Recommendations to Enhance Pediatric Cardiovascular Drug Development: Report of a Multi-Stakeholder Think Tank.
Recommendations to Enhance Pediatric Cardiovascular Drug Development: Report of a Multi-Stakeholder Think Tank.
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DOI：
10.1161/jaha.117.007283
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发表时间：
2018-02-10
影响因子：
5.4
通讯作者：
Hill KD
中科院分区：
文献类型：
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作者：
Torok RD;Li JS;Kannankeril PJ;Atz AM;Bishai R;Bolotin E;Breitenstein S;Chen C;Diacovo T;Feltes T;Furlong P;Hanna M;Graham EM;Hsu D;Ivy DD;Murphy D;Kammerman LA;Kearns G;Lawrence J;Lebeaut B;Li D;Male C;McCrindle B;Mugnier P;Newburger JW;Pearson GD;Peiris V;Percival L;Pina M;Portman R;Shaddy R;Stockbridge NL;Temple R;Hill KD
在药物试验中，儿童在历史上代表性不足，甚至完全被忽略，导致相对缺乏证据支持许多儿科疾病的适当药物治疗。1，2美国和欧盟（EU）最近的立法倡议已经创建了一个授权和激励体系，以鼓励进一步的儿科药物开发（表13-6）。总体而言，这些举措通过将儿科患者作为优先事项，在改变药物开发格局方面取得了巨大成功;自2007年实施儿科法规以来，过去20年来，美国已实施了600多项儿科标签变更，欧盟的步伐与此相似。5，7，8然而，许多儿科疾病仍然相对被忽视，许多药物仍然被“标签外”使用，因为尚未进行研究，或者因为已经进行的研究未能证明疗效。9、10在患有心血管疾病的儿童中，根据上述立法倡议成功开发的药物有限。根据监管激励条款进行的成功试验主要与儿童高血压11 -20和家族性高胆固醇血症有关。21-28尽管这些试验导致了这些特定疾病的重要变化，但它们面临着与患者招募、疾病异质性、剂量、终点选择相关的挑战，并且总体上缺乏在儿童中进行随机临床试验的经验。类似的挑战限制了药物在患有先天性或获得性心脏病、心力衰竭、动脉或静脉血栓形成和肺动脉高压的儿科患者中的开发。针对这些问题，来自学术界、美国国立卫生研究院（NIH）、美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）、行业赞助商和倡导团体的专家小组召集了一个关于儿科心血管药物开发的智囊团。会议于2016年9月8日至9日在华盛顿举行，主要目的是通过改善试验规划、设计和执行，为加强儿科心血管药物开发提供建议。在此，我们总结了本次会议的讨论情况，并提出了协商一致的建议。
Children have historically been underrepresented or, indeed, omitted entirely, in drug trials, leading to a relative dearth of evidence in support of appropriate drug treatments for many pediatric diseases. 1, 2 Recent legislative initiatives in the United States and the European Union (EU) have created a system of mandates and incentives to encourage further pediatric drug development (Table 13–6). Overall, these initiatives have been highly successful at shifting the landscape in drug development by making pediatric patients a priority;> 600 pediatric labeling changes have been implemented in the United States over the past 2 decades, with a similar pace in the EU, since implementation of the Paediatric Regulation in 2007. 5, 7, 8 Nevertheless, many pediatric diseases remain relatively neglected, with many drugs still used “off-label” because studies have yet to be conducted, or because studies that have been conducted have failed to demonstrate efficacy. 9, 10 In children with cardiovascular diseases, successful drug development under the aforementioned legislative initiatives has been limited. Successful trials conducted under the regulatory incentive provisions have been primarily related to pediatric hypertension11–20 and familial hypercholesterolemia. 21–28 Although these trials led to important changes for these particular diseases, they faced challenges related to patient recruitment, disease heterogeneity, dosing, endpoint selection, and, in general, an overall lack of experience in conducting randomized clinical trials in children. Similar challenges have limited drug development in pediatric patients with congenital or acquired heart disease, heart failure, arterial or venous thrombosis, and pulmonary hypertension. In response to these issues, a panel of experts from academia, the US National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), industry sponsors, and advocacy groups convened for a think tank on pediatric cardiovascular drug development. The meeting was held from September 8 to 9, 2016, in Washington, DC, with the primary objective of providing recommendations to enhance pediatric cardiovascular drug development by improving trial planning, design, and execution. Herein we summarize discussions from this meeting and provide consensus recommendations.