Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Engagement with the HCV care cascade among high-risk groups: A population-based study.

BACKGROUND: HCV elimination requires a thorough understanding of the care cascade. A direct-acting antiviral (DAA)-era description of the care cascade has not been undertaken in Ontario, Canada's most populous jurisdiction. Our primary objective was to describe the current population-level care cascade in the general Ontario population and among key risk groups ─ baby boomers, immigrants, and individuals experiencing residential instability. The secondary objective was to identify predictors of engagement. METHODS: We conducted a population-based cohort study of Ontario residents undergoing HCV testing between January 1, 1999, and December 31, 2018, and mapped the care cascade [antibody-diagnosed, RNA tested, RNA positive, genotyped, treated, achieved sustained virologic response, reinfected/relapsed] as of December 31, 2018. The cascade was stratified by risk groups. Cause-specific hazard modeling was used to identify demographic, and socioeconomic predictors of engagement with key steps of the cascade. RESULTS: Among 108,428 Ontario residents living with an HCV antibody diagnosis, 88% received confirmatory RNA testing; of these, 62% tested positive and 94% of positive tests were genotyped. Of those with confirmed viremia, 53% initiated treatment and 76% of treated individuals achieved sustained virologic response, while ~1% experienced reinfection or relapse. Males, older birth cohorts, long-term residents, those with a history of substance use disorder and social marginalization (eg, material deprivation, residential instability), and those initially diagnosed in the pre-DAA era exhibited lower rates of engagement with almost every step of HCV care. CONCLUSIONS: Despite DAA era improvements, treatment initiation remains a major gap. HCV screening and linkage-to-treatment, particularly for those with a history of substance use disorder and social marginalization, will be needed to equitably close gaps in HCV care in the province.

A Systematic Review of the Cost-Effectiveness of Cleft Care in Low- and Middle-Income Countries: What is Needed?

OBJECTIVE: The objective of this paper is to conduct a systematic review that summarizes the cost-effectiveness of cleft lip and/or palate (CL/P) care in low- and middle-income countries (LMICs) based on existing literature. DESIGN: We searched eleven electronic databases for articles from January 1, 2000 to December 29, 2020. This study is registered in PROSPERO (CRD42020148402). Two reviewers independently conducted primary and secondary screening, and data extraction. SETTING: All CL/P cost-effectiveness analyses in LMIC settings. PATIENTS, PARTICIPANTS: In total, 2883 citations were screened. Eleven articles encompassing 1,001,675 patients from 86 LMICs were included. MAIN OUTCOME MEASURES: We used cost-effectiveness thresholds of 1% to 51% of a country's gross domestic product per capita (GDP/capita), a conservative threshold recommended for LMICs. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) checklist. RESULTS: Primary CL/P repair was cost-effective at the threshold of 51% of a country's GDP/capita across all studies. However, only 1 study met at least 70% of the JBI criteria. There is a need for context-specific cost and health outcome data for primary CL/P repair, complications, and existing multidisciplinary management in LMICs. CONCLUSIONS: Existing economic evaluations suggest primary CL/P repair is cost-effective, however context-specific local data will make future cost-effectiveness analyses more relevant to local decision-makers and lead to better-informed resource allocation decisions in LMICs.

Pharmacotherapy vs. minimally invasive therapies as initial therapy for moderate-to-severe benign prostatic hyperplasia: a cost-effectiveness study.

BACKGROUND: Recently, minimally invasive therapies (MITs), such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH), offering symptom relief with a favorable safety profile. The objective of this study was to evaluate the cost-utility of MITs (WVTT and PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH. METHODS: In this model-based economic evaluation we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the US public payer perspective) per quality-adjusted life year (QALY), discounted at 3% annually. Various clinical scenarios were evaluated given that most men undergo several lifelong therapies up to surgical intervention and potentially thereafter. As such, in the study model men could receive up to three lines of therapy: (1) initial pharmacotherapy with MIT as second-line, and transurethral resection of the prostate (TURP) or pharmacotherapy as third-line; (2) initial MIT (WVTT or PUL) with MIT again, TURP or pharmacotherapy as second-line, and TURP as third-line. Model was populated using data from the published literature. Probabilistic analyses were performed. RESULTS: Initial treatment with WVTT led to the highest QALYs (13.05) and the lowest cost ($15,461). The cumulative QALYs and lifetime costs were 12.92 QALYs and $20,280 for pharmacotherapy followed by WVTT, 12.87 QALYs and $22,424 for pharmacotherapy followed by PUL, 12.86 QALYs and $20,930 for initial treatment with PUL. In the cost-utility analysis, WVTT as initial treatment dominated all three strategies, i.e., generated more QALYs at a lower cost. CONCLUSION: WVTT is an effective and cost-saving procedure, and may be an appropriate first-line alternative to pharmacotherapy for moderate-to-severe BPH patients who seek faster improvement and no lifelong commitment to daily medications.

Cost-utility of minimally invasive therapies vs. pharmacotherapy as initial therapy for benign prostatic hyperplasia A Canadian healthcare payer perspective.

INTRODUCTION: Recently, minimally invasive surgical therapies (MIST s) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH ). This study evaluated the cost-utility of water vapor thermal therapy (WVTT ) and prostatic urethral lift (PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH. METHODS: In this model-based economic evaluation, we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the Canadian healthcare payer perspective) per quality-adjusted life year (QALY), discounted at 1.5% annually. In the model, men could receive up to three lines of therapy: 1) initial pharmacotherapy with MIST as second-line, and TURP or pharmacotherapy as third-line; 2) initial MIST (WVTT or PUL) with MIST again, TURP, or pharmacotherapy as second-line, and TURP as third-line. The model was populated using data from the published literature. RESULTS: The expected lifetime QALYs and costs were 15.50 QALYs and $14 626 for initial treatment with WVTT, 15.35 QALYs and $11 795 for pharmacotherapy followed by WVTT, 15.29 QALYs and $13 582 for pharmacotherapy followed by PUL, and 15.29 QALYs and $19 151 for initial treatment with PUL. Strategies involving PUL procedures were dominated by strategies involving WVTT. The incremental cost per QALY gained was $18 873 for initial WVTT compared to initial pharmacotherapy followed by WVTT. CONCLUSIONS: WVTT appears to be a cost-effective procedure and may be an appropriate first-line alternative to pharmacotherapy for patients with BPH and prostate volume less than 80 cm3 who seek faster improvement and no lifelong commitment to daily medications.

Antiviral treatment for treatment-naïve chronic hepatitis B: systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options. METHODS: We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment. RESULTS: Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes. CONCLUSIONS: Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.

Pharmacotherapy vs surgery as initial therapy for patients with moderate-to-severe benign prostate hyperplasia: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of using a surgery, such as transurethral resection of the prostate (TURP) or photoselective vaporisation of the prostate using greenlight laser (GL-PVP), as initial treatment for men with moderate-to-severe benign prostate hyperplasia (BPH) compared to the standard practice of using pharmacotherapy as initial treatment followed by surgery if symptoms do not resolve. PATIENTS AND METHODS: We compared a combination of eight strategies involving upfront pharmacotherapy (i.e., α-blocker, 5α-reductase inhibitor, or combination) followed by surgery (e.g. TURP or GL-PVP) upon failure vs TURP or GL-PVP as initial treatment, for a target population of men with moderate-to-severe BPH symptoms, with a mean age of 65 years and no contraindications for treatment. A microsimulation decision-analytic model was developed to project the costs and quality-adjusted life years (QALYs) of the target population over the lifetime. The model was populated and validated using published literature. Incremental cost-effectiveness ratios (ICERs) were determined. Cost-effectiveness was evaluated using a public payer perspective, a lifetime horizon, a discount rate of 1.5%, and a cost-effectiveness threshold of $50 000 (Canadian dollars)/QALY. Sensitivity and probabilistic analyses were performed. RESULTS: All options involving an upfront pharmacotherapy followed by TURP for those who fail were economically unattractive compared to strategies involving a GL-PVP for those who fail, and compared to using either BPH surgery as initial treatment. Overall, upfront TURP was the most costly and effective option, followed closely by upfront GL-PVP. On average, upfront TURP costs $1015 more and resulted in a small gain of 0.03 QALYs compared to upfront GL-PVP, translating to an incremental cost per QALY gained of $29 066. Results were robust to probabilistic analysis. CONCLUSIONS: Surgery is cost-effective as initial therapy for BPH. However, the health and economic evidence should be considered concurrently with patient preferences and risk attitudes towards different therapy options.

Cost analysis of Greenlight photoselective vaporization of the prostate compared to transurethral resection of the prostate for benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland, which results in the development of lower urinary tract symptoms that can interfere with a patient's daily activities and negatively impact their quality of life. The gold standard treatment for moderate to severe BPH has been transurethral resection of the prostate (TURP), however, this procedure is associated with prolonged hospitalizations and increased complications. An alternative to TURP is Greenlight photoselective vaporization of the prostate (PVP), which is associated with better perioperative safety. The objectives of the research were to 1) assess the cost of Greenlight PVP compared to TURP and bipolar TURP; and 2) assess the predictors of total cost. METHODS: We conducted a descriptive costing study from the hospital perspective. We evaluated perioperative costs of patients who underwent each procedure from 2013-2015 at a tertiary academic medical centre. A multiple linear regression was performed to identify predictors of total cost. The variables included in regression analysis were patient age, type of procedure, Charlson Comorbidity Index, and distance to clinic. RESULTS: A total of 202 patients received one of the three procedures over the study period. The total cost of Greenlight PVP was $3836 per patient compared to $4963 for TURP and $4978 for bipolar TURP. The linear regression showed that the Charlson Comorbidity Index and type of procedure were independent predictors of total cost. CONCLUSIONS: The procedure costs and readmission rates are lower for Greenlight PVP compared to TURP and bipolar TURP, making it a preferable option for hospitals.

Cost-effectiveness analysis of extended adjuvant endocrine therapy in the treatment of post-menopausal women with hormone receptor positive breast cancer.

Five years of Tamoxifen (Standard TAM) is a common treatment option for early-stage, hormone receptor positive (HR+) breast cancer (BC). Extending Standard TAM by 5 additional years (Extended TAM) can improve survival and BC recurrences. In postmenopausal women, the use of extended aromatase inhibitors (Extended AI) after Standard TAM is an alternative to Extended TAM. This study examines the cost-effectiveness (CE) of extending Standard TAM with Extended TAM vs. Extended AI in postmenopausal HR+ early-stage BC patients. Three treatments were assessed: (1) Standard TAM; (2) Extended TAM; (3) Extended AI through a Markov model using a Canadian health system perspective, lifetime time-horizon, quality adjusted life years (QALYs), and a 5 % discount rate for future costs and utilities. Incremental cost-effectiveness ratios (ICERs) were calculated, and the impact of parameter uncertainty was assessed through probabilistic sensitivity analyses (SA) using conventional CE thresholds. The estimated total per person costs in 2012 Canadian dollars [$1.00 CAD = $0.99 US 2012] were the least for Extended TAM ($8,623 CAD) and most for Extended AI ($9,432 CAD). Extended AI was the most effective regimen, while Standard TAM was the least. Extended AI was cost-effective at conventional thresholds vs. Extended TAM (ICER: $3,402 CAD/QALY) which was robust to the SA. This study suggests that Extended AI and Extended TAM result in improved QALYs and lower healthcare costs vs Standard TAM. Extended AI results in the greatest improvement in QALYs and is the most cost-effective treatment alternative despite its higher drug costs.