Development of drugs for severe malaria in children.
Development of drugs for severe malaria in children.
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DOI：
10.1093/inthealth/ihw038
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发表时间：
2016-09
影响因子：
2.5
通讯作者：
Dondorp AM
中科院分区：
文献类型：
--
作者：
Cheah PY;Parker M;Dondorp AM
超过 90% 的疟疾死亡病例是 5 岁以下的非洲儿童。然而，新疗法通常主要在成年患者中进行测试，并且外推有时被证明是无效的，尤其是在给药方案中。对于严重疟疾的研究来说，另一个并发症是，成人患者中严重疟疾的减少妨碍了在成人中进行充分有效的试验，然后才能在最终目标群体（儿童严重疟疾）中测试干预措施。在本文中，我们提出了开发用于儿童严重疟疾的药物的替代途径。我们认为，在经典的 I 期和 II 期研究之后，应使用精心挑选的成人严重疟疾替代终点进行小型安全性和有效性研究，而不是更大规模的死亡率终点试验。如果该药物看起来安全且有前途，则可以使用相同的终点对儿科严重疟疾进行小型试点研究。最后，通过仔细观察的保障措施来确保高道德标准，有希望的候选干预措施可以被推进到死亡率终点、针对患有严重疟疾的非洲儿童的强有力的大型儿科研究中。鉴于现有的研究能力，可以在 III 期试验中研究有限数量的审慎选择的干预措施，并应考虑适应性设计。
Over 90% of deaths attributable to malaria are in African children under 5 years old. Yet, new treatments are often tested primarily in adult patients and extrapolations have proven to be sometimes invalid, especially in dosing regimens. For studies in severe malaria an additional complication is that the decline in severe malaria in adult patients precludes sufficiently powered trials in adults, before the intervention can be tested in the ultimate target group, paediatric severe malaria. In this paper we propose an alternative pathway to the development of drugs for use in paediatric severe malaria. We argue that following the classical phase I and II studies, small safety and efficacy studies using well-chosen surrogate endpoints in adult severe malaria be conducted, instead of larger mortality endpoint trials. If the drug appears safe and promising small pilot studies in paediatric severe malaria using the same endpoints can follow. Finally, with carefully observed safeguards in place to ensure high ethical standards, promising candidate interventions can be taken forward into mortality endpoint, well-powered, large paediatric studies in African children with severe malaria. Given the available research capacity, limited numbers of prudently selected interventions can be studied in phase III trials, and adaptive designs should be considered.
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影响因子：
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通讯作者：
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