Table 2

Characteristics of full economic evaluation studies on preparedness and response measures of influenza outbreaks, expressed in Euros (base year 2017)

Study (publication year)	Setting, Year	Population (n)	Interventions	Comparator	Economic evaluation outcomes
Non-pharmaceutical studies
Lankelma et al (2019)23	Netherlands, 2017–2018	Patients with acute RTI at the emergency department (1546 tests, 624 cases)	Point-of-care-testing for Influenza before hospital admission	2016–2017 influenza season	Net savings €388 317 (after subtraction with costs) More than 80% of the total savings are due to the shorter length of stay and decreased hospital admissions. The overall cost of intervention: €98 968 Laboratory costs at €72 202 Clinical aspects costs at €26 767
Orset (2018)25	France, 2014	200 participants, data extrapolated	7-day home confinement	No intervention	Costs associated with home confinement (a) Direct costs For adults: €742/case For elderly: €1191/case (b) Indirect costs Productivity losses/case For adults: €550. For elderly: €125 Costs of death/case The cost of death for children is estimated at €22–128, for adults at €63–361 and for elderly at €2667–15 389 Loss of productivity due to influenza/case Productivity loss in case of adult sickness: €88.70 (incl. absent from work+reduced productivity) Productivity loss in case of a sick child for the adult (mainly mother): €97.62
Sadique et al (2008)24	UK, 2005	Working parents with depending children	School closure	No intervention	Cost of school closure: between €280 million—€2.8 billion/week Cost of absenteeism: €1.4 billion Adjusting for informal care, the cost reduced between €552–€635 million per week. Adjusting for the elasticity of production the cost reduced to €970 327 320—€1.1 billion per week
Tracht et al (2012)28	USA, 2009–2010 influenza season	Simulation of the USA (302 million people:73 million children, 191 million adults and 38 million seniors)	Population use of face masks (N95) on the spread of a pandemic	No intervention	Net savings If masks are worn by 10% of the adult population: €418.75 billion If masks are worn by 50% of the adult population: €501.9 billion Economic burden, if no intervention: €728.28 billion (incl. direct and indirect costs)
Combined pharmaceutical and non-pharmaceutical strategies
Saunders-Hastings et al (2017)26	Canada, n/a	A simulation of Ottawa, Canada (1.2 million)	Vaccination+antiviral treatment Vaccination+antiviral treatment+antiviral prophylaxis Community contact reduction+personal protective measures+isolation Community-contact reduction+personal protective measures+isolation+antiviral treatment School closure+community contact reduction+personal protective measures+quarantine All interventions	No intervention	Cost/LYG vs no intervention €1700/LYG €1769/LYG €4394/LYG €4447/LYG €171 590/LYG €131 679/LYG Total economic burden For all scenarios, the economic burden ranges between €75 758 to €1 416 351
Halder et al (2011)27	Australia, 2009	A community in Western Australia (30 000)	Different combinations of durations of individual school closure, antiviral treatment, household antiviral prophylaxis, extended antiviral prophylaxis, 50% workplace closure, 50% community contact reduction	No intervention	Cost/case averted: Antiviral drug strategies+2 weeks school closure: €396 per case averted (cost-effective) Short-duration school closure: €820/case averted ISC, continuously+50% workplace. continuously: €6 204/case averted In case of 2 weeks for the above combination: €1891/case averted ISC, continuously: €2180/case averted Total cost, per 100 000 population The dual strategy of individual school closure for 2 weeks (ISC) along with the 50% community contact reduction (CCR): €3.39 million The dual strategy of continuous ISC along with the continuous—50% WP: €61.3 million. Productivity loss due to illness and interventions per 100 000 population ISC (cont.)+WP (cont.): €90.21 million Combined antiviral treatment, household antiviral prophylaxis and extended antiviral prophylaxis: €4.63
Yarmand et al (2010)29	USA, 2009–2010 influenza season	North Carolina State University undergraduate students (23 087)	Vaccination	Self-isolation	High levels of interventions Self-isolation is incrementally more cost-effective than vaccination This has been presented for most of cost ratio values. Low levels of interventions Vaccination is incrementally more cost-effective than self-isolation The results were robust, even in sensitivity analyses.
Sander et al (2009)30	USA, n/a	Residents of a 1.632-million-person city	HTAP25 with a stockpile for 25% of the population HTAP50 with a stockpile for 50% of the population HTAP with an unlimited stockpile School closure for 26 weeks Prevaccination 70% of the population with a low efficacy vaccine HTAP25+school closure HTAP50+school closure HTAP+school closure Prevaccination+school closure: prevaccinating 70% population with the low-efficacy vaccine, plus closing all schools for 26 weeks Treatment only: Treating all cases with antivirals FTAP25 for household contacts and 60% of work/school contacts, stockpile for 25% of the population FTAP50 for household contacts and 60% of work/school contacts, stockpile for 50% of population FTAP for household contacts and 60% of work/school contacts, stockpile unlimited FTAP25+school closure FTAP50+school closure FTAP+school closure	No intervention	Cost/capita and cost-effectiveness outcomes FTAP is cost-effective (54% reduction attack rate, €119 per capita) Prevaccination (48% reduction attack rate, €131 per capita) School closure in combination with each of the above is the least cost-effective (€2 524 per capita) ICUR of FTAP: €42 959 ICUR of prevaccination and school closure: €43 106 Cost-saving FTAP and prepandemic vaccination are cost-saving compared with no intervention
Pharmaceutical only strategies
Khazeni et al (2009)31	USA, n/a	A US metropolitan city (8.3 million)	Stockpiled strategy Expanded adjuvanted vaccination Expanded antiviral prophylaxis	No intervention	Intervention and treatment costs Stockpiled strategy: Total cost of €30.1 million and contribution to €288 million treatment costs Expanded adjuvanted vaccination: Total cost of €179 million and contribution to €166 million treatment costs Expanded antiviral prophylaxis: Total cost of €58.4 million and contribution to €266 million treatment costs No intervention: contribution to €462 million treatment costs Cost/QALY gained Stockpiled strategy compared with no intervention: €7894/QALY Expanded adjuvanted vaccination (at 80% effectiveness) relative to stockpiled strategy: €8600/QALY Expanded antiviral prophylaxis has a less favourable cost-effectiveness ratio than adjuvanted vaccination Expanded adjuvanted vaccination shown to be a cost-effective intervention because it contributes to 404 030 QALYs at $10 844 per QALY gained relative to stockpiled strategy.
Balicer et al (2005)32	Israel, n/a	Population of Israel (1 618 200 cases/patients)	Stockpiling with antiviral drugs Therapeutic use (all patients) Therapeutic use (high-risk patients) Pre-exposure long-term prophylaxis (all population) Pre-exposure long-term prophylaxis (high-risk population) Short-term postexposure prophylaxis for all close contacts	No intervention	CBA Therapeutic use (incl. all and high-risk patients): 2.44–3.68 Pre-exposure (incl. entire and high-risk population): 0.37–0.38 Postexposure: 2.49 Stockpiling with antiviral drugs for high-risk patients remain cost-saving strategy even if the annual probability of a pandemic remains >1 every 80 years. Overall cost The overall health-related costs: €56 234 057 The overall cost to the economy: €535 245 986 Workdays lost due to illness 6 536 240 or 4 days/patient
Medema et al (2004)33	n/a,	Developed countries (1 billion people)	Egg-based vaccines with 17% population coverage Cell culture-based vaccines with 37% population coverage	No intervention	Cost per life-year gained In general, vaccination is cost-effective. Cell culture-based vaccines: €3376/LYG (cost-effective) Cost per intervention Egg-based: €2.6 billion Cell culture-based: €5.87 billion Net savings Egg-based: €8.5 billion Cell culture-based: €5.87 billion Savings: €1.84 billion

CBA, cost-benefit ratio; CCR, community contact reduction; FTAP, full targeted antiviral prophylaxis; HTAP, household targeted antiviral prophylaxis; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; ISC, individual school closure; LYG, life-year gained; QALY, quality-adjusted life year; VSL, value of statistical life; WP, workplace closure.