ABSTRACT Background Ischaemic stroke (IS) is a major cause of death and disability and affects the quality of life of patients. Previous studies focused on urban populations. Objective To evaluate the health-related quality of life (QoL) of patients with history of IS and living in a rural area in Poland. Patients Rural population of 172 patients discharged from a district hospital in Zakopane, Poland with a diagnosis of IS in the period from 01.01.2005 to 31.10.2006. Intervention QoL was evaluated using the European Quality of Life Scale-5 Dimensions EQ-5D-3 L (EQ-5D) and the Short Form Health Survey ? 12 version 2 (SF-12). Results In the EQ-5D survey, 57.3% of patients had only some problems with mobility, 40.3% with usual activities, 63.2% with pain/discomfort, 59% with anxiety/depression, and 32.2% with self-care. In the SF-12 survey, both summary components (physical and psychological) were reduced compared to the population norm. Conclusion The quality of life in IS survivors is clearly reduced in the majority of domains assessed by the EQ-5D and SF-12 questionnaires. The most important factors affecting QoL were the functional state, depression and anxiety. A significant difference as compared to to urban and mixed populations was observed for a reduced SF-12 mental health component and for the EQ-5D visual analogue scale. We found no effect of gender, age or cognitive disorders on the outcomes of SF-12.

OBJECTIVES: Cervical cancer is a leading cause of cancer-related mortality in women in China. This analysis is a quantitative evidence synthesis pooling information about each cervical cancer risk factor. METHODS: A meta-model was developed to estimate the risk of cervical cancer for a woman aged 18-85 years in Mainland China based on her risk profile at the time of assessment. The meta-model was built using findings of a systematic literature review that identified 21 case-control studies reporting data on 105 groups of cervical cancer risk factors in Chinese women. Extracted risk factors were ranked, and 17 were selected by Chinese clinical experts for inclusion in the meta-model. Risk equations were developed for each selected study. Predicted risks for each study were dependent on the risk profile under consideration and study-specific risks were pooled to an overall risk estimate using a random-effects meta-analysis. Sensitivity analysis was conducted using 100 artificial patient profiles (in the absence of patient data). RESULTS: Predicted risks for the 100 profiles suggested that the model had good face validity and could differentiate between high and non-high cervical cancer risk profiles. CONCLUSION: This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.

Objectives: While several authors have suggested using a multi-criteria approach for orphan drug assessment and proposed lists of determinants of orphan drug value, studies on social preferences regarding these determinants remain limited. The current study aimed to identify preferences of the French general population regarding attributes characterizing the value of orphan drugs in a discrete choice experiment.Methods: The list of attributes was formed based on a literature search and was refined through expert interviews, a focus group, and a pilot study. The final list included nine attributes: disease-associated disability, disease-associated mortality, number of patients, availability of alternative treatments, treatment impact on disease disability, treatment impact on mortality, treatment safety, uncertainty around therapeutic effect, and annual treatment cost per patient. Members of the General Public were presented with 12 choice sets containing two drug profiles described according to the attributes and an option to fund neither of these treatments. The questionnaire was disseminated online. A conditional logit model with random effects was used to estimate the weight of each attribute.Results: A total of 958 persons participated in the study (48.7% male, mean age: 47.5 years). All attributes except for disease-associated disability had a statistically significant influence on the choices made by participants. The attribute with the highest weight was treatment impact on mortality (p < 0.0001), followed by uncertainty around therapeutic effect (p < 0.0001). The direction of results was generally consistent with intuition: patients preferred a drug with a larger impact on mortality, a larger impact on disability, with mild or no adverse events, with less uncertainty. Although patients appeared to prefer drugs with a lower budget impact, the relationship between patient preferences and costs was more complex.Conclusions: Preferences of the general public between orphan drugs are mostly driven by the impact on mortality and the degree of certainty regarding the available evidence.

Health state utility values (HSUVs) identified from utility elicitation studies are widely used in pharmacoeconomic evaluations for chronic hepatitis C (CHC) and are particularly instrumental in health technology assessment (HTA) evaluations such as those from the National Institute for Health and Care Excellence (NICE).

BACKGROUND: In recent years there is a growing interest in public beliefs about mental disorders. Numerous representative population-based studies have been conducted around the globe, also in European countries bordering on the Mediterranean Sea. However, relatively little is known about public beliefs in countries in Northern Africa. OBJECTIVE: To fill this gap by comparing public beliefs about mental disorders in Tunisia and Germany, focusing on causal beliefs, help-seeking recommendations and treatment preferences. METHODS: Representative national population-based surveys have been conducted in Tunisia in 2012 (N = 811) and in Germany in 2011 (N = 1852), using the same interview mode and the same fully structured interview starting with a vignette depicting a person suffering from either schizophrenia or depression. RESULTS: In Tunisia, the public was more likely to adopt psychosocial and to reject biogenetic explanations than in Germany. Correspondingly, psychological treatments were more frequently recommended and biological ones more frequently advised against. There was also a strong inclination to share religious beliefs and to recommend seeking religious advice. Tunisians tended much more than Germans to hold moralistic views and to blame the afflicted person for his or her illness. In Tunisia, the public tended less to differentiate between schizophrenia and depression than in Germany. CONCLUSION: Marked differences between Tunisia and Germany exist in public beliefs about the causes of mental disorders and their treatment, which correspond to differences in cultural orientations prevailing in these countries. Mental health professionals need to be sensitive to the particular cultural context in which they operate, in order to be able to reach those they intend to care for.

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial (RCT) data with valuable information on patient behaviours and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges.The objectives of this communication were to (1) summarise all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses.No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants (NOACs) in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results.RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines.

OBJECTIVES: Doctor shopping, double doctoring, and overlapping prescriptions are often used as synonyms for multiple physician appointments in the same disease episode. Such behaviours translate into poor patient satisfaction and patient-doctor communication as well as abuse or misuse of drugs, increasing health care costs and resulting in negative health consequences. This systematic review of the literature was conducted to identify factors that drive doctor-shopping behaviour in children’s caregivers. METHODS: The search was conducted in PubMed and grey literature and was based on the following search terms: included doctor or physician shopping, drug seeking, double doctoring, children, and combinations of those. Overall, 500 records were identified, of which 11 were selected for qualitative synthesis. Data extracted considered definitions of doctor shopping, co-morbidities, and target population characteristics. RESULTS: Definitions of doctor shopping were inconsistent. The frequency of doctor shopping was high for acute illnesses and ranged from 53% in children with a fever in Hong Kong to 18% at an emergency department in Canada. The incidence of this phenomenon was low when taking into account addictive drugs and was rated at 0.02% to 0.3% in the full paediatric population. This phenomenon was more prevalent in children younger than 1 year, in children with attention-deficit hyperactivity disorder (ADHD) and co-morbid psychiatric conditions, and in those whose caregivers themselves had psychiatric conditions. It was more frequent in cases with an acute disease (eg, fever, gastroenteritis, and urinary tract infection) than a chronic disease (eg, asthma). CONCLUSIONS: The knowledge about doctor shopping by children’s caregivers is limited, despite that this is a frequent behaviour. There is a need for further research covering a broader range of diseases. The causes and consequences of doctor shopping should be sought as well to investigate its relation to health care regulations and possibility to reduce unnecessary medical resource utilization.

ABSTRACTObjective Advanced Therapy Medicinal Products (ATMPs) present significant therapeutic advantages for inherited rare diseases. However, the development of orphan ATMPs is challenging due to their complexity and unpredictable biological activity. This study aims to comprehensively describe the current state of orphan ATMPs in Europe.Methods Orphan drugs (ODs) granted by European Commission until March 2020 were investigated. The characteristic of diseases and ATMPs were extracted from the public summary reports of ODs from Committee for Orphan Medicinal Products. The methodology for the pivotal studies of ATMPs was extracted.Results A total of 274 ATMPs were identified, covering 116 rare diseases, with metabolic, optical, and oncologic diseases being the most targeted. A total of 158 ATMPs were indicated for life-threatening diseases, 129 ATMPs targeted diseases currently lacking authorized or satisfactory treatment available. Twenty-eight ATMPs are being investigated in the phase II/IIII or phase III studies. The median patient size of pivotal studies was 127, 15 were open-label studies, 8 were single-arm trials, and 14 reported surrogate outcomes.Conclusion There are rapid growths in developing ATMPs for life-threatening diseases with high unmet clinical needs. Optimizing the study methodology and exploring innovative design to facilitate the market access is paramount.

BACKGROUND: Despite the burden of varicella, there is no universal varicella vaccination (UVV) programme in the United Kingdom (UK) due to concerns this could increase herpes zoster (HZ) incidence. This study assessed the cost-utility of a first-dose monovalent (V) or quadrivalent (MMRV) followed by a second-dose quadrivalent (MMRV) UVV programmes. GSK and MSD varicella-containing vaccines (VCVs) were considered. METHODS: A dynamic transmission and cost-effectiveness models were adapted to the UK. Outcomes measured included varicella and HZ incidences, the incremental cost-utility ratio (ICURs) over a lifetime horizon. The payer and societal perspectives were evaluated. RESULTS: The impact of V-MMRV and MMRV-MMRV UVV programmes on varicella incidence was comparable between both VCVs at equilibrium. HZ incidence increased by 1.6%-1.7% over seven years after UVV start, regardless of the strategies, then decreased by >95% at equilibrium. ICURs ranged from £5,665 (100 years) to £18,513 (20 years) per quality-adjusted life year (QALY) gained with V-MMRV; and from £9,220 to £27,101 per QALY gained with MMRV-MMRV (payer perspective). MMRV-MMRV was cost-effective in medium- and long-terms with GSK VCV, and only cost-effective at long-term with MSD VCV at £20,000 per QALY gained threshold. Without the exogenous boosting hypothesis, HZ incidence decreased through UVV implementation. ICURs were most sensitive to discount rates and MMRV price. CONCLUSIONS: A 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for money.