O'Brien John T, Oertel Wolfgang H, McKeith Ian G, Grosset Donald G, Walker Zuzana, Tatsch Klaus, Tolosa Eduardo, Sherwin Paul F, Grachev Igor D
Department of Psychiatry, University of Cambridge School of Clinical Medicine, and Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, UK.
Department of Neurology, Philipps-University of Marburg, Marburg, Germany.
BMJ Open. 2014 Jul 3;4(7):e005122. doi: 10.1136/bmjopen-2014-005122.
To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane ((123)I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies.
Pooled analysis of three phase 3 and one phase 4 clinical trials. These four trials were selected because they were the four studies used for the US new drug application to the Food and Drug Administration (FDA).
Multicentre, open-label, non-randomised.
Patients with either a movement disorder or dementia, and healthy volunteers.
Ioflupane ((123)I) was administered.
Images were assessed by panels of 3-5 blinded experts and/or on-site nuclear medicine physicians, classified as normal or abnormal and compared with clinical diagnosis (reference standard) to determine sensitivity and specificity.
Pooling the four studies, 928 participants were enrolled, 849 were dosed and 764 completed their study. Across all studies, when images were assessed by on-site readers, ioflupane ((123)I) diagnostic effectiveness had an overall (95% CI) sensitivity of 91.9% (88.7% to 94.5%) and specificity of 83.6% (78.7% to 87.9%). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8% to 90.4%) and specificity was 91.2% (89.0% to 93.0%).
In this pooled analysis, the visual assessment of ioflupane ((123)I) images provided high levels of sensitivity and specificity in detecting the presence/absence of an SDDD. Ioflupane ((123)I) imaging has the potential to improve diagnostic accuracy in patients with signs and symptoms of a movement disorder and/or dementia.
NCT00209456.
汇总设计相似的临床试验，以评估碘氟烷I123注射液（DaTSCAN或碘氟烷（（123）I））检测或排除纹状体多巴胺能缺陷障碍（SDDD）的总体敏感性和特异性，如帕金森综合征和路易体痴呆。
对三项3期和一项4期临床试验进行汇总分析。选择这四项试验是因为它们是用于向美国食品药品监督管理局（FDA）申请新药的四项研究。
多中心、开放标签、非随机。
患有运动障碍或痴呆的患者以及健康志愿者。
给予碘氟烷（（123）I）。
图像由3至5名不知情的专家小组和/或现场核医学医师评估，分类为正常或异常，并与临床诊断（参考标准）进行比较，以确定敏感性和特异性。
汇总这四项研究，共纳入928名参与者，849名接受给药，764名完成研究。在所有研究中，当由现场阅片者评估图像时，碘氟烷（（123）I）诊断有效性的总体（95%CI）敏感性为91.9%（88.7%至94.5%），特异性为83.6%（7&.7%至87.9%）。当由独立专家小组进行盲法阅片时，总体敏感性为88.7%（86.8%至90.4%），特异性为91.2%（89.0%至93.0%）。
在这项汇总分析中，对碘氟烷（（123）I）图像的视觉评估在检测SDDD的有无方面具有较高的敏感性和特异性。碘氟烷（（123）I）成像有可能提高对有运动障碍和/或痴呆体征和症状患者的诊断准确性。
NCT00209456。
