Natalya Danchenko

Challenges in measuring and valuing productivity costs, and their relevance in mood disorders

Lost productivity is often excluded from economic evaluations, which may lead to an underestimation of the societal benefits of treatment. However, there are multiple challenges in reliably estimating and reporting productivity losses. This article explores the main challenges, ie, selecting an appropriate valuation method (ie, human capital, friction cost, or multiplier), avoiding double counting, and accounting for equity. It also discusses the use of presenteeism instruments and their application in clinical trials, with a specific focus on their relevance in individuals with mood disorders. Further research and discussion is required on the development of reliable techniques for measuring and valuing productivity changes due to presenteeism.

Escitalopram and Duloxetine in Major Depressive Disorder: A Pharmacoeconomic Comparison Using UK Cost Data

AbstractBackground: Selective serotonin reuptake inhibitors (SSRIs) and serotoninnoradrenaline reuptake inhibitors (SNRIs) are approved for the treatment of major depressive disorder (MDD). The allosteric SSRI escitalopram has been shown to be at least as clinically effective as the SNRIs venlafaxine and duloxetine in MDD, with a better tolerability profile. In addition, escitalopram has been shown to be cost saving compared with venlafaxine.Objective: To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers.Methods: The pharmacoeconomic evaluation was conducted alongside a 24-week, double-blind, multinational randomized study (escitalopram 20 mg/day and duloxetine 60 mg/day) in outpatients with MDD, aged 18–65 years, with Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥26 and Clinical Global Impression Severity (CGI-S) score ≥4, and baseline duration of the current depressive episode of 12 weeks to 1 year.The analysis was conducted on the full analysis set (FAS), which included all patients with ≥1 valid post-baseline health economic assessment. Effectiveness outcomes of the cost-effectiveness analyses (CEA) included the change in Sheehan Disability Scale (SDS) score (primary CEA), treatment response (MADRS score decrease ≥50%) and remission (MADRS score ≤12) rates at week 24. Cost outcomes were assessed from the societal perspective. Healthcare resource use and sick leave were evaluated using a health economic assessment questionnaire. Unit costs of healthcare services were obtained from standard UK sources (£, year 2006 values).Results: Over the total 24-week study period, escitalopram was associated with significant cost savings compared with duloxetine (total per-patient monthly cost £188 vs £334, respectively). In the primary CEA, escitalopram dominated duloxetine (i.e. was more effective on the disability scale and less costly). Treatment with escitalopram resulted in significantly lower mean sick leave duration per patient over 24 weeks than duloxetine (30.7 days vs 62.2 days).In multivariate analyses, escitalopram as a treatment choice was associated with a 54% reduction in sick leave duration (p < 0.001). Treatment with escitalopram also resulted in 49% lower total costs than treatment with duloxetine (p = 0.002). Absenteeism accounted for about two-thirds of the overall cost. Early clinical improvement (mean change in MADRS total score, response and remission) had an independent significant impact on the sick leave duration, after controlling for key co-variates.Conclusions: Escitalopram was associated with significantly lower duration of sick leave and significant savings in the total cost compared with duloxetine; it dominated duloxetine when effectiveness was assessed on the SDS scale. Indirect costs due to sick leave accounted for the most substantial portion of the total cost and should, therefore, be an important consideration when pharmacoeconomic comparisons between treatments are made from the societal perspective. The link between decrease in absenteeism and early (8-week) clinical improvement suggested in the additional analyses may explain the reduced sick leave observed with escitalopram, given its superior short-term efficacy compared with duloxetine (demonstrated in the underlying clinical trial).

Association between depression and coronary artery calcification in women with systemic lupus erythematosus

OBJECTIVES To determine the associations between depression, cardiovascular risk factors and coronary artery calcification (CAC) in women with SLE and controls. METHODS CAC was measured using electron-beam CT (EBCT). Traditional, inflammatory and lupus-related risk factors as well as depressive symptoms (Center for Epidemiologic Studies Depression Scale-CES-D) were measured at a single study visit in 161 women with SLE and 161 age- and race frequency-matched female healthy controls. RESULTS Women with SLE reported more depressive symptoms than controls, with 27% of SLE and 15% of controls having CES-D scores suggestive of clinical depression. SLE women were more likely to have CAC, as well as more severe CAC compared with controls. Among the SLE women, depression was associated with greater than 2-fold odds of having any CAC [odds ratio (OR) 2.48; 95% CI 1.05, 5.87; P = 0.04], independent of traditional risk factors (age, hypertension and triglycerides) and inflammatory markers. However, when BMI was included among the covariates, the association between depression and CAC was attenuated, indicating the potential mediating role of BMI. Depression was not a risk factor for CAC in controls. CONCLUSIONS In women with SLE, depression was associated with CAC. This association was mediated by BMI. Depression and adiposity may add to the inflammatory burden of SLE, thus contributing to cardiovascular disease risk.

The use and performance of productivity scales to evaluate presenteeism in mood disorders.

OBJECTIVE Mood disorders are associated with a high societal cost, mainly due to presenteeism. The objective of this study was to review the use of 10 instruments that rate presenteeism in mood disorders and to provide recommendations regarding the appropriateness of instruments in different study settings. METHODS A systematic review of the literature was conducted to identify scales used to measure presenteeism, including the World Health Organization Health and Work Performance Questionnaire, the Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, the Work Limitation Questionnaire, and Work Productivity and Activity Impairment questionnaire. Study characteristics and major results (by symptom level, by treatment arm, correlation to other scales, and use of monetization) were data extracted. RESULTS Twenty-nine studies were identified. The Sheehan Disability Scale, the Work Limitation Questionnaire, and Health and Work Performance Questionnaire were the most commonly used instruments. The majority (60%) of scales demonstrated higher presenteeism in individuals with mood disorders than in individuals without. The Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, and the Work Limitation Questionnaire showed that presenteeism increased with increasing severity of disease. Few studies reported results on presenteeism by treatment, with only small between-treatment differences observed. Good correlations between presenteeism instruments and clinical or quality-of-life scales were reported. Three studies converted results from presenteeism scales into monetary units. CONCLUSIONS Limited experiential evidence exists comparing the performance of presenteeism scales in mood disorders. Therefore, recommendations for inclusion of a presenteeism tool must be driven by instrument properties (ease of administration, amenability to monetization) and the study type. Future research should focus on the responsiveness of the instrument and on how mood disorders impact self-reported assessment.

Association Between Depression and Vascular Disease in Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with increased prevalence of cardiovascular disease (CVD) and depression. Although depression may contribute to CVD risk in population-based studies, its influence on cardiovascular morbidity in SLE has not been evaluated. We evaluated the association between depression and vascular disease in SLE. Methods. A cross-sectional study was conducted from 2002–2005 in 161 women with SLE and without CVD. The primary outcome measure was a composite vascular disease marker consisting of the presence of coronary artery calcium and/or carotid artery plaque. Results. In total, 101 women met criteria for vascular disease. In unadjusted analyses, several traditional cardiovascular risk factors, inflammatory markers, adiposity, SLE disease-related factors, and depression were associated with vascular disease. In the final multivariable model, the psychological variable depression was associated with nearly 4-fold higher odds for vascular disease (OR 3.85, 95% CI 1.37, 10.87) when adjusted for other risk factors of age, lower education level, hypertensive status, waist-hip ratio, and C-reactive protein. Conclusion. In SLE, depression is independently associated with vascular disease, along with physical factors.

Patient-centered assessment of cognitive symptoms of depression.

OBJECTIVE To identify and explore concepts important to patients with cognitive symptoms of major depressive disorder (MDD) and adapt an existing patient-reported outcome (PRO) measure to assess these symptoms. METHODS Four focus groups were conducted with MDD patients (n = 33) to elicit relevant concepts and determine whether one of several PRO scales could be used to assess cognitive symptoms of depression. Following selection and minor modification of the Perceived Deficits Questionnaire (PDQ), cognitive debriefing interviews were conducted with additional patients (n = 17) to further refine and adapt this measure for use in MDD. Minor revisions based on patient input yielded the PDQ for Depression (PDQ-D). RESULTS Focus group participants reported a variety of cognitive symptoms that were classified into 7 general categories: lack of focus and clear thought, memory problems, difficulty with lexical access, difficulty with divided attention, difficulty with decision making, difficulty thinking quickly, and difficulty learning new things. Limitations in work productivity were the most commonly reported impacts of cognitive symptoms. While suggesting a few modifications, focus group participants reacted positively to the PDQ based on the breadth, specificity, and relevance of the items. Cognitive debriefing participants indicated that the modified PDQ items were generally easy to understand and relevant to their experiences with MDD. CONCLUSION Because cognitive symptoms are burdensome to patients with MDD, their assessment is important to optimize treatment outcomes. The PDQ-D has the potential to supplement existing assessment methods, providing unique information important for both comprehensive evaluation of individuals with MDD and evaluation of new treatments.

Cost-Effectiveness Evaluation in Sweden of Escitalopram Compared with Venlafaxine Extended-Release as First-Line Treatment in Major Depressive Disorder

OBJECTIVES Major depressive disorder (MDD) is a major public health concern associated with a high burden to society, the health-care system, and patients and an estimated cost of €3.5 billion in Sweden. The objective of this study was to assess the cost-effectiveness of escitalopram versus generic venlafaxine extended-release (XR) in MDD, accounting for the full clinical profile of each, adopting the Swedish societal perspective, and identifying major cost drivers. METHODS Cost-effectiveness of escitalopram versus venlafaxine XR was analyzed over a 6-month time frame, on the basis of a decision tree, for patients with MDD seeking primary care treatment in Sweden. Effectiveness outcomes for the model were quality-adjusted life-years and probability of sustained remission after acute treatment (first 8 weeks) and sustained for 6 months. Cost outcomes included direct treatment costs and indirect costs associated with sick leave. RESULTS Compared with generic venlafaxine XR, escitalopram was less costly and more effective in terms of quality-adjusted life-years (expected gain 0.00865) and expected 6-month sustained remission probability (incremental gain 0.0374). The better tolerability profile of escitalopram contributed to higher expected quality-adjusted life-years and lower health-care resource utilization in terms of pharmacological treatment of adverse events (though only a minor component of treatment costs). Expected per-patient saving was €169.15 for escitalopram versus venlafaxine. Cost from sick leave constituted about 85% of total costs. CONCLUSIONS Escitalopram was estimated as more effective and cost saving than generic venlafaxine XR in first-line MDD treatment in Sweden, driven by the effectiveness and tolerability advantages of escitalopram. The study findings are robust and in line with similar pharmacoeconomic analyses.

Cost effectiveness of escitalopram versus SNRIs in second-step treatment of major depressive disorder in Sweden

Abstract Objectives: Escitalopram is the S-enantiomer of citalopram and is the most discriminating of the selective serotonin reuptake inhibitors (SSRI). The aim of the current analysis was to assess the cost effectiveness of escitalopram versus the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine and generic venlafaxine as second-step treatment of major depressive disorder. Methods: The analysis was based on a decision analytic model. Effectiveness outcomes were quality-adjusted life-years (QALYs) and remission rates; cost outcomes were direct medical costs, including impact of treating adverse events, and indirect costs associated with lost productivity. The analysis was performed from the societal perspective in Sweden over a 6-month timeframe. Results: Estimated remission rates showed an incremental effectiveness in favour of escitalopram of 16.4 percentage points compared with both SNRI comparators. The escitalopram strategy was associated with a 0.025 increase in QALYs. Sensitivity analyses demonstrated that the model is robust and that escitalopram remains a cost-effective option when considering future predicted price reductions of generic venlafaxine. Limitations: The main limitation in this study was the lack of data available for second-step treatment. The remission rates, which are a key input to the model, were obtained from a relatively small sample of patients on second-step treatment and there are no published relapse rates for second-step treatment. The model also assumed that there was no difference in the adverse event (AE) rates between treatments after the first 8 weeks. Conclusions: This cost-effectiveness analysis indicates that, at a willingness-to-pay threshold of £30,000, escitalopram is the most cost-effective second-step treatment option for MDD in Sweden in over 85% cases compared with both venlafaxine and with duloxetine. Benefits for escitalopram included both increased effectiveness and reduced overall costs. The major contributing costs were those associated with productivity loss. The model was shown to have internal validity and robustness through the use of stochastic simulations and sensitivity analyses, which were conducted around the key efficacy parameters.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland

ABSTRACT Background: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin–norepinephrine reuptake inhibitors. Methods: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. Results: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. Conclusion: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Development of a family functioning scale for major depressive disorder

Abstract Objective: To better understand depression’s impact on family functioning from the perspectives of patients with major depressive disorder (MDD) and their partners; to develop and test patient and partner versions of a new self-reported measure, the Depression and Family Functioning Scale (DFFS), for use in clinical trials. Methods: Concept elicitation interviews were conducted with 32 adults with clinician-diagnosed moderate-to-severe MDD and their respective partners. Twenty-six items were drafted to address relevant aspects of family functioning and were then tested and refined through two iterative sets of cognitive debriefing interviews, each conducted by the same pair of highly experienced researchers, including a licensed clinical psychologist. Results: Depression negatively affects family functioning through poorer communication, increased conflicts, decreased family interaction, and decreased intimacy. No existing instrument measured all domains of interest, or had been rigorously developed and psychometrically validated in the target populations. The draft DFFS items generally tested well and only minor modifications were made to the items after the second set of interviews. Both patients and partners indicated that the final set of 15 DFFS items addresses all concepts of importance. Conclusions: The DFFS evaluates the impact of depression on family functioning and has the potential to provide important information that can facilitate a more comprehensive evaluation of new treatments in clinical trial settings. Although MDD severity was not confirmed with a standardized interview, in clinical practice in the US, MDD is generally not diagnosed with the use of a structured clinical interview or clinician-administered tool. In the current study, depression severity had little (if any) impact on the specific concepts elicited as being important to family functioning. In fact, patients with milder depression had more insight and were able to better articulate changes in family functioning with treatment.