Quelle pharmacovigilance pour les vaccins ?

Vaccines are not separate health products but anti-infectious medicines administered for the large part prophylactically and for which the effect is immunological and not pharmacological. They should be evaluated by the usual methods of clinical pharmacology and pharmacovigilance, taking into account certain specificities (mechanism of action, manufacture, frequent administration to healthy subjects, particular recommendations, etc.). Experience from some vaccination campaigns have revealed insufficiencies notably in data collection allowing evaluation of the interest of a vaccine to public health, its relevance to the recent epidemiology of the disease in question and long-term security. The absence of data can generate fear in the general population that is broadcast by anti-vaccination lobby. For a more optimal pharmacovigilance of vaccines, it is necessary to: (i) improve the coherence between the evaluating authorities; (ii) set up, in addition to the usual risk management plan, an active microbiological and epidemiological surveillance and to follow up exposed populations; (iii) have programmes of education of the medical community regarding vaccination and health education for the general public.     

Modelling and clinical trials in paediatrics

Clinical trials are more difficult to conduct in children, but they are even more necessary than in adults their scarcity is an ethical scandal. Mathematical models can be built that can describe both the disease process and the mechanism of action of drugs. These models can then be used to simulate the outcome of clinical trials. Inspection of the simulated results then facilitates optimisation of the trial design and proposed methods of analysis. Validation is a crucial issue for the good practice of modelling and simulation. The participants of Round Table No. 6 recommend: (i) that modelling be systematically employed; (ii) that all the required professional personnel be involved, at all phases; (iii) that all data needed are made accessible; (iv) that clinicians be trained; (v) that specialists develop training tool kits; and (vi) that universities provide appropriate training.     

Good clinical practice in clinical trials: training clinicians,incentives to apply good clinical practice and assessment of compliance

Fourteen years after the concept was created, it seemed important to assess how well investigators actually apply Good Clinical Practice. Various sources of information have revealed a general deficiency in their application: "investigation by the working group, Afssaps (French Agency for the Safety of Health-Care Products) inspections, industrial data". The deficiencies identified stem from different factors: lack of professionalization, lack of training, lack of motivation, the large numbers of poorly conducted studies. The working group drew up proposals intended to improve the training of investigators, to dissuade investigators from pursuing inadequate procedure and to verify the level of compliance. However in this respect, the investigator is not the only one at fault. Improved practice unavoidably requires better assistance on the part of the sponsors, more consistent supervision of monitoring, and greater vigilence by the authorities involved in the control and use of trials.     

Role of pharmacokinetic-pharmacodynamic relationships in drug development

An important part of drug development relies on the analysis of the relationships between drug doses and therapeutic and/or side effects. This analysis implies an in-depth understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug and of the relationship which links them (PK-PD relationship). The aim of this round table was to define the place of the study of PK-PD relationships in drug development. After reviewing the definitions of PK models, PD models, and of integrated PK-PD models, the article highlights the importance of studying the PK-PD relationship during the successive phases of drug development (pre-clinical, phase I/II, phase III) and in specific populations (children, elderly people). A number of examples taken from pharmaceutical development or international literature are given. They show the methodology used and the type of information which can be drawn at each step of drug development. The article also presents the difficulties which prevent a more systematic application of this kind of approach during drug development. Scientific limits, problems in relation with the misunderstanding of the approach both in academic institutions and in pharmaceutical companies, and difficulties related to the lack of specific guidelines are discussed. The conclusion emphasizes the importance of using PK-PD modeling all along drug development and presents a number of actions which could further broaden its use.     

Committee for the protection of persons

The transposition into French law of Directive 2001/20/CE, which relates to good clinical practice in the conduction of trials on drugs for human use, has required the modification of certain provisions that concern the protection of persons participating in biomedical research, in particular those provisions concerning the conditions for the authorisation of biomedical research. Declaration to the competent authorities now comes prior to authorisation and, henceforth, the prior opinion of a Committee for the Protection of Persons (CPP) must be expressly favourable in order for a trial to be undertaken. Proposals are put forward by this Round Table in order to promote the stability and professionalism of the CPPs.     

Use of the foreign studies: transposition of the results, prediction of the therapeutic effects in the french population, modelling of the public health interest

More and more frequently, the health authorities and the French assessment agencies are led to issue Marketing Authorizations (MAs), give opinions on the eligibility for reimbursement of drugs or to draft recommendations for clinical practice based on the results of foreign studies. The results of these studies are more or less difficult to transpose to French practice. These difficulties generate varying degrees of uncertainty concerning the effect to be expected of a drug. A more or less extensive loss of effect is sometimes even predictable. Some of the difficulties in transposition are discussed in this article and proposals for action are made in order to allow one, in the long term, to predict in the most precise manner possible the effects to be expected from a drug in the French population and be able to verify this prediction at an interval from its eligibility for reimbursement.