Time trade-off health state utility values for depression: a systematic review and meta-analysis.

PURPOSE: This study aims to systematically review the literature on health utility in depression generated by time trade-off (TTO) method and to compare health state vignettes. METHODS: Systematic literature search was conducted following PRISMA guideline in 2020 November (updated in 2022 March) in Pubmed, Web of Science, PsycInfo, and Cochrane Database of Systematic Reviews. Random effect meta-analysis was conducted to pool vignette-based utility values of mild, moderate, and severe depression and to compare the preferences of depressed and nondepressed population. RESULTS: Overall, 264 records were found, 143 screened by title and abstract after removing duplicates, 18 assessed full text, and 14 original publications included. Majority of the studies (n = 9) used conventional TTO method, and most of the studies (n = 8) applied 10-year timeframe. Eight studies evaluated self-experienced health (own-current depression). Six studies assessed vignette-based health states of remitted, mild, moderate, and severe depression, half of them applied McSad measure based health description. Altogether, 61 different utility values have been cataloged, mean utility of self-experienced depression states (n = 33) ranged between 0.89 (current-own depression) and 0.24 (worst experienced depression). Pooled utility estimates for vignette-based mild, moderate, and severe depression was 0.75, 0.66 and 0.50, respectively. Meta-regression showed that severe depression (ß = -0.16) and depressed sample populations (ß = -0.13) significantly decrease vignette-based utility scores. CONCLUSION: Our review revealed extent heterogeneity both in TTO methodology and health state vignette development. Patient's perception of depression health states was worse than healthy respondents.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder (MDD) after two antidepressant treatment failures: meta-analysis of randomized sham-controlled trials.

BACKGROUND: Several meta-analyses demonstrated the efficacy of unilateral High-Frequency Left-sided (HFL) repetitive Transcranial Magnetic Stimulation (rTMS) for individuals with Major Depressive Disorder (MDD); however, results are contradictory due to heterogeneity of the included studies. METHODS: A systematic literature review (SLR) of English language articles published since 2000 was performed in March 2022 on PubMed and Scopus databases. Empirical evidence on the relative efficacy of rTMS treatment compared with standard pharmacotherapy in Treatment-Resistant Depression (TRD) were extracted. Random effects models were used to assess the effects of rTMS on response and remission rates. RESULTS: 19 randomized double-blinded sham-controlled studies were included for quantitative analysis for response (n = 854 patients) and 9 studies for remission (n = 551 patients). The risk ratio (RR) for response and remission are 2.25 and 2.78, respectively for patients after two treatment failures using rTMS as add-on treatment compared to standard pharmacotherapy. Cochrane's Q test showed no significant heterogeneity. No publication bias was detected. CONCLUSIONS: rTMS is significantly more effective than sham rTMS in TRD in response and remission outcomes and may be beneficial as an adjunctive treatment in patients with MDD after two treatment failures. This finding is consistent with previous meta-analyses; however, the effect size was smaller than in the formerly published literature.

Repetitive transcranial magnetic stimulation may be a cost-effective alternative to antidepressant therapy after two treatment failures in patients with major depressive disorder.

BACKGROUND: The cost-effectiveness of treatment strategies for patients with Major Depressive Disorder (MDD) who have not responded to two adequate treatments with antidepressants (TRD) are still unclear. The aim of this analysis was to evaluate the cost-effectiveness of add-on repetitive Transcranial Magnetic Stimulation (rTMS) compared with standard treatment. METHODS: A Markov-model simulated clinical events over one year from the perspective of healthcare payer. Third- and fourth-line treatment pathways (augmentation, antidepressant switch or combination, and Electro-Convulsive Therapy (ECT)) were defined based on medical practice guidelines. Transition probabilities were derived from a recent meta-analysis and scientific publications. Resource utilization and cost estimates were based on the patient-level database of a large university hospital. RESULTS: Incremental Quality-Adjusted Life Years (QALYs) and costs were 0.053 and 785 €, respectively, corresponding to an Incremental Cost-Effectiveness Ratio (ICER) of 14,670 € per QALY. The difference in cost between standard treatment and rTMS is explained by the rTMS sessions used in acute (€660) and maintenance (€57/month) treatments, partly offset by lower hospital costs due to higher remission rates in the rTMS arm. Key parameters driving the ICER were incremental utility of remission, unit cost of rTMS treatment and remission rate. At a threshold of €22,243 add-on rTMS is a cost-effective alternative to pharmacotherapy. Evidence on long-term effectiveness is not yet available, so results are estimated for a one-year period. CONCLUSION: Not only does rTMS treatment have beneficial clinical effects compared with drug therapy in TRD, but it also appears to offer good value-for-money, especially in centres with larger numbers of patients where unit costs can be kept low.

Breast cancer stage and molecular subtype distribution: real-world insights from a regional oncological center in Hungary.

OBJECTIVE: Examining the distribution of breast cancer (BC) stage and molecular subtype among women aged below (< 45 years), within (45-65 years), and above (> 65 years) the recommended screening age range helps to understand the screening program's characteristics and contributes to enhancing the effectiveness of BC screening programs. METHODS: In this retrospective study, female patients with newly diagnosed BC from 2010 to 2020 were identified. The distribution of cases in terms of TNM stages, severity classes, and subtypes was analysed according to age groups. RESULTS: A total of 3282 women diagnosed with BC were included in the analysis. Among these cases 51.4% were detected outside the screening age group, and these were characterized by a higher TNM stage compared to those diagnosed within the screening age band. We observed significantly higher relative frequency of advanced BC in the older age group compared to both the screening age population and women younger than 45 years (14.9% vs. 8.7% and 7.7%, P < 0.001). HR-/HER2- and HER+ tumours were relatively more frequent among women under age 45 years (HR-/HER2-: 23.6%, HER2+: 20.5%) compared to those within the screening age range (HR-/HER2-: 13.4%, HER2+: 13.9%) and the older age group (HR-/HER2-: 10.4%, HER2+: 11.5%). CONCLUSIONS: The findings of our study shed light on potential areas for the improvement of BC screening programs (e.g., extending screening age group, adjusting screening frequency based on molecular subtype risk status) in Hungary and internationally, as well.

Should Hungary Pay More for a QALY Gain than Higher-Income Western European Countries?

OBJECTIVES: Cost-effectiveness thresholds (CETs) play a particularly important role in the reimbursement decisions of health technologies in countries with limited healthcare resources. Our goal is to develop a scientifically solid proposal for a revised cost-effectiveness threshold, as part of the planned review of the Hungarian health economic guidance. METHODS: The Threshold Working Group of the Hungarian Health Economics Association performed a targeted review on CETs in European countries. International trends on CETs served as a basis for our recommendation, which was discussed at the Association's workshop and deliberated at an expert committee meeting with representatives from the national health technology assessment (HTA) and healthcare payer bodies, and academic HTA centres. RESULTS: The current Hungarian CET is one of the highest among European countries relative to GDP per capita, and even higher in nominal value than the CET applied by NICE. As opposed to the current, single Hungarian threshold, other European countries apply multiple thresholds. The Working Group recommends that Hungary should also apply multiple CETs in the range of 1.5-3 times GDP per capita with stratification according to the relative quality-adjusted life-year (QALY) gain of the new technology. In addition, multiple CETs in the range of 3-10 times GDP per capita is recommended for technologies in rare diseases. CONCLUSIONS: CETs should be aligned with the country's economic performance and should reflect societal preferences. Our recommendation may increase the efficiency of healthcare resource allocation in Hungary by strengthening the role of HTA in the reimbursement decisions and favouring new technologies with higher QALY gain.

Systematic review of real-world studies evaluating the impact of medication non-adherence to endocrine therapies on hard clinical endpoints in patients with non-metastatic breast cancer.

Breast cancer, one of the most common malignancies, is associated with significant economic and health burden both at the patient and societal level. Although medication non-adherence to endocrine breast cancer therapies is common, so far only limited systematic evidence has been available on its quantitative consequences, as previous systematic reviews focused mainly on factors contributing to medication non-adherence. The objective of this review was to explore the implications of medication non-adherence to endocrine therapies on hard clinical outcomes in breast cancer based on real-world studies. A systematic literature review was conducted on PubMed; empirical evidence on hard clinical endpoints (i.e., survival, disease-free survival, metastasis and recurrence) were extracted from uni- or multivariate statistical analyses from retrospective or prospective cohort studies. Of the 2,360 identified records, 12 studies met the inclusion criteria. Two studies identified significant positive association between medication non-adherence and the risk of distant metastasis, three articles between medication non-adherence and the recurrence of breast cancer, two studies between medication non-adherence- and non-persistence and of worse disease-free survival and eight articles between medication non-adherence and mortality. There was only one study where the positive association between medication adherence and survival did not apply to all subgroups. The strong evidence on the negative health consequences of non-adherence to breast cancer treatments indicates the need for the regular monitoring of medication adherence. Furthermore, explicit inclusion of adherence enhancing interventions into health policy agenda would be warranted to improve medication adherence also at a system level.

LIFEStyle, Prevention and Risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. METHODS AND ANALYSIS: LIFESPAN is an observational, multicentre international case-control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. ETHICS AND DISSEMINATION: The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access. TRIAL REGISTRATION NUMBER: ISRCTN25940508; Pre-results.