Decentralized clinical trials (DCTs) have the potential to improve accessibility, diversity, and retention in clinical trials by moving trial activities to participants’ homes and local surroundings. In this study, we conducted semi‐structured interviews with 20 European regulators to identify regulatory challenges and opportunities for the implementation of DCTs in the European Union. The key opportunities for DCTs that were recognized by regulators include a reduced participation burden, which could facilitate the participation of underserved patients. In addition, regulators indicated that data collected in DCTs are expected to be more representative of the real world. Key challenges recognized by regulators for DCTs include concerns regarding investigator oversight and participants’ safety when physical examinations and face‐to‐face contact are limited. To facilitate future learning, hybrid clinical trials with both on‐site and decentralized elements are proposed by the respondents.

Aims: To assess the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among direct oral anticoagulant (DOAC) users.Methods: We performed a case–control study nested in a cohort of new users of DOACs (dabigatran etexilate, apixaban or rivaroxaban). Data were obtained from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (2008–2015). Cases were patients hospitalized having a primary diagnosis of major bleeding. Up to 4 controls were matched on age, sex, index date and region. Odds ratios (ORs) for the risk of major bleeding were assessed by conditional logistic regression analysis and adjusted for well‐known covariates for the risk of bleeding.Results: We identified 393 patients with a major bleeding from a total of 23 492 new users of DOACs and 1494 matched controls. Most subjects were users of rivaroxaban (58.8%) on the index date. The concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% of cases vs 13.5% of controls, adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI], 1.40–2.66). For the antiplatelet drugs the aOR was 2.01 (95% CI, 1.29–3.11) and for the selective serotonin reuptake inhibitors the aOR was 1.68 (95% CI, 1.10–2.59). We found no increased risk of major bleeding for concurrent use of pharmacokinetic interacting drugs vs DOACs alone (45.0 vs 51.2%; aOR: 0.77; 95% CI: 0.53–1.10).Conclusion: Among patients taking DOACs the concurrent use of antiplatelet drugs or selective serotonin reuptake inhibitors was associated with increased risk of major bleeding, while pharmacokinetic interacting drugs do not increase this risk.

Aim: To identify activities that pharmacists undertake to reduce medication waste, and to assess the extent to which these activities are implemented, their importance for waste-reduction and feasibility for broad implementation. Methods: A two-phase survey was conducted among community and hospital pharmacists working in different developed countries. Phase one used an open-ended questionnaire to identify activities undertaken by pharmacists. Answers were thematically analysed to construct a list of medication waste-reducing activities. In phase two, a questionnaire was disseminated among pharmacists from different countries, to assess if these activities are implemented (yes/no), their importance and feasibility (1 to 5 ranking scale). Results: In phase one, 53 pharmacists participated and 14 activities were identified. These were categorized into the pharmaceutical supply chain: prescribing, dispensing (pharmacy/patient-related) and leftover stage. In phase two, 89 pharmacists participated. Most activities were implemented by a minority of pharmacists. Reducing medication amounts in stock was most frequently implemented (dispensing stage pharmacy-related; 86%), followed by collecting unused medications (leftover stage; 77%) and performing a medication review (dispensing stage; 68%). Waste-reducing activities in the dispensing stage activities were both considered most important and feasible (ranked 4). Overall, most activities scored higher on importance than on feasibility. Conclusions: Pharmacists have various opportunities to reduce medication waste throughout the pharmaceutical supply chain, however, not all are broadly implemented. Pharmacists consider waste-reducing activities important, but they are less certain about the feasibility for implementation in practice.

Background Knowledge on factors related to preventable medication waste and waste-reducing interventions, including redispensing unused medications, is needed to maximise effectiveness. Objective To assess patient and medication factors associated with preventable medication waste and possibilities for redispensing unused medications. Setting Dutch community pharmacies. Methods In this cross-sectional study, pharmacy-staff registered patient and medication characteristics of prescription medications returned to 41 Dutch community pharmacies during 1 week in 2014. Medications were classified as preventable waste if the remaining amount could have been prevented and as theoretically eligible for redispensing if the package was unopened, undamaged and ≥ 6 months until the expiry date. Associations were analysed using multivariate logistic regression. Main outcome measures Proportion of medications classified as preventable waste and as eligible for redispensing, including factors associated with these medications. Results Overall, 279 persons returned 759 (low-cost) medications, and 39.3% was classified as preventable waste. These medications were more frequently used by men than women (OR; 1.7[1.2–2.3]) and by older (> 65 years) than younger patients (OR; 1.4[1.0–2.0]). Medications dispensed for longer periods were more often unnecessary wasted (1–3 months OR; 1.8[1.1–3.0], > 3 months 3.2[1.5–6.9]). Of all returned medications, 19.1% was eligible for redispensing. These medications were more frequently used by men than women (OR; 1.9[1.3–2.9]). Medications chronically used were more frequently eligible for redispensing than acute use (OR; 2.1[1.0–4.3]), and used for longer periods (1–3 months OR; 4.6[2.3–8.9], > 3 months 7.8[3.3–18.5]). Conclusions Over one-third of waste due to medications returned to community pharmacies can be prevented. One-fifth of returned medications can be redispensed, but this seems less interesting from an economic viewpoint.

Aims: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries.Methods: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed.Results: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93–2.60 and 0.11–8.71 users/10 000 (2011–2015) for dabigatran and rivaroxaban, respectively, and from 0.01–8.12 users/10 000 (2012–2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany).Conclusion: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH).

Real‐world data/real‐world evidence (RWD/RWE) are considered to have a great potential to complement, in some cases, replace the evidence generated through randomized controlled trials. By tradition, use of RWD/RWE in the postauthorization phase is well‐known, whereas published evidence of use in the pre‐authorization phase of medicines development is lacking. The primary aim of this study was to identify and quantify the role of potential use of RWD/RWE (RWE signatures) during the pre‐authorization phase, as presented in the initial marketing authorization applications of new medicines centrally evaluated with a positive opinion in 2018–2019 (n = 111) by the European Medicines Agency (EMA). Data for the study was retrieved from the evaluation overviews of the European Public Assessment Reports (EPARs), which reflect the scientific conclusions of the assessment process and are accessible through the EMA website. RWE signatures were extracted into an RWE Data Matrix, including 11 categories divided over 5 stages of the drug development lifecycle. Nearly all EPARs included RWE signatures for the discovery (98.2%) and life‐cycle management (100.0%). Half of them included RWE signatures for the full development phase (48.6%) and for supporting regulatory decisions at the registration (46.8%), whereas over a third (35.1%) included RWE signatures for the early development. RWE signatures were more often seen for orphan and conditionally approved medicines. Oncology, hematology, and anti‐infectives stood out as therapeutic areas with most RWE signatures in their full development phase. The findings bring unprecedented insights about the vast use of RWD/RWE in drug development supporting the regulatory decision making.