Abstract
Introduction A number of vaccines against Respiratory Syncytial Virus (RSV) infection are approaching licensure. Deciding which RSV vaccine strategy, if any, to introduce, will partly depend on cost-effectiveness analyses, which compares the relative costs and health benefits of a potential vaccination programme. Health benefits are usually measured in Quality Adjusted Life Year (QALY) loss, however, there are no QALY loss estimates for RSV that have been determined using standardised instruments. Moreover, in children under the age of five years in whom severe RSV episodes predominantly occur, there are no appropriate standardised instruments to estimate QALY loss.
Methods We estimated the QALY loss due to RSV across all ages by developing a novel regression model which predicts the QALY loss without the use of standardised instruments. To do this, we conducted a surveillance study which targeted confirmed episodes in children under the age of five years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases.) All participants were asked to complete questions regarding their health during the infection, with the suspected cases aged 5–14 and 15+ years old additionally providing Health-Related Quality of Life (HR-QoL) loss estimates through completing EQ-5D-3L-Y and EQ-5D-3L instruments respectively. The questionnaire responses from the suspected cases were used to calibrate the regression model. The calibrated regression model then used other questionnaire responses to predict the HR-QoL loss without the use of EQ-5D instruments. The age-specific QALY loss was then calculated by multiplying the HR-QoL loss on the worst day predicted from the regression model, with estimates for the duration of infection from the questionnaires and a scaling factoring for disease severity.
Findings Our regression model for predicting HR-QoL loss estimates that for the worst day of infection, suspected RSV cases in persons five years and older who do and do not seek healthcare have an HR-QoL loss of 0·616 (95% CI 0·155–1·371) and 0·405 (95% CI 0·111–1·137) respectively. This leads to a QALY loss per RSV episode of 1·950 × 10−3 (95% CI 0·185 × 10−3 –9·578 × 10−3) and 1·543 × 10−3 (95% CI 0·136 × 10−3 –6·406 × 10−3) respectively. For confirmed cases in a child under the age of five years who sought healthcare, our model predicted a HR-QoL loss on the worst day of infection of 0·820 (95% CI 0·222–1·450) resulting in a QALY loss per RSV episode of 3·823 × 10−3 (95% CI 0·492 × 10−3 –12·766 × 10−3). Combing these results with previous estimates of RSV burden in the UK, we estimate the annual QALY loss of healthcare seeking RSV episodes as 1,199 for individuals aged five years and over and 1,441 for individuals under five years old.
Interpretation The QALY loss due to an RSV episode is less than the QALY loss due to an Influenza episode. These results have important implications for potential RSV vaccination programmes, which has so far focused on preventing infections in infants—where the highest reported disease burden lies. Future potential RSV vaccination programmes should also evaluate their impact on older children and adults, where there is a substantial but unsurveilled QALY loss.
Funding National Institute for Health Research, the Medical Research Council, EU Horizon 2020 I-MOVE+, NIHR CLAHRC North Thames.
Suggested Reviewers Joke Bilcke, Philippe Beutels, Alessia Melegaro, Deborah Cromer, Peter White
Evidence before this study As Respiratory Syncytial Virus (RSV) vaccines are likely to be licensed in the near future, it is important that their cost-effectiveness (CE) is evaluated. A key requirement of cost-effectiveness analysis (CEA) is to quantify the Quality Adjusted Life Year (QALY) loss due to RSV. However, to date, there are no studies using standardised instruments that directly measure the QALY loss due to an RSV episode. In addition, there are no standardised instruments that exist for evaluating QALY loss which are aimed specifically at children under the age of five years—where the majority of the reported disease burden for RSV lies.
Added value of this study In this study, we designed questionnaires which comprised standardised EQ-5D instruments and other questions which determined the severity of an RSV episode. The questionnaires were distributed to households with confirmed RSV episodes in children under five years of age (confirmed cases). To gather information about RSV episodes across all ages, the questionnaires requested information about infections in the confirmed cases and also in suspected RSV episodes in persons five years of age and older in the same household (suspected cases). Using the questionnaire responses from the suspected cases, we calibrated a regression model which predicts the Health-Related Quality of Life (HR-QoL) loss (derived from the EQ-5D instruments) given requested indicators of disease severity including Visual Analogue Scale (VAS) score loss, effect on school/work days lost, coughing severity, age and healthcare-seeking behaviour. Combining the derived HR-QoL loss from the regression model with estimates for the duration of infection from the questionnaires, and information about the individual-level heterogeneity in symptom severity, allows for the calculation of the QALY loss across all age groups without the use of EQ-5D instruments.
Implications of all the available evidence The results of this study suggest that the QALY loss due to an episode of RSV is less than the QALY loss for an episode of Influenza. Further, by combining our age-specific QALY loss estimates with existing estimates of RSV burden in the UK, we calculate that 46% of the QALY loss due to healthcare seeking RSV episodes is due to individuals aged five years and older. For individuals aged five years and older, our study suggests that only a quarter of persons of suspected RSV episodes seek healthcare, such that when combined with our QALY loss estimates for healthcare and non-health care seeking, we calculate that approximately 70% of the QALY loss in this age group cannot be captured by surveillance systems. This has important implications for economic evalutions of potential vaccination programmes, which primarily consider the reduction in disease in infants less than one year—where the majority of the reported severe disease burden lies. We conclude that evaluations of potential non-targeted vaccination programmes should consider the entire population to accurately capture both the direct and indirect effects of immunisation.