Methodology

Comparators (Medicinal and non Medicinal) for Marketing Authorization, for Public Health, for Payers and at the European Level

¹ CHU de Bordeaux, Bordeaux, France
² Pfizer, Paris, France
³ Afssaps, Saint-Denis, France

Correspondence and offprints : Driss Berdaï, Service de Pharmacologie Clinique, CHU de Bordeaux, Zone Nord Carreire, Bâtiment 1A, Place Amélie-Raba-Léon, 33076 Bordeaux Cedex, France. E-mail: driss.berdai@u-bordeaux2.fr

Received: 29 March 2010
Accepted: 8 June 2010

Abstract

Drug evaluation is based on comparison. Thus, the choice of the comparator for any new treatment becomes a key issue, especially when there are great differences in medical practice and of use conditions of the comparators depending on the geographical zones and their evolution with time. The choice of the comparators must satisfy sometimes different expectations from the registration authorities and for insurance coverage. The universal comparator that allows answering all the clinical assessment questions does not exist. Placebo, when it can be used, remains a reference for the MA (marketing authorisation) application, but does not exclude the use of the reference drug available on the market and prescribed under optimal efficacy conditions. The reference treatment is sometimes a difficult choice due to the absence of validated therapeutic recommendations or if the recommendations vary depending on the countries. The expansion and international harmonization of prescription guidelines (clinical practice guidelines) would reinforce the robustness and efficiency of clinical research efforts with respect to the relevance of the comparison to reference treatments. This principle also applies to the use of a non-drug comparator when it has been recognized as the reference comparator in the treatment of the pathology in question. In as much as possible, the search for a consensus must also aim at defining in the clinical development recommendations significant thresholds for the size of evaluated effects. Optimization of the information made available after clinical trials could also be helped by the development of use of methodologies that allow assessing superiority on secondary criteria during a non-inferiority study on the main criterion. Finally, the development of early scientific consultations by the Haute Autorité de Santé (HAS, French Health Authority) would contribute to adapt phase III clinical trials better to questions concerning the assessment of the clinical added value of the medicinal products evaluated.