[Two decades later, the polypill revisited]. / La polypill vingt ans après : était-ce une fausse bonne idée ?

TWO DECADES LATER, THE POLYPILL REVISITED Twenty years later, the promises of the designers of the Polypill are far from being fulfilled. Its effectiveness is still open to debate, while its long-term adverse effects in healthy subjects, particularly due to aspirin, continue to cause concern. Its composition, which varies from one Polypill to another, does not always appear to be as relevant as it would be desirable. In short, it is not certain that its advantages far outweigh its disadvantages. Its validation by the Authorities granting marketing authorizations seems difficult as it stands because it requires demonstrating the benefit of each of its components compared to a placebo and the contribution of each component compared to the others. As for the idea of some of its upholders to make it an over-the-counter drug, it is a headlong rush that is hardly compatible with its target, healthy subjects, and its safety profile.

LA POLYPILL, VINGT ANS APRÈS : ÉTAIT-CE UNE FAUSSE BONNE IDÉE ? A l'ere de la medecine de precision, l'idee, datant de 2003, d'un meme comprime pour tous, en prevention primaire cardiovasculaire a partir de 55 ans, peut paraitre une provocation. Pourtant, la proposition etait seduisante et simple. Mais, apres vingt ans de speculations et de debats passionnes plutot que d'etudes irrefutables demontrant sa pertinence et son interet clinique, force est de constater que les espoirs qu'avait suscites la polypill ne sont toujours pas formellement concretises, tandis que sont remis en cause tous les avantages dont elle etait creditee et que sa securite d'emploi fait l'objet de reserves constantes, si l'on considere que sa cible est une population de sujets asymptomatiques presumes sains. Il est difficile de prevoir l'avenir de la polypill, sauf a constater que certains de ses partisans, dans le cadre d'une fuite en avant, vont jusqu'a la proposer comme un medicament d'automedication.

[The war against generics and biosimilars in France: game over?] / Génériques et biosimilaires en France : la fin des polémiques et des palinodies ?

"The war against generics and biosimilars in france: game over? French people seem get accustomed to generics use after a period of approximately two decades punctuated with reluctance, controversies, behavioral barriers, incentives, conventions and regulations. Fortunately the recent so-called Levothyrox crisis and the more confidential one about Valsartan have not had the deleterious impact that was feared. A more peaceful atmosphere if not resignation can now be noticed. Only three kinds of medically justified situations make now them out of hand: in case of narrow therapeutic margin; in the case of child under six if there is no generics adapted to him; in the case of patients showing a contraindication to excipient with known effect. The identification of these situations will ask judgement from the prescribers. The debates concerning biosimilars deployment did not find their root in biosimilars therapeutic indications which are extrapolations from the princeps indications even if biosimilars have been tested in one only of the princeps indications. They came from the French health authorities palinodes about their interchangeability. Far from assisting prescriptions, such palinodes could have generated prescribers' and patients' lack of confidence."

"Génériques et biosimilaires En france : la fin des polémiques et Des palinodies ? Les Français semblent s'accoutumer à l'utilisation des génériques au terme d'un cheminement de près de deux décennies émaillé de réticences, de freins comportementaux, de polémiques, mais aussi d'incitations, de conventions et de textes réglementaires. La récente crise dite du Levothyrox n'aura fort heureusement pas eu les répercussions délétères redoutées et l'ambiance est à l'apaisement sinon à la lassitude. Seuls trois types de situations médicalement justifiées permettent de leur échapper : en cas de médicament à marge thérapeutique étroite ; chez l'enfant de moins de 6  ans si aucun générique n'a de forme adaptée ; chez les patients ayant une contre-indication démontrée à un excipient à effet notoire, lorsque le princeps ne comporte pas cet excipient. Pour ce qui est du déploiement des biosimilaires, les débats ne sont pas venus d'où on les attendait c'est-à-dire de l'extrapolation au bénéfice du biosimilaire, de l'ensemble des indications thérapeutiques du princeps, alors que le biosimilaire n'a été cliniquement testé que dans une seule de ces indications. Ils ont résulté de la palinodie des autorités de santé à propos de leur interchangeabilité. Une palinodie qui, loin de favoriser leur prescription, a bien failli susciter la défiance des patients."

[For an optimal use of fixed drug combinations]. / Pour une utilisation optimale des associations fixes de médicaments.

Due to the increasing use of fixed-dose combination therapy (FC) for treating several pathological conditions, the authors discuss their advantages (simplification of drug intakes and thus possible better compliance, rationale of pharmacological associations and drug dosages) and their disadvantages (limited dosage flexibility, possible misunderstanding of the co-administered drugs due to non-utilization of International nonproprietary name…) versus advantages and disadvantages of free drug combinations. Several recommendations are proposed. If FC is not in fact a problem in young adults with stable diseases, it should be cautiously prescribed for all the other patients, especially in elderly suffering from several diseases. FC should be only proposed after prescribing separately the different components, and should be regularly reassessed.

The public health benefit of medicines: how it has been assessed in France? The principles and results of five years' experience.

Health technology assessment seeks to inform health policy- and decision-makers by promoting use of current best evidence and by addressing country specific factors, such as local context and values. In France, public health benefit (PHB) is one of the criteria used to inform decisions on the reimbursement of medicines. This article describes the methodological framework and the results after five years of assessment of PHB, by the French National Authority for Health. The semi-quantitative method used includes three dimensions that are: (1) the ability of a drug to improve the population's health status, (2) the drug's adequacy to cover public health needs, and; (3) the impact of the drug on the healthcare system. From 2005 to 2010, the PHB of 530 drugs was estimated, and 72% were assessed as having no PHB. The PHB was "low" for 88% of drugs expected to have a PHB, "medium" for 10%, and was considered to be "high" in only one case. The results of this experience show that it is feasible to assess the public health impact of drugs. But the high level of uncertainties at the time of a drug's first appraisal limits the assessment, which obviously has to be completed by reappraisal with post-marketing studies.

Relative effectiveness assessment of listed drugs (REAL): a new method for an early comparison of the effectiveness of approved health technologies.

OBJECTIVES: Post-listing assessment of pharmaceuticals depends on national habits. In England, the assessment is based on estimates of cost per quality-adjusted life-year. These are made some considerable time after listing (negative list). In France, effectiveness, and then efficiency, is assessed immediately after listing (positive list). We propose a new formal method--the REAL method--that can help make early comparisons of the effectiveness of medical treatments. METHODS: Relative efficacies are first obtained from randomized controlled trials (RCTs). Members of the Transparency Committee (French National Authority for Health) are then consulted by questionnaire on the transposability of these results to real life. The RCT results and experts' ratings are entered into an effect model to obtain estimates of relative effectiveness, using unidimensional scaling, and bootstrap procedures. RESULTS: Application of the REAL method to the example of a new drug to treat Parkinson's disease and three comparators used in the same indication provided graphs of the distributions of their relative efficacy and relative effectiveness. The new drug was found to provide no added value. CONCLUSIONS: The REAL method is a rational, transparent, and practical procedure for comparing the effectiveness of pharmaceuticals in an immediate post-listing setting.