Importance Clinical trials have identified numerous prescriptive predictors of mental disorder treatment response, ie, predictors of which treatments are best for which patients. However, none of these prescriptive predictors is strong enough alone to guide precision treatment planning. This has prompted growing interest in developing precision treatment rules (PTRs) that combine information across multiple prescriptive predictors, but this work has been much less successful in psychiatry than some other areas of medicine. Study designs and analysis schemes used in research on PTR development in other areas of medicine are reviewed, key challenges for implementing similar studies of mental disorders are highlighted, and recent methodological advances to address these challenges are described here. Observations Discovering prescriptive predictors requires large samples. Three approaches have been used in other areas of medicine to do this: conduct very large randomized clinical trials, pool individual-level results across multiple smaller randomized clinical trials, and develop preliminary PTRs in large observational treatment samples that are then tested in smaller randomized clinical trials. The third approach is most feasible for research on mental disorders. This approach requires working with large real-world observational electronic health record databases; carefully selecting samples to emulate trials; extracting information about prescriptive predictors from electronic health records along with other inexpensive data augmentation strategies; estimating preliminary PTRs in the observational data using appropriate methods; implementing pragmatic trials to validate the preliminary PTRs; and iterating between subsequent observational studies and quality improvement pragmatic trials to refine and expand the PTRs. New statistical methods exist to address the methodological challenges of implementing this approach. Conclusions and Relevance Advances in pragmatic precision psychiatry will require moving beyond the current focus on randomized clinical trials and adopting an iterative discovery-confirmation process that integrates observational and experimental studies in real-world clinical populations.

中文翻译：

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务实精准精神病学——优化治疗选择的新方向。

重要性 临床试验已经确定了许多精神障碍治疗反应的规范性预测因子，即哪种治疗最适合哪些患者的预测因子。然而，这些规范性预测因素都不足以单独指导精确的治疗计划。这促使人们对开发精确治疗规则 (PTR) 的兴趣日益浓厚，这些规则结合了多个处方预测因子的信息，但这项工作在精神病学中的成功远不如其他一些医学领域。回顾了其他医学领域 PTR 发展研究中使用的研究设计和分析方案，强调了实施类似的精神障碍研究的关键挑战，并描述了应对这些挑战的最新方法学进展。观察发现规范性预测变量需要大量样本。其他医学领域已经使用了三种方法来做到这一点：进行非常大型的随机临床试验，在多个较小的随机临床试验中汇总个体水平的结果，并在大型观察性治疗样本中开发初步 PTR，然后在较小的随机临床试验中进行测试试验。第三种方法对于精神障碍的研究最为可行。这种方法需要使用大型真实世界的观察性电子健康记录数据库；仔细选择样本以模拟试验；从电子健康记录中提取有关规定性预测因子的信息以及其他廉价的数据增强策略；使用适当的方法估计观测数据中的初步 PTR；实施务实的试验以验证初步 PTR；并在随后的观察性研究和质量改进实用试验之间进行迭代，以完善和扩展 PTR。存在新的统计方法来解决实施这种方法的方法学挑战。结论和相关性 实用精准精神病学的进展将需要超越目前对随机临床试验的关注，并采用一种迭代的发现-确认过程，将现实世界临床人群中的观察和实验研究相结合。存在新的统计方法来解决实施这种方法的方法学挑战。结论和相关性 实用精准精神病学的进展将需要超越目前对随机临床试验的关注，并采用一种迭代的发现-确认过程，将现实世界临床人群中的观察和实验研究相结合。存在新的统计方法来解决实施这种方法的方法学挑战。结论和相关性 实用精准精神病学的进展将需要超越目前对随机临床试验的关注，并采用一种迭代的发现-确认过程，将现实世界临床人群中的观察和实验研究相结合。