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Article ; Online: Authors' Reply to Comment on "Cost-Effectiveness Analysis of Herpes Zoster Vaccination in 50- to 85-Year-Old Immunocompetent Belgian Cohorts: A Comparison Between No Vaccination, the Adjuvanted Subunit Vaccine, and Live-Attenuated Vaccine".

Bilcke, Joke / Beutels, Philippe

2022 Volume 40, Issue 10, Page(s) 1013–1014

MeSH term(s)	Aged ; Aged, 80 and over ; Belgium ; Cost-Benefit Analysis ; Herpes Zoster/prevention & control ; Herpes Zoster Vaccine ; Humans ; Middle Aged ; Vaccines, Attenuated ; Vaccines, Subunit
Chemical Substances	Herpes Zoster Vaccine ; Vaccines, Attenuated ; Vaccines, Subunit
Language	English
Publishing date	2022-09-26
Publishing country	New Zealand
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1100273-6
ISSN	1179-2027 ; 1170-7690
ISSN (online)	1179-2027
ISSN	1170-7690
DOI	10.1007/s40273-022-01186-y
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Article ; Online: Pricey or priceless: cost-effectiveness of respiratory syncytial virus (RSV) prevention in infants.

Li, Xiao / Bilcke, Joke / Beutels, Philippe

Lancet regional health. Americas

2023 Volume 29, Page(s) 100657

Language	English
Publishing date	2023-12-22
Publishing country	England
Document type	Journal Article
ISSN	2667-193X
ISSN (online)	2667-193X
DOI	10.1016/j.lana.2023.100657
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Article ; Online: Generating, Presenting, and Interpreting Cost-Effectiveness Results in the Context of Uncertainty: A Tutorial for Deeper Knowledge and Better Practice.

Bilcke, Joke / Beutels, Philippe

Medical decision making : an international journal of the Society for Medical Decision Making

2021 Volume 42, Issue 4, Page(s) 421–435

Abstract: This tutorial aims to help make the best available methods for generating and presenting cost-effectiveness results with uncertainty common practice. We believe there is a need for such type of tutorial because some erroneous practices persist (e.g., ... ...

Abstract	This tutorial aims to help make the best available methods for generating and presenting cost-effectiveness results with uncertainty common practice. We believe there is a need for such type of tutorial because some erroneous practices persist (e.g., identifying the cost-effective intervention as the one with the highest probability to be cost-effective), while some of the more advanced methods are hardly used (e.g., the net loss statistic 'NL', expected net loss curves and frontier). The tutorial explains with simple examples the pros and cons of using ICER, incremental net benefit and NL to identify the cost-effective intervention, both with and without uncertainty accounted for probabilistically. A flowchart provides practical guidance on when and how to use ICER, incremental net benefit or NL. Different ways to express and present uncertainty in the results are described, including confidence and credible intervals, the probability that a strategy is cost-effective (as usually shown with cost-effectiveness acceptability curves (CEACs)) and the expected value of perfect information (EVPI). The tutorial clarifies and illustrates why EVPI is the only measure accounting fully for decision uncertainty, and why NL curves and the NL frontier may be preferred over CEACs and other plots for presenting cost-effectiveness results in the context of uncertainty. The easy calculations and a worked-out real-life example will help users to thoroughly understand and correctly interpret key cost-effectiveness results. Examples with mathematical calculations, interpretation, plots and R code are provided.
MeSH term(s)	Cost-Benefit Analysis ; Humans ; Probability ; Uncertainty
Language	English
Publishing date	2021-10-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604497-9
ISSN	1552-681X ; 0272-989X
ISSN (online)	1552-681X
ISSN	0272-989X
DOI	10.1177/0272989X211045070
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Zs.A 1665: Show issues

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Article ; Online: Cost-Effectiveness Analysis of Herpes Zoster Vaccination in 50- to 85-Year-Old Immunocompetent Belgian Cohorts: A Comparison between No Vaccination, the Adjuvanted Subunit Vaccine, and Live-Attenuated Vaccine.

Pieters, Zoë / Ogunjimi, Benson / Beutels, Philippe / Bilcke, Joke

PharmacoEconomics

2022 Volume 40, Issue 4, Page(s) 461–476

Abstract: Background: A new adjuvanted subunit vaccine (HZ/su), with higher vaccine efficacy than live-attenuated vaccine (ZVL), has been licensed in Europe since March 2018. Therefore, Belgian decision-makers might need to re-assess their recommendations for ... ...

Abstract	Background: A new adjuvanted subunit vaccine (HZ/su), with higher vaccine efficacy than live-attenuated vaccine (ZVL), has been licensed in Europe since March 2018. Therefore, Belgian decision-makers might need to re-assess their recommendations for vaccination against herpes zoster (HZ). Methods: We conducted a cost-effectiveness analysis, using a Markov decision tree, of vaccinating 50- to 85-year-old immunocompetent Belgian cohorts with no vaccination, HZ/su, ZVL, and ZVL with booster after 10 years. Due to the uncertainty in vaccine waning of HZ/su vaccine beyond 4 years, we used a logarithmic and 1-minus-exponential function to model respectively a long and short duration of protection. We used a lifetime time horizon and implemented the health care payer perspective throughout the analysis. Results: HZ/su had the greatest impact in avoiding health and economic burden. However, it would never become cost-effective at a willingness-to-pay threshold of €40,000 per quality-adjusted life year (QALY) gained at its market price set by the manufacturer in the USA. Depending on the waning function assumed for HZ/su, the price per dose needs to drop 60% or 83% such that vaccination with HZ/su, assuming respectively a long or short duration of protection, would become cost-effective in 50- and 80-year-old individuals. At €40,000 per QALY gained, ZVL or ZVL with booster was never found cost-effective compared with HZ/su, even if only administration cost was considered. Conclusion: HZ/su is cost-effective in the 50-year-old age cohort at the unofficial Belgian threshold of €40,000 per QALY gained, if its price drops to €55.40 per dose. This result is, however, very sensitive to the assumed duration of protection of the vaccine, and the assumed severity and QALY loss associated with HZ and post-herpetic neuralgia (PHN).
MeSH term(s)	Adjuvants, Immunologic ; Aged ; Aged, 80 and over ; Belgium ; Cost-Benefit Analysis ; Herpes Zoster/prevention & control ; Herpes Zoster Vaccine ; Herpesvirus 3, Human ; Humans ; Middle Aged ; Neuralgia, Postherpetic/prevention & control ; Vaccination ; Vaccines, Attenuated ; Vaccines, Subunit
Chemical Substances	Adjuvants, Immunologic ; Herpes Zoster Vaccine ; Vaccines, Attenuated ; Vaccines, Subunit
Language	English
Publishing date	2022-01-30
Publishing country	New Zealand
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1100273-6
ISSN	1179-2027 ; 1170-7690
ISSN (online)	1179-2027
ISSN	1170-7690
DOI	10.1007/s40273-021-01099-2
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Article ; Online: The age profile of respiratory syncytial virus burden in preschool children of low- and middle-income countries: A semi-parametric, meta-regression approach.

Antillón, Marina / Li, Xiao / Willem, Lander / Bilcke, Joke / Jit, Mark / Beutels, Philippe

PLoS medicine

2023 Volume 20, Issue 7, Page(s) e1004250

Abstract: Background: Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of ... ...

Abstract	Background: Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. Methods and findings: We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. Conclusions: We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children.
MeSH term(s)	Humans ; Child, Preschool ; Infant ; Respiratory Syncytial Viruses ; Developing Countries ; Hospital Mortality ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus Infections/prevention & control ; Hospitalization ; Respiratory Syncytial Virus, Human ; Respiratory Tract Infections/epidemiology
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1004250
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Article ; Online: Strategies for typhoid conjugate vaccines in endemic nations - Authors' reply.

Pitzer, Virginia E / Pollard, Andrew J / Bilcke, Joke

The Lancet. Infectious diseases

2021 Volume 21, Issue 3, Page(s) 321–322

MeSH term(s)	Cost-Benefit Analysis ; Humans ; Salmonella typhi/immunology ; Typhoid Fever/epidemiology ; Typhoid Fever/prevention & control ; Typhoid-Paratyphoid Vaccines ; Vaccines, Conjugate
Chemical Substances	Typhoid-Paratyphoid Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00018-9
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Zs.A 5743: Show issues

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Article ; Online: Sponsorship Bias in Base-Case Values and Uncertainty Bounds of Health Economic Evaluations? A Systematic Review of Herpes Zoster Vaccination.

Bilcke, Joke / Verelst, Frederik / Beutels, Philippe

Medical decision making : an international journal of the Society for Medical Decision Making

2018 Volume 38, Issue 6, Page(s) 730–745

MeSH term(s)	Aged ; Aged, 80 and over ; Conflict of Interest ; Cost-Benefit Analysis/methods ; Costs and Cost Analysis ; Drug Industry/methods ; Economics, Pharmaceutical ; Herpes Zoster Vaccine/administration & dosage ; Herpes Zoster Vaccine/economics ; Humans ; Neuralgia, Postherpetic/economics ; Neuralgia, Postherpetic/prevention & control ; Quality-Adjusted Life Years ; Uncertainty
Chemical Substances	Herpes Zoster Vaccine
Language	English
Publishing date	2018-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	604497-9
ISSN	1552-681X ; 0272-989X
ISSN (online)	1552-681X
ISSN	0272-989X
DOI	10.1177/0272989X18776636
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Zs.A 1665: Show issues

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Article ; Online: Cost-effectiveness of Respiratory Syncytial Virus Disease Prevention Strategies: Maternal Vaccine Versus Seasonal or Year-Round Monoclonal Antibody Program in Norwegian Children.

Li, Xiao / Bilcke, Joke / Vázquez Fernández, Liliana / Bont, Louis / Willem, Lander / Wisløff, Torbjørn / Jit, Mark / Beutels, Philippe

The Journal of infectious diseases

2022 Volume 226, Issue Suppl 1, Page(s) S95–S101

Abstract: Background: Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention ... ...

Abstract	Background: Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs. Methods: Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease. Results: We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb. Conclusions: Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/therapeutic use ; Child ; Child, Preschool ; Communicable Diseases/drug therapy ; Cost-Benefit Analysis ; Humans ; Infant ; Infant, Newborn ; Palivizumab/therapeutic use ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Viruses ; Seasons ; Vaccines/therapeutic use
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antiviral Agents ; Vaccines ; Palivizumab (DQ448MW7KS)
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac064
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Zs.MO 445: Show issues

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Article ; Online: Economic Burden and Health-Related Quality of Life of Respiratory Syncytial Virus and Influenza Infection in European Community-Dwelling Older Adults.

Mao, Zhuxin / Li, Xiao / Korsten, Koos / Bont, Louis / Butler, Christopher / Wildenbeest, Joanne / Coenen, Samuel / Hens, Niel / Bilcke, Joke / Beutels, Philippe

The Journal of infectious diseases

2022 Volume 226, Issue Suppl 1, Page(s) S87–S94

Abstract: Background: Respiratory syncytial virus (RSV) and influenza virus infections result in a considerable mortality and morbidity among the aging population globally. Influenza vaccination for older adults before the seasonal influenza epidemic has been ... ...

Abstract	Background: Respiratory syncytial virus (RSV) and influenza virus infections result in a considerable mortality and morbidity among the aging population globally. Influenza vaccination for older adults before the seasonal influenza epidemic has been evaluated to be cost-effective in many countries. Interventions against RSV in older adults are in the pipeline, and evaluating their cost-effectiveness is crucial for decision making. To inform such evaluations, our aim was to estimate average costs and health-related quality of life (HRQoL) in older adults with RSV and influenza infection. Methods: The European RESCEU observational cohort study followed 1040 relatively healthy community-dwelling older adults aged 60 years and older during 2 consecutive winter seasons. Health care resource use and HRQoL were collected and analyzed during RSV episodes, and also during influenza episodes. Country-specific unit cost data were mainly obtained from national databases. Direct costs were estimated from a patient, health care provider, and health care payers' perspective, whereas indirect costs were estimated from a societal perspective. Due to small sample size, no formal statistical comparisons were made. Results: Thirty-six RSV and 60 influenza episodes were reported, including 1 hospitalization. Means (median; first-third quartile) of €26.4 (€5.5; 0-47.3) direct and €4.4 (€0; 0-0) indirect costs were reported per nonhospitalized RSV episode, and €42.5 (€36; 3.3-66.7) direct and €32.1 (€0; 0-0) indirect costs per nonhospitalized influenza episode. For RSV episodes, the utility value decreased from 0.896 (0.928; 0.854-0.953) to 0.801 (0.854; 0.712-0.937) from preseason to 1 week after symptom onset; for influenza, the change was from 0.872 (0.895; 0.828-0.953) to 0.664 (0.686; 0.574-0.797). Conclusions: The average costs and HRQoL estimates of older adults treated outside the hospital can be used to inform the design of future studies and the decision making regarding interventions to prevent RSV infection in older adults. Larger studies are needed to provide better country-specific and complementary cost estimates and to allow for formal statistical comparison of costs between RSV and influenza. Clinical trials registration: NCT03621930.
MeSH term(s)	Aged ; Financial Stress ; Hospitalization ; Humans ; Independent Living ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Middle Aged ; Quality of Life ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Virus, Human
Language	English
Publishing date	2022-08-12
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac069
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Article ; Online: Health and economic burden of respiratory syncytial virus (RSV) disease and the cost-effectiveness of potential interventions against RSV among children under 5 years in 72 Gavi-eligible countries.

Li, Xiao / Willem, Lander / Antillon, Marina / Bilcke, Joke / Jit, Mark / Beutels, Philippe

BMC medicine

2020 Volume 18, Issue 1, Page(s) 82

Abstract: Background: Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, ... ...

Abstract	Background: Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, including vaccines and monoclonal antibody (mAb) candidates, are under development, we aim to evaluate the key drivers of the cost-effectiveness of maternal vaccination and infant mAb for 72 Gavi countries. Methods: A static Multi-Country Model Application for RSV Cost-Effectiveness poLicy (MCMARCEL) was developed to follow RSV-related events monthly from birth until 5 years of age. MCMARCEL was parameterised using country- and age-specific demographic, epidemiological, and cost data. The interventions' level and duration of effectiveness were guided by the World Health Organization's preferred product characteristics and other literature. Maternal vaccination and mAb were assumed to require single-dose administration at prices assumed to align with other Gavi-subsidised technologies. The effectiveness and the prices of the interventions were simultaneously varied in extensive scenario analyses. Disability-adjusted life years (DALYs) were the primary health outcomes for cost-effectiveness, integrated with probabilistic sensitivity analyses and Expected Value of Partially Perfect Information analysis. Results: The RSV-associated disease burden among children in these 72 countries is estimated at an average of 20.8 million cases, 1.8 million hospital admissions, 40 thousand deaths, 1.2 million discounted DALYs, and US$611 million discounted direct costs. Strategy 'mAb' is more effective due to its assumed longer duration of protection versus maternal vaccination, but it was also assumed to be more expensive. Given all parameterised uncertainty, the optimal strategy of choice tends to change for increasing willingness to pay (WTP) values per DALY averted from the current situation to maternal vaccination (at WTP > US$1000) to mAB (at WTP > US$3500). The age-specific proportions of cases that are hospitalised and/or die cause most of the uncertainty in the choice of optimal strategy. Results are broadly similar across countries. Conclusions: Both the maternal and mAb strategies need to be competitively priced to be judged as relatively cost-effective. Information on the level and duration of protection is crucial, but also more and better disease burden evidence-especially on RSV-attributable hospitalisation and death rates-is needed to support policy choices when novel RSV products become available.
MeSH term(s)	Child, Preschool ; Cost of Illness ; Cost-Benefit Analysis/methods ; Humans ; Infant ; Respiratory Syncytial Virus Infections/economics ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Viruses/pathogenicity
Language	English
Publishing date	2020-04-06
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ISSN	1741-7015
ISSN (online)	1741-7015
DOI	10.1186/s12916-020-01537-6
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