Systematic Review on the Cost-Effectiveness of Seasonal Influenza Vaccines in Older Adults.

OBJECTIVES: Older adults are at high risk of influenza-related complications or hospitalization. The purpose of this systematic review is to assess the relative cost-effectiveness of all influenza vaccine options for older adults. METHODS: This systematic review identified economic evaluation studies assessing the cost-effectiveness of influenza vaccines in adults ≥65 years of age from 5 literature databases. Two reviewers independently selected, extracted, and appraised relevant studies using the JBI Critical Appraisal Checklist for Economic Evaluations and Heyland's generalizability checklist. Costs were converted to 2019 Canadian dollars and adjusted for inflation and purchasing power parity. RESULTS: A total of 27 studies were included. There were 18 comparisons of quadrivalent inactivated vaccine (QIV) versus trivalent inactivated vaccine (TIV): 5 showed QIV dominated TIV (ie, lower costs and higher health benefit), and 13 showed the results depended on willingness to pay (WTP). There were 9 comparisons of high-dose TIV (TIV-HD) versus TIV: 5 showed TIV-HD dominated TIV, and 4 showed the results depended on WTP. There were 8 comparisons of adjuvanted TIV (TIV-ADJ) versus TIV: 4 showed TIV-ADJ dominated TIV, and 4 showed the results depended on WTP. There were few pairwise comparisons among QIV, TIV-HD, and TIV-ADJ. CONCLUSIONS: The evidence suggests QIV, TIV-HD, and TIV-ADJ are cost-effective against TIV for a WTP threshold of $50 000 per quality-adjusted life-year. Future studies should include new and existing vaccine options for broad age ranges and use more robust methodologies-such as real-world evaluations or modeling studies accounting for methodological, structural, and parameter uncertainty.

Gap analyses to assess Canadian readiness for respiratory syncytial virus vaccines: Report from an expert retreat.

Respiratory syncytial virus (RSV) can cause severe disease in infants and older adults. Various vaccine candidates are in development and may become authorized for use in Canada within the next 2-5 years. The Public Health Agency of Canada sought to enhance preparedness for RSV vaccine and passive immunization candidates by organizing an expert retreat to identify knowledge gaps in surveillance and research and development in the context of provincial and territorial RSV public health priorities. We determined that RSV candidate vaccines in development directly address four out of five identified public health priorities, and identified remaining data gaps around vaccine efficacy and effectiveness. We determined that limited or sufficient surveillance data is available to support decision-making for four out of five RSV public health priorities and identified data gaps for several key populations: (i) for RSV cases under 17 years of age, gaps remain for denominator data to calculate incidence and data on medically attended outpatient visits; (ii) for RSV cases in Indigenous and remote communities, gaps remain for data on incidence, prevalence, specific risk factors, feasibility and acceptability; and (iii) for RSV cases in older adults, gaps remain for data on incidence. This process demonstrated the feasibility of, and stakeholder support for, gap analyses in surveillance data to support decisions about prospective vaccines and immune products.

Comparison of the expected rewards between probabilistic and deterministic analyses in a Markov model.

Objectives: In Markov models that evaluate the cost-effectiveness of health-care technologies, it is generally recommended to use probabilistic analysis instead of deterministic analysis. We sought to compare the performance of probabilistic and deterministic analysis in estimating the expected rewards in a Markov model.Methods: We applied Jensen's inequality to compare the expected Markov rewards between probabilistic and deterministic analysis and conducted a simulation study to compare the bias and accuracy between the two approaches.Results: We provided mathematical justification why probabilistic analysis is associated with greater Markov rewards (life-years and quality-adjusted life-years) compared with deterministic analysis. In our simulations, probabilistic analyses tended to generate greater life-years, bias, and mean square error for the estimated rewards compared with deterministic analyses. When the expected values of transition probabilities were the same, weaker evidence derived from smaller sample sizes resulted in larger Markov rewards compared with stronger evidence derived from larger sample sizes. When longer time horizons were applied in cases of weak evidence, there was a substantial increase in bias where the rewards in both probabilistic and deterministic analysis were overestimated.Conclusion: Authors should be aware that probabilistic analysis may lead to increased bias when the evidence is weak.

Health-related quality of life in persons with West Nile virus infection: a longitudinal cohort study.

BACKGROUND: West Nile virus (WNV) infections are predominantly asymptomatic, although almost 1% become neuroinvasive and debilitating. We describe the impact of neuroinvasive and non-neuroinvasive disease on patient health-related quality of life (HRQoL). METHODS: Short Form 36 questionnaire data came from a Canadian WNV cohort (Loeb 2008) of 154 patients followed for up to three years. We generated health utilities using the SF-6D. We calculated mean utility scores throughout follow-up and examined predictors using a linear mixed-effects model. We summarized HRQoL post-acute infection as: (i) long-term utility (mean of scores one year onward); (ii) area under the curve (AUC) one year onward. We examined predictors using beta regression. We used multiple imputation for sensitivity analysis. RESULTS: Mean utility scores improved from 0.59 (95% CI: 0.38, 0.93) at baseline to 0.77 (0.53, 1) at six months, before plateauing for the remaining two years. Mean long-term utility was 0.81 (0.78, 0.85) and mean AUC was 0.80 (0.76, 0.84). Patients with neuroinvasive disease had consistently worse scores than their non-neuroinvasive counterparts, with the gap nearly closed after six months. After adjusting for confounding, neuroinvasive disease was not a significant predictor of HRQoL either throughout follow-up or post-acute infection. Rather, number of comorbidities and baseline utility scores were. Sensitivity analysis showed similar findings. CONCLUSIONS: Patients with WNV infection reported low HRQoL during acute illness, but improved rapidly by six months, regardless of neuroinvasive disease status. This is the first study reporting health utilities for WNV infection.

Epidemiologic and clinical parameters of West Nile virus infections in humans: a scoping review.

BACKGROUND: Clinical syndromes associated with West Nile virus (WNV) infection range from fever to neuroinvasive disease. Understanding WNV epidemiology and disease history is important for guiding patient care and healthcare decision-making. The objective of this review was to characterize the existing body of peer-reviewed and surveillance literature on WNV syndromes and summarize epidemiologic and clinical parameters. METHODS: We followed scoping review methodology described by the Joanna Briggs Institute. Terms related to WNV epidemiology, hospitalization, and surveillance were searched in four bibliographic databases (MEDLINE, EMBASE, Scopus, and CINAHL) for literature published from January 1999 to December 2015. RESULTS: In total, 2334 non-duplicated titles and abstracts were screened; 92 primary studies were included in the review. Publications included one randomized controlled trial and 91 observational studies. Sample sizes ranged from under 25 patients (n = 19) to over 400 patients (n = 28). Eight studies were from Canada, seven from Israel, and the remaining (n = 77) from the United States. N = 17 studies were classified as outbreak case investigations following epidemics; n = 37 with results of regional/national surveillance and monitoring programs. Mean patient ages were > 40 years old; three studies (3%) focused on the pediatric population. Patients with encephalitis fared worse than patients with meningitis and fever, considering hospitalization, length of stay, discharge, recovery, and case-fatality. Several studies examined risk factors; however, age was the only risk factor for neuroinvasive disease/death consistently identified. Overall, patients with acute flaccid paralysis or encephalitis fared worse than patients with meningitis and West Nile fever in terms of hospitalization and mortality. Among the included studies, proportion hospitalized, length of stay, proportion discharged home and case-fatality ranged considerably. CONCLUSION: Our review highlights the heterogeneity among reporting clinical WNV syndromes and epidemiologic parameters of WNV-related illness. Presently, there is potential for further synthesis of the risk factors of WNV-illness and mortality; undertaking further analysis through a systematic review and meta-analysis may benefit our understanding of risk factors for emerging mosquito-borne diseases. Future research on the burden of WNV can build on existing evidence summarized in this review, not only to support our understanding of endemic WNV, but also to strengthen research on emerging arboviruses with similar clinical manifestations.

Health-related quality of life, comorbidities and mortality in pulmonary nontuberculous mycobacterial infections: A systematic review.

Nontuberculous mycobacterial (NTM) infections are increasing in disease frequency worldwide. This systematic review examines health-related quality of life (HRQOL), comorbidities and mortality associated with pulmonary NTM disease. We searched MEDLINE, EMBASE, CINAHL, Scopus Life Sciences, conference proceedings and Google (earliest date available to February 2015) for primary studies. Eligible studies compared populations with and without pulmonary NTM disease in high-income jurisdictions. We excluded studies on HIV/AIDS. All languages were accepted. Two reviewers followed MOOSE and PRISMA reporting guidelines and independently appraised quality using STROBE. All studies were summarized qualitatively regardless of quality. Of 3193 citations screened, we included 17 studies mostly from Taiwan (n = 5) and the USA (n = 4). Two studies assessed HRQOL; one assessed comorbidities, 11 assessed mortality, and three assessed multiple outcomes. Populations with pulmonary NTM reported significantly worse or similar HRQOL than the general population, depending on the instruments used. Some suggested greater prevalence of having bronchiectasis (n = 2) and greater risk of developing pulmonary tuberculosis (n = 1). Most (n = 7) suggested no difference in mortality, although only one was age-matched and gender-matched to the general population. Four suggested NTM populations had higher mortality-two of which compared with the general population and were deemed of high quality, while two compared with non-NTM patients from hospital. High clinical heterogeneity in study design may explain discordant results. Bias assessments and controlling for confounding were carried out poorly. No consistent trends were observed although there is suggestion of an increased health burden from respiratory diseases and increased mortality associated with pulmonary NTM disease.

The cost-utility of integrated cervical cancer prevention strategies in the Ontario setting - Can we do better?

INTRODUCTION: A universal, publicly funded, school-based human papillomavirus (HPV) vaccination program in grade eight girls was initiated in Ontario in 2007. We present a cost-utility analysis of integrated cervical cancer prevention programs from the healthcare payer perspective. METHODS: Our analysis was based on linked HPV transmission and disease history models. We obtained data from the literature, provincial surveys and Ontario population-based linked health administrative datasets. We modeled combinations of vaccination and screening strategies. We considered vaccination based on the Ontario experience, as well as conservative and optimistic scenarios, varying coverage, vaccine effectiveness and duration of protection. We considered 900 screening scenarios (screening start age: 21-70 years, screening interval: 3-20 years; 1-year time steps). The current schedule screens every 3 years starting at age 21 years. We examined (1) first vaccinated cohort (low herd-immunity), and (2) steady state, i.e. all cohorts were vaccinated (high herd-immunity). RESULTS: Adding vaccination to the current screening schedule was cost-effective (

Changes in quality of life, healthcare use, and substance use in HIV/hepatitis C coinfected patients after hepatitis C therapy: a prospective cohort study.

OBJECTIVE: Clinical benefits of achieving a sustained virologic response (SVR) with hepatitis c virus (HCV) therapy beyond reducing liver-related outcomes have not been documented in HIV-coinfected patients, who have multiple competing health problems. To gauge the potential benefits of curing HCV in coinfected people, we examined changes in health-related quality of life (HRQOL), healthcare and substance use, and overall mortality after treatment for HCV Coinfection. DESIGN: Prospective multicentre cohort study. METHODS: Among patients treated for HCV in the Canadian Coinfection Cohort study, self-reported HRQOL (using the EQ-5D), inpatient and outpatient medical visits, and substance use were assessed before, 6 months and 1 year after completing HCV therapy, comparing SVR-achievers and non-responders. Analysis of covariance and zero-inflated negative binomial regression were used to model the effects of SVR on HRQOL and healthcare use, respectively. RESULTS: Of 1145 patients chronically infected with HCV, 223 (19%) received treatment while under follow-up in the cohort and had HRQOL data collected - 86 (36%) achieved SVR, 68 (29%) did not, 30 (13%) had ongoing treatment, and 39 (17%) had unknown responses. Compared to non-responders, those achieving a SVR had higher HRQOL scores over time (11-unit increase 1 year posttreatment, 95% CI: 2, 21 measured 1 year posttreatment) and a lower rate of health service utilization (adjusted incidence rate ratio: 0.5, 95% CI: 0.3, 0.9). Short-term mortality was low but appeared lower in SVR-achievers (incidence rates: 0.10 vs 0.12 deaths per 100 person-years). However, after successful treatment, a substantial number of patients increased alcohol consumption and continued to inject drugs. CONCLUSIONS: Successful HCV treatment results in a range of health benefits for HIV/HCV-coinfected patients. Ongoing substance use, however, may mitigate the short- and long-term benefits associated with curing HCV.

Cost effectiveness of hepatitis C-related interventions targeting substance users and other high-risk groups: a systematic review.

BACKGROUND AND OBJECTIVE: In developed countries, injection drug users have the highest prevalence and incidence of hepatitis C virus (HCV) infection. Clinicians and policy makers have several options for reducing morbidity and mortality related to HCV infection, including preventing new infections, screening high-risk populations, and optimizing uptake and delivery of antiviral therapy. Cost-effectiveness analyses provide an estimate of the value for money associated with adopting healthcare interventions. Our objective was to determine the cost effectiveness of hepatitis C interventions (prevention, screening, treatment) targeting substance users and other groups with a high proportion of substance users. METHODS: We conducted a systematic search of MEDLINE, EMBASE, CINAHL, HealthSTAR and EconLit, and the grey literature. Studies were critically appraised using the Drummond and Jefferson, Neumann et al. and Philips et al. checklists. We developed and applied a quality appraisal instrument specific to cost-effectiveness analyses of HCV interventions. In addition, we summarized cost-effectiveness estimates using a single currency and year ($US, year 2009 values). RESULTS: Twenty-one economic evaluations were included, which addressed prevention (three), screening (ten) and treatment (eight). The quality of the analyses varied greatly. A significant proportion did not incorporate important aspects of HCV natural history, disease costs and antiviral therapy. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (less costly and more effective) to $US603,352 per QALY. However, many ICERs were less than $US100,000 per QALY. Screening and treatment interventions involving pegylated interferon and ribavirin were generally cost effective at the $US100,000 per QALY threshold, with the exception of some subgroups, such as immune compromised patients with genotype 1 infections. CONCLUSIONS: No clear consensus emerged from the studies demonstrating that prevention, screening or treatment provides better value for money as each approach can be economically attractive in certain subgroups. More high-quality economic evaluations of preventing, identifying and treating HCV infection in substance users are needed.