How can we improve transfer of outcomes from randomized clinical trials to clinical practice with disease-modifying drugs in Alzheimer's disease?

Neurodegener Dis. 2014;13(2-3):197-9. doi: 10.1159/000353748. Epub 2013 Aug 7.


Background: Randomized clinical trials (RCTs) for putative disease-modifying drugs in Alzheimer's disease (AD) are using cognitive outcomes, such as the Alzheimer's Disease Assessment Scale--cognitive subscale, activities of daily living scales, such as the Alzheimer's Disease Cooperative Study Activities of Daily Living, and time from mild cognitive impairment to AD dementia.

Objective: It was the aim of this study to build clinically relevant outcomes for future use in clinical practice into RCT designs and help third-party payers to measure benefit.

Methods: We used a literature review for analysis.

Results: The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) appears to be the most reliable primary outcome for RCT at different stages of AD, with the Relevant Outcome Scale for Alzheimer's Disease (ROSA) as a suitable alternative. The importance of current AD biomarkers vis-à- vis determination of efficacy of disease-modifying drugs has yet to be established; however, it is likely that at least one amyloid-specific test will be required prior to treatment with a drug acting predominantly on β-amyloid (Aβ42). Furthermore, serial MRI may be required to monitor adverse side effects associated with such drugs.

Conclusions: Global clinical scales such as CDR-SB and ROSA should be considered for use with treatments aiming at slowing disease progression.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Humans
  • Neuroprotective Agents / therapeutic use*
  • Outcome Assessment, Health Care*
  • Randomized Controlled Trials as Topic*
  • Severity of Illness Index
  • Translational Medical Research / standards*


  • Neuroprotective Agents