Skip to main content
Log in

Study design considerations: Conducting global clinical trials in early Alzheimer’s disease

  • Published:
The journal of nutrition, health & aging


An increasing number of Alzheimer’s disease (AD) clinical trials are being conducted in countries in which such trials have infrequently, if ever, been conducted. The infrastructure for conducting trials in many of these regions is not well developed, leading to particular challenges in collection of biomarkers, which are becoming increasingly important in trials in early AD. Linguistic and cultural differences make scale translation, adaptation, validation and implementation across countries and regions difficult. In addition, multiple translations and versions of scales and differences in their administration increase variability and thus decrease the chance of detecting a signal. These issues are magnified in trials in early AD, where detecting subtle neuropsychological deficits is even more challenging. Two additional significant factors for global AD research include: 1) Differing regulatory authority requirements resulting in the need for repeat studies to satisfy diverse regulatory requirements in different parts of the world; and 2) reimbursement and access may be limited due to different data requirements for country specific economic evaluations. While standardization of biochemical assays and neuroimaging protocols have recently been undertaken, there remains a pressing need for standardization of clinical measures (including translation, linguistic and cultural validation and administration). In addition, a global consensus on regulatory requirements for approval of drugs for the treatment of early AD and identification of universally accepted variables from a cost-effectiveness or value perspective would have significant impact on advancing drug development in early AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others


  1. Alzheimer’s Disease Facts and Figures, 2007. Available at:’s_disease_facts_figures.asp

  2. Sabbagh M. Drug development for Alzheimer’s disease: Where are we now and where are we headed? The American Journal of Geriatric Pharmacotherapy. 2009;7(3):167–185.

    Article  CAS  PubMed  Google Scholar 

  3. Verhey FR, Houx P, Van Lang N, Huppert F, Stoppe G, Saerens J, Bohm P, de Vreese L, Nordlund A, DeDeyn PP, Neri M, Pena-Casanova J, Wallin A, Bollen E, Middelkoop H, Nargeot MC, Puel, M, Fleischman UM, Jolles J. Cross-national comparison and validation of the Alzheimer’s Disease Assessment Scale: results form the European Harmonization Project for Instruments in Dementia (EURO_HARPID). In J Geriatr Psychiatry 2004;19: 41–50.

    Article  Google Scholar 

  4. Chiu HFK, Lam LCW. Relevance of outcome measures in different cultural groups - does one size fit all? International Psychogeriatrics 2007, 19:3, 457–3, 466.

    Google Scholar 

  5. Hobart JC, Cano S, Zajicek JP, Thompson AJ. Rating scales as outcome measures for clinical trials in neurology: problems, solutions, and recommendations. Lancet Neurol 2007;6:1094–1105.

    Article  PubMed  Google Scholar 

  6. Black R, Greenberg, B, Ryan JM, Posner H, Seeburger J, Amatniek J, Resnick M, Mohs R, Miller DS, Saumier D, Carillo M, Stern Y. Scales as outcome measures for Alzheimer’s disease. Alzheimers Dement 2009 Jul;5(4):324–339.

    Article  PubMed  Google Scholar 

  7. Jonsson B. time for a common standard for cost-effectiveness in Europe? Eur J Health Econ 2006, 7: 223–224.

    Article  PubMed  Google Scholar 

  8. European Medicines Agency, (EMEA) Committee for Medicinal Products for Human Use (CHMP), Doc. Ref EMEA/CHMP/EWP/692702/2008. Reflection paper on the extrapolation of results from clinical studies conducted outside Europe to the EUPopulation.

  9. Broich, K, Outcome measures in clinical trials on medicinal products for the treatment of dementia: a European regulatory perspective. Int Psychogeriatr. 2007 Jun;19(3):509–524.

    Article  PubMed  Google Scholar 

  10. Sampaio, C, Biomarkers in clinical trials of Alzheimer’s disease: what is expected from regulatory agencies? J Nutr Health Agiong. 2009 Apr;13(4):339–340

    Article  CAS  Google Scholar 

  11. Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jagust W, Trojanowski JQ, Toga AW, Beckett L. Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimer’s & Dement, 2005 Jul;1(1): 55–66.

    Article  Google Scholar 

  12. Weiner MW. Alzheimer’s Disease Neuroimaging Initiative. Int. Conf. Alzheimer’s Disease. Chicago IL., 2008, July

  13. Petersen RC, Jack CR. Imaging and biomarkers in early Alzheimer’s disease and Mild Cognitive Impairment. Clin Pharm Therapeutics 2009, 86(4): 438–441.

    Article  CAS  Google Scholar 

  14. Ivinson AJ, Lane R, May PC, Hosford DA, Carrillo MC, Siemers ER. Partnership between academia and industry for drug discovery in Alzheimer’s disease. Alzheimer’s Dement 2008 Mar;4(2):80–0.

    Article  Google Scholar 

  15. Becker RE, Greig NH. Alzheimer’s disease drug development in 2008 and beyond: problems and opportunities. Curr. Alz. Res., 2008, 5, 346–357.

    Article  CAS  Google Scholar 

  16. Anand R. Barriers to Alzheimer disease drug discovery and drug development in the pharmaceutical industry. Alzheimer Dis Assoc Disord. 2002;16Suppl 1:S33–S39.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to R. J. Schindler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schindler, R.J. Study design considerations: Conducting global clinical trials in early Alzheimer’s disease. J Nutr Health Aging 14, 312–314 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key words