Marine Diviné

Translational Research: Precision Medicine, Personalized Medicine, Targeted Therapies: Marketing or Science?

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research.

Monoclonal Antibodies for Therapeutic Use: Specific Characteristics of Clinical Development, Evaluation by the Agencies, and Long-term Monitoring of Safety

Monoclonal antibodies (MoAb) are very different from other drugs. The Round Table aimed to determine whether the specific characteristics of MoAb have repercussions on their clinical development, evaluation by the health authorities, and long-term monitoring. As regards the structure-activity relationship of MoAb, classification according to mechanism of action (neutralising or agonist MoAb, cytolytic MoAb) is more relevant than to their degree of humanisation. Recommendations on their clinical development would be useful since the early phases give rise to a number of problems and are insufficiently codified. The pharmacokinetic profile is very different from that of other drugs. The concentration-effect relationship is difficult to study since the biomarkers may be apparently disconnected from the therapeutic effect. The methodology for evaluation of MoAb by the agencies, and postmarketing surveillance do not differ from the procedures used for other drugs; however, MoAb bring together a number of specific characteristics as compared with other drugs.

Comment mesure-t-on le bénéfice net d’un traitement ?

Resume L’estimation du benefice net permet d’expliciter les fondements des decisions therapeutiques, individuelles et collectives. Cette explicitation est une exigence dans la decision medicale partagee et la pratique de la medecine factuelle ou evidence-based medicine. De nombreuses methodes existent, sans qu’aucune ne puisse s’imposer face a un cahier des charges complexe et devant s’ajuster a l’attente de l’acteur central, le patient ou la societe, et a un eventail infini des contextes possibles. Les enjeux, les limites, les contraintes et les competences a acquerir par tous les acteurs, ont ete discutees par les participants de la table ronde et font l’objet de cet article, permettant de conclure a quelques messages cles et des recommandations. Les efforts de formation de tous les acteurs representent la priorite essentielle.

How to measure the net benefit of treatment

Estimating net benefit makes possible to clarify the basis for therapeutic decisions on an individual and collective level. This clarification is a must in shared medical decision-making and evidence-based medicine. Numerous methods are available, although none outweigh the others. The complex specifications of net benefit estimation should be tailored to the expectations of the central stakeholder, patient or society, and the unlimited range of potential contexts. The challenges, limitations, constraints and skills to be acquired by all stakeholders were discussed by the participants of the round table. They are described in this article, enabling key messages and guidelines to be presented. The essential priority is to ensure that all stakeholders receive the required training.