Analysis of the Authorized Target Populations for Fixed Dose Combination Products Between 2000 and 2017 Reveals Discrepancies Between EMA's and FDA's Views on Initial Dual-Therapy.

Background: A fixed dose combination (FDC) product containing two components can be authorized for the use in 3 conceptual scenarios (1) as substitution for a treatment regimen containing both components given separately (substitution therapy) or (2) as replacement for a treatment regimen where the patient currently receives one of the components (add-on therapy) or (3) initial treatment of patients naïve to both components (initial combination therapy).

Method: Trends in European Medicine Agency (EMA) and Food and Drug Administration (FDA) approvals of FDC products for the 3 scenarios were explored by comparing the therapeutic indications retrieved from the EMA and FDA websites for FDCs approved between January 2000 and April 2017 within 5 selected therapeutic areas: type 2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease, hypertension, and human immunodeficiency virus (HIV) infection.

Result: Approval decisions between EMA and FDA were largely aligned for the substitution therapy and add-on therapy scenarios.

Demonstrating Contribution of Components of Fixed-Dose Drug Combinations Through Longitudinal Exposure-Response Analysis.

Exposure-response (ER) modeling for fixed-dose combinations (FDC) has previously been found to have an inflated false positive rate (FP), i.e., observing a significant effect of FDC components when no true effect exists.

Body of evidence and approaches applied in the clinical development programme of fixed-dose combinations in the European Union from 2010 to 2016.

Aims: To provide insights into the clinical development pathway for fixed-dose combinations (FDCs), to consider strategies, and to elucidate the path to approval by assessing the body of evidence, as summarized in the European Public Assessment Reports.

Methods: The main resource was the European Public Assessment Reports for 36 FDCs, which included 239 clinical trials with 157 514 patients. The analyses focused on how prior knowledge of the active substances or combination, use of pharmacokinetic-pharmacodynamic modelling, and clinical trial design choice impact the size and strategy of the clinical development programme.

Glutamate transport system as a key constituent of glutamosome: Molecular pathology and pharmacological modulation in chronic pain.

Neural uptake of glutamate is executed by the structurally related members of the SLC1A family of solute transporters: GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, ASCT2. These plasma membrane proteins ensure supply of glutamate, aspartate and some neutral amino acids, including glutamine and cysteine, for synthetic, energetic and signaling purposes, whereas effective removal of glutamate from the synaptic cleft shapes excitatory neurotransmission and prevents glutamate toxicity. Glutamate transporters (GluTs) possess also receptor-like properties and can directly initiate signal transduction.

Identifying Off-Label Prescriptions Through Data Mining in Danish Community Pharmacy Servers: An Exploratory Study on Desmopressin, Diclofenac, Fucidin, Mirtazapine and Quetiapine.

The term off-label use describes the prescription and administration of medicines outside of the terms for which it officially has been approved, including age, dose and indication. Off-label data can be generated from the Danish National Prescription Registry through combinations with diagnoses; however, the community pharmacy servers provide equal, local, albeit less data through a faster and less constrained collection process. The data collection for this exploratory study took place at five community pharmacies in Denmark.

Glutamate Transport System as a Novel Therapeutic Target in Chronic Pain: Molecular Mechanisms and Pharmacology.

The vast majority of peripheral neurons sensing noxious stimuli and conducting pain signals to the dorsal horn of the spinal cord utilize glutamate as a chemical transmitter of excitation. High-affinity glutamate transporter subtypes GLAST/EAAT1, GLT1/EAAT2, EAAC1/EAAT3, and EAAT4, differentially expressed on sensory neurons, postsynaptic spinal interneurons, and neighboring glia, ensure fine modulation of glutamate neurotransmission in the spinal cord. The glutamate transport system seems to play important roles in molecular mechanisms underlying chronic pain and analgesia.

A Paradigm Shift Towards Patient Involvement in Medicines Development and Regulatory Science: Workshop Proceedings and Commentary.

The Copenhagen Centre for Regulatory Science (CORS) and Biopeople at the University of Copenhagen held a workshop in May 2015 titled "Patient Involvement in Medicines Development and Approvals: A Paradigm Shift Towards True Patient Impact in Medicines Development and Regulatory Science" that acknowledged the importance of having patients more involved in the entire process of medicines research and development (R&D) and life cycle management. Four key stakeholders, representing patients, academia, industry, and regulatory authorities, each gave their view and perspective on the status and challenges of current patient involvement. From the 3 breakout sessions, it was concluded that patient-reported outcomes (ie, the report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else), was considered as an important tool when deciding endpoints.

Detection of adverse drug reactions among ordinary users of liraglutide on the occasion of drug dispensing in the community pharmacy setting.

Objectives: Postmarketing studies of drugs forms an essential part of safety surveillance. In particular, this concerns new drugs as safety information of these by large rests on randomized clinical studies conducted on a limited number of subjects before licensing. Pharmacists in community pharmacies are in a unique position for detection of user experienced adverse drug reactions (ADRs) in relation to drug dispensing.

Pharmacy student driven detection of adverse drug reactions in the community pharmacy setting.

Purpose: Post-marketing safety studies of adverse drug reactions (ADRs) form an important part of pharmacovigilance. Countries having a formal pharmacovigilance system to a large extent rely on voluntary ADR reporting from health professionals through spontaneous report systems. The contribution of pharmacists in ADR reporting, although varies significantly among countries.