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Signal detection is a crucial step in the discovery of post-marketing adverse drug reactions. There is a growing interest in using routinely collected data to complement established spontaneous report analyses. This work aims to systematically review the methods for drug safety signal detection using routinely collected healthcare data and their performance, both in general and for specific types of drugs and outcomes.We conducted a systematic review following the PRISMA guidelines, and registered a protocol in PROSPERO. MEDLINE, EMBASE, PubMed, Web of Science, Scopus, and the Cochrane Library were searched until July 13, 2021.The review included 101 articles, among which there were 39 methodological works, 25 performance assessment papers, and 24 observational studies. Methods included adaptations from those used with spontaneous reports, traditional epidemiological designs, methods specific to signal detection with real-world data. More recently, implementations of machine learning have been studied in the literature. Twenty-five studies evaluated method performances, 16 of them using the area under the curve (AUC) for a range of positive and negative controls as their main measure. Despite the likelihood that performance measurement could vary by drug-event pair, only 10 studies reported performance stratified by drugs and outcomes, in a heterogeneous manner. The replicability of the performance assessment results was limited due to lack of transparency in reporting and the lack of a gold standard reference set.A variety of methods have been described in the literature for signal detection with routinely collected data. No method showed superior performance in all papers and across all drugs and outcomes, performance assessment and reporting were heterogeneous. However, there is limited evidence that self-controlled designs, high dimensional propensity scores, and machine learning can achieve higher performances than other methods.

ObjectiveTesticular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18–45 years.MethodsThe TESTIS study is a multicenter case–control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d’Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression.ResultsA positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6–2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4–51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8–5; OR≥2 years1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings.ConclusionsOur findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development.Trial registration numberNCT02109926.

Epidemiological studies of children's cancer risks associated with background gamma radiation exposure have used geographic exposure models to estimate exposure at their locations of residence. We measured personal exposure to background gamma radiation, and we investigated the extent to which it was associated with children's whereabouts. We collected data on whereabouts and exposure to background gamma radiation over a 5-day period among children aged 4-15 years in Switzerland. We used D-Shuttle dosimeters to measure children's exposure, and we asked parents to write their children's activities in diaries. We used Poisson mixed-effects and linear regression models to investigate the association of hourly and overall doses, respectively, with children's reported whereabouts. During the observed time, 149 participating children spent 66% indoors at home; 19% indoors away from home; and 15% outdoors. The mean personal exposure was 85.7 nSv/h (range 52.3 nSv/h-145 nSv/h). Exposure was 1.077 (95% CI 1.067, 1.087) times higher indoors than outdoors and varied by building material and (predicted) outdoor dose rates. Our study provides detailed information about children's patterns of exposure to background gamma radiation in Switzerland. Dwelling building materials and outdoor dose rates are important determinants of children's exposure. Future epidemiological studies may benefit from including information about building materials.

Coste, Astrid Goujon, Stephanie Boniol, Mathieu Marquant, Fabienne Faure, Laure Dore, Jean-Francois Hemon, Denis Clavel, Jacqueline eng Research Support, Non-U.S. Gov't Netherlands 2015/07/15 06:00 Cancer Causes Control. 2015 Sep;26(9):1339-49. doi: 10.1007/s10552-015-0629-x. Epub 2015 Jul 14.; International audience; PURPOSE: Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between residential UV exposure at diagnosis and the incidence of types and subtypes of CHM, by age and gender, in France, over a long period, on the fine scale of the 36,326 Communes that constitute mainland France. METHODS: The 9,082 cases of acute leukemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to 2009 were provided by the French National Registry of Childhood Hematological Malignancies. The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the EUROSUN database. RESULTS: The annual daily average UV exposure of the children ranged from 85.5 to 137.8 J/cm(2). For each additional 25 J/cm(2), there was a significant increase in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) in children aged less than 5 years (SIR 1.18; 95% CI 1.10-1.27). Further analysis of PBC-ALL in the young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm(2), for which the SIR was 1.24 (95% CI 1.14-1.36) for a 25 J/cm(2) increase. The results remained stable in analyses stratifying by deprivation index or degree of urbanization of the Communes. CONCLUSION: The study suggests that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood.

Background: A French ecological study based on 20 years of registration and 9,082 ALL described a positive association between Precursor B-cell childhood acute lymphoblastic leukemia (ALL) and resi...

Introduction: Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between r...

Contexte Dans une etude ecologique francaise, une association positive entre les leucemies aigues lymphoblastiques a precurseurs B (LAL pre B) et l’exposition residentielle aux ultraviolets (UV) naturels a ete observee, qui demeurait apres prise en compte de variables contextuelles. L’objectif de la presente etude est de determiner si la prise en compte de variables soupconnees d’etre des facteurs de risque des LAL pre B modifiait l’association ecologique entre UV et LAL pre B. Materiel et methodes Deux etudes cas-temoins francaises, fondees sur des interviews telephoniques individuelles, ont ete poolees. L’etude Escale (2003–2004) et l’etude Estelle (2010–2011) incluaient respectivement 764 et 740 cas de leucemie, 1681 et 1423 temoins de meme âge et de meme sexe en moyenne que les cas, selectionnes par quotas en population generale. Une selection des variables disponibles dans ces etudes et soupconnees d’etre des facteurs de risques des LA de l’enfant a ete realisee. Resultats Les analyses montrent une association positive entre l’exposition aux UV residentiels et les LAL pre B (OR 3 derniers deciles versus les 7 premiers = 1,30 [1,16–1,45]), qualitativement et quantitativement similaire a l’association ecologique, et similaire dans les deux etudes individuelles. L’utilisation de pesticides domestiques par la mere, la mise en garde collective avant 1 an et les infections repetees precoces etaient associees a l’exposition aux UV residentiels chez les temoins dans au moins une des deux etudes. En stratifiant et ajustant sur les variables selectionnees par etude, et en poolant les deux etudes, nous n’avons observe aucune modification de l’association ecologique entre UV residentiels et LAL pre B. Conclusion L’association ecologique positive entre UV residentiels et LAL pre B n’est pas modifiee par la prise en compte des variables individuelles soupconnees comme facteurs de risque des LAL pre B.