Qualification opinion of novel methodologies in the predementia stage of Alzheimer's disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden--regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials

Eur Neuropsychopharmacol. 2011 Nov;21(11):781-8. doi: 10.1016/j.euroneuro.2011.08.003. Epub 2011 Sep 7.

Abstract

The European Medicines Agency (EMA) in London is responsible for the Regulatory review of new medicinal products for Marketing Authorisation, through which pharmaceutical companies may obtain first Marketing Authorisation and subsequent Variations valid throughout the EU and EFTA. The qualification opinion of novel methodologies is a new procedure where applicants can obtain scientific advice on new methodologies for regulatory clinical trials of efficacy of new compounds. It will help benefit/risk assessment of the CHMP. The definition of prodromal AD is acceptable. The "Dubois Criteria" as criteria to define the population must be validated in full at the time of the submission of the dossiers. Including a positive CSF biomarker profile is considered predictive for the evaluation of the AD-dementia type. However, although high CSF tau and low CSF Aβ42 are predictive of Alzheimer's disease, the criterion "positive CSF tau/Aβ42 ratio" is not well defined. The qualification of biomarkers in the pre-dementia stage of Alzheimer's disease will allow better inclusion criteria of patients in pre-dementia trials in which the benefit/risk is higher for treatment with these novel compounds.

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Dementia
  • Europe
  • Humans
  • Logistic Models
  • Meta-Analysis as Topic
  • Organizations / standards*
  • Peptide Fragments / cerebrospinal fluid*
  • Reproducibility of Results
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins