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Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.

ABSTRACT: BACKGROUND:Globalization of clinical trials has important consequences for trial planning and interpretation. This study investigated heterogeneity in patient characteristics and outcomes among world regions in the global idalopirdine Phase 3 clinical program. METHODS:Data were pooled from three 24-week randomized controlled trials in patients aged ??50 years with mild-to-moderate Alzheimer's disease (AD) (n =?2506). Patients received idalopirdine (10, 30, or 60 mg/day) or placebo, added to cholinesterase inhibitor treatment. Patients were categorized into the following regions: Eastern Europe/Turkey (n =?759), Western Europe/Israel (n =?709), USA/Canada (n =?444), South America/Mexico (n =?361), Asia (n =?134), and Australia/South Africa (n =?99). For each region, operational characteristics, baseline demographic and clinical characteristics, adverse events, and mean change from baseline to week 24 in clinical rating scale scores (placebo group only) were summarized using descriptive statistics. RESULTS:Completion rates were 0.86-0.90 in all regions. Heterogeneity among global regions was evident. Protocol deviations were twice as common in South America/Mexico as in USA/Canada (2.64 vs 1.35 per patient screened). Educational level ranged from 9.2 years in South America/Mexico to 13.4 years in USA/Canada. APOE ?4 carriage was 80.6% in Australia/South Africa, 63.1% in Western Europe/Israel, and?

SUBMITTER: Cummings JL

PROVIDER: S-EPMC6260857 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.

Cummings Jeffrey L JL Atri Alireza A Ballard Clive C Boneva Neli N Frölich Lutz L Molinuevo José Luis JL Raket Lars Lau LL Tariot Pierre N PN

Alzheimer's research & therapy 20181124 1

<h4>Background</h4>Globalization of clinical trials has important consequences for trial planning and interpretation. This study investigated heterogeneity in patient characteristics and outcomes among world regions in the global idalopirdine Phase 3 clinical program.<h4>Methods</h4>Data were pooled from three 24-week randomized controlled trials in patients aged ≥ 50 years with mild-to-moderate Alzheimer's disease (AD) (n = 2506). Patients received idalopirdine (10, 30, or 60 mg/day) or placebo ...[more]

PMID: 30474567

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Project description: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.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.North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ?4 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.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.

Project description:PurposeTo evaluate the correlation between the choriocapillaris (CC) flow alterations around geographic atrophy (GA) and the GA yearly growth rate (yGR) in patients with dry age-related macular degeneration (AMD).MethodsWe retrospectively reviewed and analyzed spectral domain optical coherence tomography (SD-OCT) and SD-OCT angiography images of consecutive patients with GA acquired using the Cirrus OCT at the Doheny Eye Centers between 2015 and 2017. All eligible patients had one 6 x 6 mm OCTA scan acquired during the first visit (considered as baseline) and two fovea-centered 512 x 128 macular cubes (6 x 6 mm) acquired at baseline and after a minimum of 12 months.Main outcome measuresThe fundus images from the OCT volumes were used to manually delineate the GA area and calculate the yGR after square root transformation. The en-face angiogram at the level of the CC was analyzed for the percentage of flow voids (FV) outside the atrophic lesion (FVOUT) and in the para- and peri-atrophy regions (FV500 and FV1000 respectively; two concentric 500 ?m wide rings around the atrophy edge). These values, together with the difference between FV500 and FV1000 (?FV), were then correlated with the corresponding yGR.ResultsThirty-three eyes of 23 patients were eligible for the analysis. The mean yGR was 0.23 ± 0.17 mm/years. At baseline, the mean FVOUT was 41.86 ± 2.71%, while FV500 and FV1000 were 46.4 ± 4.17% and 42.51 ± 2.65% respectively. The mean ?FV was 3.89 ± 2.6%. While in the univariable analysis, the yGR was significantly associated with FV500 and with ?FV (both p < 0.001), in multivariable model the association remained significant only with ?FV (p < 0.001).ConclusionsOur study reports a correlation between the CC flow impairment around the atrophic lesions and their yGR in patients with GA. If replicated in future longitudinal studies, the choriocapillaris FV in the para-and peri-atrophy regions may prove to be useful parameters for evaluating the prognosis of these eyes.

Dataset Information

Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.

Publications

Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.

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