Unraveling the Mystery of Polyvalent Immunoglobulins in Belgium: Do We Have an Indication?

INTRODUCTION: Worldwide, polyvalent immunoglobulin (Ig) use is rising. Together with the limited supply, this puts pressure on Ig availability. A clear overview on a country's usage pattern helps in forecasting future needs. This research aims to provide an overview of Ig use in Belgium on the different indications, including an estimation of off-label use. METHODS: Multiple data sources were used. Existing claims data were explored for reimbursed Ig use between 2010 and 2018. General 2018 sales data from the firms were compared to the reimbursed use to serve as a proxy for off-label use. Indication-specific information was retrieved via a proxy: diagnostic codes available during day-care and inpatient hospitalization. RESULTS: In 2018, 7,556 patients had reimbursed Ig. The most prevalent indication, both in terms of patient numbers and volume, was primary immunodeficiency (PID). In Belgian hospitals, the currently reimbursed indications represented 84.4% of patients (PID [≈35%], secondary immunodeficiency [SID] [≈21%], primary immune thrombocytopenia [≈10%], chronic inflammatory demyelinating neuropathy [CIDP] [≈8%], Guillain-Barre syndrome [≈6%], Kawasaki [≈2%], streptococcal toxic shock [≈2%] and multiple motor neuropathy [≈1%]), and 82.4% of Ig use (predominantly PID [≈33%] and CIDP [≈21%]). Although no direct data on off-label use were available, crude estimates derived from indirect sources showed a proportion of around 15.4%. CONCLUSION: Our research offers the first comprehensive overview on Ig use in Belgium, including a detailed description of reimbursed use, as well as approximations to off-label use. In view of increasing pressure on Ig availability, better understanding Ig needs and trends, would benefit from an effective indication-specific national registry system (ideally covering both reimbursed and nonreimbursed use).

Obstacles to the recognition of medical prescriptions issued in one EU country and presented in another.

A study involving the presentation of 192 Belgian or Finnish prescriptions in pharmacies in five other member states was undertaken to assess whether, as envisaged by European Union law, prescriptions issued in one member state are dispensed by pharmacists in another and to identify factors that influence such decisions. Overall, pharmacists were willing to dispense in 108 cases. Detailed results show important differences depending on the country where prescriptions are presented and whether prescriptions were written by International Nonproprietary Name and in English, as opposed to prescriptions written by brand in a national language.

Study designs for clinical trials applied to personalised medicine: a scoping review.

OBJECTIVE: Personalised medicine (PM) allows treating patients based on their individual demographic, genomic or biological characteristics for tailoring the 'right treatment for the right person at the right time'. Robust methodology is required for PM clinical trials, to correctly identify groups of participants and treatments. As an initial step for the development of new recommendations on trial designs for PM, we aimed to present an overview of the study designs that have been used in this field. DESIGN: Scoping review. METHODS: We searched (April 2020) PubMed, Embase and the Cochrane Library for all reports in English, French, German, Italian and Spanish, describing study designs for clinical trials applied to PM. Study selection and data extraction were performed in duplicate resolving disagreements by consensus or by involving a third expert reviewer. We extracted information on the characteristics of trial designs and examples of current applications of these approaches. The extracted information was used to generate a new classification of trial designs for PM. RESULTS: We identified 21 trial designs, 10 subtypes and 30 variations of trial designs applied to PM, which we classified into four core categories (namely, Master protocol, Randomise-all, Biomarker strategy and Enrichment). We found 131 clinical trials using these designs, of which the great majority were master protocols (86/131, 65.6%). Most of the trials were phase II studies (75/131, 57.2%) in the field of oncology (113/131, 86.3%). We identified 34 main features of trial designs regarding different aspects (eg, framework, control group, randomisation). The four core categories and 34 features were merged into a double-entry table to create a new classification of trial designs for PM. CONCLUSIONS: A variety of trial designs exists and is applied to PM. A new classification of trial designs is proposed to help readers to navigate the complex field of PM clinical trials.

An evaluation of managed entry agreements in Belgium: A system with threats and (high) potential if properly applied.

OBJECTIVE: To evaluate the strengths and weaknesses of managed entry agreements (MEAs) in Belgium. METHODS: All Belgian MEAs signed between 2010 and 2015 (n = 71) were studied, including the re-evaluations of 16 reimbursement requests for which the initial MEA had ended. The analysis was supported by the findings from a systematic literature review and structured interviews with Belgian stakeholders. RESULTS: The current application of MEAs provides the short-term advantage of getting a positive reimbursement decision with lower confidential prices. However, it is not clear whether the negotiated prices are in line with the added value of the interventions. Furthermore, the contracts do not provide incentives for manufacturers to gather evidence or to set public prices at an acceptable level. CONCLUSIONS: Based on our analysis of the Belgian MEAs and discussions with Belgian stakeholders, an overview of various issues and pitfalls related to the current application of the system is given. Recommendations are made related to providing correct incentives to deliver good evidence, establishing a correct link between identified uncertainties/problems and the type and content of the MEA, reducing the risk of making the system non-transparent, the importance of international collaboration, etc. in order to optimize the potential of this system. These recommendations are addressed to both the Belgian policymakers and stakeholders in other countries making use of MEAs.

The Burden of Pressure Ulcers in Spain.

Pressure ulcers are a serious and debilitating condition treated in all care settings and have a significant impact on both patients and healthcare resources. The objective of this study was to estimate overall treatment costs to the Spanish healthcare system by using a bottom-up costing approach. This study demonstrates that the cost to heal a pressure ulcer increases substantially with the severity of the ulcer, ranging from €24 ([$32.16], Grade I) to €6802 ([$9115], Grade IV) for patients treated in hospitals. Ulcer severity increases overall costs because the time to heal is longer and the incidence of complications is higher in more severe cases. The total cost of pressure ulcer treatment in Spain is approximately €461 million ([$618 million], roughly 5% of total annual healthcare expenditure). Of this, 15% represents the cost of dressings and other materials, while 19% represents the cost of nursing time, and 45% represents the cost of ulcer-related hospital stays.

Evaluating fracture risk in acute ankle sprains: Any news since the Ottawa Ankle Rules? A systematic review.

BACKGROUND: Ankle sprain is frequently encountered, both in primary care and in emergency departments. Since 1992, the Ottawa ankle rules (OAR) can assist clinicians in determining whether an X-ray should be performed to exclude a fracture. Several guidelines recommend the use of OAR based on a systematic review from 2003. Ten years later, one can wonder if this recommendation should be changed. OBJECTIVE: To review systematically the current evidence on the most accurate method to assess the fracture risk after an ankle sprain in adults. METHODS: A methodical search for systematic reviews, meta-analyses and primary studies was carried out in Medline, Cochrane Database of systematic reviews, Embase, Pedro, CINAHL, Medion and specific guideline search engines. At least two independent researchers performed selection, quality appraisal (with validated checklists) and data extraction. RESULTS: One systematic review and 21 primary studies were selected. Sensitivity and specificity of the OAR range from 92-100% and from 16-51%, respectively. To improve the OAR specificity, other tools are proposed such as the Bernese ankle rules. Vibrating tuning fork test and ultrasound could be useful in patient with OAR positive to decrease the need for radiographs. No evidence was found in favour of the use of magnetic resonance imaging (MRI) or computed tomography (CT) in the acute phase of ankle sprain. CONCLUSION: The findings confirm the value of the OAR at ruling out fractures after an ankle sprain and propose other or additional tools to decrease the need for X-rays.

The importance of test accuracy in economic evaluations of companion diagnostics.

BACKGROUND: Economic evaluations of companion diagnostics often fail to include the impact that tests have on the overall economic value of test-drug combinations.  METHODS: To illustrate the importance of test accuracy on the cost-effectiveness of companion diagnostics by means of examples. Data were extracted from the literature. RESULTS: The accuracy of a test and in particularly its specificity, is often more influential on the overall cost-effectiveness results than the price of the test. Specificity becomes more crucial when prevalence of the biomarker is low. Multiple, simultaneous testing faces specific challenges regarding its overall specificity. CONCLUSION: This article opens a discussion on some fundamental points linked to economic evaluations of test-therapy combinations.

What to do when presented with a prescription from another European country: insight from a qualitative study of pharmacists in England.

OBJECTIVES: Prescriptions for medicines issued by healthcare professionals in other parts of the European Union are legally valid in the UK. However, it is not known whether this is fully understood by British community pharmacists. In this study we aimed to understand the implementation of UK pharmacy policy on dispensing prescriptions from other parts of the European Union and to investigate pharmacists' knowledge and interpretation of the relevant provisions in a mystery shopping exercise in English pharmacies. METHODS: We reviewed the policy literature on regulations and practices pertaining to the prescribing and dispensation of prescription-only medicines in the UK. We interviewed key English informants in pharmacy. We then conducted a 'mystery shopping' exercise in 60 randomly selected pharmacies in urban, peri-urban and rural areas of England to investigate how community pharmacists manage four different types of prescriptions from another EU country. KEY FINDINGS: From the eight interviews conducted there was broad consensus that existing processes for verifying the authenticity of foreign prescriptions could be improved. Of the 60 pharmacies visited, only 27% (16 out of 60) were willing to dispense the medication. Pharmacists unwilling to dispense were invited to explain their reasons for refusal. The most common were that they believed that English pharmacists are unauthorised to dispense foreign prescriptions, and that prescriptions must be in the English language or issued by a UK-recognised prescriber. CONCLUSION: Existing processes available to English pharmacists for verifying the authenticity of foreign prescriptions seem to be insufficient. Strategies to overcome these problems were proposed by pharmacists and key informants, and include the creation of a database or registry of all authorised European Economic Area/Swiss prescribers, development of EU standards on prescription content and on dosage of medications, consistent international non-proprietary name (INN) prescribing and the use of an agreed common language for key information on prescriptions.