Relevance of the Evaluation Criteria Used in Clinical Trials for Alzheimer's Disease

¹ Sanofi Aventis, Antony, France
² EA 1046, Faculté de Médecine, Université de Lille II, Département Universitaire de Pharmacologie, Lille, France
³ SPIM, Faculté de Médecine René Descartes, Université Paris V, Paris, France

Received: 15 October 2008
Accepted: 20 November 2008

Abstract

The roundtable 1 “Relevance of the evaluation criteria used in clinical trials for Alzheimer's disease” made reference to the guideline published by the EMEA (European Medicines Agency) in July 2008 on the development of new treatments for Alzheimer's disease (AD) and other dementias, and addressed principally two of the three indications listed in the guideline: symptomatic improvement and disease-modification (primary prevention was hardly discussed). The discussions focussed on two main aspects: improvement of the selection of patients in clinical trials and clinical evaluation and biomarkers. The following suggestions were made:
Reinforce the interest for clinical trials at the early stages of AD (including prodromal stage), particularly for disease-modifiers. Strengthen the research centers' expertise with biomarkers, in a perspective of subsequent use in clinical trials, either for the description of the patients included, or as part of selection criteria. Furthermore, ongoing intercenter validation studies, in France, of neuro-imaging and biomarker assays in CSF, are essential for preparing multicenter clinical trials. Facilitate the conduct of ancillary studies with biomarkers, grafted on clinical studies. Further develop the training and experience of raters with functional scales, which are now required as one of the two primary endpoints in pivotal clinical trials, and with the additional items of ADAS-cog (Alzheimer's Disease Assessment scale, Cognitive sub scale), which are useful for the early stages of AD. Improve knowledge of functional clinical scales by in depth analysis of available databases, through public/private collaborations. Improve knowledge of relationship between rating scales used in clinical trials and tools used in clinical practice (which are usually different), in order to provide supporting evidence for the interpretation of the clinical relevance of clinical trials results. Consider the potential needs of adaptation of rating scales to the societal changes, in particular for the evaluation of cognitive performance. Discuss the possibility of measures for extending data protection for candidate disease-modifiers, considering the negative impact for all players of the constraints of duration and the difficulties of clinical trials. Further discuss the ethics and acceptability of placebo-controlled monotherapy studies on durations of 6-9 months.