Epidemiological surveillance of drug safety using cumulative sequential analysis in electronic healthcare data.

Background: Methods for safety signal detection in electronic healthcare data analysing data sequentially are being developed to meet the limitations of spontaneous reporting systems.

Objectives: This study aims to provide an overview of the literature on sequential analysis of electronic healthcare data and describe the development and testing of a novel epidemiological surveillance system.

Methods: We searched Medline, Embase, PubMed, Scopus, Web of Science, and the Cochrane Library applying similar in- and exclusion criteria as those of a previous systematic review.

Perspectives on how to build bridges between regulation, health technology assessment and clinical guideline development: a qualitative focus group study with European experts.

Objective: Improving synergy among regulation, health technology assessment (HTA) and clinical guideline development is relevant as these independent processes are building on shared evidence-based grounds. The two objectives were first to assess how convergence of evidentiary needs among stakeholders may be achieved, and second, to determine to what extent convergence can be achieved.

Design: Qualitative study using eight online dual-moderator focus groups.

Impact of a Treatment Guide on Intravenous Fluids in Minimising the Risk of Hospital-Acquired Hyponatraemia in Denmark.

Hypotonic intravenous (IV) fluids are associated with an increased risk of hospital-acquired hyponatraemia, eventually leading to brain injury and death. We evaluated the effectiveness of a treatment guide to improve prescribing practices of IV fluids. We conducted a before-and-after cross-sectional survey among physicians working at Danish emergency departments.

The role of Real-World Data and evidence in oncology medicines approved in EU in 2018-2019.

Use of Real-World Data (RWD) has gained the interest of different stakeholders in cancer care. The aim of this study was to identify and describe the use of RWD/RWE during the pre-authorization phase of products authorized by the EMA in 2018 and 2019 (n = 111), with the focus on oncology medicines (n = 24). Information was extracted from the European Public Assessment Report (EPAR) summaries and recorded for 5 stages (11 categories) of the drug development lifecycle (discovery, early development, clinical development, registration/market launch, lifecycle management).

Regional Disparity in First-in-Class Anticancer Drug Development in the US, EU, and Japan.

A cancer diagnosis is devastating for both patients and their caregivers. With high morbidity and mortality, cancer is a serious disease area with unmet medical needs. Thus, innovative anticancer drugs are in high demand worldwide but are unequally available.

New Information on Old Medicinal Products: A Cross-Sectional Analysis of Guidance for Paediatric Use for Substances on the European Priority List of Off-Patent Medicinal Products.

Background: As part of the European Paediatric Regulation, the European Medicines Agency (former European Medicines Evaluation Agency) and the Paediatric Working Party (precursor for the Paediatric Committee) revised a priority list for studies on off-patent medicinal products in 2007 where a need for studies on paediatric medicinal products was emphasised.

Objectives: We aimed to evaluate the status of guidance for paediatric use in the Summary of Product Characteristics for medicinal products on the priority list as well as the presence and status of Paediatric Investigation Plans for these medicinal products.

Methods: We included active pharmaceutical ingredients on the priority list authorised through the centralised procedure and/or marketed in Denmark.

Magistral Compounding with 3D Printing: A Promising Way to Achieve Personalized Medicine.

Background: Magistral compounding has always been an integral part of pharmacy practice. The increasing demand worldwide for personalized drug treatments might be accommodated by an increase in magistral compounding. The new, flexible technology of 3D medicine printing could advance this process even further.

Serious arrhythmia in initiators of citalopram, escitalopram, and other selective serotonin reuptake inhibitors: A population-based cohort study in older adults.

The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued.

Scenarios for 3D printing of personalized medicines - A case study.

Background: 3D printing is a promising new technology for medicines' production. It employs additive manufacturing techniques, and is ideal for producing personalized medicines (e.g.

Investigation of the potential association between the use of fluoxetine and occurrence of acute pancreatitis: a Danish register-based cohort study.

Background: There is currently conflicting evidence of the association between the use of selective serotonin reuptake inhibitors (SSRIs) and acute pancreatitis. The SSRI fluoxetine has been suspected to be the driver of this serious outcome. Therefore, this study aims to investigate the potential association between fluoxetine use and the occurrence of acute pancreatitis.

Interchangeability of biosimilars: A study of expert views and visions regarding the science and substitution.

Healthcare systems have reached a critical point regarding the question of whether biosimilar substitution should become common practice. To move the discussion forward, the study objective was to investigate the views of experts from medicines agencies and the pharmaceutical industry on the science underpinning interchangeability of biosimilars. We conducted an empirical qualitative study using semi-structured interviews informed by a cross-disciplinary approach encompassing regulatory science, law, and pharmaceutical policy.

Use of Real-World Data and Evidence in Drug Development of Medicinal Products Centrally Authorized in Europe in 2018-2019.

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).

Surveillance of Antidepressant Safety (SADS): Active Signal Detection of Serious Medical Events Following SSRI and SNRI Initiation Using Big Healthcare Data.

Introduction: The current process for generating evidence in pharmacovigilance has several limitations, which often lead to delays in the evaluation of drug-associated risks.

Objectives: In this study, we proposed and tested a near real-time epidemiological surveillance system using sequential, cumulative analyses focusing on the detection and preliminary risk quantification of potential safety signals following initiation of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Methods: We emulated an active surveillance system in an historical setting by conducting repeated annual cohort studies using nationwide Danish healthcare data (1996-2016).

A cross-sectional survey of knowledge pertaining to IV fluid therapy and hyponatraemia among nurses working at emergency departments in Denmark.

Introduction: Inappropriate fluid therapy may induce or worsen existing hyponatraemia with potentially life-threatening consequences. Nurses have an important role in assisting physicians in IV fluid prescribing. However, research is lacking in Denmark about nurses' knowledge pertaining to IV fluid therapy and hyponatraemia.

Regulatory density as a means to refine current regulatory approaches for increasingly complex medicines.

The continuous scientific, societal, and technological advancements have shifted drug development toward increasingly complex and ever more targeted treatments. This creates new and unprecedented challenges for global regulatory systems. To address the increased risks and uncertainties of increasingly complex medicine, we advocate for a more tailored and flexible regulatory approach, which is explained here with the concept of 'regulatory density'.

Evolving Biosimilar Clinical Requirements: A Qualitative Interview Study with Industry Experts and European National Medicines Agency Regulators.

Background: A biosimilar is a biological medicine highly similar to another already approved biological medicine (reference product). The availability of biosimilars promotes competition and subsequently lower prices. Changing the current biosimilar clinical comparability trial requirements may lead to lower biosimilar development costs that potentially could increase patients' access to biologics.

Improving Interactions Between Health Technology Assessment Bodies and Regulatory Agencies: A Systematic Review and Cross-Sectional Survey on Processes, Progress, Outcomes, and Challenges.

The need to optimize drug development and facilitate faster access for patients has ignited discussions around the importance of improving interactions between health technology assessment (HTA) bodies and regulatory agencies. In this study, we conducted a systematic review to examine processes, progress, outcomes, and challenges of harmonization/interaction initiatives between HTA bodies and regulatory agencies. MEDLINE, EMBASE, and the International Pharmaceutical Abstracts database were searched up to 21 October 2019.

Are Further Interventions Needed to Prevent and Manage Hospital-Acquired Hyponatraemia? A Nationwide Cross-Sectional Survey of IV Fluid Prescribing Practices.

Background: Hyponatraemia is associated with increased morbidity, increased mortality and is frequently hospital-acquired due to inappropriate administration of hypotonic fluids. Despite several attempts to minimise the risk, knowledge is lacking as to whether inappropriate prescribing practice continues to be a concern.

Methods: A cross-sectional survey was performed in Danish emergency department physicians in spring 2019.

Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis involving 594,138 patients with type 2 diabetes.

Aims: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors.

Methods: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019.

Cancer is associated with severe disease in COVID-19 patients: a systematic review and meta-analysis.

Cancer patients are vulnerable to complications of respiratory viruses. This systematic review and meta-analysis sought to examine the prevalence of cancer and its association with disease severity in patients with novel coronavirus disease 2019 (COVID-19). Searches were performed in MEDLINE, EMBASE and ScienceDirect from their inception until 28 April 2020.

Poor adherence and persistence to sodium glucose co-transporter 2 inhibitors in real-world settings: Evidence from a systematic review and meta-analysis.

Aims: Despite increasing prescription of sodium glucose co-transporter 2 (SGLT2) inhibitors, there is limited insight of the patterns of use among patients with diabetes prescribed these drugs. This study aimed to summarize available real-world data on the adherence and persistence to SGLT2 inhibitors.

Materials And Methods: A systematic review for observational studies reporting the adherence and persistence to SGLT2 inhibitors was performed in Medline, Embase, and Web of Science from their inception to October 2019.

Are monitoring instructions provided in direct healthcare professional communications (DHPCs) of sufficient quality? A retrospective analysis of DHPCs sent out between 2007 and 2018.

Objective: To assess whether direct to healthcare professional communications (DHPCs) are of sufficient quality to be applicable in clinical practice and study how the quality differs according to safety concerns and type of monitoring.

Design: Retrospective cohort study.

Setting: DHPCs containing monitoring instructions were identified among all DHPC issued in Denmark between 2007 and 2018.