Combining data from EHR databases of different countries to identify drug-adverse event associations is feasible and can set the stage for changing and enlarging the scale for drug safety monitoring.

IMPORTANCE Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials. OBJECTIVE To determine prevalence and outcomes of amyloid positivity in a population without dementia. DESIGN, SETTING, AND PARTICIPANTS In the prospective, population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, participants without dementia were randomly selected from the county population and were clinically and cognitively evaluated at baseline and every 15 months from August 1, 2008, to September 18, 2018. They were also invited to undergo carbon 11-Pittburgh compound B positron emission tomography (PET) imaging. EXPOSURES Amyloid positivity (defined as a standardized uptake value ratio >1.42 on PET). MAIN OUTCOMES AND MEASURES Prevalence of amyloid positivity in the Olmsted County population without dementia and risk of progression from no cognitive impairment (ie, normal cognition for age) to incident amnestic MCI (aMCI) and from MCI or aMCI to incident AD dementia. RESULTS Of 3894 participants, 1671 underwent PET imaging and were included in the study; 2198 did not undergo imaging, and 25 were excluded for other reasons. The mean (SD) age of participants was 71.3 (9.8) years; 892 (53.4%) were men, and 179 (10.7%) had prevalent MCI. The prevalence of amyloid positivity without cognitive impairment in the population without dementia increased from 2.7% (95% CI, 0.5% to 4.9%) in persons aged 50 to 59 years to 41.3% (95% CI, 33.4% to 49.2%) in those aged 80 to 89 years at baseline. Prevalence of amyloid-positive MCI in the population without dementia increased from 0% in persons aged 50 to 59 years to 16.4% (95% CI, 10.3% to 22.5%) in those aged 80 to 89 years. The incident aMCI risk increased more than 2-fold in participants without cognitive impairment who were amyloid positive vs those who were amyloid negative (hazard ratio [HR], 2.26; 95% CI, 1.52 to 3.35; P < .001). The risk of AD dementia was 1.86 (95% CI, 0.89 to 3.88; P = .10) for amyloid-positive participants with MCI vs amyloid-negative participants with MCI, 1.63 (95% CI, 0.78 to 3.41; P = .20) for participants with aMCI who were amyloid positive vs amyloid negative, and 2.56 (95% CI, 1.35 to 4.88; P = .004) for amyloid-positive participants who were either without cognitive impairment or had aMCI vs those who were amyloid negative. Global cognitive and memory domain z scores declined significantly in amyloid-positive individuals during follow-up. The mean (SD) follow-up time from baseline was 3.7 (1.9) years to incident aMCI and 3.8 (2.0) years to incident AD dementia. CONCLUSIONS AND RELEVANCE Population-based prevalence of amyloid-positive status and progression rates of amyloid positivity provide valid information for designing AD prevention trials and assessing the public health outcomes of AD preventi...

A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

A ranked list of 23 adverse drug events judged as important in pharmacovigilance was created to permit focused data mining. The list will need to be updated periodically as knowledge on drug safety evolves and new issues in drug safety arise.

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