Cost-effectiveness of vortioxetine compared with levomilnacipran and vilazodone in patients with major depressive disorder switching from an initial antidepressant.

Introduction: Many patients with major depressive disorder (MDD) do not achieve remission with their first antidepressant (AD), resulting in a high burden due to treatment failure. Vortioxetine is a valid treatment option for patients with MDD only partially responding to their first AD. Characterization of vortioxetine's potential benefits versus other approved treatments is important. Areas covered: The cost-effectiveness of vortioxetine, including cognitive outcomes, was modeled in comparison with levomilnacipran and vilazodone for patients switched to these medications after inadequate responses to a first AD. Expert opinion: Vortioxetine was associated with incremental quality-adjusted life-year (QALY) gains versus levomilnacipran (0.008) or vilazodone (0.009). Vortioxetine was dominant versus levomilnacipran and cost-effective versus vilazodone (incremental cost-effectiveness ratio [ICER],33,829 USD/QALY). In sensitivity analyses using residual cognitive dysfunction rates (vortioxetine, 49%; levomilnacipran, 58%, and vilazodone, 64%), incremental QALY gains for vortioxetine versus levomilnacipran (0.0085) or vilazodone (0.0109) were found. Vortioxetine remained dominant versus levomilnacipran and cost-effective versus vilazodone (ICER, 27,633 USD/QALY). ICER reduction was found with cognition outcomes inclusion. This model provides additional support for considering vortioxetine for patients requiring a switch of MDD treatments, although its conclusions are limited by the data available for inclusion. Additional research and real-world trials are needed to confirm the findings.

Systematic Literature Review and Network Meta-analysis of the Efficacy and Acceptability of Interventions in Actinic Keratoses.

A systematic literature review was conducted to identify and qualitatively assess randomized controlled trials in immunocompetent patients ≥ 18 years with head- region lesions of actinic keratoses who were treated with field-directed, lesion-directed and other therapies. Network meta-analysis was used to quantitatively evaluate field-directed therapies (5-fluorouracil formulations, diclofenac sodium, imiquimod, ingenol mebutate, 5-aminolevulinic acid or methyl aminolevulinate plus photodynamic therapy) using complete clearance or partial clearance of actinic keratoses lesions, and adverse event-related withdrawals as a proxy of acceptability. Of 2,863 references identified, 75 trials reported in 151 publications were included. In summary, comparative network meta-analysis evaluation showed that 5-fluorouracil formulations were the most efficacious interventions examined. 5-fluorouracil 4%, which was recently approved, showed a comparable efficacy profile to 5-fluorouracil 5%, and had satisfactory acceptability outcomes.

Use of complete clearance for assessing treatment efficacy for 5-fluorouracil interventions in actinic keratoses: how baseline lesion count can impact this outcome.

Background: Many trials in actinic keratoses (AK) use complete clearance rate (100% reduction in number of lesions) as the primary endpoint. We explore limitations (predominantly baseline factors) associated with this outcome. Objective: This analysis assessed the effect of baseline lesion count on complete clearance rate using randomized controlled trials (RCTs) that evaluated 5-fluorouracil (5-FU) formulations, alone or with 10% salicylic acid solution, in patients with AK. Methodology: Correlation between baseline lesion count and complete clearance rate at week 8 was assessed using Pearson's coefficient. Results: Five RCTs assessing 5-FU (4%, 5%, or 0.5% in 10% salicylic acid solution) in 1,080 patients with AK were included. Mean lesion count at baseline ranged from 8.1 to 21.2 lesions per patient. Complete clearance rate was negatively associated with number of lesions at baseline. Correlation between mean number of lesions at baseline and complete clearance rate was strong (r2 = 0.94) and statistically significant (p < 0.001). Conclusion: This analysis showed that, in a homogenous set of trials, complete clearance rates achieved with 5-FU interventions are inversely related to number of lesions at baseline. These findings highlight the limits of restricting treatment evaluation to complete clearance rate and the relevance of alternative measures.

From investigational product to active reference: evolution of oral sumatriptan efficacy versus placebo for the treatment of acute migraine episodes and potential impact in comparative analyses.

Background: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. Objective: To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. Methods: A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. Results: Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67-5.86) around approval (1991-1994) and increased up to 4.14 (3.67-4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. Conclusions: The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs.

Characteristics of patients with depression initiating or switching antidepressant treatment: baseline analyses of the PERFORM cohort study.

BACKGROUND: Patients who require a switch in their antidepressant therapy may have different clinical profiles and treatment needs compared with patients initiating or maintaining a first-line antidepressant therapy. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (MDD) (PERFORM) study was a 2-year observational cohort study in outpatients with MDD in five European countries. Enrolled patients were either initiating or undergoing the first switch to an antidepressant monotherapy. Baseline data on patients' clinical status, functioning, productivity, quality of life and medical-resource use were compared in a cross-sectional baseline analysis. RESULTS: A total of 1402 patients were enrolled, of whom 1159 (82.7%) provided analysable baseline data. The majority (78.7%) of the analysable population were initiating antidepressant treatment and most (83.6%) were enrolled and followed up by general practitioners. Compared with patients initiating antidepressants, those switching antidepressants (21.3%) tended to have more severe depressive symptoms, greater anxiety, worse health-related quality of life, greater functional impairment, greater medical-resource use and had a different medical history. Limitations included an over-representation of switches due to lack of efficacy among patients who were switching treatment, as patients were selected based on presence of depressive symptoms. CONCLUSIONS: Patients with MDD who are switching treatment for the first time have a different profile and different depression-associated health needs compared with those initiating treatment. Therapeutic management should therefore be adapted for patients who switch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01427439 ; Retrospectively registered 26 August 2011.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

Background: Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. Methods: MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. Results: The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. Conclusions: This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder.

Comparative evaluation of vortioxetine as a switch therapy in patients with major depressive disorder.

Switching antidepressant therapy is a recommended strategy for depressed patients who neither respond to nor tolerate an initial pharmacotherapy course. This paper reviews the efficacy and tolerability of switching to vortioxetine. All three published studies of patients with major depressive disorder (MDD) switched from SSRI/SNRI therapy to vortioxetine due to lack of efficacy or tolerability were selected. Vortioxetine was evaluated versus agomelatine directly (REVIVE) and versus sertraline, venlafaxine, bupropion, and citalopram in an indirect treatment comparison (ITC) from switch studies retrieved in a literature review. Vortioxetine׳s impact on SSRI-induced treatment-emergent sexual dysfunction (TESD) was assessed directly versus escitalopram (NCT01364649) in stable patients with MDD. Vortioxetine׳s tolerability in the switch population was compared to the overall MDD population. Vortioxetine showed significant benefits over agomelatine on efficacy, functioning, and quality-of-life outcomes, with fewer withdrawals due to adverse events (AEs) (REVIVE). Vortioxetine had numerically higher remission rates versus all therapies included (ITC). Withdrawal rates due to AEs were significantly lower for vortioxetine versus sertraline, venlafaxine, and bupropion, and numerically lower versus citalopram. Switching to vortioxetine was statistically superior to escitalopram in improving TESD (NCT01364649). Tolerability was similar in the switch and overall MDD populations. These findings suggest that vortioxetine is an effective switch therapy for patients with MDD whose response to SSRI/SNRI therapy is inadequate. Vortioxetine was well tolerated and, for patients with a history of TESD, showed significant advantages versus escitalopram. Vortioxetine appears to be a valid option for patients with MDD who have not been effectively treated with first-line pharmacotherapies.

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder.

BACKGROUND: The objectives of this meta-analysis of data from randomized, placebo-controlled studies were to assess the effect of vortioxetine on overall functioning (primary) and functional remission (secondary) using the Sheehan Disability Scale (SDS) in adults with major depressive disorder (MDD). METHODS: Data from nine short-term (6/8 weeks) pivotal studies that included patient functioning assessments were included in this random-effects meta-analysis, which used aggregated study-level data for all therapeutic vortioxetine doses and a mixed-effect model for repeated measures using the full analysis set. RESULTS: A total of 4,216 patients received ≥1 dose of study treatment (1,522 placebo, 2,694 vortioxetine 5-20 mg/day). At study end, the meta-analysis showed improvement for vortioxetine versus placebo (n = 911) in SDS total score (vortioxetine 5 mg, n = 564, change from baseline versus placebo [Δ] -0.24, p = NS; 10 mg, n = 445, Δ -1.68, p ≤ .001; 15 mg, n = 204, Δ -0.91, p = NS; 20 mg, n = 340, Δ -1.94, p ≤ .01). Functional remission (SDS total score ≤6) was observed with vortioxetine 10 mg (n = 170/573; odds ratio [OR] relative to placebo 1.7, p < .001) and 20 mg (n = 144/447; OR 1.6, p < .05), but not 5 mg (n = 207/757; OR 1.1, p = NS) or 15 mg (n = 92/295; OR 1.3, p = NS). CONCLUSION: Vortioxetine 5-20 mg for 6/8 weeks improved overall patient functioning in patients with MDD. Relative to placebo, vortioxetine 10 and 20 mg demonstrated significant improvement in SDS total score and functional remission.

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

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.

Cost-effectiveness of vortioxetine versus venlafaxine (extended release) in the treatment of major depressive disorder in South Korea.

OBJECTIVE: To assess the cost-effectiveness of vortioxetine versus venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea. METHODS: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states. RESULTS: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US$530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations. CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.

Efficacy and tolerability of switching therapy to vortioxetine versus other antidepressants in patients with major depressive disorder.

OBJECTIVES: To assess the relative efficacy and tolerability of vortioxetine against different antidepressant monotherapies in patients with major depressive disorder (MDD) with inadequate response to selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) therapy. METHODS: A systematic search was conducted for monotherapy studies in patients with MDD with inadequate response to first-line therapy. Treatments included SSRIs, SNRIs, and other antidepressants. Identified studies underwent a three-stage screening/data extraction process and critical appraisal. Adjusted indirect treatment comparisons (ITCs) on systematic literature review outputs were made using Bucher's method, comparing remission rates and withdrawal rates due to adverse events (AEs). RESULTS: Of 27 studies meeting the inclusion criteria, a few studies were of high quality according to the National Institute of Health and Care Excellence checklist. Three studies contributed to an evidence network for quantitative assessment comparing vortioxetine with agomelatine, sertraline, venlafaxine XR, and bupropion SR. Vortioxetine had a statistically significantly higher remission rate than agomelatine (risk difference [RD]: -11.0% [95% CI: -19.4; -2.6]), and numerically higher remission rates than sertraline (RD: -14.4% [95% CI: -29.9; 1.1]), venlafaxine (RD: -7.20% [95% CI: -24.3; 9.9]), and bupropion (RD: -10.70% [95% CI: -27.8; 6.4]). Withdrawal rates due to AEs were statistically significantly lower for vortioxetine than sertraline (RD: 12.1% [95% CI: 3.1; 21.1]), venlafaxine XR (RD: 12.3% [95% CI: 0.8; 23.8]), and bupropion SR (RD: 18.3% [95% CI: 6.4; 30.1]). CONCLUSIONS: The current systematic literature review found a few high quality switch studies assessing monotherapies in patients with MDD with inadequate response to SSRI/SNRIs. ITCs indicated that switching to vortioxetine leads to numerically higher remission rates compared with other antidepressants. Vortioxetine is a well tolerated treatment, showing statistically lower withdrawal rates due to AEs compared with other antidepressants. Vortioxetine is a relevant therapeutic alternative in patients experiencing inadequate response to prior SSRI or SNRI therapy.

The effect of vortioxetine on health-related quality of life in patients with major depressive disorder.

PURPOSE: Major depressive disorder (MDD) has detrimental effects on health-related quality of life (HRQoL). We describe the effect of vortioxetine on HRQoL in MDD patients by using patient-reported outcome instruments. METHODS: HRQoL was evaluated in 5 short-term (6-8 weeks), randomized studies of vortioxetine (5-20 mg/d; n = 2155) versus placebo (n = 1316) in adults with MDD by using the 36-item Short-Form Health Survey (SF-36), the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, the EuroQol 5-Dimension Questionnaire (EQ-5D), and the 12-item Health Status Questionnaire in 1 study in elderly patients. Only patients receiving the approved doses of vortioxetine 5, 10, 15, or 20 mg/d were included in the analysis. A random effects meta-analysis was performed on the 4 adult MDD studies that used the SF-36. A within-studies mixed model for repeated measures analysis based on the full analysis set (FAS) was used unless otherwise specified. Standardized effect size (SES) was calculated to reflect clinical relevance, based on a Cohen's d of 0.2. FINDINGS: Vortioxetine produced significantly better results compared with placebo in the SF-36 mental component summary score (5 mg: 2.6, P = 0.001, SES of 0.22, n = 604; 10 mg: 4.8, P < 0.001, SES of 0.42, n = 328) and 4 domain scores (vitality, social functioning, role emotional, and mental health). Vortioxetine was also significantly better in the EuroQoL-5 Dimension Questionnaire Health State score (10 mg: 7.5, P < 0.05, SES of 0.33, n = 86) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form total score (15 mg: 3.3, P < 0.01, SES of 0.38, n = 127; 20 mg: 4.5, P < 0.0001, SES of 0.52, n = 134) (FAS, last-observation-carried-forward). In the study of elderly patients, vortioxetine 5 mg (n = 136) improved 12-item Health Status Questionnaire scores significantly more than placebo (n = 148) for the domains of health perception (10.4, P < 0.0001, SES of 0.54), mental health (7.9, P < 0.001, SES of 0.44), and energy (6.4, P < 0.05, SES of 0.28) (FAS, mixed model for repeated measures). IMPLICATIONS: Vortioxetine yielded significant, meaningful HRQoL improvements in 6 MDD studies of 6 to 8 weeks' duration.

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram.

OBJECTIVE: To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. METHODS: The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989-2002) and up to 5 years later (1989-2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery-Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. RESULTS: The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants' relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. CONCLUSIONS: Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability.

Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.

INTRODUCTION: Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012). METHODS: We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events). RESULTS: For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking. CONCLUSION: These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.

Cost-effectiveness analysis of pharmaceutical treatment options in the first-line management of major depressive disorder in Belgium.

OBJECTIVE: The objective of this study was to assess the cost effectiveness of commonly used antidepressants as first-line treatment of major depressive disorder (MDD) in Belgium. METHODS: The model structure was based on a decision tree developed by the Swedish TLV (Tandvårds- och läkemedelsförmånsverket) and adapted to the Belgium healthcare setting, using primary local data on the patterns of treatment and following KCE [Federal Knowledge Center (Federaal Kenniscentrum voor de Gezondheidszorg)] recommendations. Comparators were escitalopram, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, and mirtazapine. In the model, patients not achieving remission or relapsing after remission on the assessed treatment moved to a second therapeutic step (titration, switch, add-on, or transfer to a specialist). In case of failure in the second step or following a suicide attempt, patients were assumed to be referred to secondary care. The time horizon was 1 year and the analysis was conducted from the National Institute for Health and Disability Insurance (NIHDI; national health insurance) and societal perspectives. Remission rates were obtained from the TLV network meta-analysis and risk of relapse, efficacy following therapeutic change, risk of suicide attempts and related death, utilities, costs (2012), and resources were derived from the published literature and expert opinion. The effect of uncertainty in model parameters was estimated through scenario analyses and a probabilistic sensitivity analysis (PSA). RESULTS: In the base-case analysis, escitalopram was identified as the optimal strategy: it dominated all other treatments except venlafaxine from the NIHDI perspective, against which it was cost effective with an incremental cost-effectiveness ratio of 6,352 per quality-adjusted life-year (QALY). Escitalopram also dominated all other treatments from the societal perspective. At a threshold of 30,000 per QALY and from the NIHDI perspective, the PSA showed that the probability of escitalopram being identified as the optimal strategy ranged from 61 % (vs. venlafaxine) to 100 % (vs. fluoxetine). CONCLUSION: Escitalopram was associated with the highest probability of being the optimal treatment from the NIHDI and societal perspectives. This analysis, based on new Belgian clinical practice data and following KCE requirements, provides additional information that may be used to guide the choice of treatments in the management of MDD in Belgium.

Cost-effectiveness of escitalopram in major depressive disorder in the Dutch health care setting.

OBJECTIVE: This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective. METHODS: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs). RESULTS: Escitalopram was associated with a cost savings per patient of €263 versus venlafaxine XR and €1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram. CONCLUSION: Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands.

A multicenter prospective observational study of the conformity of temozolomide prescriptions in France.

CONTEXT: Temozolomide (TMZ) is approved for the treatment of high-grade gliomas such as glioblastoma (GBM) multiforme and refractory anaplastic astrocytoma, but it is also used in indications not mentioned in the summary of product characteristics (SPC). The main objective of this study was to evaluate the conformity of TMZ prescriptions to the French SPC and prescription guidebook. METHODS: We conducted a prospective observational study of all consecutive patients treated with TMZ in 21 French hospitals between September 2006 and February 2007, accounting for 39% of total TMZ consumption in France. The conformity of TMZ prescriptions was evaluated in terms of the indication, dosage, treatment duration, and combination with other treatments, with respect to the SPC and prescription guidebook. RESULTS: We enrolled 831 patients (median age, 56 years) who received a total of 5982 TMZ treatment cycles. TMZ was mainly prescribed to patients with newly diagnosed GBM (384 patients), GBM in progression/relapse (28 patients), or anaplastic astrocytoma in progression/relapse (19 patients). Prescriptions conformed to the SPC in 51.9% of cases and to the prescription guidebook in 91.5% of cases. Global conformity with the SPC, in terms of the dosage, treatment duration, and combination with other treatments, was 62% for newly diagnosed GBM treated with radiotherapy plus TMZ, 72% for TMZ maintenance monotherapy, and 66% for GBM and anaplastic astrocytoma in progression/relapse. CONCLUSION/DISCUSSION: In France, routine TMZ prescriptions conform to the SPC and practice guidebook. This is one of the largest studies of drug use in neuro-oncology in terms of the number of patients and cycles analyzed.

Perception of alopecia by patients requiring chemotherapy for non-small-cell lung cancer: a willingness to pay study.

OBJECTIVE: Chemotherapy-induced alopecia may have a substantial impact on the quality of life (QOL) of lung cancer patients, but very few data are available. The aim of this study was to assess the perceived impact of alopecia based on a "willingness to pay" (WTP) approach. METHODS: We conducted a prospective multicenter WTP study of patients receiving chemotherapy for non-small-cell lung cancer (NSCLC). The perceived impact of alopecia was assessed with a visual analogue scale (VAS; 0: no impact, 10: major impact), and from the patients' willingness to pay for chemotherapy that had the same efficacy, dosing schedule and tolerability as the standard treatment but that cut the risk of alopecia from 40% to 5%. RESULTS: Among the 135 patients enrolled in this study, the mean score on the VAS for the perceived likely impact of alopecia was 4.4 ± 0.3. The mean WTP for a 3-week chemotherapy cycle reducing the risk of alopecia from 40% to 5% was €83.4 ± 10.2 (€median 37.5), representing 2.1% of total income, while 27% of patients were unwilling to pay anything. There was a significant association between WTP and gender (women, p < 0.01), annual incomes (p < 0.01), but not with marital status, level of education or occupations. CONCLUSION: Alopecia appears to be an important outcome for patients receiving chemotherapy for NSCLC. Women and patients with high annual incomes were more willing to pay.

[Management and follow-up of patients treated with antiretroviral prophylaxis: an evaluation of professional practices]. / Prise en charge et suivi des patients traités par prophylaxie antirétrovirale : évaluation des pratiques professionnelles.

The care management of patients treated for cases of sexual or blood exposure requires stringent clinical and biological follow-up procedures. Despite the provision of information about the importance of regular follow-up, the number of patients dropping out of screening consultations at the Hospital Lariboisière-Fernand Widal (Assistance Publique-Hôpitaux de Paris) has increased. The main purpose of this study is to improve follow-up for patients treated with anti-retroviral prophylaxis following a known sexual or blood exposure. An investigation based on 5 markers of a targeted clinical audit form ("drop-outs" or lost to follow-up, conduct of HIV serology tests, traceability of clinical, biological and compliance monitoring) was carried out. A review of practices was conducted on the basis of an analysis of patient cases over a six-month period, followed by the implementation and evaluation of corrective measures over a two-year period. A significant decline in the number of patients lost to follow-up was observed. The study shows a significant improvement in other markers: serological follow-up, compliance traceability, and clinical and biological monitoring. These results were observed between 2005 and 2007. Two distinctive effects were identified: improvement in patient care management and the quality of care, and the empowerment of actors, thereby ensuring a certain continuity of action. The decline in the rate of lost to follow-up patients and improved monitoring of compliance and iatrogenic risks confirm these effects. The overall approach is incorporated into an evaluation of professional practices.