How are physicians prescribing the direct renin inhibitor aliskiren in the management of essential hypertension? A French observational study.

OBJECTIVES: The aim of this French observational study was to evaluate how the direct renin inhibitor aliskiren is being prescribed to treat hypertension by primary care providers (PCPs) and office-based cardiologists. METHODS: Each participating physician included the first three consecutive hypertensive patients who had been prescribed aliskiren at least 4 weeks beforehand and noted whether aliskiren was prescribed: alone or as part of a combination; as first-line therapy, to replace another drug or as an add-on therapy. RESULTS: Five thousand, four hundred and eleven patients were analyzed [mean age, 63; 58% men; 24% diabetic; mean blood pressure (BP) 148/85 mmHg]. A total of 23.6% of patients had a controlled BP. Aliskiren was prescribed alone in 49.4% patients and as part of a combination in 50.6% (bitherapy 28.3%, tritherapy 14.7%, and quadri+therapy 7.6%), at the higher recommended dosage (300 mg daily) to two-thirds of cases. Aliskiren replaced another drug in 71.9% [mainly an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEi)] and was added to an existing regimen in 22.5%. For bitherapy, aliskiren was combined with a diuretic (D; 39%) or a calcium channel blocker (CCB; 32%). For tritherapy, it was prescribed with CCB and D in 28% and ß-blocker and D in 26%. In 8.9% of patients, aliskiren was prescribed with an ACEi or an ARB. CONCLUSION: French physicians are generally following the current prescribing recommendations for aliskiren, but the place of this new class of antihypertensive in the management of essential hypertension will become clearer with longer experience, especially concerning effective doses and combinations.

How can the quality of medical data in pharmacovigilance, pharmacoepidemiology and clinical studies be guaranteed?

The development of medicinal products is subject to quality standards aimed at guaranteeing that database contents accurately reflect the source documents. Paradoxically, these standards hardly address the quality of the source data itself. The objective of this work was to propose recommendations to improve data quality in three fields (pharmacovigilance, pharmacoepidemiology and clinical studies). The analysis was focused on the data and on the critical stages presenting critical quality problems, for which the current guidelines are insufficiently detailed, unsuitable and/or poorly applied. Finally, recommendations have been proposed, mainly focused on the origin of the data and its transcription.

Exploratory clinical trials: implementation modes & guidelines, scope and regulatory framework.

The working group focused on defining exploratory trials on medicinal products and developing recommendations for their implementation in France (notably concerning non-clinical requirements, the pharmaceutical quality of the investigational medical product and the conditions under which this type of clinical trial may be performed).To this end, the working group took account of existing guidelines (notably those in the USA and Belgium) and a draft revision of the ICH M3 guideline.Exploratory trials are clinical trials performed early in Phase I, prior to dose escalation and safety and tolerability trials. These trials are de facto first-in-man studies but lack a therapeutic or diagnostic goal and do not seek to establish the maximum tolerated dose (MTD). The objective is to answer precise questions which condition the continuation or suspension of the drug's development program. Exploratory trials include a small number of patients or healthy subjects and expose them (over a short period of time) to a low dose of an investigational medicinal product.The draft revision of M3 describes five approaches (two involving microdoses and three with pharmacological doses).The group's main recommendations can be summarized as follows:An exploratory trial may be performed when it is (i) justified, (ii) useful for product development and (iii) consistent with prerequisites. The pharmaceutical dossier should take account of the low quantity of product available, the short period of product administration and the low doses used. Good Manufacturing Practices can be adapted accordingly. The non-clinical dossier should also be adapted to suit the development phase and particular features of product use. In this respect, the group has commented on the recommendations in the draft revision of M3. The protocol must be designed to provide answers to a set of specific, pertinent questions concerning this administration phase - particularly on choice of the initial dose, the size of the dose escalation and the rules for subject withdrawal and trial suspension. In general, so-called "vulnerable" populations should not be involved in this type of trial, apart from duly justified exceptions. The group considered that approaches 3 to 5 should only apply to a medicinal product intended for treatment of a severe or rare disease or a condition with significant unmet medical needs. Pre-filing at the Afssaps (the French Agency for Healthcare Product Safety) is recommended, notably for approaches using pharmacological doses.