Regulatory agencies are increasing the pharmacogenomic information in their official drug labeling. However, despite the importance of regulatory harmonization, this implementation may not be running in parallel among major agencies. Comparing labeling of medicines approved by different agencies may identify gaps to solve. Our study compared the cytochrome P450 pharmacogenetic information included in the United States (US) Food and Drug Administration (FDA) drug labels and European Union (EU) Summaries of Product Characteristics (SmPCs). US labels presented significantly more specific pharmacogenetic subheadings (51 vs 26%), more prevalence and pharmacokinetic data for each metabolic phenotype (59 vs 25% and 82 vs 48%, respectively) and more applicable information about dose modifications required (25 vs 5%). Approximately 75% of the US labels evaluated scored higher on the overall quality than the analogous EU SmPCs, and this difference was not associated with the time since the EU SmPCs' last review. To enhance harmonization, regulatory agencies should simultaneously introduce the pharmacogenetic information in their drug labeling.

Rheumatoid arthritis (RA) is among the most prevalent chronic autoimmune and inflammatory diseases worldwide. The aim of this study was to establish a pooled estimate of the RA prevalence in South America by means of a meta-analysis of the available epidemiologic studies. Systematic searches in PubMed, Lilacs, SciELO, Scopus, and Web of Science databases (updated May 2019) were done followed by a systematic grey literature search to identify original research articles and reports, published after 2000, providing data of RA prevalence in any South American country. Proportion meta-analysis of weighted pooled was performed, with between-trial heterogeneity assessed by the inconsistency relative index. Sensitivity analyses and sub-group analyses were also done. A total of 25 articles, representing 27 population-based studies were included. Pooled prevalence of RA resulted in 0.48% with 591,981 cases in a population of 114,537,812 individuals (I2=99%). Brazil and Colombia presented the lowest rates of RA prevalence 0.22%, and 0.24%, respectively. RA prevalence in indigenous population was higher 1.45%, and studies using COPCORD method reported also the highest rates 1.07%.

Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. Methods:The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDD YEAR ) and by the DDD last-year approach (DDD LAST ). PDDs were calculated according to the year-by-year approach (PDD YEAR ). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDD YEAR and DDD YEAR units. Results:The DDD YEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDD LAST and PDD YEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDD YEAR /1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009.Conclusions: A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies. K E Y W O R D S defined daily dose, drug utilization, reproducibility of results Isabel V. Figueiredo and Fernando Fernandez-Llimos equally contributed.