Hybrid studies allow investigators to simultaneously study an intervention effectiveness outcome and an implementation research outcome. In particular, type 2 hybrid studies support research that places equal importance on both outcomes rather than focusing on one and secondarily on the other (i.e., type 1 and type 3 studies). Hybrid 2 studies introduce the statistical issue of multiple testing, complicated by the fact that they are typically also cluster randomized trials. Standard statistical methods do not apply in this scenario. Here, we describe the design methodologies available for validly powering hybrid type 2 studies and producing reliable sample size calculations in a cluster-randomized design with a focus on binary outcomes. Through a literature search, 18 publications were identified that included methods relevant to the design of hybrid 2 studies. Five methods were identified, two of which did not account for clustering but are extended in this article to do so, namely the combined outcomes approach and the single 1-degree of freedom combined test. Procedures for powering hybrid 2 studies using these five methods are described and illustrated using input parameters inspired by a study from the Community Intervention to Reduce CardiovascuLar Disease in Chicago (CIRCL-Chicago) Implementation Research Center. In this illustrative example, the intervention effectiveness outcome was controlled blood pressure, and the implementation outcome was reach. The conjunctive test resulted in higher power than the popular p-value adjustment methods, and the newly extended combined outcomes and single 1-DF test were found to be the most powerful among all of the tests.

翻译：混合研究使研究者能够同时考察干预措施的有效性结果与实施研究结果。特别是，混合型2研究支持对两种结果赋予同等重要性的研究，而非侧重其中一项而将另一项作为次要考量（即混合型1与混合型3研究）。混合型2研究引入了多重检验的统计问题，且因其通常采用群集随机化试验设计而更趋复杂。标准统计方法在此情境下并不适用。本文系统阐述了在关注二分类结果的群集随机化设计中，为混合型2研究进行有效功效分析与可靠样本量计算可用的设计方法学。通过文献检索，共识别出18篇包含混合型2研究设计相关方法的出版物。其中归纳出五种核心方法，本文对其中两种未考虑群集效应的方法（即合并结果法与单自由度合并检验法）进行了扩展以纳入群集设计。文中详细说明了使用这五种方法进行混合型2研究功效分析的步骤，并借鉴芝加哥社区心血管疾病干预实施研究中心（CIRCL-Chicago）一项研究的参数设置进行实例演示。在该示例中，干预有效性结果为血压受控情况，实施结果为干预覆盖率。分析表明，合取检验法相较于常用的p值校正方法具有更高统计功效，而新扩展的合并结果法与单自由度检验法在所有检验方法中显示出最优功效。