The European Medicines Agency's approval of new medicines for type 2 diabetes.

Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency.

New strategies for the development of lipid-lowering therapies to reduce cardiovascular risk.

The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels.

EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

Unlabelled: On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins.

New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment.

Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure.

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases.

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members.

Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary.

Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers.

Implications of a clinical medication review and a pharmaceutical care plan of polypharmacy patients with a cardiovascular disorder.

Background A clinical medication review, including patient involvement, is expected to improve pharmaceutical care. Objective To determine whether a clinical medication review followed by a pharmaceutical care plan decreases the number of potential drug-related problems (DRPs) and pharmaceutical care issues (PCIs) and leads to a positive effect on relevant clinical and laboratory parameters for elderly cardiovascular patients with multiple drug use. Setting Randomized controlled trial in eight primary care settings in the Netherlands.

The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

Background: On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option.

Materials And Methods: Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody (recombinant chimeric IgG1) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE).

Understanding drug preferences, different perspectives.

Aims: To compare the values regulators attach to different drug effects of oral antidiabetic drugs with those of doctors and patients.

Methods: We administered a 'discrete choice' survey to regulators, doctors and patients with type 2 diabetes in The Netherlands. Eighteen choice sets comparing two hypothetical oral antidiabetic drugs were constructed with varying drug effects on glycated haemoglobin, cardiovascular risk, bodyweight, duration of gastrointestinal complaints, frequency of hypoglycaemia and risk of bladder cancer.

Post-approval safety issues with innovative drugs: a European cohort study.

Background: At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval.

The Additional Value of an E-Mail to Inform Healthcare Professionals of a Drug Safety Issue: A Randomized Controlled Trial in the Netherlands.

Background: The usefulness and the impact of Direct Healthcare Professional Communications (DHPCs, or 'Dear Doctor letters') in changing the clinical behaviour of physicians have been debated. Changes in the current risk communication methods should preferably be based on the preferences of the healthcare professionals, to optimize the uptake of the message.

Objective: The aim of this study was to assess whether safety issues are communicated more effectively with an additional e-mail sent by the Dutch Medicines Evaluation Board (MEB) than with the DHPC only.

Risk perception of prescription drugs: results of a survey among experts in the European regulatory network.

Background: Experts are perceived to be veridical and to focus only on objective data when evaluating risk. Only a few research studies have attempted to characterize the subjectivity in risk evaluation among experts.

Objective: The hypothesis of this study is that expert evaluation of a pharmaceutical drug can be partly explained by dimensions that describe the drug and by individual characteristics.

Healthcare professionals' self-reported experiences and preferences related to direct healthcare professional communications: a survey conducted in the Netherlands.

Background: In Europe, Direct Healthcare Professional Communications (DHPCs) are important tools to inform healthcare professionals of serious, new drug safety issues. However, this tool has not always been successful in effectively communicating the desired actions to healthcare professionals.

Objective: The aim of this study was to explore healthcare providers' experiences and their preferences for improvement of risk communication, comparing views of general practitioners (GPs), internists, community pharmacists and hospital pharmacists.

Impact of safety-related regulatory action on clinical practice: a systematic review.

Background: After market approval, new serious safety issues are regularly identified for drugs that lead to regulatory action to inform healthcare professionals. However, the effectiveness of these safety-related regulatory actions is under question. We currently lack a comprehensive overview of the effects of these drug safety warnings on clinical practice to resolve the debate about their effectiveness.

Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers.

Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy.

Effect of safety issues with HIV drugs on the approval process of other drugs in the same class: an analysis of European Public Assessment Reports.

Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required ≥1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval.

Objective: The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs.

Regulatory pathways for development of antiarrhythmic drugs for management of atrial fibrillation/flutter.

New antiarrhythmic drugs are urgently required for the treatment of atrial fibrillation (AF), an increasingly common sustained cardiac arrhythmia seen predominantly in the elderly population. Pharmaceutical companies are generally interested in this important group of patients and a relatively large number of antiarrhythmic agents are under development for several indications relating to AF, predominantly rhythm and rate management. Because of the significant clinical consequences of the arrhythmia, it has been recognized that controlled trials in patients with AF should assess the effect of therapy in several major outcome domains such as mortality, morbidity, and hospitalization, with an emphasis on stroke and heart failure.

Additional safety risk to exceptionally approved drugs in Europe?

Aims: Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear 'unmet medical need'. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues.