{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:57:28Z","timestamp":1758635848282},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T00:00:00Z","timestamp":1468368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non\u2010investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP\u2010related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective descriptive study including all cases of NIMP\u2010related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP\u2010related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP\u2010related SAEs were known as \u2018rare\u2019 or \u2018very rare\u2019 and two were \u2018unlabelled\u2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As far as we know, this is the first study to focus about NIMP\u2010related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP\u2010related SAE collection. Globally, we propose that NIMP\u2010related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP\u2010related SAEs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13035","type":"journal-article","created":{"date-parts":[[2016,6,8]],"date-time":"2016-06-08T22:42:12Z","timestamp":1465425732000},"page":"1069-1075","source":"Crossref","is-referenced-by-count":4,"title":["Serious adverse drug events related to non\u2010investigational drugs in academic clinical trials: another source of safety data for risk assessment?"],"prefix":"10.1111","volume":"82","author":[{"given":"Pascale","family":"Olivier","sequence":"first","affiliation":[{"name":"Service de Pharmacologie m\u00e9dicale et clinique, Centre Midi\u2010Pyr\u00e9n\u00e9es de Pharmacovigilance, d'informations sur le m\u00e9dicament et de Pharmaco\u00e9pid\u00e9miologie du CHU de Toulouse Facult\u00e9 de M\u00e9decine  37 all\u00e9es Jules Guesde 31000 TOULOUSE"},{"name":"Vigilance des essais cliniques Direction de la Recherche et de l'Innovation du CHU de Toulouse  2 rue Viguerie 31059 Toulouse Cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Gimbert","sequence":"additional","affiliation":[{"name":"Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unit\u00e9 de s\u00e9curit\u00e9 et de vigilance \u2010 D\u00e9partement promotion interne Direction G\u00e9n\u00e9rale des h\u00f4pitaux de Bordeaux  12 rue Dubernat 33 404 Talence cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Laur\u00e8ne","family":"Colin","sequence":"additional","affiliation":[{"name":"Vigilance des essais cliniques Direction de la Recherche et de l'Innovation du CHU de Toulouse  2 rue Viguerie 31059 Toulouse Cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Salvo","sequence":"additional","affiliation":[{"name":"Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unit\u00e9 de s\u00e9curit\u00e9 et de vigilance \u2010 D\u00e9partement promotion interne Direction G\u00e9n\u00e9rale des h\u00f4pitaux de Bordeaux  12 rue Dubernat 33 404 Talence cedex"},{"name":"INSERM, UMR1219, Bordeaux Population Health Research Center, Pharmacoepidemiology team University of Bordeaux  Bordeaux"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madlyne","family":"Becker","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance de Lorraine Laboratoire de Pharmacologie Clinique et de Toxicologie H\u00f4pital Central  29 avenue du Mar\u00e9chal de Lattre de Tassigny CO 60034 54035 Nancy cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Marty","sequence":"additional","affiliation":[{"name":"Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unit\u00e9 de s\u00e9curit\u00e9 et de vigilance \u2010 D\u00e9partement promotion interne Direction G\u00e9n\u00e9rale des h\u00f4pitaux de Bordeaux  12 rue Dubernat 33 404 Talence cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Louis","family":"Montastruc","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie m\u00e9dicale et clinique, Centre Midi\u2010Pyr\u00e9n\u00e9es de Pharmacovigilance, d'informations sur le m\u00e9dicament et de Pharmaco\u00e9pid\u00e9miologie du CHU de Toulouse Facult\u00e9 de M\u00e9decine  37 all\u00e9es Jules Guesde 31000 TOULOUSE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Petitpain","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance de Lorraine Laboratoire de Pharmacologie Clinique et de Toxicologie H\u00f4pital Central  29 avenue du Mar\u00e9chal de Lattre de Tassigny CO 60034 54035 Nancy cedex"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,13]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Directive 2001\/20\/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Official Journal of the European Communities (1.5.2001)http:\/\/eur\u2010lex.europa.eu\/legal\u2010content\/EN\/TXT\/PDF\/?uri=CELEX:32001L0020&qid=1449676545569&from=EN(lsat accessed 9\/12\/2015)."},{"key":"e_1_2_9_3_1","unstructured":"European Parliament and Council.Regulation (EU) No 536\/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001\/20\/EC.2014. Available athttp:\/\/ec.europa.eu\/health\/files\/eudralex\/vol\u20101\/reg_2014_536\/reg_2014_536_en.pdf(last accessed 9\/12\/2015)."},{"key":"e_1_2_9_4_1","unstructured":"Detailed guidance on the collection verification and presentation of adverse event\/reaction reports arising from clinical trials on medicinal products for human use (\u2018CT\u20103\u2019) (2011\/C 172\/01). Available athttp:\/\/ec.europa.eu\/health\/files\/eudralex\/vol\u201010\/2011_c172_01\/2011_c172_01_en.pdf(last accessed 02\/11\/2015)."},{"key":"e_1_2_9_5_1","unstructured":"ICH guideline E2B (R3) on electronic transmission of individual case safety reports (ICSRs) \u2010 data elements and message specification \u2010 implementation guide (25 August 2015). Available athttp:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500002767.pdf(last accessed 7\/1\/2016)."},{"key":"e_1_2_9_6_1","unstructured":"The rules governing medicinal products in the European Union volume 10 \u2010 Guidance documents applying to clinical trials. Guidance on \u201cinvestigational medicinal products\u201d (IMPs) and \u201cnon Investigational medicinal products\u201d (NIMPs) (rev. 1 March 2011). Available athttp:\/\/ec.europa.eu\/health\/files\/eudralex\/vol\u201010\/imp_03\u20102011.pdf(last accessed 02\/11\/2015)."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200831010-00003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.therap.2016.02.010"},{"key":"e_1_2_9_9_1","unstructured":"Note for guidance \u2013 EudraVigilance Human \u2013 Processing of safety messages and individual case safety reports (ICSRs). 15 October 2010. Available athttps:\/\/eudravigilance.ema.europa.eu\/human\/docs\/guid%C2%AFP%C2%AFTechnical%20Documentation%C2%AFEMEA\u2010H\u201020665\u201004\u2010en\u2010Final_Revision_2.pdf(last accessed 13\/1\/2016)."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199920020-00002"},{"key":"e_1_2_9_11_1","unstructured":"Base de donn\u00e9es publiques des medicaments. Available athttp:\/\/base\u2010donnees\u2010publique.medicaments.gouv.fr\/(last accessed 26 May 2016)."},{"key":"e_1_2_9_12_1","unstructured":"European public assessment reports (EPAR) for human medicines published by the European Medicines Agency (EMA). Available athttp:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/landing\/epar_search.jsp&mid=WC0b01ac058001d124(last accessed 26 May 2016)."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12611"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2009.306"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2009.313"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.03.005"},{"key":"e_1_2_9_17_1","unstructured":"Xarelto (Rivaroxaban) risk minimization plan evaluation: patient and phycisian knowledge of key safety messages. 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