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Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.
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Introduction: Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. Methods: The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. Results: The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Discussion: Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.