Economic evaluation of smoking cessation in Ontario's regional cancer programs.

Quitting smoking after a diagnosis of cancer results in greater response to treatment and decreased risk of disease recurrence and second primary cancers. The objective of this study was to evaluate the potential cost-effectiveness of two smoking cessation approaches: the current basic smoking cessation program consisting of screening for tobacco use, advice, and referral; and a best practice smoking cessation program that includes the current basic program with the addition of pharmacological therapy, counseling, and follow-up. A Markov model was constructed that followed 65-year-old smokers with cancer over a lifetime horizon. Transition probabilities and mortality estimates were obtained from the published literature. Costs were obtained from standard costing sources in Ontario and reports. Probabilistic and deterministic sensitivity analyses were conducted to address parameter uncertainties. For smokers with cancer, the best practice smoking cessation program was more effective and more costly than the basic smoking cessation program. The incremental cost-effectiveness ratio of the best practice smoking cessation program compared to the basic smoking cessation program was $3367 per QALY gained and$5050 per LY gained for males, and $2050 per QALY gained and$4100 per LY gained for females. Results were most sensitive to the hazard ratio of mortality for former and current smokers, the probability of quitting smoking through participation in the program and smoking-attributable costs. The study results suggested that a best practice smoking cessation program could be a cost-effective option. These findings can support and guide implementation of smoking cessation programs

Cost effectiveness of adding budesonide/formoterol to tiotropium in COPD in four Nordic countries

Objective: Assess the cost effectiveness of budesonide/formoterol (BUD/FORM) Turbuhaler®+tiotropium (TIO) HandiHaler® vs. placebo (PBO)+TIO in patients with chronic obstructive pulmonary disease (COPD) eligible for inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Methods: The cost-effectiveness analysis was based on the 12-week, randomised, double-blind CLIMB trial. The study included 659 patients with pre-bronchodilator forced expiratory volume in 1 s ≤ 50% and ≥1 exacerbation requiring systemic glucocorticosteroids or antibiotics the preceding year. Patients received BUD/FORM 320/9 μg bid + TIO 18 μg qd or PBO bid + TIO 18 μg qd. Effectiveness was defined as the number of severe exacerbations (hospitalisation/emergency room visit/systemic glucocorticosteroids) avoided. A sub-analysis included antibiotics in the definition of an exacerbation. Resource use from CLIMB was combined with Danish (DKK), Finnish (€), Norwegian (NOK) and Swedish (SEK) unit costs (2010). The incremental cost-effectiveness ratios (ICERs) for BUD/FORM + TIO vs. PBO + TIO were estimated using descriptive statistics and uncertainty around estimates using bootstrapping. Analyses were conducted from the societal and healthcare perspectives in Denmark, Finland, Norway and Sweden. Results: From a societal perspective, the ICER was estimated at €174/severe exacerbation avoided in Finland while BUD/FORM + TIO was dominant in the other countries. From the healthcare perspective, ICERs were DKK 1580 (€212), €307 and SEK 1573 (€165) per severe exacerbation avoided for Denmark, Finland and Sweden, respectively, while BUD/FORM + TIO was dominant in Norway. Including antibiotics decreased ICERs by 8–15%. Sensitivity analyses showed that results were overall robust. Conclusion: BUD/FORM + TIO represents a clinical and economic benefit to health systems and society for the treatment of COPD in the Nordic countries.publishedVersio

Advantages of the net benefit regression framework for trial-based economic evaluations of cancer treatments: an example from the Canadian Cancer Trials Group CO.17 trial.

BackgroundEconomic evaluations commonly accompany trials of new treatments or interventions; however, regression methods and their corresponding advantages for the analysis of cost-effectiveness data are not widely appreciated.MethodsTo illustrate regression-based economic evaluation, we review a cost-effectiveness analysis conducted by the Canadian Cancer Trials Group's Committee on Economic Analysis and implement net benefit regression.ResultsNet benefit regression offers a simple option for cost-effectiveness analyses of person-level data. By placing economic evaluation in a regression framework, regression-based techniques can facilitate the analysis and provide simple solutions to commonly encountered challenges (e.g., the need to adjust for potential confounders, identify key patient subgroups, and/or summarize "challenging" findings, like when a more effective regimen has the potential to be cost-saving).ConclusionsEconomic evaluations of patient-level data (e.g., from a clinical trial) can use net benefit regression to facilitate analysis and enhance results

Impact of smoking on health system costs among cancer patients in a retrospective cohort study in Ontario, Canada

Objective Smoking is the main modifiable cancer risk factor. The objective of this study was to examine the impact of smoking on health system costs among newly diagnosed adult patients with cancer. Specifically, costs of patients with cancer who were current smokers were compared with those of non-smokers from a publicly funded health system perspective. Methods This population-based cohort study of patients with cancer used administrative databases to identify smokers and non-smokers (1 April 2014-31 March 2016) and their healthcare costs in the 12-24 months following a cancer diagnosis. The health services included were hospitalisations, emergency room visits, drugs, home care services and physician services (from the time of diagnosis onwards). The difference in cost (ie, incremental cost) between patients with cancer who were smokers and those who were non-smokers was estimated using a generalised linear model (with log link and gamma distribution), and adjusted for age, sex, neighbourhood income, rurality, cancer site, cancer stage, geographical region and comorbidities. Results This study identified 3606 smokers and 14 911 non-smokers. Smokers were significantly younger (61 vs 65 years), more likely to be male (53%), lived in poorer neighbourhoods, had more advanced cancer stage,and were more likely to die within 1 year of diagnosis, compared with non-smokers. The regression model revealed that, on average, smokers had significantly higher monthly healthcare costs ($5091) than non-smokers ($4847), p<0.05. Conclusions Smoking status has a significant impact on healthcare costs among patients with cancer. On average, smokers incurred higher healthcare costs than non-smokers. These findings provide a further rationale for efforts to introduce evidence-based smoking cessation programmes as a standard of care for patients with cancer as they have the potential not only to improve patients' outcomes but also to reduce the economic burden of smoking on the healthcare system

Changes in healthcare costs and survival in the era of immunotherapy and targeted systemic therapy for melanoma.

Objectives Melanoma treatment has evolved over the past decade with the adoption of adjuvant and palliative immunotherapies and targeted therapies and changes in use of sentinel node biopsy. The impact on real-world healthcare costs and outcomes is uncertain. Here we examine changes in healthcare costs and survival using administrative data. Approach Using data from the universal healthcare system in Ontario, Canada, we examine a propensity-matched, retrospective cohort of patients aged 20+ years with Stage I-IV invasive cutaneous melanoma from 2018-2019 compared with those from 2007-2012. The primary outcomes were public payer’s mean healthcare per-person costs, and overall survival (OS). Costs were estimated with an established case-mix and claim-based costing algorithm for Ontario, in which person-level costs are allocated for the various healthcare utilizations over time. Standardized mean differences were used to compare costs, and the log-rank test and Cox regression were used to compare survival among stage-stratified, propensity-score matched cohorts. Results We identified 1,138 patients with melanoma from 2018-2019 and 7,654 from 2007-2012. After stage stratification and propensity-matching (N=1,101 per cohort), sentinel lymph node biopsy (62.3% vs. 43.4%) and systemic therapy use (27.3% vs. 12.5%) were more frequent in 2018-2019 compared to 2007-2012. 2018-2019 patients had greater mean healthcare (including systemic therapy) costs compared to 2007-2012 with Stage II ($27,835 vs.$21,179), III ($90,508 vs.$46,242) and IV disease ($118,398 vs.$46,500). There was a seven-to-twelve-fold increase in mean systemic therapy costs for treated patients with Stage III ($68,207 vs.$9,832) and IV disease ($80,905 vs.$6,883). OS was greater in 2018-2019 versus 2007-2012 (2-year OS: 87.8% [95% Confidence Interval {CI}: 85.8-89.6%] vs. 83.7% [95% CI: 81.3-85.7%]; Hazard Ratio {HR}: 0.72 [95% CI: 0.59-0.89]; p<0.05). Conclusion These real-world data highlight trade-offs with adoption of new effective systemic therapies for melanoma, with a greater economic burden to the healthcare system but an associated improvement in survival. Such evolving paradigm changes may prompt dynamic evaluations of healthcare resources and policies to ensure cancer care is sustainable

Is Any Job Better than No Job? Labor Market Experiences and Depressive Symptoms in People Living with HIV

The purpose of this study is to determine the relationship between the psychosocial work environment and labor market experiences (including unemployment) on mental health among adults living with HIV. We used data provided by 538 participants at clinical and community sites across Ontario, Canada. Generalized estimating equation models showed that employment was associated with lower depressive symptoms. For employed participants, adverse psychosocial work conditions, specifically job insecurity, psychological demands, and decision authority were associated with depressive symptoms. For the entire sample, the number of adverse psychosocial work conditions was associated with higher depressive symptoms while participants working in poor quality jobs reported similar levels of depressive symptoms than those who were unemployed or not in the labor force. This study showed that poor quality employment (as assessed by having a high number of adverse psychosocial work exposures) was associated with a similar level of depressive symptoms as unemployment, suggesting that “bad jobs” may not offer the same mental health benefits as “good jobs.” Policies to improve employment outcomes should take the quality of employment into account to maximize mental health benefits as better employment may lead to better mental health

Metabotropic glutamate receptor subtype 7 controls maternal care, maternal motivation and maternal aggression in mice

The group III metabotropic glutamate receptor subtype 7 (mGlu7) is an important regulator of glutamatergic and GABAergic neurotransmission and known to mediate emotionality and male social behavior. However, a possible regulatory role in maternal behavior remains unknown to date. Adequate expression of maternal behavior is essential for successful rearing and healthy development of the young. By understanding genetic and neural mechanisms underlying this important prosocial behavior, we gain valuable insights into possible dysregulations. Using genetic ablation as well as pharmacological modulation, we studied various parameters of maternal behavior in two different mouse strains under the influence of mGlu7. We can clearly show a regulatory role of mGlu7 in maternal behavior. Naive virgin female C57BL/6 mGlu7 knockout mice showed more often nursing postures and less spontaneous maternal aggression compared to their heterozygous and wildtype littermates. In lactating C57BL/6 wildtype mice, acute central activation of mGlu7 by the selective agonist AMN082 reduced arched back nursing and accelerated pup retrieval without affecting maternal aggression. In addition, in lactating CD1 wildtype mice the selective mGlu7 antagonist XAP044 increased both pup retrieval and maternal aggression. With respect to receptor expression levels, mGlu7 mRNA expression was higher in lactating vs virgin C57BL/6 mice in the prefrontal cortex, but not hypothalamus or hippocampus. In conclusion, these findings highlight a significant role of the mGlu7 receptor subtype in mediating maternal behavior in mice. Region-dependent studies are warranted to further extend our knowledge on the specific function of the brain glutamate system in maternal behavior

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I).

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention

The Movember Prostate Cancer Landscape Analysis: an assessment of unmet research needs

Prostate cancer is a heterogeneous cancer with widely varying levels of morbidity and mortality. Approaches to prostate cancer screening, diagnosis, surveillance, treatment and management differ around the world. To identify the highest priority research needs across the prostate cancer biomedical research domain, Movember conducted a landscape analysis with the aim of maximizing the effect of future research investment through global collaborative efforts and partnerships. A global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy. Men with prostate cancer and thought leaders from a variety of disciplines provided a range of key insights through a range of interviews. Insights were prioritized against predetermined criteria to understand the areas of greatest unmet need. From these efforts, 17 research needs in prostate cancer were agreed on and prioritized, and 3 received the maximum prioritization score by the LAC: first, to establish more sensitive and speci

The efficacy and effectiveness of antidepressants in elderly depressed patients, meta-analytic and pharmacoepidemiological methodologies for the assessment of antidepressant pharmacotherapy

grantor: University of TorontoObjective. The efficacy and effectiveness of antidepressants in depressed elderly patients is unclear. Methods. Meta-analyses (random effects model) aggregated published literature of randomized controlled trials for atypical antidepressants (ATYPs), reversible inhibitors of monoamine oxidase A (RIMAs), selective serotonin reuptake inhibitors (SSRIs), tricyclic anti-depressants (TCAs) and placebo in patients $\ge$60 years old for $\ge$4 weeks. Outcome measures included efficacy, safety and dropout. The effectiveness of antidepressants was examined with a prospective practice-based observational study (1991-1994), rationale for prescribing, survival analysis (Kaplan Meier; Cox Regression), adverse event profile and medication changes. Consecutive outpatients at least 65 years of age, diagnosis of depression and prescribed antidepressant medications were included. Results. Overall meta-analyses, for ATYP indicated that 33.4% (Number of studies = 2, Number of patients = 30; (CI95%: 5.2% to 61.7%)) responded to treatment, 37.5% (12, 280; (29.1% to 45.9%)) reported adverse events and 11.2% (16, 374; (6.9% to 15.6%)) dropped out, respectively. For RIMAs, no efficacy results; 57.7% (4, 106; (35.7% to 79.7%)) and 27.1% (3, 96; ($-$1.2% to 55.5%)). For SSRIs, 54.8% (9, 624; (43.1% to 66.4%)); 59.1% (10, 501; (44.2% to 74.0%)) and 18.5% (20, 1395, (14.3% to 22.6%)). For the TCA, 67.0% (5, 200; (57.4% to 76.7%)); 60.3% (8, 276; (31.3% to 89.2%)) and 23.2% (20, 902; (17.0% to 29.4%)). For placebo, 27.2% (2, 302; (22.1% to 32.2%)); 39.6% (4, 111; (6.9% to 72.4%)) and 25.6% (6, 476, (11.5% to 39.7%)). Comparative meta-analyses indicated no significant differences between antidepressants except for ATYP minus SSRI efficacy $-$36.9% (CI95%: $-$65.4% to $-$8.4%, p = 0.01). For the effectiveness evaluation, 259 patients were seen over 2922 visits (mean age $\pm$ SD 75.1 $\pm$ 6.1 years). "Physician knows medication, feels comfortable prescribing it" was the most common rationale for prescribing. 80% of patients did not have depressive symptoms after four weeks of antidepressant treatment, whereas, 70% had depressive symptoms after 6 months and 60% after 2 years. There was no statistical difference in survival time to depressive symptoms between antidepressant classes. 76.0% of visits reported adverse events (mean = 2.7 $\pm$ 1.8). All classes reported similar adverse event profiles. 74.9% study patients had 1223 medication changes. TCAs, MAOI/RIMAs and ATYPs were most commonly changed to SSRIs. Conclusions. There is little advantage for prescribing one antidepressant class over another, acutely or chronically.Ph.D