Adaptive licensing: taking the next step in the evolution of drug approval.

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.

Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed.

European regulatory perspectives for innovative therapies.

The current regulatory requirements offer accelerated assessment of innovative therapies in Europe. Future perspectives include the need for increased interaction between stakeholders in pharmaceutical development. Development of new, high quality, effective and safe medicines in Europe is the common goal of academia, pharmaceutical industry and regulatory authorities. To achieve this, it is important that regulatory requirements do not hinder innovation and vice versa, innovation cannot be allowed to proceed without concerns for public health. Interaction between stakeholders in pharmaceutical development is of the utmost importance. A dialogue has begun and in the future it will be the responsibility of all stakeholders to ensure continuous exchanges in an environment that is characterised by new scientific advances and global development programmes.

[Economic aspects of pharmacovigilance in the pharmaceutical industry]. / Aspects économiques de la pharmacovigilance dans l'industrie pharmaceutique.

The economical aspects of pharmacovigilance in the pharmaceutical industry can be assessed by two ways. First the balance between cost of avoiding adverse drug reactions (ADR) and cost of ADR should be evaluated during the development. The company will have to take into account both efficacy and safety of its compound. However if it increases the costs of avoiding ADR it will reduce the costs of avoiding ADR occurring after commercialisation. On the other hand the cost of side effects of a marketed compound can also be appreciated. This assessment will always have to be comparative with an other drug and to take into account the benefit of both drugs, if their efficacy is not deemed identical.

[How and when to create a pediatric file for authorization to market a new drug. A proposal of the SNIP clinical group (National Syndicate of Pharmaceutical Industry)]. / Comment et quand bâtir un dossier pédiatrique pour l'Autorisation de Mise sur le Marché d'un nouveau médicament. Une proposition du groupe clinique du SNIP.

In order to recommend the pediatric use of a new drug, the registration file should include several types of studies. Existing data on toxicological and pharmacological studies in animal and human have to be thoroughly examined. In addition, the splitting potential of single doses to be adapted to the child should be studied, according to the galenic formula. In all cases, the clinical file should have one pharmacokinetic study on acute intake of one or several doses in the specific age bracket. When the efficacy of a drug has been demonstrated in adults for the same disease, and if the results are extrapolated to children, the file should include one or several open studies designs in order to assess the tolerability. On the contrary, for example when the disease is different in or specific for children, one or several double blind randomized studies against reference treatment are necessary. All those studies should show the therapeutical value of the drug, and should allow precise recommendations for the dosages, depending on the body weight and/or the body surface compatible with the galenic formula.