The design of embedded pragmatic clinical trials: methodological developments and statistical lessons learned from the first cycle of the NIA IMPACT collaboratory

INTRODUCTION: The National Institute on Aging-funded IMbedded Pragmatic Alzheimer's disease and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory was established to build capacity for conducting embedded pragmatic clinical trials (ePCTs) within healthcare systems for people living with dementia and their care partners. Here we present methodology and describe lessons learned from the first five years of IMPACT's Design and Statistics Core (DSC). METHODS: The DSC assembled a multidisciplinary team focused on advancing the design, analysis, and implementation of ePCTs. RESULTS: The DSC developed and disseminated methods for design and sample size of cluster randomized designs with complex correlation structures; guidance for pilot ePCTs; approaches to patient-care partner ePCTs; approaches to testing health-equity-relevant hypotheses; and guidance for training quantitative and clinical scientists developing ePCTs. DISCUSSION: Key gaps remain in applying dyadic designs and when studying heterogeneity of treatment effects, which will be major priorities for the next funding cycle.