Status: FinalisedLast updated on: 25/08/2017
1. Study identification
EU PAS Register NumberEUPAS2895
Official titleSafety Evaluation of Adverse Reactions in Diabetes - Comparative studies
Study title acronymSAFEGUARD
Study typeObservational study
Brief description of the studySafety issues associated with blood glucose lowering drugs are not new, the safety of these treatments has been questioned and highly publicized. It has been reported that some of them increase the risk or modify the prognosis of cancer, cardiovascular (CVD) or pancreatic diseases. The primary objective of the comparative studies in SAFEGUARD is to estimate the risk of myocardial infarction (MI), heart failure (HF), ventricular arrhythmia (VA)/sudden cardiac death (SCD), ischemic stroke (IS), hemorrhagic stroke (HS), acute pancreatitis (AP), pancreatic cancer (PC), bladder cancer (BC) and total mortality (TM) associated with the use of non-insulin blood glucose lowering drugs (NIBGLD), insulins and insulin analogs in subjects with T2DM. Data collected in 9 different electronic health databases from 5 different European countries the USA will be used. Nested case control studies in a cohort of T2DM patients will be conducted to assess the association of NIBGLD, insulins, and insulin analogs with MI, HF, VA/SCD, IS, HS, AP, BC and PC and a dynamic retrospective cohort study to estimate the association with TM. For the estimation of the risk, in the case control studies, cases will be compared with matched controls and adjusted for potential confounders. Conditional logistic regression will be used to calculate the unadjusted and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) with reference to another active compound. For the cohort studies, hazard ratios and incidence rates (IR) and the relative risk for TM with their 95% CIs will be estimated using Cox-regression. Time varying analyses will be conducted for estimation of the effect of duration of treatment. All analyses will be performed for each database separately and the heterogeneity among databases will be examined (e.g., I2). Advanced methodologies, subanalyses and sensitivity analyses will be carried out to deal with methodological issues.(i.e propensity scores, etc).
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)? Not applicable
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsErasmus MC Pharmacoepi
Department/Research groupPharmacoepidemiology Erasmus University
Organisation/affiliationErasmus University Medical Center
Website/Homepagewww.erasmusmc.nl
Details of (Primary) lead investigator
Title Professor
Last name Sturkenboom
First name Miriam
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres

In total how many centres are involved in this Study?10

AEMPS, Spain
UNIMIB, Italy
BWH, United States of America
Countries in which this study is being conducted
International study

Germany
Italy
Netherlands
Spain
United Kingdom
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed23/08/201123/08/2011
Start date of data collection20/09/201220/09/2012
Start date of data analysis
Date of interim report, if expected
Date of final study report30/09/201530/09/2015
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding schemeHealth Area of the European Commission under the VII Framework Programme100
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Sturkenboom
First name Miriam
Address line 1Heidelberglaan 100
Address line 2Julius Clinical, Utrecht University 
Address line 3 
CityUtrecht 
Postcode 
CountryNetherlands
Phone number (incl. country code)31-6-57831983 
Alternative phone number 
Fax number (incl. country code) 
Public Enquiries
Title Professor 
Last name Sturkenboom 
First name Miriam 
Address line 1Heidelberglaan 
Address line 2 
Address line 3 
CityUtrecht 
Postcode 
CountryNetherlands 
Phone number (incl. country code)31-657831983 
Alternative phone number 
Fax number (incl. country code) 
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