Traditionally, studies in experimental physiology have been conducted in small groups of human participants, animal models or cell lines. Important challenges include achieving sufficient statistical power in statistical hypothesis tests of small sample sizes and identifying optimal study designs. Here, we introduce N-of-1 trials as an innovative study design which can have high relevance to innovate and improve studies in experimental physiology. N-of-1 trials are multi-crossover trials in single participants that allow valid statistical inference on the individual level. Also, series of N-of-1 trials conducted on multiple study participants can be aggregated for population-level inference and provide a more efficient study design compared to standard randomized controlled trials. In this manuscript, we first introduce key components and design features of N-of-1 trials. Then we lay out how N-of-1 trials can be analyzed statistically and give different examples of their applicability in experimental physiological studies. In summary, we provide here an overview of all main components for designing N-of-1 trials, give direct examples in experimental physiology and practical recommendations on their proper use.

翻译：传统上，实验生理学研究通常在少量人类参与者、动物模型或细胞系中进行。重要挑战包括在小样本统计假设检验中实现足够的统计功效，以及确定最优研究设计。本文引入N-of-1试验作为一种创新研究设计，其对革新和改进实验生理学研究具有高度相关性。N-of-1试验是在单个参与者中进行的多次交叉试验，可在个体层面进行有效的统计推断。此外，在多个研究参与者中进行的系列N-of-1试验可被聚合用于群体水平推断，并提供相较于标准随机对照试验更高效的研究设计。在本手稿中，我们首先介绍N-of-1试验的关键组成部分和设计特征。随后阐述如何对N-of-1试验进行统计分析，并给出其在实验生理学研究中适用性的不同示例。总之，本文概述了设计N-of-1试验的所有主要组成部分，提供了实验生理学中的直接案例及其正确使用的实践建议。