Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Neurodegeneration, 1081 HV, Amsterdam, The Netherlands.
Alzheimers Res Ther. 2023 Nov 2;15(1):189. doi: 10.1186/s13195-023-01332-4.
The mismatch between the limited availability versus the high demand of participants who are in the pre-dementia phase of Alzheimer's disease (AD) is a bottleneck for clinical studies in AD. Nevertheless, potential enrollment barriers in the pre-dementia population are relatively under-reported. In a large European longitudinal biomarker study (the AMYPAD-PNHS), we investigated main enrollment barriers in individuals with no or mild symptoms recruited from research and clinical parent cohorts (PCs) of ongoing observational studies.
Logistic regression was used to predict study refusal based on sex, age, education, global cognition (MMSE), family history of dementia, and number of prior study visits. Study refusal rates and categorized enrollment barriers were compared between PCs using chi-squared tests.
535/1856 (28.8%) of the participants recruited from ongoing studies declined participation in the AMYPAD-PNHS. Only for participants recruited from clinical PCs (n = 243), a higher MMSE-score (β = - 0.22, OR = 0.80, p < .05), more prior study visits (β = - 0.93, OR = 0.40, p < .001), and positive family history of dementia (β = 2.08, OR = 8.02, p < .01) resulted in lower odds on study refusal. General study burden was the main enrollment barrier (36.1%), followed by amyloid-PET related burden (PC = 27.4%, PC = 9.0%, X = 10.56, p = .001), and loss of research interest (PC = 46.3%, PC = 16.5%, X = 32.34, p < .001).
The enrollment rate for the AMYPAD-PNHS was relatively high, suggesting an advantage of recruitment via ongoing studies. In this observational cohort, study burden reduction and tailored strategies may potentially improve participant enrollment into trial readiness cohorts such as for phase-3 early anti-amyloid intervention trials. The AMYPAD-PNHS (EudraCT: 2018-002277-22) was approved by the ethical review board of the VU Medical Center (VUmc) as the Sponsor site and in every affiliated site.
在阿尔茨海默病（AD）的痴呆前阶段，参与者的数量有限，而需求却很高，这种供需之间的不匹配是 AD 临床研究的一个瓶颈。然而，痴呆前人群中的潜在入组障碍相对报道较少。在一项大型欧洲纵向生物标志物研究（AMYPAD-PNHS）中，我们调查了从正在进行的观察性研究的研究和临床母队列（PC）中招募的无或轻度症状个体的主要入组障碍。使用逻辑回归基于性别、年龄、教育、总体认知（MMSE）、痴呆家族史和之前研究就诊次数预测研究拒绝情况。使用卡方检验比较了 PC 之间的研究拒绝率和分类入组障碍。
对来自正在进行的研究的 1856 名参与者中的 535 名（28.8%）进行了调查，他们拒绝参与 AMYPAD-PNHS。仅对来自临床 PC（n=243）的参与者，较高的 MMSE 评分（β=-0.22，OR=0.80，p<.05）、更多的之前研究就诊次数（β=-0.93，OR=0.40，p<.001）和阳性痴呆家族史（β=2.08，OR=8.02，p<.01）导致研究拒绝的可能性降低。一般研究负担是主要的入组障碍（36.1%），其次是淀粉样蛋白-PET 相关负担（PC=27.4%，PC=9.0%，X=10.56，p=.001）和研究兴趣丧失（PC=46.3%，PC=16.5%，X=32.34，p<.001）。
AMYPAD-PNHS 的入组率相对较高，这表明通过正在进行的研究进行招募具有优势。在这个观察性队列中，减少研究负担和制定针对性策略可能会潜在地提高试验准备队列（如 3 期早期抗淀粉样蛋白干预试验）的参与者入组率。AMYPAD-PNHS（EudraCT：2018-002277-22）获得了 VU 医学中心（VUmc）伦理审查委员会的批准，作为赞助商站点和每个附属站点。
