Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial.

Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin, N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The "Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)" is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing. Clinical trial registration: http://www.drks.de/DRKS00029044 and https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044.

Establishing a comprehensive list of mental health-related services and resource use items in Austria: A national-level, cross-sectoral country report for the PECUNIA project.

BACKGROUND: A comprehensive, comparable assessment of the economic disease burden and the value of relevant care forms a major challenge in the case of mental diseases. This study aimed to inform the development of a resource use measurement (RUM) instrument and harmonized reference unit costs valid for multi-sectoral and multi-national cost assessments for mental health diseases as part of the European PECUNIA project. METHODS: An iterative, multi-methods approach was applied. Systematic literature reviews appended with national grey literature searches in six European countries were conducted to generate preliminary, literature-based, international, mental health-related service and resource use lists for all investigated sectors in 2018. As part of a multi-national expert survey, these lists were reviewed by 18 Austrian sector-specific experts regarding the clarity, relevance, comprehensiveness and availability in the Austrian context. RESULTS: Out of 295 items included in the preliminary, international, sector-specific lists (health and social care-201 items, criminal justice-35 items, education-39 items; patient, family and informal care-20 items), a total of 261 items and descriptions (88%) were considered clear by all experts. 42 items (14%) were considered not existing in Austria, and 111 items (38%) were prioritized regarding their relevance in the national context. Thirteen additional items (4%) were suggested to be added to accommodate for Austria-specific features of the individual sectors. Major typological difficulties based on item names were observed. CONCLUSIONS: The identified country-specific variations and general typological bias and their potential contributions to service and resource use cost variations across countries and sectors call for further systematic investigation. Next, PECUNIA will develop internationally harmonized and comparable definitions of the listed items and their units of analysis based on a new conceptual multi-sectoral costing framework. The developed lists will require consolidation and further prioritization for the development of a patient-reported RUM instrument and consequent reference unit cost valuation.

Harmonization issues in unit costing of service use for multi-country, multi-sectoral health economic evaluations: a scoping review.

BACKGROUND: Valuation is a critical part of the costing process in health economic evaluations. However, an overview of specific issues relevant to the European context on harmonizing methodological requirements for the valuation of costs to be used in health economic evaluation is lacking. We aimed to inform the development of an international, harmonized and multi-sectoral costing framework, as sought in the European PECUNIA (ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions) project. METHODS: We conducted a scoping review (information extraction 2008-2021) to a) to demonstrate the degree of heterogeneity that currently exists in the literature regarding central terminology, b) to generate an overview of the most relevant areas for harmonization in multi-sectoral and multi-national costing processes for health economic evaluations, and c) to provide insights into country level variation regarding economic evaluation guidance. A complex search strategy was applied covering key publications on costing methods, glossaries, and international costing recommendations augmented by a targeted author and reference search as well as snowballing. Six European countries served as case studies to describe country-specific harmonization issues. Identified information was qualitatively synthesized and cross-checked using a newly developed, pilot-tested data extraction form. RESULTS: Costing methods for services were found to be heterogeneous between sectors and country guidelines and may, in practice, be often driven by data availability and reimbursement systems in place. The lack of detailed guidance regarding specific costing methods, recommended data sources, double-counting of costs between sectors, adjustment of unit costs for inflation, transparent handling of overhead costs as well as the unavailability of standardized unit costing estimates in most countries were identified as main drivers of country specific differences in costing methods with a major impact on valuation and cost-effectiveness evidence. CONCLUSION: This review provides a basic summary of existing costing practices for evaluative purposes across sectors and countries and highlights several common methodological factors influencing divergence in cost valuation methods that would need to be systematically incorporated and addressed in future costing practices to achieve more comparable, harmonized health economic evaluation evidence.

Patient-reported outcome measures suitable for quality of life/well-being assessment in multisectoral, multinational and multiperson mental health economic evaluations.

QUESTION: The aim was to systematically collate and synthesise existing, publicly available patient-reported outcome measure (PROM) information suitable for quality of life (QOL)/well-being measurement in mental health economic evaluations, with specific focus on their applicability in multisectoral, multinational, multiperson economic evaluations and to develop an electronic PROM compendium with meta-data. STUDY SELECTION AND ANALYSIS: A systematic literature search for non-disease-pecific PROMs and their versions suitable for the measurement of QOL/well-being or recovery was conducted from 2008 to February 2020. Six criteria were applied to judge their suitability in multisectoral, multinational, multiperson economic evaluations: (i) availability of separate adult and child/adolescent versions, (ii) availability of a proxy-completion option, (iii) assessing outcomes beyond health, (iv) availability of translations (≥2 language versions), (v) availability of a preference-based valuation, (vi) availability of value sets in more than one country. FINDINGS: The final ProgrammE in Costing, resource use measurement and outcome valuation for Use in multisectoral National and International health economic evaluAtions (PECUNIA) PROM-MH Compendium includes 204 unique scales, out of which 88 are individual instruments, while the remaining 116 scales belong to 46 PROM families with more than one distinctive version. Out of the total 134 individual PROMs/PROM families, 72% have at least two language versions, 8% measure broader well-being beyond health-related QOL, 11% have preference-based valuation, with multiple country sets available for 60% of these. None of the identified PROMs met all six proposed criteria. CONCLUSIONS: The PECUNIA PROM-MH Compendium provides a unique overview of the relevant PROMs and their linked meta-data, and should be a helpful tool when choosing a suitable instrument for future mental health economic evaluations.

Headline indicators for monitoring the performance of health systems: findings from the european Health Systems_Indicator (euHS_I) survey.

BACKGROUND: Cross-country comparisons of health system performance have become increasingly important. Clear evidence is needed on the prioritization of health system performance assessment (HSPA) indicators. Selected "leading" or "headline" HSPA indicators may provide early warnings of policy impacts. The goal of this paper is to propose a set of headline indicators to frame and describe health system performance. METHODS: We identified overlaps and gaps in the availability of reported indicators by looking at HSPA initiatives in Member States (MSs) of the European Union (EU), the European Commission as well as international institutions (e.g. OECD, WHO-EUR). On that basis, we conducted a two-stage online survey, the european Health System_Indicator (euHS_I) survey. The survey sought to elicit preferences from a wide range of HSPA experts on i) the most relevant HSPA domain(s), i.e. access, efficiency, quality of care, equity, for a specific indicator, and ii) the importance of indicators regarding their information content, i.e. headline, operational, explanatory. Frequency analysis was performed. RESULTS: We identified 2168 health and health system indicators listed in 43 relevant initiatives. After adjusting for overlaps, a total of 361 indicators were assessed by 28 experts in the 1st stage of the survey. In the 2nd stage, a more balanced set of 95 indicators was constructed and assessed by 72 experts from 22 EU MSs and 3 non-EU countries. In the domain access experts assessed share of population covered by health insurance as the top headline indicator. In the domain efficiency, the highest rank was given to Total health care expenditure by all financing agents, and in the domain quality of care to rate of hospital-acquired infections. Percentage of households experiencing high levels/catastrophic of out-of-pocket health expenditures results as the top headline indicator for domain equity. CONCLUSIONS: HSPA indicators from different initiatives largely overlap and public health indicators dominate over health systems aspects. The survey allowed to quantify overlaps and gaps in HSPA indicators, their expert allocation to domain areas and establishment of an informed hierarchy structure. Yet, results show that more multidisciplinary work is needed to ensure the availability of accurate efficiency indicators which are comparable across countries.

Health system performance assessment landscape at the EU level: a structured synthesis of actors and actions.

BACKGROUND: Many policy makers and other stakeholders in the EU have expressed interest in better understanding the performance of their own health systems to identify opportunities for improvement in effectiveness, efficiency and equity. Health system performance assessment (HSPA) has received considerable attention at EU level as an instrument to improve transparency and accountability. This is equally important for population health and sustainable health spending. The goal of this paper is to synthesise and map the current state and developments in the field of HSPA relevant in the EU context and by this aid the navigation in the growing HSPA system, understand the available tools and identify opportunities for improvement. METHODS: Structured synthesis of the literature on initiatives in the field of HSPA at EU level was carried out. Key literature was identified by a focused review performed between October 2015 and June 2016 on websites of key institutions including the EU, OECD and WHO and Google engine. We used six predefined criteria for identifying key literature. Identified initiatives were classified according to analytical and conceptual output or whether a guiding or advisory role was resumed. A visual map of the relationships between the different actions and actors involved in HSPA was developed. In addition, expert opinion was sought to refine the map. RESULTS: We identified a total of 64 relevant initiatives and their relationships in the field of HSPA. These include institutions such as the European Commission (73%), European Council (8%), OECD (9%) and WHO-EUR (9%). 24 initiatives produced analytical outputs, four developed conceptual outputs and six had a guiding role. The role of the EU in HSPA and collaboration with other key actors have intensified considerably since the adoption of the EU Health Strategy in 2013. The EU HSPA landscape is complex with seemingly few streamlining activities. CONCLUSIONS: Knowledge transfer and exchange of expertise are key to HSPA. While cooperation between the key actors have intensified recently and clearly reflect the "Health in all Policies" (HIAP) approach, there is considerable room for improved streamlining activities to share knowledge and avoid overlapping efforts, especially within the European Commission.