Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project

Olaf H Klungel; Xavier Kurz; Mark C H de Groot; Raymond G Schlienger; Stéphanie Tcherny-Lessenot; Lamiae Grimaldi-Bensouda; Luisa Ibáñez; Rolf H H Groenwold; Robert F Reynolds; Yolanda Alvarez; Gianmario Candore; Jean-Louis Durand; Jim Slattery; J. Hasford; Marietta Rottenkolber; Sven Schmiedl; F. de Abajo Iglesias; M Gil; Juan R González; C. Huerta Alvarez; E. Martin; Baldomero Oliva; Gema Requena; J. Amelio; Ruth Brauer; Gerald Downey; M. Feudjo-Tepie; M. Schoonen; S. Johansson; J. Robinson; M. Schuerch; I. Tatt; Helle Petri; L. A. Garcia; Ana Ruigomez; J J Campbell; A Gallagher; Kwee Eng Ng; Tjeerd P. van Staa; O. Demol; N. Boudiaf; K Davis; John Logie; J. Pimenta; R. Beau-Lejdstrom; Lamiae Grimaldi-Bensouda; Lucien Abenhaim; Lamiae Grimaldi-Bensouda; Michel Rossignol; M. L. De Bruin; On behalf of the members of work-package 2 of PROTECT

doi:10.1002/pds.3968

Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project

Olaf H Klungel, Xavier Kurz, Mark C H de Groot, Raymond G Schlienger, Stéphanie Tcherny-Lessenot, Lamiae Grimaldi-Bensouda, Luisa Ibáñez, Rolf H H Groenwold, Robert F Reynolds, Yolanda Alvarez, Gianmario Candore, Jean-Louis Durand, Jim Slattery, J. Hasford, Marietta Rottenkolber, Sven Schmiedl, F. de Abajo Iglesias, M Gil, Juan R González, C. Huerta AlvarezE. Martin, Baldomero Oliva, Gema Requena, J. Amelio, Ruth Brauer, Gerald Downey, M. Feudjo-Tepie, M. Schoonen, S. Johansson, J. Robinson, M. Schuerch, I. Tatt, Helle Petri, L. A. Garcia, Ana Ruigomez, J J Campbell, A Gallagher, Kwee Eng Ng, Tjeerd P. van Staa, O. Demol, N. Boudiaf, K Davis, John Logie, J. Pimenta, R. Beau-Lejdstrom, Lamiae Grimaldi-Bensouda, Lucien Abenhaim, Lamiae Grimaldi-Bensouda, Michel Rossignol, M. L. De Bruin, On behalf of the members of work-package 2 of PROTECT

26 Citations (Scopus)

Abstract

Purpose: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases. Methods: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases. Results: The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10years and different types of cancer. Conclusions: A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines.

Original language	English
Journal	Pharmacoepidemiology and Drug Safety
Volume	25
Pages (from-to)	156-165
Number of pages	10
ISSN	1053-8569
DOIs	https://doi.org/10.1002/pds.3968
Publication status	Published - 1 Mar 2016
Externally published	Yes

Keywords

Electronic healthcare databases
European Medicines Agency
Innovative Medicines Initiative
Methodology
Observational studies
Pharmacoepidemiology
Pharmacoepidemiology (PE)
PROTECT

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Klungel, O. H., Kurz, X., de Groot, M. C. H., Schlienger, R. G., Tcherny-Lessenot, S., Grimaldi-Bensouda, L., Ibáñez, L., Groenwold, R. H. H., Reynolds, R. F., Alvarez, Y., Candore, G., Durand, J-L., Slattery, J., Hasford, J., Rottenkolber, M., Schmiedl, S., de Abajo Iglesias, F., Gil, M., González, J. R., ... On behalf of the members of work-package 2 of PROTECT (2016). Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project. Pharmacoepidemiology and Drug Safety, 25, 156-165. https://doi.org/10.1002/pds.3968

Klungel, OH, Kurz, X, de Groot, MCH, Schlienger, RG, Tcherny-Lessenot, S, Grimaldi-Bensouda, L, Ibáñez, L, Groenwold, RHH, Reynolds, RF, Alvarez, Y, Candore, G, Durand, J-L, Slattery, J, Hasford, J, Rottenkolber, M, Schmiedl, S, de Abajo Iglesias, F, Gil, M, González, JR, Huerta Alvarez, C, Martin, E, Oliva, B, Requena, G, Amelio, J, Brauer, R, Downey, G, Feudjo-Tepie, M, Schoonen, M, Johansson, S, Robinson, J, Schuerch, M, Tatt, I, Petri, H, Garcia, LA, Ruigomez, A, Campbell, JJ, Gallagher, A, Ng, KE, van Staa, TP, Demol, O, Boudiaf, N, Davis, K, Logie, J, Pimenta, J, Beau-Lejdstrom, R, Grimaldi-Bensouda, L, Abenhaim, L, Grimaldi-Bensouda, L, Rossignol, M, De Bruin, ML & On behalf of the members of work-package 2 of PROTECT 2016, 'Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project', Pharmacoepidemiology and Drug Safety, vol. 25, pp. 156-165. https://doi.org/10.1002/pds.3968

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title = "Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project",

abstract = "Purpose: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases. Methods: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases. Results: The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10years and different types of cancer. Conclusions: A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines.",

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year = "2016",

month = mar,

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doi = "10.1002/pds.3968",

language = "English",

volume = "25",

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journal = "Pharmacoepidemiology and Drug Safety",

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T1 - Multi-centre, multi-database studies with common protocols

T2 - Lessons learnt from the IMI PROTECT project

AU - Klungel, Olaf H

AU - Kurz, Xavier

AU - de Groot, Mark C H

AU - Schlienger, Raymond G

AU - Tcherny-Lessenot, Stéphanie

AU - Grimaldi-Bensouda, Lamiae

AU - Ibáñez, Luisa

AU - Groenwold, Rolf H H

AU - Reynolds, Robert F

AU - Alvarez, Yolanda

AU - Candore, Gianmario

AU - Durand, Jean-Louis

AU - Slattery, Jim

AU - Hasford, J.

AU - Rottenkolber, Marietta

AU - Schmiedl, Sven

AU - de Abajo Iglesias, F.

AU - Gil, M

AU - González, Juan R

AU - Huerta Alvarez, C.

AU - Martin, E.

AU - Oliva, Baldomero

AU - Requena, Gema

AU - Amelio, J.

AU - Brauer, Ruth

AU - Downey, Gerald

AU - Feudjo-Tepie, M.

AU - Schoonen, M.

AU - Johansson, S.

AU - Robinson, J.

AU - Schuerch, M.

AU - Tatt, I.

AU - Petri, Helle

AU - Garcia, L. A.

AU - Ruigomez, Ana

AU - Campbell, J J

AU - Gallagher, A

AU - Ng, Kwee Eng

AU - van Staa, Tjeerd P.

AU - Demol, O.

AU - Boudiaf, N.

AU - Davis, K

AU - Logie, John

AU - Pimenta, J.

AU - Beau-Lejdstrom, R.

AU - Grimaldi-Bensouda, Lamiae

AU - Abenhaim, Lucien

AU - Grimaldi-Bensouda, Lamiae

AU - Rossignol, Michel

AU - De Bruin, M. L.

AU - On behalf of the members of work-package 2 of PROTECT

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Purpose: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases. Methods: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases. Results: The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10years and different types of cancer. Conclusions: A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines.

AB - Purpose: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases. Methods: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases. Results: The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10years and different types of cancer. Conclusions: A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines.

KW - Electronic healthcare databases

KW - European Medicines Agency

KW - Innovative Medicines Initiative

KW - Methodology

KW - Observational studies

KW - Pharmacoepidemiology

KW - Pharmacoepidemiology (PE)

KW - PROTECT

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U2 - 10.1002/pds.3968

DO - 10.1002/pds.3968

M3 - Journal article

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AN - SCOPUS:84962809848

SN - 1053-8569

VL - 25

SP - 156

EP - 165

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

ER -

Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project

Abstract

Keywords

UN SDGs

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