{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:22:59Z","timestamp":1787336579621,"version":"build-2736575974"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Drug\u2013drug interactions (DDIs) are a significant contributor to adverse drug reactions (ADRs) in clinical practice. Despite established pharmacovigilance systems, underreporting and inconsistent causality assessment remain challenges. Switzerland and Austria offer a unique comparative setting due to similar healthcare infrastructures but different pharmacovigilance system designs. This study aims to compare pharmacovigilance system outcomes of Switzerland and Austria by examining how system designs may influence DDI reporting patterns and report quality. We retrospectively analysed 1,499 individual case safety reports involving DDIs submitted between January 2008 and April 2024 to the national pharmacovigilance systems of Switzerland (n\u2009=\u20091,159) and Austria (n\u2009=\u2009340). As indicators of system performance, reports were assessed for demographics, reporter categories, seriousness of outcomes in relation to polypharmacy (expressed as reporting odds ratios [RORs] and confidence intervals [CIs]), ADR types, and pharmacological plausibility. Cross-national disparities were evident: Switzerland reported 3.4 times more DDI cases than Austria (mean 5.8 vs. 1.7 cases\/month), with comparable patient demographics and differing reporter proportions. Most reports were classified as serious (80% Switzerland, 84% Austria), with polypharmacy strongly associated with serious outcomes in both countries (Switzerland: ROR 3.71, 95% CI 3.26\u20134.23, p\u2009&lt;\u20090.0001; Austria: ROR 1.98, 95% CI 1.60\u20132.44, p\u2009&lt;\u20090.0001). Reported ADRs differed qualitatively, with Switzerland predominantly reporting mechanisms whereas Austria reported more frequently symptoms. Differences were also found in the pharmacological consistency between ADR and associated drugs. These cross-national disparities in DDI reporting volume, content, and quality suggest that pharmacovigilance system design and specialist involvement influence reporting. The integration of clinical pharmacologists and pharmacists in ADR processing warrants further investigation, given its potential to strengthen DDI-related pharmacovigilance practices. These findings provide actionable insights for policymakers and regulatory agencies seeking to strengthen their pharmacovigilance systems through strategic specialist integration.<\/jats:p>","DOI":"10.1371\/journal.pone.0356774","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:22:56Z","timestamp":1787332976000},"page":"e0356774","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-national disparities in drug interaction reporting and assessment between Switzerland and Austria: A retrospective, registry-based study using pharmacovigilance data"],"prefix":"10.1371","volume":"21","author":[{"given":"Marcel","family":"Rainer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Martinez De la Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romuald","family":"Bellmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Michelle","family":"Burden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1087-7597","authenticated-orcid":true,"given":"Stefan","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"issue":"1","key":"pone.0356774.ref001","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12916-024-03384-1","article-title":"Prevalence and differences in the co-administration of drugs known to interact: an analysis of three distinct and large populations","volume":"22","author":"J S\u00e1nchez-Valle","year":"2024","journal-title":"BMC Med"},{"key":"pone.0356774.ref002","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1472-6904-7-8","article-title":"Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study","volume":"7","author":"KJ Patel","year":"2007","journal-title":"BMC Clin Pharmacol"},{"issue":"3","key":"pone.0356774.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0033236","article-title":"Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions--a meta-analysis","volume":"7","author":"KM Hakkarainen","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"pone.0356774.ref004","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1365-2796.2010.02303.x","article-title":"Drug-drug interactions that reduce the formation of pharmacologically active metabolites: a poorly understood problem in clinical practice","volume":"268","author":"B Mannheimer","year":"2010","journal-title":"J Intern Med"},{"issue":"1","key":"pone.0356774.ref005","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s11096-019-00951-y","article-title":"Potential drug-drug interactions associated with clinical and laboratory findings at hospital admission","volume":"42","author":"M Kova\u010devi\u0107","year":"2020","journal-title":"Int J Clin Pharm"},{"issue":"5","key":"pone.0356774.ref006","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/imj.13404","article-title":"Life-threatening drug interactions: what the physician needs to know","volume":"47","author":"RO Day","year":"2017","journal-title":"Intern Med J"},{"issue":"1","key":"pone.0356774.ref007","doi-asserted-by":"crossref","first-page":"2417399","DOI":"10.1080\/20523211.2024.2417399","article-title":"Pharmacovigilance: the evolution of drug safety monitoring","volume":"17","author":"MAA Khan","year":"2024","journal-title":"J Pharm Policy Pract"},{"key":"pone.0356774.ref008","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/978-1-0716-4003-6_16","article-title":"Investigating the benefit-risk profile of drugs: from spontaneous reporting systems to real-world data for pharmacovigilance","volume":"2834","author":"P Imbrici","year":"2025","journal-title":"Methods Mol Biol"},{"issue":"8","key":"pone.0356774.ref009","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s40264-023-01319-y","article-title":"Hospitalisations related to adverse drug reactions in Switzerland in 2012-2019: characteristics, in-hospital mortality, and spontaneous reporting rate","volume":"46","author":"PE Beeler","year":"2023","journal-title":"Drug Saf"},{"key":"pone.0356774.ref010","volume-title":"Population structure and ageing","author":"Eurostat","year":"2024"},{"key":"pone.0356774.ref011","volume-title":"Healthcare resource statistics - beds","author":"Eurostat","year":"2024"},{"key":"pone.0356774.ref012","unstructured":"Swissmedic. 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