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Purpose: For this article, the authors compiled, summarized, and analyzed data from 27 cases in which real-world data (RWD) were applied in regulatory approval. The aims were to provide an overview of RWD, based on classifications per therapeutic area, age group, drivers of acceptability, utility, data sources, and timelines, and to present insights on how it has been applied in regulatory decision making to date., Methods: Clarivate Analytics was commissioned to collect data from cases in which RWD was used for new drug applications and line extensions submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), Health Canada, and Japan's Pharmaceuticals and Medical Devices Agency. The query resulted in 27 cases in which regulatory approval was associated with RWD. The data were then categorized and elaborated with supporting information gathered from public databases and company websites., Findings: There were 17 identified cases in which RWD were used for new drug applications, and 10 for line extensions, between the years 1998 and 2019. Approvals were spread across regulatory bodies: the EMA alone (6 cases), the FDA alone (4 cases), or jointly between the EMA and FDA or other regulatory bodies. The applications were also distributed across age groups and therapeutic areas but were mostly applied in oncology and metabolism. The new drug applications of all 17 products were approved, with drugs from new drug applications initially marketed as orphan drugs. In most cases, RWD were used either as primary data, when noncomparative data were available to demonstrate tolerability and efficacy, or as supportive data when validating findings. Common sources of RWD have been health or medical records (16 cases) and registries (8 cases). Review timelines in which RWD were applied were than 1 year for new drug applications and between 3 and 10 months for line extensions., Implications: The analysis of this study was limited in that the data were gathered from the commissioned query and may therefore have been nonexhaustive. Nonetheless, we recognize that the use of RWD has been gaining attention across the community and is expected to expand as a result of the various initiatives and efforts carried out in the sector. While the current application of RWD has been limited to specific cases, there is a potential to further explore and develop its application. Further refinements in the analytical processes, methodologies, and techniques would need to be established to achieve similar effects observed in randomized controlled trials., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The use of admixed human populations to scan the genome for chromosomal segments affecting complex phenotypic traits has proved a powerful analytical tool. However, its potential in other organisms has not yet been evaluated. Here, we use DNA microsatellites to assess the feasibility of this approach in hybrid zones between two members of the 'model tree' genus Populus: Populus alba (white poplar) and Populus tremula (European aspen). We analyzed samples of both species and a Central European hybrid zone (N=544 chromosomes) for a genome-wide set of 19 polymorphic DNA microsatellites. Our results indicate that allele frequency differentials between the two species are substantial (mean delta=0.619+/-0.067). Background linkage disequilibrium (LD) in samples of the parental gene pools is moderate and should respond to sampling schemes that minimize drift and account for rare alleles. LD in hybrids decays with increasing number of backcross generations as expected from theory and approaches background levels of the parental gene pools in advanced generation backcrosses. Introgression from P. tremula into P. alba varies strongly across marker loci. For several markers, alleles from P. tremula are slightly over-represented relative to neutral expectations, whereas a single locus exhibits evidence of selection against P. tremula genotypes. We interpret our results in terms of the potential for admixture mapping in these two ecologically divergent Populus species, and we validate a modified approach of studying genotypic clines in 'mosaic' hybrid zones.