Economic burden of varicella in children 1–12 Years of age in Hungary, 2011–2015

This was a multicenter, observational study that evaluated the burden of illness associated with varicella through the use of a retrospective chart review design and was conducted in accordance with the generally accepted standards of Good Pharmacoepidemiology Practice (GPP). In line with the local regulations, the study was approved by the Hungarian Ministry of Health (MOH) and no review by Independent Ethics Committees (IECs) was required. Patient consent was also not required, as data were retrospectively collected in an anonymous manner by treating physicians and identified only by an encrypted patient number.

Based on the recommendations of the Hungarian primary care pediatricians’ society and the board of the society of infectious diseases, 15 potential physician sites were selected to participate in the study. Those that expressed preliminary interest (n = 8) were surveyed to estimate the number of patients potentially eligible for the study within the five years prior to study initiation and, eventually, 6 sites (5 public hospitals - Miskolci Semmelweis Hospital and University Teaching Hospital [MISEK], Markusovszky University Hospital, Pándy Kálmán Hospital, Szent György University Teaching Hospital, St. László Hospital for Infectious Diseases - and 1 private practice of a general practitioner) agreed to participate in the study and contributed patient charts. Of these, 5 were in urban areas [Budapest (n = 2), Miskolc, Székesfehérvár, Szombathely] and 1 was in a rural area (Gyula). For case selection, investigators were instructed to screen patient charts in their practices for eligibility for the study starting from the most recent year and going back as much as five years. The date of first primary varicella infection was defined as the index date, and each patient’s chart was reviewed from this date until the resolution of the disease occurred or the last date of contact, if the resolution date was unavailable. This observational study aimed to include the charts of 150 patients as a sample of convenience, equally divided between outpatient and inpatient settings.

Patients 1–12 years of age with a primary varicella diagnosis between 2011 and 2015, in roughly equal numbers of outpatients and inpatients, were targeted for inclusion. The outpatient group included patients who visited either the doctor’s office (family doctor, general practitioner, pediatrician, and infectious disease specialist), outpatient clinic/department of hospital, or emergency department (ER) without hospitalization for varicella, and inpatients were defined as those admitted to a hospital for their primary varicella. Patients who had received prior varicella vaccination and who had a diagnosis of breakthrough varicella, or a second case of varicella, were excluded from the study.

The varicella-related clinical complications that were evaluated in this study included, but were not limited to, skin and soft tissue infection, meningitis, encephalitis, pneumonia, sepsis, acute osteomyelitis, septic arthritis, cerebellitis, keratoconjunctivitis, hepatitis, nephritis, febrile seizure, dehydration, severe pain, and coagulation disorder. The distribution of these complications was assessed descriptively by calculating the number and proportion of patients with at least one complication. Any other complications aside from those listed above were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 18.0, and were reported by preferred term. HCRU was assessed using the number and proportion of patients using each resource, the frequency of use, and the duration of healthcare resource use for varicella and varicella-related complications. The healthcare resources that were evaluated involved outpatient visits, allied healthcare contacts, doctor’s visits, tests/procedures performed, prescription medications prescribed, over-the-counter (OTC) medications, hospitalizations, ER visits/stays, and intensive care unit (ICU) stays. The direct cost of HCRU was determined by multiplying the amount of resources used per patient by the unit cost of each resource, as assessed by local expert opinion (Table 1). The indirect costs were calculated as the loss of revenue of caregivers who cared for varicella infected children, using the national average income statistics reported by the Organization for Economic Co-Operation (OECD) [26] and the number of work days missed by the caregiver. The number of work days that were missed was estimated as the total days spent in the hospital/ICU for inpatients during this study and 2.5 days for outpatients, as estimated in previous studies [27, 28]. All costs are presented in 2015 HUF / Euros (€) [29].

All enrolled patients were included in the statistical analysis, and subgroup analysis was performed for outpatients and inpatients. Descriptive statistics were produced to address all study objectives, which included measures of central tendency (mean) and dispersion statistics (SD and 95% CI) for continuous variables, and frequency distributions (number and percentage) for categorical variables. Due to the low number of cases in some outcome measures, logarithmic transformation was used for the calculation of 95% CIs. All statistical analyses were performed using SAS® software version 9.4 (SAS Institute Inc., Cary, NC, USA).