Health state utilities and quality of life in patients with hepatitis B.

BACKGROUND: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized. OBJECTIVE: To measure utility scores and HRQoL across disease states associated with CHB infection. METHODS: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities. RESULTS: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores. CONCLUSIONS: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.

How much are we spending? The estimation of research expenditures on cardiovascular disease in Canada.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in Canada and is a priority area for medical research. The research funding landscape in Canada has changed quite a bit over the last few decades, as have funding levels. Our objective was to estimate the magnitude of expenditures on CVD research for the public and charitable (not-for profit) sectors in Canada between 1975 and 2005. METHODS: To estimate research expenditures for the public and charitable sectors, we compiled a complete list of granting agencies in Canada, contacted each agency and the Canadian Institutes of Health Research (CIHR), and extracted data from the organizations' annual reports and the Reference Lists of health research in Canada. Two independent reviewers scanned all grant and fellowship/scholarship titles (and summary/key words, when available) of all research projects funded to determine their inclusion in our analysis; only grants and fellowships/scholarships that focused on heart and peripheral vascular diseases were selected. RESULTS: Public/charitable sector funding increased 7.5 times, from close to $13 million (in constant dollars) in 1975 to almost $96 million (in constant dollars) in 2005 (base year). The Medical Research Council of Canada (MRCC)/CIHR and the Heart & Stroke Foundation of Canada have been the main founders of this type of research during our analysis period; the Alberta Heritage Foundation for Medical Research and the Fonds de la recherche en santé du Quebec have played major roles at the provincial level. The Indirect Costs Research Program and Canada Foundation for Innovation have played major roles in terms of funding in the last years of our analysis. CONCLUSION: Public/charitable-funded research expenditures devoted to CVD have increased substantially over the last three decades. By international standards, the evidence suggests Canada spends less on health-related research than the UK and the US, at least in absolute terms. However, this may not be too problematic as Canada is likely to free-ride from research undertaken elsewhere. Understanding these past trends in research funding may provide decision makers with important information for planning future research efforts. Future work in this area should include the use of our coding methods to obtain estimates of funded research for other diseases in Canada.

Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses.

BACKGROUND & AIMS: The relative efficacies of licensed antiviral therapies for treatment-naive chronic hepatitis B (CHB) infection in randomized controlled trials have not been determined. We evaluated the relative efficacies of the first 12 months of CHB treatments. METHODS: Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir, telbivudine, and tenofovir, as monotherapies and combination therapies, in treatment-naive individuals. Databases were searched for randomized controlled trials of the first 12 months of therapy in hepatitis B e antigen (HBeAg)-positive and/or HBeAg-negative patients with CHB published in English before October 31, 2009. Bayesian mixed treatment comparisons were used to calculate the odds ratios, including 95% credible intervals and predicted probabilities of surrogate outcomes to determine the relative effects of each treatment. RESULTS: In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (predicted probability, 88%), normalization of alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and hepatitis B surface antigen loss (5%); it ranked third in histologic improvement of the liver (53%). Entecavir was most effective in improving liver histology (56%), second for inducing undetectable levels of HBV DNA (61%) and normalization of ALT levels (70%), and third in loss of hepatitis B surface antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable levels of HBV DNA (94%) and improving liver histology (65%); it ranked second for normalization of ALT levels (73%). CONCLUSIONS: In the first year of treatment for CHB, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients.

Cost effectiveness of screening immigrants for hepatitis B.

BACKGROUND: The prevalence of chronic hepatitis B (CHB) infection among the immigrants of North America ranges from 2 to 15%, among whom 40% develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. AIMS: The objective of this study is to estimate the health and economic effects of screening strategies for CHB among immigrants. METHODS: We used the Markov model to examine the cost-effectiveness of three screening strategies: (i) 'No screening'; (ii) 'Screen and Treat' and (iii) 'Screen, Treat and Vaccinate' for 20-65 years old individuals who were born abroad but are currently living in Canada. Model data were obtained from the published literature. We measured predicted hepatitis B virus (HBV)-related deaths, costs (2008 Canadian Dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Our results show that screening all immigrants will prevent 59 HBV-related deaths per 10, 000 persons screened over the lifetime of the cohort. Screening was associated with an increase in quality-adjusted life expectancy (0.024 QALYs) and cost ($1665) per person with an ICER of $69, 209/QALY gained compared with 'No screening'. The 'Screen, Treat and Vaccinate' costs an additional $81, generates an additional 0.000022 QALYs per person, with an ICER of $3, 648,123/QALY compared with the 'Screen and Treat'. Sensitivity analyses suggested that the 'Screen and Treat' is likely to be moderately cost-effective. CONCLUSION: We show that a selective hepatitis B screening programme targeted at all immigrants in Canada is likely to be moderately cost-effective. Identification of silent CHB infection with the offer of treatment when appropriate can extend the lives of immigrants at reasonable cost.

Cost-effectiveness analysis of implantable venous access device insertion using interventional radiologic versus conventional operating room methods in pediatric patients with cancer.

PURPOSE: Percutaneous image-guided techniques are associated with less tissue trauma and morbidity than open surgical techniques. Interventional radiology has received significant health care investment. The purpose was to determine the cost effectiveness of inserting implantable venous access devices (IVADs) by interventional radiologic means versus conventional operating room surgery in pediatric patients with cancer. MATERIALS AND METHODS: In a retrospective cohort analysis, patients presenting with a new tumor diagnosis and receiving a first-time IVAD in January to June 2000 (operative group; n = 30) and January to June 2004 (interventional group; n = 30) were included. A societal costing perspective was adopted. Costs included labor, materials, equipment, inpatient wards, parent travel, and parental productivity losses for 30 days after insertion. Severe complications related to IVAD insertion were microcosted. Costs related to cancer therapy were not included. Incremental cost-effectiveness analysis and sensitivity analysis were performed. RESULTS: Interventional patients were older (7.3 years vs 4.1 years; P = .01). There were no significant differences between groups in sex, American Society of Anesthesiologists score, or length of hospital stay. Interventional radiologic procedures were shorter (84.9 minutes vs 112.8 minutes; P = 0.01). Interventional radiologic insertion was slightly less costly than operative insertion (Can$622,860 and Can$627,005 per 30-patient group, respectively) and more effective in reducing the complication rate (two vs eight complications per group, respectively; P = .039). The results were sensitive to the cost of operating the operating room. CONCLUSIONS: Interventional radiology was slightly less costly than operative IVAD insertion and resulted in fewer serious complications. It should be considered for IVAD insertions in pediatric patients with cancer.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies.

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

Disease burden of chronic hepatitis B among immigrants in Canada.

BACKGROUND: The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. OBJECTIVE: To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB. METHODS: Markov cohort models were used to estimate life years, quality-adjusted life years and lifetime direct medical costs (adjusted to 2008 Canadian dollars) for a cohort of immigrants with CHB living in Canada in 2006, and an age-matched control cohort of immigrants without CHB living in Canada in 2006. Parameter values were derived from the published literature. RESULTS: At the baseline estimate, the model suggested that the cohort of immigrants with CHB lost an average of 4.6 life years (corresponding to 1.5 quality-adjusted life years), had an increased average of $24,249 for lifetime direct medical costs, and had a higher lifetime risk for decompensated cirrhosis (12%), hepatocellular carcinoma (16%) and need for liver transplant (5%) when compared with the control cohort. DISCUSSION: Results of the present study showed that the socio-economic burden of CHB among immigrants living in Canada is substantial. Governments and health systems need to develop policies that promote early recognition of CHB and raise public awareness regarding hepatitis B to extend the lives of infected immigrants.

The cost and public health burden of invasive meningococcal disease outbreaks: a systematic review.

BACKGROUND: Invasive meningococcal disease (IMD) is a serious disease with a rapid onset, high mortality rate, and risk of long-term complications. Numerous reports in the literature conclude that IMD outbreaks are associated with substantial costs to society and significant burden on communities due to the cost associated with the prevention of secondary cases. OBJECTIVE: To systematically review the literature on the costs and public health burden associated with IMD outbreaks. METHODS: Studies were primarily identified through searching MEDLINE and EMBASE. Reports were included if they provided cost data related to the containment of an IMD outbreak after 1990 and were written in English, French, or Spanish. Costs were converted to 2010 United States dollars. Outbreaks were categorized by low-income countries (LIC) and high-income countries (HIC) based on gross domestic product per capita. Outbreak containment strategies were classified as small (e.g., targeting members of the school/institution where the outbreak occurred) or large (e.g., targeting everyone in the community). RESULTS: Sixteen articles reporting data on 93 IMD outbreaks fulfilled the eligibility criteria and were included. The majority of outbreaks occurred in HIC. Five studies reported the use of small containment strategies including targeted vaccination and chemoprophylaxis, all occurring in HIC. The average cost per small containment strategy was $299,641 and the average cost per IMD case was $41,857. Eight studies reported large containment strategies involving widespread vaccination targeting a specific age group or community. For HIC, the average cost per large containment strategy was $579,851 and the average cost per IMD case was $55,755. In LIC, the average cost per large containment strategy was $3,407,590 and the average cost per IMD case was $2,222. CONCLUSION: IMD outbreaks were associated with substantial costs. We found that although there were numerous reports on IMD outbreaks, data on containment costs were very limited. More research in this area is warranted.

Canada's contribution to global research in cardiovascular diseases.

The burden of cardiovascular disease (CVD) in Canada and other developed countries is growing, in part because of the aging of the population and the alarming rise of obesity. Studying Canada's contribution to the global body of CVD research output will shed light on the effectiveness of investments in Canadian CVD research and inform if Canada has been responding to its CVD burden. Search was conducted using the Web-of-Science database for publications during 1981 through 2010 on major areas and specific interventions in CVD. Search was also conducted using Canadian and US online databases for patents issued between 1981 and 2010. Search data were used to estimate the proportions of the world's pool of research publications and of patents conducted by researchers based in Canada. The results indicate that Canada contributed 6% of global research in CVD during 1981 through 2010. Further, Canada's contribution shows a strong upward trend during the period. Based on patent data, Canada's contribution level was similar (5%-7%). Canada's contribution to the global pool of CVD research is on par with France and close to the UK, Japan, and Germany. Canada's contribution in global CVD research is higher than its average contribution in all fields of research (6% vs 3%). As the burden of chronic diseases including CVD rises with Canada's aging population, the increase in Canadian research into CVD is encouraging.

Estimating the payoffs from cardiovascular disease research in Canada: an economic analysis.

BACKGROUND: Investments in medical research can result in health improvements, reductions in health expenditures and secondary economic benefits. These "returns" have not been quantified in Canada. Our objective was to estimate the return on cardiovascular disease research funded by public or charitable organizations. METHODS: Our primary outcome was the internal rate of return on cardiovascular disease research funded by public or charitable sources. The internal rate of return is the annual monetary benefit to the economy for each dollar invested in cardiovascular disease research. Calculation of the internal rate of return involved the following: measuring expenditures on cardiovascular disease research, estimating the health gains accrued from new treatments for cardiovascular disease, determining the proportion of health gains attributable to cardiovascular disease research and the time lag between research expenditures and health gains, and estimating the spillovers from public- or charitable-sector investments to other sectors of the economy. RESULTS: Expenditures by public or charitable organizations on cardiovascular disease research from 1981 to 1992 amounted to $392 million (2005 dollars). Health gains associated with new treatments from 1994 to 2005 (13-yr lag) amounted to 2.2 million quality-adjusted life-years. We calculated an internal rate of return of 20.6%. CONCLUSION: Canadians obtain relatively high health and economic gains from investments in cardiovascular disease research. Every $1 invested in cardiovascular disease research by public or charitable sources yields a stream of benefits of roughly $0.21 to the Canadian economy per year, in perpetuity.

Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis.

PURPOSE: Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with antiviral prophylaxis. It remains unclear whether HBV screening is cost effective. METHODS: A decision model was developed to compare the clinical outcomes, costs, and cost effectiveness of three HBV screening strategies for patients with lymphoma before R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy: screen all patients for hepatitis B surface antigen (HBsAg; Screen-All), screen patients identified as being at high risk for HBV infection (Screen-HR), and screen no one (Screen-None). Patients testing positive were administered antiviral therapy until 6 months after completion of chemotherapy. Those not screened were initiated on antiviral therapy only if HBV hepatitis occurred. Probabilities of HBV and lymphoma outcomes were derived from systematic literature review. A third-party payer perspective was adopted, costs were expressed in 2011 Canadian dollars, and a 1-year time horizon was used. RESULTS: Screen-All was the dominant strategy. It was least costly at $32,589, compared with $32,598 for Screen-HR and $32,657 for Screen-None. It was also associated with the highest 1-year survival rate at 84.99%, compared with 84.96% for Screen-HR and 84.86% for Screen-None. The analysis was sensitive to the prevalence of HBsAg positivity in the low-risk population, with Screen-HR becoming least costly when this value was ≤ 0.20%. CONCLUSION: In patients receiving R-CHOP for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients.