrolled in a recent clinical trial comparing anidulafungin and fluconazole for C/IC were reviewed. Patients who were in the ICU at study entry were identified, and the following data, collected during the 13-week study period, were compared between treatment groups: global response at end of study treatment, number of days patients survived after hospital discharge ('hospital-free' days), hospital resource use, and C/IC-related costs (year 2008 values) to a US hospital payer. These comparisons were also conducted for all non-ICU hospitalized patients, and for survivors in both study populations. Sensitivity analyses explored the cost impact of variability in the hospitalization costs between ICUs and non-ICU wards and of reduced duration intravenous therapy. Statistical comparisons between the two treatment groups were conducted for clinical outcomes, resource use and cost measures, using regression models. All statistical comparisons were adjusted for baseline co-variates (Acute Physiology and Chronic Health Evaluation [APACHE] II score, absolute neutrophil count and catheter removal status). RESULTS: For ICU patients with C/IC (n = 63), global response was significantly higher for anidulafungin than fluconazole (68.6% vs 42.9%; p = 0.03). ICU patients treated with anidulafungin had an average of 13.9 more hospital-free days (18.2 vs 4.3 days; p = 0.04) than those treated with fluconazole. After adjustment for co-variates, although lower costs were observed for anidulafungin vs fluconazole in ICU patients and in ICU patients who survived, no statistical differences were found. For all hospitalized patients (n = 159), global response was also higher for anidulafungin (78.3% vs 60.5%; p < 0.01). There was no difference in average length of hospitalization (29.6 days) or hospital-free days. After adjustment for co-variates, anidulafungin treatment resulted in an incremental C/IC-related cost of $US2680 (p = 0.73). For hospitalized patients who survived (anidulafungin 81.9%, fluconazole 69.7%), anidulafungin treatment was associated with an incremental cost of $US231 (p = 0.98). CONCLUSION: Anidulafungin as first-line treatment of C/IC appears to be of particular benefit to ICU patients, improving clinical outcomes and possibly decreasing costs, driven by reduced ICU and hospital stay, when compared with fluconazole. Anidulafungin also yielded significantly improved treatment outcomes in the general inpatient population, with total costs similar to fluconazole.

BLISS index using WOMAC index detects between-group differences at low-intensity symptom states in osteoarthritis.

OBJECTIVES: The ability of the Bellamy et al. Low-Intensity Symptom State-attainment (BLISS) Index to differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis was explored using the stiffness, function, and total index (TI) components of the WOMAC. STUDY DESIGN AND SETTING: Six different BLISS measures were analyzed using five WOMAC score thresholds: