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Although postmarketing studies conducted in population-based databases often contain information on patients in the order of millions, they can still be underpowered if outcomes or exposure of interest is rare, or the interest is in subgroup effects. Combining several databases might provide the statistical power needed. A multi-database study (MDS) uses at least two healthcare databases, which are not linked with each other at an individual person level, with analyses carried out in parallel across each database applying a common study protocol. Although many MDSs have been performed in Europe in the past 10 years, there is a lack of clarity on the peculiarities and implications of the existing strategies to conduct them. In this review, we identify four strategies to execute MDSs, classified according to specific choices in the execution: (A) local analyses, where data are extracted and analyzed locally, with programs developed by each site; (B) sharing of raw data, where raw data are locally extracted and transferred without analysis to a central partner, where all the data are pooled and analyzed; (C) use of a common data model with study-specific data, where study-specific data are locally extracted, loaded into a common data model, and processed locally with centrally developed programs; and (D) use of general common data model, where all local data are extracted and loaded into a common data model, prior to and independent of any study protocol, and protocols are incorporated in centrally developed programs that run locally. We illustrate differences between strategies and analyze potential implications., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: The role of frailty in postmarketing drug safety is increasingly acknowledged. Few European electronic medical records (EMRs) have been used to explore frailty in observational drug safety research., Objective: The aim of this study was to identify data elements, beyond multimorbidity and polypharmacy, that could potentially contribute to measuring frailty among older adults in the Dutch nationwide Integrated Primary Care Information (IPCI) database., Methods: Persons aged between 65 and 90 years in the IPCI database were identified from 2008 to 2013. Clinical non-disease, non-drug measurements that could potentially contribute to measuring frailty were identified and selected if they were recorded in > 0.005% of patients and could be included in at least one of three definitions of frailty: the frailty phenotype model, the cumulative deficit model, and direct evaluations of frailty through standardized frailty scores. The frequency of these measures was calculated., Results: Overall, 314,191 (17% of the source population) elderly persons were identified. Of these, 7948 (2.53%) had one or more of 12 clinical measurements identified that could potentially contribute to measuring frailty, such as clinical evaluations of cognition, mobility, and cachexia, as well as direct measures of frailty, such as the Groningen Frailty Index. Three of five measurements required for the frailty phenotype were identified in < 0.5% of the population: cachexia, reduced walking speed, and reduced physical activity; weakness and fatigue were not identified. The measurements outlined above may be appropriate for the cumulative deficit definition of frailty, provided that at least 30 deficits, including comorbidities and drug utilization, are evaluated in total. The most commonly recorded item identified that could potentially be used in a cumulative frailty model was the Mini-Mental State Examination score (N= 2850; 0.91%); the only recorded direct measurement of frailty was the Groningen Frailty Index (N = 2382; 0.76%)., Conclusion: Non-disease, non-drug clinical data that could potentially contribute to a frailty model was not commonly recorded in the IPCI; less than 3% of a cohort of elderly persons had these data recorded, suggesting that the use of these data in postmarketing drug safety evaluation may be limited.