Patient Preferences to Assess Value IN Gene Therapies: Protocol Development for the PAVING Study in Hemophilia.

Gene therapies are innovative therapies that are increasingly being developed. However, health technology assessment (HTA) and payer decision making on these therapies is impeded by uncertainties, especially regarding long-term outcomes. Through measuring patient preferences regarding gene therapies, the importance of unique elements that go beyond health gain can be quantified and inform value assessments.

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial.

Background: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19.

Methods: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole.

Patient Preferences in Rare Diseases: A Qualitative Study in Neuromuscular Disorders to Inform a Quantitative Preference Study.

Introduction: It has become increasingly important to include patient preference information in decision-making processes for drug development. As neuromuscular disorders represent multisystem, debilitating, and progressive rare diseases with few treatment options, this study aimed to explore unmet health care needs and patient treatment preferences for two neuromuscular disorders, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM) to inform early stages of drug development.

Methods: Fifteen semi-structured interviews and five focus group discussions (FGDs) were held with DM1 and MM adult patients and caregivers.

Conducting Non-COVID-19 Clinical Trials during the Pandemic: Can Today's Learning Impact Framework Efficiency?

The COVID-19 pandemic has severely disrupted non-coronavirus clinical trials. In the case of life-threatening diseases, such as cancer, this is particularly dangerous, as treatment cannot simply be stopped. In the EU, guidelines for the management of ongoing studies were issued; however, national coordination is still lacking.

Prevalence of Antibiotic Allergy Labels in a Tertiary Referral Center in Belgium.

Background: Antibiotic (AB) allergies are among the most frequently occurring adverse drug reactions. In US literature, AB allergy labels (AAL) are reported in 10% to 15% of patients' charts; however, large-scale European analyses are scarce.

Objectives: To retrospectively assess the prevalence of AAL in a tertiary referral hospital in Belgium between 2010 and 2018.

A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients: A Short Communication.

Background: Posaconazole oral suspension emerged as a promising candidate for prophylaxis of invasive fungal infections in immunocompromised children. Its pharmacodynamic advantages include a broad-spectrum activity and a favorable safety profile; however, they are overshadowed by its large pharmacokinetic (PK) variability, which might cause subtherapeutic exposure. The aim of this study was to develop a population (pop) PK model based on rich sampling data to better understand the PK of posaconazole oral suspension in pediatric patients.

A comprehensive review on non-clinical methods to study transfer of medication into breast milk - A contribution from the ConcePTION project.

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe.

Ghrelin Levels and Decreased Kidney Function in Patients with Early Stages of Chronic Kidney Disease Against the Background of Obesity.

The importance of kidney damage in obese patients is due to the increasing incidence of nephropathies associated with metabolic disorders, their predisposition to a progressive course of the disease, and the need to optimize early disease detection. The purpose of our work is to study the level of cystatin C, ghrelin, and their interrelation in patients with early stages (I-II) of chronic kidney disease (CKD) against the background of obesity. The indicators of daily microalbuminuria in patients of both groups were studied, and it was found that in patients with stage 2 CKD with obesity, it was 1.

Barriers and Opportunities for Implementation of Outcome-Based Spread Payments for High-Cost, One-Shot Curative Therapies.

The challenging market access of high-cost one-time curative therapies has inspired the development of alternative reimbursement structures, such as outcome-based spread payments, to mitigate their unaffordability and answer remaining uncertainties. This study aimed to provide a broad overview of barriers and possible opportunities for the practical implementation of outcome-based spread payments for the reimbursement of one-shot therapies in European healthcare systems. A systematic literature review was performed investigating published literature and publicly available documents to identify barriers and implementation opportunities for both spreading payments and for implementing outcome-based agreements.

Market access of gene therapies across Europe, USA, and Canada: challenges, trends, and solutions.

This review can inform gene therapy developers on challenges that can be encountered when seeking market access. Moreover, it provides an overview of trends among challenges and potential solutions.

Cross-Border Access to Clinical Trials in the EU: Exploratory Study on Needs and Reality.

To analyze the current situation of cross-border access to clinical trials in the EU with an overview of stakeholders' real-life experience, and to identify the needs, challenges, and potential for facilitation of cross-border access. We employed a mixed methods design. Semi-structured interviews and an online survey were conducted with a wide range of stakeholders: patient representatives, investigators/physicians, policy and regulatory experts, academic and commercial sponsor representatives, ethics committee members.

Patient perspectives regarding gene therapy in haemophilia: Interviews from the PAVING study.

Introduction: Exploring patient perceptions regarding gene therapies may provide insights about their acceptability to patients.

Objective: To investigate opinions of people with haemophilia (PWH) regarding gene therapies. Moreover, this study aimed to identify patient-relevant attributes (treatment features) that influence PWH's treatment choices.

Regulatory Science to 2025: An Analysis of Stakeholder Responses to the European Medicines Agency's Strategy.

The pace of innovation is accelerating, and so medicines regulators need to actively innovate regulatory science to protect human and animal health. This requires consideration and consultation across all stakeholder groups. To this end, the European Medicines Agency worked with stakeholders to draft its and launched it for public consultation.

Development and External Validation of an Online Clinical Prediction Model for Augmented Renal Clearance in Adult Mixed Critically Ill Patients: The Augmented Renal Clearance Predictor.

Objectives: Augmented renal clearance might lead to subtherapeutic plasma levels of drugs with predominant renal clearance. Early identification of augmented renal clearance remains challenging for the ICU physician. We developed and validated our augmented renal clearance predictor, a clinical prediction model for augmented renal clearance on the next day during ICU stay, and made it available via an online calculator.

Implementation of Electronic Informed Consent in Biomedical Research and Stakeholders' Perspectives: Systematic Review.

Background: Informed consent is one of the key elements in biomedical research. The introduction of electronic informed consent can be a way to overcome many challenges related to paper-based informed consent; however, its novel opportunities remain largely unfulfilled due to several barriers.

Objective: We aimed to provide an overview of the ethical, legal, regulatory, and user interface perspectives of multiple stakeholder groups in order to assist responsible implementation of electronic informed consent in biomedical research.

SARS-CoV-2 Infections and Impact of the COVID-19 Pandemic in Pregnancy and Breastfeeding: Results from an Observational Study in Primary Care in Belgium.

COVID-19 also affects pregnant and breastfeeding women. Hence, clinicians and policymakers require reliable evidence on COVID-19 epidemiology and consequences in this population. We aimed to assess the susceptibility of pregnant women to SARS-CoV-2 and women's perceived impact of the pandemic on their breastfeeding practices, medical counseling and social support.

Use of Patient Preferences in Health Technology Assessment: Perspectives of Canadian, Belgian and German HTA Representatives.

Objective: Patient preferences can be informative for health technology assessment (HTA) and payer decision making. However, applications may be different per country. The aim of this study therefore was to investigate HTA representatives' opinions on whether and how to incorporate patient preferences in HTA in their respective countries.

Practical Implications From European Hospital Pharmacists on Prospective Risk Assessment for Medicine Shortages.

This study aimed to obtain a comprehensive overview on the perception, attitudes, and experience of European pharmacists with prospective risk assessment procedures in everyday practice, as well as to identify challenges and solutions. This is a follow-up study to the surveys on prospective risk assessment previously carried out within the COST Action 15105 among pharmacists across Europe. In-depth interviews were performed using an interview guide comprising 25 questions.

Past, Current, and Future Cancer Clinical Research Collaborations: The Case of the European Organisation for Research and Treatment of Cancer.

Although collaborations between academic institutions and industry have led to important scientific breakthroughs in the discovery stage of the pharmaceutical research and development process, the role of multistakeholder partnerships in the clinical development of anticancer medicines necessitates further clarification. The benefits associated with such cooperation could be undercut by the conflicting goals and motivations of the actors included. The aim of this review was to identify and characterize past, present, and future stakeholder partnership models in cancer clinical research through the lens of the European Organisation for Research and Treatment of Cancer (EORTC).

Cefepime therapeutic drug monitoring: Evaluation of agreement between peripheral and central venous blood sampling.

Background: Therapeutic drug monitoring for cefepime is increasingly being performed because of the potential relation between exposure and neurotoxicity. An in vitro pilot study suggested significant carryover of cefepime from central venous catheters when blood sampling is carried out via the same catheter used for administration of cefepime. Therefore, the aim of this study was to evaluate carryover of cefepime in a real-life clinical setting.

Dietary Intake of Parkinson's Disease Patients.

Dietary management, as an adjuvant therapy in Parkinson's disease (PD), provides clear benefits to patients. However, baseline information about the usual dietary intake of Parkinson's patients is lacking. We conducted an observational cross-sectional study, investigating the dietary intake in Belgian PD patients, as well as their medication use and knowledge of possible food-drug interactions.

Association of conflicting information from healthcare providers and poor shared decision making with suboptimal adherence in direct oral anticoagulant treatment: A cross-sectional study in patients with atrial fibrillation.

Objective: To assess direct oral anticoagulant (DOAC) adherence and to determine possible determinants for suboptimal adherence in Dutch patients with atrial fibrillation (AF).

Methods: Cross-sectional study of DOAC users who completed a self-reported questionnaire. Adherence was measured with Morisky8-item Medication Adherence Scale (MMAS-8).