Department of Toxicology, Department of Pharmacy, Universidad Nacional de Colombia, Bogotá, Colombia; Institute of Pharmaceutical Research, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.
Institute of Pharmaceutical Research, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela; Laboratory of Neuropeptides, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.
J Pharmacol Toxicol Methods. 2020 May-Jun;103:106684. doi: 10.1016/j.vascn.2020.106684. Epub 2020 Mar 12.
The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly, in order for those assays to influence nonclinical and clinical evaluations and decisions better. Critical issues related to the performance and predictive values of nonclinical testing were highlighted and discussed in this article, specifically, to help pharmacologists, toxicologists, and regulators in the evaluation of the reliability of such tests, and basing the prospective decisions on the true predictivity of selected screening tests. This review addressed two common mistakes in drug and chemical testing, namely, (a) the assumption of either sensitivity or specificity as automatically "predictive," and (b) the reporting of the predictive values disregarding a truly representative prevalence. This review also discussed a statistical basis to apply for (industry standpoint) or grant (regulatory standpoint) authorization for the waiving of selected nonclinical tests. Furthermore, this review can be guiding for those who are entering into the field of drug and chemical testing. Through application, investigation, and enhancement of the conceptual framework discussed in this review, nonclinical testing is expected to provide a higher contribution to drug and chemical development, regulatory science, and public health.
药品和化学物质的上市前测试现在是保障公共卫生的典范。正如 ICH 概念文件 E14/S7B 所指出的，需要基于科学的框架，以便更好地设计、进行和解释非临床和毒性测试，特别是为了使这些检测更好地影响非临床和临床评估和决策。本文重点讨论了非临床测试的性能和预测值方面的关键问题，特别是为了帮助药理学家、毒理学家和监管机构评估此类测试的可靠性，并基于所选筛选测试的真正预测性做出前瞻性决策。本文综述了药物和化学物质测试中的两个常见错误，即(a) 假设灵敏度或特异性自动“具有预测性”，以及(b) 报告预测值而不考虑真正具有代表性的流行率。本文还讨论了应用统计学基础（从工业角度）或授予（从监管角度）授权豁免某些非临床测试。此外，本文综述还可以为那些进入药物和化学物质测试领域的人提供指导。通过应用、调查和增强本文讨论的概念框架，非临床测试有望为药物和化学物质开发、监管科学和公共卫生做出更大的贡献。
