Determinants of biological drug survival in rheumatoid arthritis:Evidence from a Hungarian rheumatology center over 8 years of retrospective data

OBJECTIVE: To compare drug survival of biological therapies in patients with rheumatoid arthritis (RA), and analyze the determinants of discontinuation probabilities and switches to other biological therapies. MATERIALS AND METHODS: Consecutive RA patients initiating first biological treatment in one rheumatology center between 2006 and 2013 were included. Log-rank test was used to analyze the differences between the survival curves of different biological drugs. Cox regression was applied to analyze the discontinuation due to inefficacy, the occurrence of adverse events, or to any reasons. RESULTS: A total of 540 patients were included in the analysis. The most frequently used first-line biological treatments were infliximab (N=176, 33%), adalimumab (N=150, 28%), and etanercept (N=132, 24%). Discontinuation of first tumor necrosis factor-alpha (TNF-α) treatment was observed for 347 (64%) patients, due to inefficacy (n=209, 60%), adverse events (n=103, 30%), and other reasons (n=35, 10%). Drug survival rates for TNF-α and non-TNF-α therapies were significantly different, and were in favor of non-TNF-α therapies. Every additional number of treatment significantly increased the risk of inefficacy by 27% (p<0.001) and of adverse events by 35% (p=0.002). After the discontinuation of the initial TNF-α treatment, switching to rituximab and tocilizumab was associated with significantly longer treatment duration than switching to a second TNF-α. The non-TNF-α therapies resulted in significantly longer treatment duration, due to both less adverse events and longer maintenance of effectiveness. CONCLUSION: Non-TNF-α therapies resulted in significantly longer treatment duration, and lost their effectiveness later. Increase in the number of switches significantly increased the risk of discontinuation of any biological therapy

EQ-5D in skin conditions: an assessment of validity and responsiveness

Aims and objectives This systematic literature review aims to assess the reliability, validity and responsiveness of three widely used generic preference-based measures of health-related quality of life (HRQL), i.e., EQ-5D, Health Utility Index 3 (HUI3) and SF-6D in patients with skin conditions. Methods A systematic search was conducted to identify studies reporting health state utility values obtained using EQ-5D, SF-6D, or HUI3 alongside other HRQL measures or clinical indices for patients with skin conditions. Data on test-retest analysis for reliability, known group differences or correlation and regression analyses for validity, and change over time or responsiveness indices analysis were extracted and reviewed. Results A total of 16 papers reporting EQ-5D utilities in people with skin conditions were included in the final review. No papers for SF-6D and HUI3 were found. Evidence of reliability was not found for any of these measures. The majority of studies included in the review (12 out of 16) examined patients with plaque psoriasis or psoriatic arthritis and the remaining four studies examined patients with either acne, hidradenitis suppurativa, hand eczema, or venous leg ulcers. The findings were generally positive in terms of performance of EQ-5D. Six studies showed that EQ-5D was able to reflect differences between severity groups and only one reported differences that were not statistically significant. Four studies found that EQ-5D detected differences between patients and the general population, and differences were statistically different for three of them. Further, moderate-to-strong correlation coefficients were found between EQ-5D and other skin-specific HRQL measures in four studies. Eight studies showed that EQ-5D was able to detect change in HRQL appropriately over time and the changes were statistically significant in seven studies. Conclusions Overall, the validity and responsiveness of the EQ-5D was found to be good in people with skin diseases, especially plaque psoriasis or psoriatic arthritis. No evidence on SF-6D and HUI3 was available to enable any judgments to be made on their performance

International comparability of reference unit costs of education services: when harmonizing methodology is not enough (PECUNIA project)

Background: Health problems can lead to costs in the education sector. However, these costs are rarely incorporated in health economic evaluations due to the lack of reference unit costs (RUCs), cost per unit of service, of education services and of validated methods to obtain them. In this study, a standardized unit cost calculation tool developed in the PECUNIA project, the PECUNIA RUC Template for services, was applied to calculate the RUCs of selected education services in five European countries. Methods: The RUCs of special education services and of educational therapy were calculated using the information collected via an exploratory gray literature search and contact with service providers. Results: The RUCs of special education services ranged from €55 to €189 per school day. The RUCs of educational therapy ranged from €6 to €25 per contact and from €5 to €35 per day. Variation was observed in the type of input data and measurement unit, among other. Discussion: The tool helped reduce variability in the RUCs related to costing methodology and gain insights into other aspects that contribute to the variability (e.g. data availability). Further research and efforts to generate high quality input data are required to reduce the variability of the RUCs

Magnitude of terminological bias in international health services research: a disambiguation analysis in mental health

Aims Health services research (HSR) is affected by a widespread problem related to service terminology including non-commensurability (using different units of analysis for comparisons) and terminological unclarity due to ambiguity and vagueness of terms. The aim of this study was to identify the magnitude of the terminological bias in health and social services research and health economics by applying an international classification system. Methods This study, that was part of the PECUNIA project, followed an ontoterminology approach (disambiguation of technical and scientific terms using a taxonomy and a glossary of terms). A listing of 56 types of health and social services relevant for mental health was compiled from a systematic review of the literature and feedback provided by 29 experts in six European countries. The disambiguation of terms was performed using an ontology-based classification of services (Description and Evaluation of Services and DirectoriEs – DESDE), and its glossary of terms. The analysis focused on the commensurability and the clarity of definitions according to the reference classification system. Interrater reliability was analysed using κ. Results The disambiguation revealed that only 13 terms (23%) of the 56 services selected were accurate. Six terms (11%) were confusing as they did not correspond to services as defined in the reference classification system (non-commensurability bias), 27 (48%) did not include a clear definition of the target population for which the service was intended, and the definition of types of services was unclear in 59% of the terms: 15 were ambiguous and 11 vague. The κ analyses were significant for agreements in unit of analysis and assignment of DESDE codes and very high in definition of target population. Conclusions Service terminology is a source of systematic bias in health service research, and certainly in mental healthcare. The magnitude of the problem is substantial. This finding has major implications for the international comparability of resource use in health economics, quality and equality research. The approach presented in this paper contributes to minimise differentiation between services by taking into account key features such as target population, care setting, main activities and type and number of professionals among others. This approach also contributes to support financial incentives for effective health promotion and disease prevention. A detailed analysis of services in terms of cost measurement for economic evaluations reveals the necessity and usefulness of defining services using a coding system and taxonomical criteria rather than by ‘text-based descriptions’

Budget impact analysis of medicines : updated systematic review and implications

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001 to 2015 on "budget impact analysis" with "drug" interventions were assessed, selected based on their titles/abstracts and full texts, with their characteristics checked according to key criteria. Out of 1984 studies, 92 were identified. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 6 or 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions