重视儿科的药物临床试验课件.ppt

李 智 平复旦大学附属儿科医院zplifudan@2012. 4 . 20 Impact of Pediatric Legislative Initiatives:USA FDAMA (1/2002) Food and Drug Administration Modernization Act 食品药品管理现代化法案 BPCA (1/2002) Best Pharmaceuticals for Children Act 儿科最佳药品法案 PREA (12/2003) Pediatric Research Equity Act 儿科研究权益法案 Impact of Pediatric Legislative Initiatives:USA WR Written Request 书面要求 PPSR Proposed Pediatric Study Request 对儿童临床试验的要求 ICH International Conference on Harmonization 国际协调会议 Inability to demonstrate ffectiveness 12 / 04以下的药物无法证明其有效性 Sumatriptan: 5 trials in 12-17 year olds when compared to placebo 舒马普坦 : 在12-17岁儿童中进行了5组设空白对照的试验，结果提示可能无效 Zolmitriptan: 12-17 year olds in placebo controlled trial 佐米曲坦: 在12-17岁儿童中进行了设空白对照的试验，结果提示可能无效 Ineffective Dosing of an Effective Therapy有效的药物，无效的剂量 Double the clearance rate of Ultiva (Remifentanil) in neonates Ultiva (瑞芬太尼)在新生儿中的清除率翻倍 Higher clearance of Lotensin (Benazepril) in hypertensive children 高血压儿童对洛汀新 (贝那普利) 的清除率较高 Overdosing of an Effective Therapy有效的药物，过度的剂量 Reduced clearance of Arava (Leflunomide) in pediatric patients 40 kg 40 kg患儿对Arava（含来氟米特 ）的清除率较低 Decreased clearance of Pepcid (Famotidine) in infants 0-3 months of age and of Epivir (Lamivudine) for HIV in 1 week old neonates 0-3月婴儿对Pepcid (法莫替丁 )，1周内的艾滋病新生儿对Epivir (拉米夫定) 的清除率均较低 Undefined Unique Pediatric Adverse Effects定义不明确的仅发生于儿童的不良事件 Increase of suicidal ideation with Rebetron (Ribavirin/Intron A) 在儿科中应用Rebetron (利巴韦林 /干扰能 )，可能增加自杀想法的发生率 New Adverse EventsExamples (2)新发现的儿科不良反应实例 Effects on Growth  Developmental Behavior对生长和行为的影响 Neurontin (Gabapentin): Neuropsychiatric AE’s identified in 3-12 year olds, including aggressive behavior and school problems 诺立汀 (加巴喷丁 )： 在3~12岁儿童中已证实可发生神经心理方面的不良事件，包括攻击行为和校园问题 Growth and Development (2)对生长和发育的影响 Effexor XR (Venlafaxine): 18% vs 3.6% in placebo had wt loss; height increase 0.3 vs 1cm in placebo Effexor XR