Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Adoption in Canada of an international risk scoring tool to predict respiratory syncytial virus hospitalization in moderate-to-late preterm infants.

OBJECTIVE: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST. METHODS: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed. RESULTS: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores (p < .001) and risk categories (p < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%). CONCLUSIONS: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Challenges in the prevention or treatment of RSV with emerging new agents in children from low- and middle-income countries.

INTRODUCTION: Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs). AREAS COVERED: There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs. EXPERT OPINION: We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.

Introduction of biosimilar pegfilgrastim in France: Economic analysis of switching from originator.

OBJECTIVES: To assess the economic impact of introducing biosimilar pegfilgrastim compared to the current standard granulocyte colony-stimulating factor (G-CSF) practice in France. METHODS: A budget impact model was developed to investigate the impact of introducing pegfilgrastim biosimilar over 5 years. The model analysed drug acquisition costs, ambulatory costs, as well as costs associated with poor outcomes, and compared the current standard practice of long-acting and short-acting G-CSF to a revised practice including pegfilgrastim biosimilar in addition to standard practice treatments. The cost of switching to pegfilgrastim biosimilar, within a pharmacy setting, was analysed within the model using data from a survey of French pharmacists. RESULTS: The budget impact model calculated a cost saving of €51,007,531 over 5 years switching from the current standard practice to pegfilgrastim biosimilar. A sensitivity analysis accounting for variation in pegfilgrastim biosimilar uptake of 1) 15% in year 1 and 1% in years 2-5 and 2) 15% in years 1-5, estimated savings ranging between €29,377,784 and €79,847,194, respectively. A further analysis predicted cost savings of €287,344,835 over 5 years with the extension of pegfilgrastim biosimilar, at an uptake of 15% in year 1 and 7% in years 2-4, to both long-acting and short-acting G-CSF groups compared to unchanged current practice. CONCLUSIONS: The introduction of pegfilgrastim biosimilar will help to reduce cost and alleviate some of the financial pressure on the French healthcare system.

IBD2020 global forum: results of an international patient survey on quality of care.

BACKGROUND/AIMS: IBD2020 is a global forum for standards of care in inflammatory bowel disease (IBD). The aim of the IBD2020 survey was to identify and describe variations in quality care of IBD. METHODS: Patients with IBD from Finland, Italy, France, Canada, Germany, UK, Spain and Sweden were surveyed during 2013 to 2014, covering: disease characteristics; impact on life and work; organization and perceived quality of care. RESULTS: Seven thousand five hundred and seven patients participated (median age, 39 years [range, 10-103 years]; 2,354 male [31.4%]), including 4,097 (54.6%) with Crohn's disease (CD) and 3,410 (45.4%) with ulcerative colitis (UC). Median time from symptom onset to diagnosis was 1 year for both CD (range, 0-47 years) and UC (range, 0-46 years), with no clear evidence of improvement in diagnostic delay over the preceding 24 years. Half of the patients (3,429; 50.0%) rated their care as "excellent" or "very good," with similar results for CD and UC across countries. Five factors were significantly (P<0.01) associated with perceived good quality of care: quality of specialist communication; review consultation being long enough; failure to share information; no access to a dietician; speed of advice. CONCLUSIONS: The IBD2020 survey has highlighted areas related to quality of care of IBD from the patients' perspective, with scope for improvement.

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants.

BACKGROUND: The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere. METHODS: Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated. RESULTS: The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3). CONCLUSIONS: This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).

AIM: We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This survey-based, observational study was conducted during 2014-2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important). RESULTS: The five most important factors for parents were: healthcare professionals' awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support. CONCLUSION: The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.

The influence of birth weight amongst 33-35 weeks gestational age (wGA) infants on the risk of respiratory syncytial virus (RSV) hospitalisation: a pooled analysis.

OBJECTIVE: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33°-356 weeks' gestational age (wGA) infants. STUDY DESIGN: Pooled analysis of data (n = 1218) from Spain, Germany, France and Italy. RESULT: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14 kg; p < 0.001) for both males (2.25 versus 2.18 kg; p = 0.049) and females (2.22 versus 2.11 kg, p = 0.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95 kg versus non-hospitalised 1.95 kg, p = 0.976; 34 wGA: 2.26 versus 2.14 kg, p = 0.007; 35 wGA: 2.37 versus 2.29 kg, p = 0.070), particularly female 34 wGA infants (female: 2.24 versus 2.08 kg, p = 0.019; male: 2.27 versus 2.20, p = 0.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation. CONCLUSIONS: In 33-35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation.

Can we improve the targeting of respiratory syncytial virus (RSV) prophylaxis in infants born 32-35 weeks' gestational age with more informed use of risk factors?

OBJECTIVE: To evaluate the key risk factors for respiratory syncytial virus (RSV) hospitalisation in 32-35 weeks' gestational age (wGA) infants. METHODS: Published risk factors were assessed for predictive accuracy (area under the receiver operating characteristic curve [ROC AUC]) and for number needed to treat (NNT). RESULTS: Key risk factors included: proximity of birth to the RSV season; having siblings; crowding at home; day care; smoking; breast feeding; small for GA; male gender; and familial wheezing/eczema. Proximity of birth to the RSV season appeared the most predictive. Risk factors models from Europe and Canada were found to have a high level of predictive accuracy (ROC AUC both > 0.75; NNT for European model 9.5). A model optimised for three risk factors (birth ± 10 weeks from start of RSV season, number of siblings ≥ 2 years and breast feeding for ≤ 2 months) had a similar level of prediction (ROC AUC: 0.776; NNT: 10.2). An example two-risk factor model (day care attendance and living with ≥ 2 siblings < 5 years old) had a lower level of predictive accuracy (ROC AUC: 0.55; NNT: 26). CONCLUSIONS: An optimised combination of risk factors has the potential to improve the identification of 32-35 wGA infants at heightened risk of RSV hospitalisation.