Ward R M, Lane R H, Albertine K H
Pediatric Pharmacology Program, University of Utah Department of Pediatrics, Salt Lake City, 84108, USA.
J Perinatol. 2006 Jul;26 Suppl 2:S8-S12. doi: 10.1038/sj.jp.7211423.
Pharmacologic study is needed in the extremely immature newborns who currently survive. Study is needed of both the drug treatment previously established in more mature neonates and of novel drug therapy. Carefully controlled studies are needed to identify accurately both beneficial and harmful drug therapy and the mechanisms of that toxicity. Careful pharmacologic study of drug disposition and its mechanisms might lead to dosing paradigms or patient selection that minimize toxicity and maximize efficacy. In vivo, translational models of neonatal diseases are limited, but can be used to identify novel treatments and study mechanisms of established, successful therapy. Findings from such studies can generate hypotheses for study in humans leading to a continuing scientific interchange from bedside to bench to bedside. Similarly, clinical observations can generate hypotheses for study in translational models where more invasive analyses are possible. Specific areas of drug treatment should focus on neonatal disorders with long-term, adverse outcomes, such as chronic lung disease, that is amenable to translational study with animal models. National data show a progressive decrease in the clinician-scientist pool entering biomedical research. The future of neonatal pharmacology studies requires an increase in training programs for the physician-scientist whose clinical education in neonatology can be complemented by rigorous basic-science training. Success as a clinician-scientist will require collaboration with full-time basic scientists who can continue studies during periods of clinical work and provide critical study methodology to the overall study design. Such a work environment must be supported by academic institutions and may require more flexibility in the promotion and tenure schedule and process, such as the nature of what it rewards. To complement this, the NIH could modify its grant reporting process to identify co-investigators in studies who may provide unique input to the study concepts and design, such as clinical correlations or clinical investigations.
对于目前存活的极不成熟的新生儿，需要进行药理学研究。需要对先前在更成熟的新生儿中确立的药物治疗以及新型药物疗法进行研究。需要进行严格控制的研究，以准确识别有益和有害的药物治疗及其毒性机制。对药物处置及其机制进行仔细的药理学研究可能会导致给药模式或患者选择，从而将毒性降至最低并将疗效最大化。在体内，新生儿疾病的转化模型有限，但可用于识别新的治疗方法并研究既定成功疗法的机制。此类研究的结果可以为人类研究产生假设，从而实现从床边到实验室再回到床边的持续科学交流。同样，临床观察可以为在更具侵入性分析的转化模型中的研究产生假设。药物治疗的特定领域应侧重于具有长期不良后果的新生儿疾病，如慢性肺病，这种疾病适合用动物模型进行转化研究。国家数据显示，进入生物医学研究领域的临床科学家队伍在逐渐减少。新生儿药理学研究的未来需要增加针对临床科学家的培训项目，他们在新生儿学方面的临床教育可以通过严格的基础科学培训得到补充。作为一名临床科学家取得成功将需要与全职基础科学家合作，这些基础科学家可以在临床工作期间继续进行研究，并为整体研究设计提供关键的研究方法。这样的工作环境必须得到学术机构的支持，并且可能需要在晋升和任期安排及过程中更加灵活，比如奖励的性质。作为补充，美国国立卫生研究院可以修改其资助报告流程，以识别研究中的共同研究者，他们可能为研究概念和设计提供独特的见解，如临床相关性或临床研究。
