Collaborative experience

Members of the SIGMA consortium have extensive experience in collaborating in several multi-country studies under the principles of the European Network of Centres for Pharmacoepidemiology & Pharmacovigilance (ENCePP). All members are dedicated to excellence in research by adhering to the ENCePP Guide on Methodological Standards and promoting scientific independence and transparency. Past and current examples of collaborative experience are highlighted below. All studies are registered in the EU PAS register, a publicly accessible resource for the registration of pharmacoepidemiological and pharmacovigilance studies (See Table ‘EU Collaborations‘).

Each SIGMA member has access to different data, as summarized in the Table ‘Data availability‘ below.

The SIGMA consortium was presented virtually at ISPE’s 37th International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE 2021 All Access) held August 23-25 2021. The presented poster can be found here.

EU collaborations

Full Title & EUPAS LinkFunding EntityCoord. CenterOther Participating SIGMA Partners Start year

Post-Authorization Active Surveillance Safety Study Using Secondary Data to Monitor Real-World Safety of Spikevax in Europe (COVID-19)
ModernaIDIAP, ARS2021

A post-authorisation/post-marketing observational study to evaluate the association between exposure to AZD1222 and safety concerns using existing secondary health data sources (COVID-19)

Post Conditional Approval Active Surveillance Study Among Individuals in Europe Receiving the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine
PfizerARS, IDIAP2020
Cohort monitoring of Adverse Events of Special Interest and COVID-19 diagnoses prior to and after COVID-19 vaccination EMAARS, PHARMO, UU2020
Description of international collaboration in the area of medicines use and effects in COVID-19 affected pregnancies (CONSIGN-International))EMAAARHUS, ARS, BIPS, BPE, RTI-HS, UU2020
Data source heterogeneity in multi-database pharmacoepidemiologic studies: a scoping reviewISPEARS2020
CONSIGN study: COVID-19 infection and medicines in pregnancy - a multinational registry based studyEMAAARHUS, ARS, BIPS, BPE, RTI-HS, UMCU, UU2020
Strengthening Use of Real-World Data in Medicines Development: Metadata for Data Discoverability and Study ReplicabilityEMAAARHUS, ARS, BIPS, BPE, PHARMO, UMCU, UU
Drug-drug interactions between dicloxacillin/flucloxacillin and DOACsN/AUU2020
Background rates of Adverse Events of Special Interest for monitoring COVID-19 vaccinesEMAAARHUS, ARS, BIPS, BPE, IDIAP, PHARMO, RTI-HS, UU2020
First-line anticancer drugs in patients with advanced, primary Non-Small Cell Lung Cancer: drug-utilization and effectiveness studies from Tuscany Region healthcare databaseN/AARS2020
Renin-angiotensin-aldosterone system inhibitors and adverse outcomes of COVID-19: a Danish nationwide cohort studyAARHUSSDU2020
Drug utilisation study of Radium 223 under routine clinical practice in EuropeBayerAARHUS, BIPS2019
Impact of EU label changes and revised pregnancy prevention programme for oral retinoid containing medicinal products: utilization and prescribing trendsEMAARS, BPE, IDIAP, PHARMO2019
Impact of EU label changes and pregnancy prevention programme for medicinal products containing valproate and related substances: risk awareness and adherenceEMAUMCU, ARS, PHARMO2019
Impact of EU label changes for hydroxyzine products: post-referral prescribing trendsEMADUNDEE, PHARMO, SDU2018
Adherence, persistence and switching patterns – once- and twice-daily direct oral anticoagulantsDaiichi SankyoARS, BIPS, PHARMO2019
A Retrospective Cohort Study to Assess Drug Utilisation and Long-Term Safety of Galcanezumab in European Patients in the Course of Routine Clinical CareLillyARS, BIPS, BPE, IDIAP, PHARMO2019
Pregnancy outcomes in women exposed to oral cladribine: a multi-country cohort database studyMerck KGaADUNDEE2019
The BRodalumab Assessment of Hazards: A Multinational Safety (BRAHMS) study in electronic healthcare databasesLeo PharmaARS, BIPS, PHARMO2018
Non-interventional post-authorization multi-database safety study to characterize the risk of angioedema and other specific safety events of interest in association with use of Entresto® (sacubitril/valsartan) in adult patients with heart failure NovartisAARHUS, ARS, BIPS, IDIAP2017
Non-interventional post-authorization multi-database safety study to assess the risk of myotoxicity, hepatotoxicity and acute pancreatitis in statin-exposed heart failure patients with or without concomitant use of sacubitril/valsartan (Entresto®)NovartisAARHUS, ARS, BIPS, IDIAP2017
Cohort Study of the Incidence of Major Cardiovascular Events in New Adult Users of Lisdexamfetamine and Remote Adult Users of Other ADHD TreatmentsShireAARHUS2017
Intravenous Iron Postauthorisation Safety Study (PASS): Evaluation of the Risk of Severe Hypersensitivity ReactionsVifor (Iron Consortium)AARHUS, BIPS, PHARMO2017
Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus, Pimecrolimus, and CorticosteroidsLEOPHARMO, SDU2017
Malignancies in Multiple Sclerosis: multi-country cohort database studies (feasibility study)Merck KGaAAARHUS, BPE, PHARMO2017
Impact of EU label changes for systemic diclofenac products: post-referral prescribing trendsEMADUNDEE, PHARMO, SDU2017
Multisource Surveillance Study of Pregnancy and Infant Outcomes in Ocrelizumab-Exposed Women With Multiple SclerosisRocheAARHUS2017
An Observational Post-Authorisation Safety Study of Lesinurad PatientsAstra ZenecaIDIAP2016
Post-authorisation safety study in patients with type 2 diabetes mellitus to assess the risk of acute liver injury, acute kidney injury and chronic kidney disease, severe complications of urinary tract infection, genital infections, and diabetic ketoacidosis among patients treated with empagliflozin compared to patients treated with DPP-4 inhibitorsBIAARHUS2016
Drug utilization study of mirabegron (Betmiga®) using real-world healthcare databases from the Netherlands, Spain, United Kingdom and FinlandAstellasIDIAP, PHARMO2016
Characterising the risk of major bleeding in patients with Non-Valvular Atrial Fibrillation: non-interventional study of patients taking Direct Oral Anticoagulants in the EUEMA tenderBPE2016
Post-authorization Safety Study Evaluation of Cardiovascular Events in Users of Mirabegron and Other Treatments for Overactive BladderAstellasRTI-HS, SDU2016
European Program of Post-Authorization Safety Studies for Protelos®/Osseor® through EU-ADR AllianceStudyAARHUS2015
Post-Authorisation Safety Study of Agomelatine and the Risk of Hospitalisation for Acute Liver InjuryServierBIPS, IDIAP, SDU2015
Comparison of the Risk of Cancer Between Patients With Type 2 Diabetes Exposed to Dapagliflozin and Those Exposed to Other Antidiabetic Treatments Astra ZenecaPHARMO2015
Drug Utilisation Study for OlodaterolBIAARHUS, PHARMO2015
Cohort study of cardiovascular events in patients with chronic obstructive pulmonary disease initiating olodaterol or other long-acting beta2-agonists BIAARHUS2015
Aclidinium Bromide Drug Utilisation Post-Authorisation Safety Studies (DUS): Common Protocol for Aclidinium (DUS1) and Aclidinium/Formoterol Fixed-Dose Combination (DUS2)Astra ZenecaBIPS, SDU2014
A multinational active safety surveillance study of crizotinib in EuropePfizerAARHUS, PHARMO2014
Post-Authorization Safety Program—Validation of the Danish Data Resources for the Study of Cardiovascular and Neoplasm Events in Users of Treatments for Overactive BladderAstellas SDU2014
Cohort Study of the Relative Incidence of Major Cardiovascular Events Among Patients Initiating Prucalopride Versus a Matched Comparator CohortShireBIPS, DUNDEE2014
Cilostazol Drug Utilisation StudyOtsukaBIPS, IDIAP2013
Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus, Pimecrolimus, and CorticosteroidsAstellas/LEOPHARMO, SDU2013
Safety Evaluation of Adverse Reactions in Diabetes - Drug utilisation studiesECBIPS, PHARMO, RTI-HS2013
Evaluation of the Use of Nepafenac in Selected European PopulationsAlconPHARMO, SDU2013
Evaluation of potential off-label use of dabigatran etexilate in EuropeBISDU2013
Testing new approaches to monitoring benefit/risk with pertussis vaccines as test case: Incidence rates of pertussis and pertussis related outcomes of whole-cell pertussis and acellular pertussis vaccines in pre-school childrenECAARHUS ARS, IDIAP2013
ADVANCE POC I Risk pillar - Testing new approaches to monitoring benefit/risk with pertussis vaccines as test case: Incidence rates of safety outcomes of whole-cell pertussis and acellular pertussis vaccines in pre-school childrenECAARHUS, ARS, IDIAP2013
ADVANCE POC Study Protocol - Testing new approaches to monitoring benefit/risk with pertussis vaccines as test case. Coverage rates of acellular and whole-cell pertussis-containing vaccines in preschool childrenECAARHUS, ARS, IDIAP2013
ADVANCE POC I Benefit-Risk pillar – testing new approaches to monitoring benefit/risk with pertussis vaccines as test case: benefit-risk analysis of pertussis vaccines in pre-school children comparing whole-cell and acellular formulations in the post-marketing settingECAARHUS, ARS, IDIAP2013
Exposure and coverage to routine schedule vaccines in different EU countriesECAARHUS, ARS, IDIAP, UMCU2013
CAncer Risk and INsulin analoGuesEUAARHUS2011
Patterns and Determinants of Use of Oral Contraceptives in the European UnionEMAARS, PHARMO2011
Safety Evaluation of Adverse Reactions in Diabetes - Comparative studiesECBIPS, PHARMO, RTI-HS2011
Study of Acute Liver Transplant: A study of NSAIDs-exposed acute liver failure in European transplant centresHelsinn Healthcare S.A.RTI-HS2008

Data availability

Name of database/CountryARS Toscana/
Danish Health
PHARMO Database
Scottish Prescribing
Information System/
Prescription/dispensings data
Hospital data
Primary care data
Laboratory data
Cancer data
Pregnancy data
Emergency data
ARS = Agenzia regionale di sanità della Toscana; EMR = Electronic medical records; GePaRD = German Pharmacoepidemiological Research Database; SNDS = French National Healthcare System database; SIDIAP = Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primaria

The SIGMA Members RTI-HS and UU also have the ability to access and work with CPRD data.