This was a non-interventional, cross-sectional survey study conducted among parents or legal guardians of children aged 17 years or younger diagnosed with varicella in the previous six weeks and residing in France. Respondents were excluded if their child was vaccinated against varicella since the focus of this study was to evaluate the economic burden of varicella in unvaccinated children. Varicella in vaccinated children is rarer, milder, and shorter in duration than varicella in an unvaccinated child [1, 3, 6, 11]. The survey collected data on the sociodemographic characteristics of parents/guardians and their children, the healthcare resource utilization (HCRU), and costs associated with varicella, including doctor and emergency room (ER) visits, hospitalizations, medications, and out-of-pocket expenses incurred by the family. Information was also collected on schooldays missed by the sick child, workdays lost by the parents or other caregivers to care for the sick child, and the impact on caregiving arrangements. Respondents who had multiple sick children with varicella were asked to consider only the youngest eligible child in their responses.

The family perspective included only the direct out-of-pocket expenses incurred by the family; that is, direct out-of-pocket medical expenses (such as co-payments made by the family for a doctor’s visit or medications, and not reimbursed by social security or private insurance) and direct non-medical costs (such as payments made by the family for transportation, paid caregivers, or isolation of high-risk family members). The societal perspective included the direct medical and non-medical costs incurred by the family, the French social security system, or private insurance, and the indirect costs due to productivity losses [16, 17].

The survey was developed after conducting a targeted literature review of instruments available to assess caregiver burden associated with varicella or other pediatric infectious diseases, along with inputs from a pediatric infectious disease expert in France. It was translated into French, verified by a native French speaker, and validated through cognitive pre-testing (See Supplementary Information 1). The study was approved by the Commission Nationale de l'Informatique et des Libertes (CNIL) and the ethics committee, Comités de Protection des Personnes Ouest IV – Nantes, France.

Participants were recruited by a third-party recruitment agency, Global Perspectives, through a multifaceted approach, including referrals of potentially eligible parents from family physicians, pediatricians, and pharmacists from across France; social media/digital outreach; advertisement through daycare, schools, and other locations; and a general population panel. Quotas were used to ensure that the study sample reflected the age distribution of varicella cases in France and the regional distribution of the French population, with restrictions put to avoid over-representation of certain groups; e.g. limiting children below one year of age (≤ 10%), 13 years or older (≤ 20%), and children requiring hospitalization (≤ 10%) [3, 18]. The final web-based survey was fielded from April 2022 to July 2022, after the end of COVID-19 lockdowns and school closures in France, to capture the burden of varicella accurately [19, 20]. After screening, eligible participants were informed about the study procedure, including the risks/benefits, and completed an electronic informed consent form before survey participation. Participants were paid an honorarium for their time. All data were anonymized. A copy of the survey in English is included in the supplementary information 2.

Descriptive statistics were used to analyze the demographic characteristics of parents and children, HCRU, and missed work or school days. Analyses were performed using SAS software version 9.4 (SAS Institute, Cary, NC); p-values < 0.05 were considered statistically significant. Data were summarized overall and by age strata (< 3 years, 3 to < 6 years, 6 to < 10 years, and ≥ 10 years), using means, standard deviations (SD), medians, and interquartile ranges [IQR] for continuous variables and counts and percentages for categorical ones. Mann Whitney, analysis of variance (ANOVA), and chi-square tests were conducted as appropriate. Using unit cost data from the literature (see supplementary information 1) and HCRU and productivity loss data from the study, a micro-costing approach was employed to calculate direct and indirect costs for varicella for each child [21, 22]. All costs were reported in 2022 Euros. Given that the response to questions 1 through 36 was obligatory, and surveys that were not completed in their entirety were omitted from the principal set for analysis, there was no need for imputation of any missing data.

For the direct cost calculations, we assumed that the family paid out-of-pocket for all direct medical costs not covered by the French social security system and insurance [23]. Since the exact burden to the family varies depending on the type of HCRU, income, and type of private insurance, we assumed, for the primary analysis, that the French social security system bore 70%, 80%, and 65% of the total costs associated with medical visits, hospitalizations, and medications respectively, to avoid double counting [17, 24,25,26]. These costs (calculated for each child using HCRU data reported in the survey and unit costs from the French health department) were added to the various out-of-pocket direct costs reported by the family to provide the mean total direct cost [24,25,26,27]. We also conducted a scenario analysis where we assumed that the family had no direct medical expenses and that the French social security system or private insurance bore 100% of the total costs associated with medical visits, hospitalizations, and medications. These were added to the out-of-pocket expenses reported by the family to provide the mean direct medical cost for the scenario analysis.

Productivity losses were calculated using a human capital approach [28]. Indirect costs were calculated by multiplying the missed workdays by parents and unpaid caregivers (e.g., grandparents or other family members and friends, but not paid caregivers) with an average daily wage of €182.3/day, derived by dividing the annual wage in France by 220 working days [29]. The societal cost was obtained by summing the direct and indirect costs. The mean societal cost per child with varicella from our study was multiplied by the annual number of pediatric varicella cases in France (525,184 cases in 2019) reported to the French health sentinel surveillance system to estimate the annual societal burden [5].