Status: Finalised First registered on: 06/06/2012
Last updated on: 25/08/2017
1. Study identification
EU PAS Register NumberEUPAS2616
Official titleRisk of cardiac valve disorders associated with the use of biphosphonates
Study title acronymCardiac valve disorders and biphosphonate use
Study typeActive surveillance
Brief description of the studyA signal of disproportionate reporting concerning the risk of cardiac valve calcification leading to cardiac valve insufficiency associated with the use of bisphosphonates was found in EudraVigilance. A similar association between bisphosphonate use and valvular and vascular calcification in women has also been previously described in a cohort study conducted in the United States (MESA study). The primary objective of this signal strengthening study is to confirm or refute the presence of a possible risk of cardiac valve disorders (all types of disorders, confirmed by cardiac imaging) in patients treated with bisphosphonates using EU longitudinal healthcare data from the EU-ADR Alliance. This signal strengthening study will determine the need for, and feasibility of conducting a traditional hypothesis testing study. Signal strengthening will be performed using the most recently updated demographic, clinical, and prescription data from six databases in three EU member states (Italy, Netherlands, the United Kingdom), pooled using a distributed network approach by generation of common input data followed by local aggregation through custom-built software, Jerboa©. Potential cases of cardiac valve disorders in the database network will be identified using database-specific coding algorithms. Exposure to bisphosphonates will be assessed with drug prescription/dispensing data using the World Health Organisation’s (WHO) Anatomical Therapeutic Chemical (ATC) classification system. Several signal detection/strengthening methods will be employed to assess the association of cardiac valve disorder and use of bisphosphonates
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)? Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
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?
Yes
EU-ADR Alliance
Other centres where this study is being conducted
Multiple centres

In total how many centres are involved in this Study?5

PHARMO Institute
SSRI Toscana, Tuscany, Italy
SSRI Lombardia, Lombardy, Italy
Countries in which this study is being conducted
International study

Italy
Netherlands
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed02/12/201102/12/2011
Start date of data collection11/06/201218/06/2012
Start date of data analysis18/06/201222/06/2012
Date of interim report, if expected02/07/201216/07/2013
Date of final study report02/08/201208/01/2014
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 bodyEMA100
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Sturkenboom
First name Miriam
Address line 1POBOX 2040
Address line 2dep. Medical Informatics 
Address line 3 
CityRotterdam 
Postcode3000 CA 
CountryNetherlands
Phone number (incl. country code)31-6-57831983 
Alternative phone number 
Fax number (incl. country code) 
Email address mcjm.sturkenboom@gmail.com
Public Enquiries
Title Professor 
Last name Sturkenboom 
First name Miriam 
Address line 1POBOX 2040 
Address line 2dep. Medical Informatics 
Address line 3 
CityRotterdam 
Postcode3000 CA 
CountryNetherlands 
Phone number (incl. country code)31-6-57831983 
Alternative phone number 
Fax number (incl. country code) 
Email address mcjm.sturkenboom@gmail.com 
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