Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials

Joshua D. Grill, Rema Raman, Karin Ernstrom, Paul Aisen, Sherie A. Dowsett, Yun Fei Chen, Hong Liu-Seifert, Ann Hake, David S. Miller, Rachelle S. Doody, David B. Henley, Jeffrey L. Cummings

Research output: Contribution to journalArticle

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Abstract

Introduction: Most Alzheimer's disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region. Methods: We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). We assigned 31 participating nations to 7 geographic regions: North America, South America/Mexico, Western Europe/Israel, Eastern Europe/Russia, Australia/South Africa, Asia, and Japan. Results: North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ε4 carriers, and participants with spouse study partners, whereas Asia, Eastern Europe/Russia, and South America/Mexico had lower proportions for these variables. North America and South America/Mexico enrolled older subjects, whereas Asia and South America/Mexico enrolled less-educated participants than the remaining regions. Approved AD therapy use differed among regions (range: 73% to 92%) and was highest in North America, Western Europe/Israel, and Japan. Dual therapy was most frequent in North America (48%). On the MMSE, North America, Western Europe/Israel, Japan, and Australia/South Africa had higher (better) scores, and Asia, South America/Mexico, and Eastern Europe/Russia had lower scores. Eastern Europe/Russia had more impaired ADAS-cog11 scores than all other regions. Eastern Europe/Russia and South America/Mexico had more impaired scores for the ADCS-ADL and the CDR-SB. Mean scores for the CDR-SB in Asia were milder than all regions except Japan. NPI scores were lower in Asia and Japan than in all other regions. Participants in North America and Western Europe/Israel reported more adverse events than those in Eastern Europe/Russia and Japan. Conclusions: These findings suggest that trial populations differ across geographic regions on most baseline characteristics and that multinational enrollment is associated with sample heterogeneity. The data provide initial guidance with regard to the regional differences that contribute to this heterogeneity and are important to consider when planning global trials.

Original languageEnglish (US)
Article number39
JournalAlzheimer's Research and Therapy
Volume7
Issue number1
DOIs
StatePublished - Jun 25 2015

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Eastern Europe
North America
South America
Russia
Mexico
Alzheimer Disease
Israel
Clinical Trials
Japan
Safety
South Africa
Dementia
Equipment and Supplies
Activities of Daily Living
Apolipoprotein E4
Western Australia
Spouses
Research Personnel
Demography
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cognitive Neuroscience

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Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials. / Grill, Joshua D.; Raman, Rema; Ernstrom, Karin; Aisen, Paul; Dowsett, Sherie A.; Chen, Yun Fei; Liu-Seifert, Hong; Hake, Ann; Miller, David S.; Doody, Rachelle S.; Henley, David B.; Cummings, Jeffrey L.

In: Alzheimer's Research and Therapy, Vol. 7, No. 1, 39, 25.06.2015.

Research output: Contribution to journalArticle

Grill, JD, Raman, R, Ernstrom, K, Aisen, P, Dowsett, SA, Chen, YF, Liu-Seifert, H, Hake, A, Miller, DS, Doody, RS, Henley, DB & Cummings, JL 2015, 'Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials', Alzheimer's Research and Therapy, vol. 7, no. 1, 39. https://doi.org/10.1186/s13195-015-0122-5
Grill, Joshua D. ; Raman, Rema ; Ernstrom, Karin ; Aisen, Paul ; Dowsett, Sherie A. ; Chen, Yun Fei ; Liu-Seifert, Hong ; Hake, Ann ; Miller, David S. ; Doody, Rachelle S. ; Henley, David B. ; Cummings, Jeffrey L. / Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials. In: Alzheimer's Research and Therapy. 2015 ; Vol. 7, No. 1.
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AU - Dowsett, Sherie A.

AU - Chen, Yun Fei

AU - Liu-Seifert, Hong

AU - Hake, Ann

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N2 - Introduction: Most Alzheimer's disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region. Methods: We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). We assigned 31 participating nations to 7 geographic regions: North America, South America/Mexico, Western Europe/Israel, Eastern Europe/Russia, Australia/South Africa, Asia, and Japan. Results: North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ε4 carriers, and participants with spouse study partners, whereas Asia, Eastern Europe/Russia, and South America/Mexico had lower proportions for these variables. North America and South America/Mexico enrolled older subjects, whereas Asia and South America/Mexico enrolled less-educated participants than the remaining regions. Approved AD therapy use differed among regions (range: 73% to 92%) and was highest in North America, Western Europe/Israel, and Japan. Dual therapy was most frequent in North America (48%). On the MMSE, North America, Western Europe/Israel, Japan, and Australia/South Africa had higher (better) scores, and Asia, South America/Mexico, and Eastern Europe/Russia had lower scores. Eastern Europe/Russia had more impaired ADAS-cog11 scores than all other regions. Eastern Europe/Russia and South America/Mexico had more impaired scores for the ADCS-ADL and the CDR-SB. Mean scores for the CDR-SB in Asia were milder than all regions except Japan. NPI scores were lower in Asia and Japan than in all other regions. Participants in North America and Western Europe/Israel reported more adverse events than those in Eastern Europe/Russia and Japan. Conclusions: These findings suggest that trial populations differ across geographic regions on most baseline characteristics and that multinational enrollment is associated with sample heterogeneity. The data provide initial guidance with regard to the regional differences that contribute to this heterogeneity and are important to consider when planning global trials.

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