PURPOSE: The European Committee for Human Medicinal Products (CHMP) requested a multinational study with the aim to investigate the risk of acute liver failure (ALF) leading to registration for transplantation in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational, multicentre, retrospective case-population study, named SALT (Study of Acute Liver Transplant), is documented here. METHODS: This was a multicentre, multinational retrospective case-population study performed in France, Italy, Portugal, Greece, Ireland, the Netherlands and the UK. The study period was 3 years (1 January 2005-31 December 2007). Cases were patients ≥ 18 years of age with ALF at the time of registration on the transplant list for liver transplantation who had been exposed to an NSAID within 30 days preceding the initial symptoms of liver disease (index date). Exposure was defined as exposure to any NSAID. Per country rates of NSAID-exposed transplantation-registered ALF were computed as the ratio of the number of cases identified in the country to total population exposure. Overall and per-drug sales for NSAIDs and for paracetamol were obtained from Intercontinental Marketing Services (IMS) Health for all participating countries. Population exposure was measured as the defined daily dose and as estimated annual number of patients exposed (primary endpoint) with 95 % confidence intervals. RESULTS: The study protocol was approved by the CHMP. Of the 57 eligible liver transplant centres, 54 agreed to participate in the study. All national authorizations were received with relevant administrative burden, mainly due to bureaucracy. CONCLUSION: The present study created a multinational research network to estimate population-based absolute rates of drug-exposed ALF leading to registration on the transplantation list. This study design was chosen to obtain a fast response to a public health issue, namely, that of an increased risk of a rare, very serious adverse reaction. This model could be used to study other drug-related issues in ALF.
%0 Journal Article
%1 Gulmez2013
%A Gulmez, Sinem Ezgi
%A Larrey, Dominique
%A Pageaux, Georges-Philippe
%A Lignot-Maleyran, Séverine
%A de Vries, Corinne
%A Sturkenboom, Miriam
%A Perez-Gutthann, Susana
%A Bénichou, Jacques
%A Bissoli, Franco
%A Horsmans, Yves
%A Bernuau, Jacques
%A Stricker, Bruno
%A Thorburn, Douglas
%A Blin, Patrick
%A Moore, Nicholas
%D 2013
%J European journal of clinical pharmacology
%K AcuteDisease Anti-InflammatoryAgents CooperativeBehavior Drug-InducedLiverInjury Drug-InducedLiverInjury:epidemiology Drug-InducedLiverInjury:surgery Europe Europe:epidemiology Humans InternationalCooperation LiverTransplantation LiverTransplantation:statistics&numericaldata Non-Steroidal Non-Steroidal:adverseeffects OddsRatio Pharmacoepidemiology Pharmacoepidemiology:methods Pharmacoepidemiology:statistics&numericaldata ResearchDesign ResearchDesign:statistics&numericaldata RetrospectiveStudies RiskAssessment RiskFactors TimeFactors WaitingLists
%N 3
%P 605-16
%R 10.1007/s00228-012-1357-8
%T Methodology for a multinational case-population study on liver toxicity risks with NSAIDs: the Study of Acute Liver Transplant (SALT).
%U http://www.ncbi.nlm.nih.gov/pubmed/22878690
%V 69
%X PURPOSE: The European Committee for Human Medicinal Products (CHMP) requested a multinational study with the aim to investigate the risk of acute liver failure (ALF) leading to registration for transplantation in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational, multicentre, retrospective case-population study, named SALT (Study of Acute Liver Transplant), is documented here. METHODS: This was a multicentre, multinational retrospective case-population study performed in France, Italy, Portugal, Greece, Ireland, the Netherlands and the UK. The study period was 3 years (1 January 2005-31 December 2007). Cases were patients ≥ 18 years of age with ALF at the time of registration on the transplant list for liver transplantation who had been exposed to an NSAID within 30 days preceding the initial symptoms of liver disease (index date). Exposure was defined as exposure to any NSAID. Per country rates of NSAID-exposed transplantation-registered ALF were computed as the ratio of the number of cases identified in the country to total population exposure. Overall and per-drug sales for NSAIDs and for paracetamol were obtained from Intercontinental Marketing Services (IMS) Health for all participating countries. Population exposure was measured as the defined daily dose and as estimated annual number of patients exposed (primary endpoint) with 95 % confidence intervals. RESULTS: The study protocol was approved by the CHMP. Of the 57 eligible liver transplant centres, 54 agreed to participate in the study. All national authorizations were received with relevant administrative burden, mainly due to bureaucracy. CONCLUSION: The present study created a multinational research network to estimate population-based absolute rates of drug-exposed ALF leading to registration on the transplantation list. This study design was chosen to obtain a fast response to a public health issue, namely, that of an increased risk of a rare, very serious adverse reaction. This model could be used to study other drug-related issues in ALF.
@article{Gulmez2013,
abstract = {PURPOSE: The European Committee for Human Medicinal Products (CHMP) requested a multinational study with the aim to investigate the risk of acute liver failure (ALF) leading to registration for transplantation in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational, multicentre, retrospective case-population study, named SALT (Study of Acute Liver Transplant), is documented here. METHODS: This was a multicentre, multinational retrospective case-population study performed in France, Italy, Portugal, Greece, Ireland, the Netherlands and the UK. The study period was 3 years (1 January 2005-31 December 2007). Cases were patients ≥ 18 years of age with ALF at the time of registration on the transplant list for liver transplantation who had been exposed to an NSAID within 30 days preceding the initial symptoms of liver disease (index date). Exposure was defined as exposure to any NSAID. Per country rates of NSAID-exposed transplantation-registered ALF were computed as the ratio of the number of cases identified in the country to total population exposure. Overall and per-drug sales for NSAIDs and for paracetamol were obtained from Intercontinental Marketing Services (IMS) Health for all participating countries. Population exposure was measured as the defined daily dose and as estimated annual number of patients exposed (primary endpoint) with 95 % confidence intervals. RESULTS: The study protocol was approved by the CHMP. Of the 57 eligible liver transplant centres, 54 agreed to participate in the study. All national authorizations were received with relevant administrative burden, mainly due to bureaucracy. CONCLUSION: The present study created a multinational research network to estimate population-based absolute rates of drug-exposed ALF leading to registration on the transplantation list. This study design was chosen to obtain a fast response to a public health issue, namely, that of an increased risk of a rare, very serious adverse reaction. This model could be used to study other drug-related issues in ALF.},
added-at = {2023-02-03T11:44:35.000+0100},
author = {Gulmez, Sinem Ezgi and Larrey, Dominique and Pageaux, Georges-Philippe and Lignot-Maleyran, Séverine and de Vries, Corinne and Sturkenboom, Miriam and Perez-Gutthann, Susana and Bénichou, Jacques and Bissoli, Franco and Horsmans, Yves and Bernuau, Jacques and Stricker, Bruno and Thorburn, Douglas and Blin, Patrick and Moore, Nicholas},
biburl = {https://www.bibsonomy.org/bibtex/264f330ceceb214cdf6b8a065e91a1336/jepcastel},
doi = {10.1007/s00228-012-1357-8},
interhash = {b507e4df149149b27593979053a119f3},
intrahash = {64f330ceceb214cdf6b8a065e91a1336},
issn = {1432-1041},
journal = {European journal of clinical pharmacology},
keywords = {AcuteDisease Anti-InflammatoryAgents CooperativeBehavior Drug-InducedLiverInjury Drug-InducedLiverInjury:epidemiology Drug-InducedLiverInjury:surgery Europe Europe:epidemiology Humans InternationalCooperation LiverTransplantation LiverTransplantation:statistics&numericaldata Non-Steroidal Non-Steroidal:adverseeffects OddsRatio Pharmacoepidemiology Pharmacoepidemiology:methods Pharmacoepidemiology:statistics&numericaldata ResearchDesign ResearchDesign:statistics&numericaldata RetrospectiveStudies RiskAssessment RiskFactors TimeFactors WaitingLists},
month = {3},
note = {Disseny},
number = 3,
pages = {605-16},
pmid = {22878690},
timestamp = {2023-02-03T11:44:35.000+0100},
title = {Methodology for a multinational case-population study on liver toxicity risks with NSAIDs: the Study of Acute Liver Transplant (SALT).},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22878690},
volume = 69,
year = 2013
}