{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:42:06Z","timestamp":1791412926292,"version":"4.3.3"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100001734","name":"Copenhagen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Saf"],"published-print":{"date-parts":[[2024,9]]},"DOI":"10.1007\/s40264-024-01430-8","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:02:12Z","timestamp":1714449732000},"page":"895-907","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Timing Matters: A Machine Learning Method for the Prioritization of Drug\u2013Drug Interactions Through Signal Detection in the FDA Adverse Event Reporting System and Their Relationship with Time of Co-exposure"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-9593","authenticated-orcid":false,"given":"Vera","family":"Battini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Cocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4696","authenticated-orcid":false,"given":"Maria Antonietta","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4107-196X","authenticated-orcid":false,"given":"Carla","family":"Carnovale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-8270","authenticated-orcid":false,"given":"Emilio","family":"Clementi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-3653","authenticated-orcid":false,"given":"Andrew","family":"Bate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-4744","authenticated-orcid":false,"given":"Maurizio","family":"Sessa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"1430_CR1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s40264-012-0003-9","volume":"36","author":"J Strandell","year":"2013","unstructured":"Strandell J, Nor\u00e9n GN, H\u00e4gg S. Key elements in adverse drug interaction safety signals: an assessment of individual case safety reports. Drug Saf. 2013;36:63\u201370.","journal-title":"Drug Saf"},{"key":"1430_CR2","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/bib\/bbx010","volume":"19","author":"S Vilar","year":"2018","unstructured":"Vilar S, Friedman C, Hripcsak G. Detection of drug\u2013drug interactions through data mining studies using clinical sources, scientific literature and social media. Brief Bioinf. 2018;19:863\u201377.","journal-title":"Brief Bioinf"},{"key":"1430_CR3","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1002\/sim.3247","volume":"27","author":"GN Nor\u00e9n","year":"2008","unstructured":"Nor\u00e9n GN, Sundberg R, Bate A, Edwards IR. A statistical methodology for drug\u2013drug interaction surveillance. Stat Med. 2008;27:3057\u201370.","journal-title":"Stat Med"},{"key":"1430_CR4","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.3390\/pharmaceutics13101531","volume":"13","author":"Y Noguchi","year":"2021","unstructured":"Noguchi Y, Yoshizawa S, Aoyama K, Kubo S, Tachi T, Teramachi H. Verification of the \u201cUpward variation in the reporting odds ratio scores\u201d to detect the signals of drug\u2013drug interactions. Pharmaceutics. 2021;13:1531.","journal-title":"Pharmaceutics"},{"key":"1430_CR5","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s40264-013-0053-7","volume":"36","author":"J Strandell","year":"2013","unstructured":"Strandell J, Caster O, Hopstadius J, Edwards IR, Nor\u00e9n GN. The development and evaluation of triage algorithms for early discovery of adverse drug interactions. Drug Saf. 2013;36:371\u201388.","journal-title":"Drug Saf"},{"key":"1430_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/pds.1742","volume":"18","author":"A Bate","year":"2009","unstructured":"Bate A, Evans SJW. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009;18:427\u201336.","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"1430_CR7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s11095-020-02801-3","volume":"37","author":"Y Noguchi","year":"2020","unstructured":"Noguchi Y, Tachi T, Teramachi H. Comparison of signal detection algorithms based on frequency statistical model for drug\u2013drug interaction using spontaneous reporting systems. Pharm Res. 2020;37:86.","journal-title":"Pharm Res"},{"key":"1430_CR8","doi-asserted-by":"publisher","first-page":"253","DOI":"10.2165\/11586990-000000000-00000","volume":"34","author":"J Strandell","year":"2011","unstructured":"Strandell J, Caster O, Bate A, Nor\u00e9n N, Edwards IR. Reporting patterns indicative of adverse drug interactions: a systematic evaluation in VigiBase. Drug Saf. 2011;34:253\u201366.","journal-title":"Drug Saf"},{"key":"1430_CR9","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1093\/jamia\/ocv153","volume":"23","author":"TA Kass-Hout","year":"2016","unstructured":"Kass-Hout TA, Xu Z, Mohebbi M, Nelsen H, Baker A, Levine J, et al. OpenFDA: an innovative platform providing access to a wealth of FDA\u2019s publicly available data. J Am Med Inf. 2016;23:596\u2013600.","journal-title":"J Am Med Inf"},{"key":"1430_CR10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41597-022-01159-y","volume":"9","author":"E Kontsioti","year":"2022","unstructured":"Kontsioti E, Maskell S, Dutta B, Pirmohamed M. A reference set of clinically relevant adverse drug\u2013drug interactions. Sci Data. 2022;9:72.","journal-title":"Sci Data"},{"key":"1430_CR11","unstructured":"Agency EM. Guideline on good pharmacovigilance practices (GVP)\u2013Annex I\u2013Definitions (Rev 4). Heads Med Agencies; 2017. p. 1\u201333."},{"key":"1430_CR12","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1080\/14740338.2021.1955101","volume":"20","author":"M Sessa","year":"2021","unstructured":"Sessa M, Kragholm K, Hviid A, Andersen M. Thromboembolic events in younger women exposed to Pfizer-BioNTech or Moderna COVID-19 vaccines. Expert Opin Drug Saf. 2021;20:1451\u20133.","journal-title":"Expert Opin Drug Saf"},{"key":"1430_CR13","unstructured":"European Medicine Agency. MedDRA (Medical Dictionary for Regulatory Activities)\u2014important medical event terms list, version 26.1; 2023."},{"key":"1430_CR14","first-page":"706","volume":"52","author":"GN Fox","year":"2003","unstructured":"Fox GN, Moawad NS. Up to date: a comprehensive clinical database. J Fam Pract. 2003;52:706\u201310.","journal-title":"J Fam Pract"},{"key":"1430_CR15","unstructured":"Frishauf P. Medscape\u2014the first 5 years, vol. 7. Medscape Gen Med. WebMD\/Medscape Health Network; 2005. p. 5."},{"key":"1430_CR16","first-page":"41","volume":"18","author":"AL Plumb","year":"2004","unstructured":"Plumb AL. Drugs.Com: drug information online 2004. Ref Rev. 2004;18:41.","journal-title":"Ref Rev"},{"key":"1430_CR17","first-page":"328","volume":"170","author":"RB Dessau","year":"2008","unstructured":"Dessau RB, Pipper CB. \u2018\u2018R\u201d\u2014project for statistical computing. Ugeskr Laeger. 2008;170:328\u201330.","journal-title":"Ugeskr Laeger"},{"key":"1430_CR18","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1182\/bloodadvances.2018024893","volume":"2","author":"DM Witt","year":"2018","unstructured":"Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2:3257\u201391.","journal-title":"Blood Adv"},{"key":"1430_CR19","doi-asserted-by":"publisher","first-page":"e44S","DOI":"10.1378\/chest.11-2292","volume":"141","author":"W Ageno","year":"2012","unstructured":"Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e44S-e88S.","journal-title":"Chest"},{"key":"1430_CR20","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1055\/s-0037-1613471","volume":"89","author":"C Lidell","year":"2003","unstructured":"Lidell C, Svedberg L-E, Lindell P, Bandh S, Job B, Wallentin L. Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation. Thromb Haemost. 2003;89:842\u20136.","journal-title":"Thromb Haemost"},{"key":"1430_CR21","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/S0140-6736(17)30770-5","volume":"390","author":"L Li","year":"2017","unstructured":"Li L, Geraghty OC, Mehta Z, Rothwell PM. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017;390:490\u20139.","journal-title":"Lancet"},{"key":"1430_CR22","doi-asserted-by":"publisher","first-page":"791285","DOI":"10.3389\/fnagi.2022.791285","volume":"14","author":"K-H Chang","year":"2022","unstructured":"Chang K-H, Chen C-M, Wang C-L, Tu H-T, Huang Y-T, Wu H-C, et al. Major bleeding risk in patients with non-valvular atrial fibrillation concurrently taking direct oral anticoagulants and antidepressants. Front Aging Neurosci. 2022;14:791285.","journal-title":"Front Aging Neurosci"},{"key":"1430_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003821","volume":"18","author":"C Bhanu","year":"2021","unstructured":"Bhanu C, Nimmons D, Petersen I, Orlu M, Davis D, Hussain H, et al. Drug-induced orthostatic hypotension: a systematic review and meta-analysis of randomised controlled trials. PLoS Med. 2021;18: e1003821.","journal-title":"PLoS Med"},{"key":"1430_CR24","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1517\/14740338.2014.936376","volume":"13","author":"M Oelke","year":"2014","unstructured":"Oelke M, Gericke A, Michel MC. Cardiovascular and ocular safety of \u03b11-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms. Expert Opin Drug Saf. 2014;13:1187\u201397.","journal-title":"Expert Opin Drug Saf"},{"key":"1430_CR25","doi-asserted-by":"publisher","first-page":"k341","DOI":"10.1136\/bmj.k341","volume":"360","author":"E Crellin","year":"2018","unstructured":"Crellin E, Mansfield KE, Leyrat C, Nitsch D, Douglas IJ, Root A, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study. BMJ. 2018;360:k341.","journal-title":"BMJ"},{"key":"1430_CR26","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1002\/cpt.1434","volume":"105","author":"J Niu","year":"2019","unstructured":"Niu J, Straubinger RM, Mager DE. Pharmacodynamic drug\u2013drug interactions. Clin Pharmacol Ther. 2019;105:1395\u2013406.","journal-title":"Clin Pharmacol Ther"},{"key":"1430_CR27","doi-asserted-by":"publisher","first-page":"923939","DOI":"10.3389\/fphar.2022.923939","volume":"13","author":"H Jiang","year":"2022","unstructured":"Jiang H, Lin Y, Ren W, Fang Z, Liu Y, Tan X, et al. Adverse drug reactions and correlations with drug\u2013drug interactions: a retrospective study of reports from 2011 to 2020. Front Pharmacol. 2022;13:923939.","journal-title":"Front Pharmacol"},{"key":"1430_CR28","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/B978-0-323-98367-9.00007-X","volume-title":"Pharmacokinetics and toxicokinetic considerations","author":"S Polaka","year":"2022","unstructured":"Polaka S, Koppisetti HP, Tekade M, Sharma MC, Sengupta P, Tekade RK. Drug\u2013drug interactions and their implications on the pharmacokinetics of the drugs. In: Polaka S, editor. Pharmacokinetics and toxicokinetic considerations. Amsterdam: Elsevier; 2022. p. 291\u2013322."},{"key":"1430_CR29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s40264-022-01258-0","volume":"46","author":"D Sartori","year":"2023","unstructured":"Sartori D, Aronson JK, Nor\u00e9n GN, Onakpoya IJ. Signals of adverse drug reactions communicated by pharmacovigilance stakeholders: a scoping review of the global literature. Drug Saf. 2023;46:109\u201320.","journal-title":"Drug Saf"},{"key":"1430_CR30","doi-asserted-by":"publisher","first-page":"727687","DOI":"10.3389\/fpsyt.2021.727687","volume":"12","author":"R Zeiss","year":"2021","unstructured":"Zeiss R, Connemann BJ, Sch\u00f6nfeldt-Lecuona C, Gahr M. Risk of bleeding associated with antidepressants: impact of causality assessment and competition bias on signal detection. Front Psychiatry. 2021;12:727687.","journal-title":"Front Psychiatry"},{"key":"1430_CR31","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1002\/pds.3529","volume":"23","author":"F Maignen","year":"2014","unstructured":"Maignen F, Hauben M, Hung E, Van Holle L, Dogne JM. Assessing the extent and impact of the masking effect of disproportionality analyses on two spontaneous reporting systems databases. Pharmacoepidemiol Drug Saf. 2014;23:195\u2013207.","journal-title":"Pharmacoepidemiol Drug Saf"}],"container-title":["Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40264-024-01430-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40264-024-01430-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40264-024-01430-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T10:23:48Z","timestamp":1723631028000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40264-024-01430-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":31,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["1430"],"URL":"https:\/\/doi.org\/10.1007\/s40264-024-01430-8","relation":{},"ISSN":["0114-5916","1179-1942"],"issn-type":[{"value":"0114-5916","type":"print"},{"value":"1179-1942","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]},"assertion":[{"value":"3 April 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No ethical approval is required for studies using publicly available data from FAERS.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The data sources are open access, and the datasets generated during and\/or analysed during the current study are available from the corresponding author on reasonable request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Code is available from the corresponding author upon reasonable request.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Not applicable. FAERS spontaneous reports are anonymous and publicly available.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable. FAERS spontaneous reports are anonymous and publicly available.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"VB, GP, AB, and MS conceived and designed the study. VB and MS designed and supervised the research and analysed the data. VB wrote the original draft, and MAB, CC, GP, AB, EC, and MS reviewed and edited, with inputs from all authors. VB, MC, MAB, GP, AB, CC, EC, and MS participated in the interpretation of data and revised and approved the final article as submitted.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}},{"value":"Open access funding provided by Copenhagen University.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Greg Powell and Andrew Bate are both employees of GSK and hold stock and stock options. All the other authors have no conflict of interest to declare.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}