Effect of ribociclib on productivity losses due to breast cancer in young women in Brazil.

OBJETIVE: To evaluate the effect of ribociclib versus endocrine therapy on productivity losses due to advanced breast cancer. METHODS: Productivity data from the MONALEESA-7 trial, obtained from the results of the application of the Work Productivity and Activity Impairment (WPAI) questionnaire on progression-free survival state (43-month follow-up), were extrapolated to the 10,936 Brazilian prevalent cases of premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Productivity loss was determined by quantifying the economic costs of workforce dropout over time in both treatment arms and by discounting the economic costs of absenteeism and presenteeism from workforce retention. A human capital approach was used. RESULTS: Net productivity gains in the ribociclib arm were estimated at USD 4,285,525.00, representing 316,609 added work hours over 43 months and a mean of 2,009 added work weeks per year. CONCLUSIONS: The phase III MONALEESA-7 trial productivity results applied to the Brazilian premenopausal prevalent cases of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer showed that treatment with ribociclib + endocrine therapy improves workforce participation compared with endocrine therapy alone in premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer, with potential economic gains for the Brazilian society.

Correlation between work productivity loss and EORTC QLQ-C30 and -BR23 domains from the MONALEESA-7 trial of premenopausal women with HR+/HER2- advanced breast cancer.

BACKGROUND: The phase III MONALEESA-7 trial (NCT02278120) assessed ribociclib + endocrine therapy (ET) versus ET in premenopausal women with HR+/HER2- advanced breast cancer (ABC). The relationship between work productivity loss (WPL) and domains of European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and the breast cancer (BC)-specific module (QLQ-BR23) has not been explored in ABC. In this post hoc analysis (data cutoff, November 30, 2018), we assessed the correlation between the WPL component of the Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire and EORTC QLQ-C30/BR23 domains. METHODS: We analyzed EORTC and WPAI:GH data from 329 patients in both treatment arms of MONALEESA-7 who were employed during the trial. Separate univariable mixed-model repeated measures (MMRM) regression models were fitted for each domain, with WPL as dependent variable and each EORTC domain score as a single fixed-effect covariate. Linear and quadratic relationships were considered based on the Akaike information criterion. Next, two separate multivariable MMRM regression models were fitted with WPL a dependent variable and all QLQ-C30/BR23 domain scores as fixed-effect covariates. The strength of correlation between WPL and EORTC domains was assessed in terms of minimally important differences for the QLQ-C30/BR23 modules. RESULTS: Our univariable analysis showed that greater WPL was statistically significantly associated with lower levels of overall quality of life (QoL) and other functional domains and with higher levels of all symptomatic domains of the QLQ-C30/BR23 modules. Our multivariable analysis determined that this correlation was primarily driven by changes in QoL; physical, role, social, and future perspective domains; and BC-specific symptomatic domains. CONCLUSION: This analysis determined the QoL domains that correlate with WPL in premenopausal patients with HR+/HER2- ABC. These results may inform prognostic tools to identify and characterize patients with greater risk for WPL and help design interventional strategies to minimize WPL.

Effect of ribociclib on productivity losses due to breast cancer in young women in Brazil

ABSTRACT OBJETIVE To evaluate the effect of ribociclib versus endocrine therapy on productivity losses due to advanced breast cancer. METHODS Productivity data from the MONALEESA-7 trial, obtained from the results of the application of the Work Productivity and Activity Impairment (WPAI) questionnaire on progression-free survival state (43-month follow-up), were extrapolated to the 10,936 Brazilian prevalent cases of premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Productivity loss was determined by quantifying the economic costs of workforce dropout over time in both treatment arms and by discounting the economic costs of absenteeism and presenteeism from workforce retention. A human capital approach was used. RESULTS Net productivity gains in the ribociclib arm were estimated at USD 4,285,525.00, representing 316,609 added work hours over 43 months and a mean of 2,009 added work weeks per year. CONCLUSIONS The phase III MONALEESA-7 trial productivity results applied to the Brazilian premenopausal prevalent cases of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer showed that treatment with ribociclib + endocrine therapy improves workforce participation compared with endocrine therapy alone in premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer, with potential economic gains for the Brazilian society.

Cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole or letrozole as monotherapy in first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer: a Brazilian private payer perspective.

BACKGROUND: The global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2-, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective. METHODS: A model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2- aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained. CONCLUSIONS: As demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2- aBC, warranting incorporation in the private healthcare system.

Investing in a healthy lifestyle strategy: is it worth it?

OBJECTIVES: In Quebec, various actors fund activities aimed at increasing physical activity, improving eating habits and reducing smoking. The objective was to evaluate how effective does the healthy lifestyle habits promotion (HLHP) strategy need to be to make to offset its costs. METHODS: First, we built the logic model of the HLHP strategy. We then assessed the strategy's total cost as well as the direct health care expenditures associated with lifestyle-related risk factors (smoking, physical inactivity, insufficient intake of fruits and vegetables, obesity and overweight). Finally, we estimated the break-even point beyond which the economic benefits of the HLHP strategy would outweigh its costs. RESULTS: The HLHP strategy cost for 2010-2011 was estimated at $110 million. Direct healthcare expenditures associated with lifestyle-related risk factors were estimated at $4.161 billion. We estimated that 47 % of these expenditures were attributable to these risk factors. CONCLUSIONS: We concluded that the HLHP strategy cost corresponded to 5.6 % of the annual healthcare expenditures attributable to these risk factors. This study compared the economic value of HLHP activities against healthcare expenditures associated with targeted risk factors.

The Impact of Recent Generic Drug Price Policies on Pharmaceutical Innovation: A Theoretical Rationale and Proposal of a Method Supporting Innovation in Areas of Unmet Medical Need.

New discoveries are a critical priority for the pharmaceutical industry. However, the use of fixed incremental cost-effectiveness (ICER) thresholds for health technology assessment (HTA) may compromise incentives to innovate and affect future treatment options. This paper highlights the impact of generic drug price policies on pharmaceutical innovation in the context of fixed ICER thresholds and proposes a new consideration for the cost-effectiveness analysis (CEA). There is a direct causal relationship between HTA and the market price of a drug; in jurisdictions where HTA agencies apply fixed ICER thresholds as an important reimbursement listing criterion, the incremental cost of a new drug is expected to be proportional to its incremental benefit over the comparator. However, the comparator price is subject to market forces or sudden policies and may change markedly affecting the cost-effectiveness assessment (e.g. where the comparator patent has expired). Since recent generic price regulations increased the price gap between drugs' generic and patented versions, it is harder to achieve a sufficient level of incremental benefits in order to offset incremental prices of new treatments. Consequently, even promising drugs may have challenges to show attractive ICERs and research and development (R&D) investments may become unattractive in certain disease area. In order to promote innovation in therapeutic fields with unmet medical needs, a compromise would be to include the comparator's patented price in the CEA instead of the generic drug. By identifying the relevant disease areas, decision makers and HTA authorities could therefore convey the importance of investing in these therapeutic areas to manufacturers.

The economic value of Quebec's water fluoridation program.

AIM: Dental caries is a major public health problem worldwide, with very significant deleterious consequences for many people. The available data are alarming in Canada and the province of Quebec. The water fluoridation program has been shown to be the most effective means of preventing caries and reducing oral health inequalities. This article analyzes the cost-effectiveness of Quebec's water fluoridation program to provide decision-makers with economic information for assessing its usefulness. METHODS: An approach adapted from economic evaluation was used to: (1) build a logic model for Quebec's water fluoridation program; (2) determine its implementation cost; and (3) analyze its cost-effectiveness. Documentary analysis was used to build the logic model. Program cost was calculated using data from 13 municipalities that adopted fluoridation between 2002 and 2010 and two that received only infrastructure grants. Other sources were used to collect demographic data and calculate costs for caries treatment including costs associated with travel and lost productivity. RESULTS: The analyses showed the water fluoridation program was cost-effective even with a conservatively estimated 1 % reduction in dental caries. The benefit-cost ratio indicated that, at an expected average effectiveness of 30 % caries reduction, one dollar invested in the program saved $71.05-$82.83 per Quebec's inhabitant in dental costs (in 2010) or more than $560 million for the State and taxpayers. CONCLUSION: The results showed that the drinking-water fluoridation program produced substantial savings. Public health decision-makers could develop economic arguments to support wide deployment of this population-based intervention whose efficacy and safety have been demonstrated and acknowledged.

The excess healthcare costs associated with depression and anxiety in elderly living in the community.

OBJECTIVE: To estimate the excess healthcare costs attributable to depression and anxiety in a public managed care system. METHODS: The data were retained from a population-based health survey on 2,494 community-dwelling older adults age 65 years or more participating in the ESA (Étude sur la Santé des Aînés) study. Depression and anxiety were assessed using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria and measured at two time points 1 year apart. Annual healthcare costs considered included hospitalizations, emergency and outpatient visits, physician fees, and outpatient medications. Health service use and costs were identified from provincial administrative databases. Costs were studied as a function of the presence (yes/no) of depression and anxiety, and as persistence, incidence/remission, and no illness. Generalized linear models with a gamma distribution (log link) were used to control for a number of factors. RESULTS: Participants with depression had higher outpatient mental health-related costs. Participants with anxiety had higher total healthcare costs and specifically outpatient costs and inpatient costs. As opposed to people without depression and anxiety, persistent cases had higher mean costs followed by people with the disorders for only part of the year. Most of these differences were explained by sociodemographic and clinical factors. The excess annual adjusted healthcare costs of depression, anxiety, and comorbid depression and anxiety reached $27.4, $80.0, and $119.8 million per 1,000,000 population of elderly, respectively. CONCLUSION: The excess costs of depression and anxiety in community-dwelling elderly are just as significant as those observed for adults even when productivity losses are not considered. Adequately managing depression and anxiety in the older adult population may lead to important healthcare cost savings for society.

The costs associated with antidepressant use in depression and anxiety in community-living older adults.

OBJECTIVE: To determine the costs associated with antidepressant (AD) use by depression and anxiety status in a public-managed health care system. METHODS: Data were obtained from a population-based health survey of 1869 older adults. Depression and anxiety were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and measured at 2 time points 1 year apart. AD and health service use and costs were identified from provincial administrative databases and included hospitalizations, physician fees, outpatient medications, and ambulatory visits. Patient costs considered were related to drug copayments, transportation, and time spent seeking medical care. Annual costs associated with AD use were studied as a function of mental health status at baseline and follow-up interviews (persistence, incidence, remission, or no illness). Generalized linear models with a gamma distribution were used to control for individual factors. RESULTS: The costs incurred by participants using ADs as a whole (17.8%) reached $6678 (95% CI $5449 to $8182), significantly more than in participants not using ADs ($4698; 95% CI $3710 to $5949). AD use was associated with greater total adjusted costs among respondents with no depression (adjusted difference = $1769; 95% CI $236 to $3702) and no anxiety (adjusted difference = $1845; 95% CI $203 to $3486). CONCLUSION: The results showed that AD use was not associated with cost savings in any group, and indeed with greater costs among participants who were neither depressed nor anxious at any time point. Future cost studies may consider the analyses of different AD classes regarding the different clinical mental health profiles in older adults.

Economic impact of inappropriate benzodiazepine prescribing and related drug interactions among elderly persons.

OBJECTIVES: The purpose of this study was to describe, from a health care system perspective, potentially inappropriate benzodiazepine prescribing among elderly persons in a publicly funded health system in Canada as well as health service use and costs associated with such prescriptions and the related drug interactions. METHODS: The sample (N=2,320) was representative of Quebec's community-dwelling elderly population (≥ 65 years) and consisted of respondents to the 2006 ESA survey (Enquête sur la Santé des Aînés, or Survey on the Health of the Elderly). The definition of potentially inappropriate benzodiazepine prescription was based on Beers criteria and on the potential for benzodiazepine-related drug interactions. Using a retrospective design, logistic regressions tested the association between inappropriate prescribing and health service use incurred over 12 months. The cost analysis used a generalized linear model with a gamma distribution. RESULTS: Thirty-two percent (N=744) had received a benzodiazepine prescription, and 44% of this group received at least one potentially inappropriate prescription. Participants susceptible to benzodiazepine-related drug interactions, unlike those with inappropriate prescriptions according to Beers criteria, had a greater risk of hospitalizations and of emergency department and outpatient visits and higher health care costs ($3,076 higher per year, p<.001) than those with appropriate prescriptions. CONCLUSIONS: Use of administrative and survey data permitted control for several factors, and a significant association between benzodiazepine-related drug interactions and health care costs among elderly persons was found. Research should further examine this association and evaluate the potential of shared medical electronic databases to decrease life-threatening drug interactions affecting this population.

Correlates of potentially inappropriate prescriptions of benzodiazepines among older adults: results from the ESA study.

ESA study data were paired with Quebec medical and pharmaceutical services records to document potentially inappropriate benzodiazepines (Bzs) prescriptions among community-dwelling adults aged 65 and older. Results indicate that 32 per cent of respondents took a mean daily dose of 6.1 mg of equivalent diazepam for, on average, 205 days per year. Almost half (48%) of Bzs users received a potentially inappropriate benzodiazepine prescription at least once during the year preceding the survey. About 23 per cent received at least one concomitant prescription of a Bz and another drug that could result in serious interaction. In addition, individuals aged 75 and older were more likely to receive Bzs for a longer period of time than those aged 65-74. Number of pharmacies used was associated with inappropriate Bzs prescriptions. Our results argue in favour of a more integrated health services system, including a regular review of older adults' drug regimens.

Pattern of psychotropic drug use among older adults having a depression or an anxiety disorder: results from the longitudinal ESA study.

OBJECTIVE: To document the use of psychotropic drugs in Quebec older adult population with a depressive or anxiety disorder. METHOD: Data from the Enquête sur la Santé des Aînés (ESA) study conducted between 2005 and 2008 using a representative sample (n = 1869) of community-dwelling adults aged 65 years and older were used to examine the use of psychotropic drugs in the Quebec older adult population. RESULTS: Our results indicate that only 46.9% of the older adults with a diagnosis of depression or anxiety during the 24-month period studied according to the Régie de l'assurance maladie du Quebec (RAMQ) register used antidepressants (AD) for 400 days (12.9 months) on average during this period. Also, 59% of the RAMQ's mental health disorder patients used a mean daily dose of 5 mg of a diazepam equivalent for 338 days (10.9 months) on average during the same period. However, 10.0% of the older adults without any symptoms (ESA) at T1 and at T2 and any RAMQ depression and anxiety diagnosis between T0 and T2 were AD users during the 24-month period studied. They represent 26.2% of the AD users and consumed them for 494 days (15.9 months) on average during the 24-month period studied. Finally, the number of days of AD and benzodiazepine use was not associated with partial or total remission. CONCLUSIONS: This result questions the population effectiveness of these drugs in this population.