A critical examination of best dose analysis for determining cognitive-enhancing potential of drugs: studies with rhesus monkeys and computer simulations.
A critical examination of best dose analysis for determining cognitive-enhancing potential of drugs: studies with rhesus monkeys and computer simulations.
复制标题
用于确定药物认知增强潜力的最佳剂量分析的严格检查：恒河猴研究和计算机模拟。
DOI：
10.1007/s00213-013-3070-4
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发表时间：
2013
影响因子：
3.4
通讯作者：
Katz,BrianR
中科院分区：
文献类型：
--
作者：
Soto,PaulL;Dallery,Jesse;Ator,NancyA;Katz,BrianR
最佳剂量分析包括确定与每个受试者的表现最大改善相关的剂量，并将与这些单独确定的最佳剂量相关的表现与对照表现进行比较。哌醋甲酯对恒河猴延迟匹配样本（DMTS：n= 7; SOSS：n= 6）和自序空间搜索（SOSS）性能的影响，以确定最佳剂量效应的有效性和可靠性。实验2使用Monte Carlo计算机模拟来估计获得显着结果的可能性时，最佳剂量的方法被施加到随机生成的数据集，没有差异existing.ResultsSignificant效果时，获得最佳剂量分析应用于非药物会议的性能，最佳剂量性能没有显着不同的最佳非药物性能。从两次尼古丁剂量-反应曲线测定中确定为最佳剂量的剂量不相关，并且当重复给药时，在第一次剂量-反应曲线测定期间观察到的与最佳剂量相关的改善不可靠。最后，有一个很高的可能性，获得一个统计学上显着的差异时，没有真实的差异existing.ConclusionsBest剂量分析识别潜在的治疗药物，应取代单受试者设计。
RationaleBest dose analysis involves identifying the dose associated with the greatest improvement in performance for each subject and comparing performances associated with these individually determined best doses to control performances.ObjectivesThe current experiments were conducted to examine whether significant best dose effects might result from the selective analysis of data rather than an actual drug effect.MethodsExperiment 1 examined the effects of nicotine and methylphenidate on delayed matching-to-sample (DMTS) and self-ordered spatial search (SOSS) performances in rhesus monkeys (DMTS:n= 7; SOSS:n= 6) to determine the validity and reliability of best dose effects. Experiment 2 used Monte Carlo computer simulations to estimate the likelihood of obtaining a significant outcome when the best dose method was applied to randomly generated data sets for which no difference existed.ResultsSignificant effects were obtained when the best dose analysis was applied to performances from nondrug sessions, and best dose performances were not significantly different from the best nondrug performances. The doses identified as best doses from two nicotine dose–response curve determinations were unrelated, and the improvement associated with the best dose observed during the first dose–response curve determination was not reliable when the dose was administered repeatedly. Finally, there was a high likelihood of obtaining a statistically significant difference when no real difference existed.ConclusionsBest dose analysis for the identification of potential therapeutic agents should be replaced by single-subject designs.