Burden of Respiratory Syncytial Virus (RSV) in Children in Sweden (BRICS): A Retrospective Study in Sweden

Study Overview
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Brief Summary
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Primary Objective: -Estimate the hospital-associated healthcare resource use (HCRU), and associated costs, of RSV infection in children in comparison to the non-RSV control cohort (general population) and patients with rhinovirus infection. Secondary Objectives: Describe demographic and clinical patient characteristics of RSV infected children. Estimate and compare the incidence of RSV infection and acute respiratory infections (ARIs) in children. Estimate the mortality associated with RSV infection in children. Estimate the social economic burden of RSV infection in children in relation to parents staying home from work to care for their sick child (VAB leave) in comparison to non-RSV control cohort (i.e. parents to children in the general population). Estimate the net days with VAB leave and the compensation disbursed (temporary parental benefit) associated with RSV infection in children. Estimate the indirect costs that can be attributed to VAB leave. Examine the medium- and long-term complications associated with an RSV diagnosis in children in comparison to the non-RSV control chart (general population) and patients with rhinovirus infection. Examine and describe risk factors associated with an RSV infection in children Estimate the healthcare resource use (HCRU), and associated costs, of RSV infection in children, for a subset of patients where primary care data is available, in comparison to the non-RSV control cohort (general population).

Detailed Description
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The overall study period will be between July 1st 2001 and to latest available date (likely June 30th 2022). Patients will be identified for inclusion in the study population between July 1st 2006 and June 30th 2021. Patients will be followed from time of inclusion until end of the study period or until death. All patients will have an index date corresponding to the date of diagnosis of incident infection in primary and/or hospital care during the identification period. An incident infection is defined as the occurrence of infections more than 30 (>30) days apart. This implies that a patient can have more than one index date during the study period. Patients that are included in both the RSV cohort and the regional primary care RSV cohort may have two different index dates for the same incident infection, depending on the objective. This is if a patient is first treated in primary care and then hospitalized. The index date is defined differently for the two cohorts, as the first diagnosis in hospital care for the RSV cohort and first diagnosis in primary care OR hospital care for the regional primary care cohort. The non-RSV controls will have the same index date as their matched RSV patient. The look-back period will be used to inform baseline characteristics as well as patients' medical and diagnosis history. All patients will have possible look-back from birth for information on the patient's hospital care history and from 2005 for information on the patient's prescribed drugs history. The individual look-back and follow-up will depend on the time of inclusion in the study population as well as age at inclusion.

Official Title
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Burden of Respiratory Syncytial Virus (RSV) in Children in Sweden (BRICS): A Retrospective Study in Sweden

Conditions
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Respiratory Syncytial Virus (RSV)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Children (≤5 years of age) with an RSV infection or any acute respiratory infection (ARI) between July 1st 2001 and latest available date, identified in either hospital care, regional primary care or laboratory database. Exclusion Criteria: •There are no exclusion criteria for this study.

Ages Eligible for Study
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Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RSV cohort<br>Children (<5 years of age at diagnosis) with a diagnosis of RSV (ICD-10 code) in hospital care between July 1st 2006 and June 30th 2021 | |
| Regional primary care RSV cohort<br>Children (<5 year of age) with a diagnosis of RSV (ICD-10 code) in primary care identified in regional databases (Region Skåne, Region Halland and VGR) between July 1st 2006 and June 30th 2021 | |
| Regional laboratory RSV cohort<br>Children (<5 years of age) with a positive laboratory RSV test result (multiplex/rapid PCR, antigen, immunofluorescence or immunochromatography rapid test) in primary or hospital care, identified in regional laboratory databases (Region Skåne and Region Halland) between July 1st 2006 and June 30th 2021 | |
| Acute Respiratory Infections (ARI) cohort<br>Children (<5 of age) with a diagnosis of ARI (ICD-10 code,) in hospital care between July 1st 2006 and June 30th 2021 | |
| Regional ARI cohort<br>Children (<5 years of age) with a diagnosis of RSV (ICD-10 code, see Table 1) in primary care, identified in regional databases (Region Skåne, Region Halland and VGR) | |
| Rhinovirus cohort<br>Children (<5 of age) with a diagnosis of rhinovirus (ICD-10 code,) in hospital care between July 1st 2006 and June 30th 2021 | |
| Human Metapneumovirus (HMPV) cohort<br>Children (<5 of age) with a diagnosis of HMPV (ICD-10 code,) in hospital care between July 1st 2006 and June 30th 2021 | |
| Parainfluenza cohort<br>Children (<5 of age) with a diagnosis of parainfluenza (ICD-10 code,) in hospital care between July 1st 2006 and June 30th 2021 | |
| Parent cohort<br>Parents to all children will be linked to the study population, which is possible through linkage between children and parents by their personal identifiers | |
| Non-RSV control cohort<br>A non-RSV control population consisting of children (<5 years of age) will be extracted to estimate the burden compared to the general population | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term healthcare: Number of specialist outpatient visits | Number of RSV specialist outpatient hospital visits during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Number of hospitalizations | Number of hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Length of hospitalizations | The length of hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Number of Intensive Care Unit (ICU) hospitalizations | Number of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Length of ICU hospitalizations | The length of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Number of RSV-related medical/surgical procedures | Number of RSV-related medical/surgical procedures during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: Number of dispensed prescriptions of RSV-related medications | Number of dispensed prescriptions of RSV-related medications during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: The costs of direct medical (in- and outpatient care) | Direct medical (in- and outpatient care) costs related to RSV infection | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Short-term healthcare: The costs of RSV-related medications | The costs of dispensed prescriptions of RSV-related medications based on pharmacy retail price | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Medium-term healthcare: Number of specialist outpatient visits | Number of RSV specialist outpatient hospital visits during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Number of hospitalizations | Number of hospitalizations/stays related to RSV during follow up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Length of hospitalizations | The length of hospitalizations/stays related to RSV during follow up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Number of Intensive Care Unit (ICU) hospitalizations | Number of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Length of ICU hospitalizations | The length of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Number of RSV-related medical/surgical procedures | Number of RSV-related medical/surgical procedures during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: Number of dispensed prescriptions of RSV-related medications | Number of dispensed prescriptions of RSV-related medications during follow-up | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: The costs of direct medical (in- and outpatient care) | Direct medical (in- and outpatient care) costs related to RSV infection | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Medium-term healthcare: The costs of RSV-related medications | The costs of dispensed prescriptions of RSV-related medications based on pharmacy retail price | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient characteristics | Age at diagnosis, sex distribution, region of residence, birth weight, birth height, gestational age, mothers age at birth, high-risk conditions, parent's education, parent's income, household status | Analysis period: July 1st 2006 - June 30th 2021 Reporting period: at index date or during look-back period | 
| Incidence of RSV/ARIs | Incidence of RSV/ARI per 100,000 population | Analysis period: July 1st 2006 - June 30th 2021 Reporting period: by respiratory years | 
| Number of laboratory-confirmed RSV cases with RSV diagnosis | Number of laboratory confirmed RSV cases with RSV diagnosis code (ICD-10) | Analysis period: July 1st 2006 - June 30th 2021 Reporting period: at index date or during look-back period | 
| Number of laboratory-confirmed RSV cases with no RSV diagnosis | Number of laboratory confirmed RSV cases with no RSV diagnosis code (ICD-10) | Analysis period: July 1st 2006 - June 30th 2021Reporting period: at index date or during look-back period | 
| Number of diagnosed RSV cases with no RSV laboratory tests conducted | Number of diagnosed RSV cases (ICD-10) with no laboratory test conducted | Analysis period: July 1st 2006 - June 30th 2021 Reporting period: at index date or during look-back period | 
| Mortality | All-cause 30-day death from index date | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 30 days from index date | 
| Socioeconomic burden: Net days of VAB leave | Net days of temporary parental leave (VAB) during follow-up period due to child with RSV diagnosis | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Socioeconomic burden: Net VAB leave benefit | Net temporary parental leave (VAB) benefit during follow-up period due to child with RSV diagnosis | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Socioeconomic burden: Indirect costs of VAB leave due to RSV | Productivity loss due to RSV-related temporary parental leave during follow-up period, calculated by human capital method and average wage | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: 12 months from (first) index date | 
| Proportion of patients that develop respiratory complications (ICD-10 codes) | Proportion of patients that develop respiratory complications (ICD-10 codes) | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: per year during 5 years from index date | 
| Incidence of RSV per 1000 person-years | Incidence of RSV per 1000 person-years in RSV, non-RSV control cohorts and rhinovirus cohorts | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: per year during 5 years from index date | 
| Incidence rate ratios (IRR) | Incidence rate ratios (IRR) in RSV, non-RSV control and rhinovirus cohorts | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: per year during 5 years from index date | 
| Hazard ratios (HR) | Hazard ratios (HR) in RSV, non-RSV control and rhinovirus cohorts | Analysis period: July 1st 2006 - July 31st 2021 Reporting period: per year during 5 years from index date | 
| Estimation of hazard ratio of each risk factor on being diagnosed with RSV | A Cox proportional hazards regression model will be used to estimate the hazard ratio of each risk factor on being diagnosed with RSV. Predictors for RSV diagnosis presented as hazard ratios, including premature birth, high-risk conditions, APGAR, seasonality, mother's age at birth, number of children in household, birth order, parent's education, parent's income, household status, maternal smoking, mother's BMI | Analysis period: July 1st 2006 - July 31st 2021Reporting period: look back period | 
| Primary Care: Number of primary care contacts | Number of primary care contacts during follow-up period | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Number of specialized outpatient care visits | Number of specialized outpatient care visits during follow-up period | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Number of hospitalizations | Number of hospitalizations/stays related to RSV during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Length of hospitalizations | Length of hospitalizations/stays related to RSV during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Number of ICU hospitalizations | Number of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Length of ICU hospitalizations | Length of ICU hospitalizations/stays related to RSV during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Number of RSV-related medical/surgical procedures | Number of RSV-related medical/surgical procedures during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: Number of dispensed prescriptions of RSV-related medications | Number of dispensed prescriptions of RSV-related medications during follow-up | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: The costs of direct medical (in- and outpatient care) | Direct medical (in- and outpatient care) costs related to RSV infection | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date | 
| Primary Care: The costs of RSV-related medications | The costs of dispensed prescriptions of RSV-related medications based on pharmacy retail price | Analysis period: Date of first available data - July 31st 2021 Reporting period: 30 days from index date |