Lessons learned on the design and the conduct of Post-Authorization Safety Studies: review of 3 years of PRAC oversight

TY - JOUR

T1 - Lessons learned on the design and the conduct of Post-Authorization Safety Studies

T2 - review of 3 years of PRAC oversight

AU - Engel, Pierre

AU - Almas, Mariana Ferreira

AU - De Bruin, Marieke Louise

AU - Starzyk, Kathryn

AU - Blackburn, Stella

AU - Dreyer, Nancy Ann

PY - 2017

Y1 - 2017

N2 - Aims: To describe and characterize the first cohort of Post-Authorization Safety Study (PASS) protocols reviewed under the recent European pharmacovigilance legislation. Methods: A systematic approach was used to compile all publicly available information on PASS protocols and assessments submitted from July 2012 to July 2015 from Pharmacovigilance Risk Assessment Committee (PRAC) minutes, European Medicines Agency (EMA) and European Network of Pharmacovigilance and Pharmacoepidemiology (ENCePP) webpages. Results: During the study period, 189 different PASS protocols were submitted to the PRAC, half of which were entered in the ENCePP electronic register of post-authorization studies (EU-PAS) by July 2015. Those protocols were assessed during 353 PRAC reviews. The EMA published only 31% of the PRAC feedback, of which the main concerns were study design (37%) and feasibility (30%). Among the 189 PASS, slightly more involved primary data capture (58%). PASS assessing drug utilization mainly leveraged secondary data sources (58%). The majority of the PASS did not include a comparator (65%) and 35% of PASS also evaluated clinical effectiveness endpoints. Conclusions: To the best of our knowledge this is the first comprehensive review of three years of PASS protocols submitted under the new pharmacovigilance legislation. Our results show that both EMA and PASS sponsors could respectively increase the availability of protocol assessments and documents in the EU-PAS. Protocol content review and the high number of PRAC comments related to methodological issues and feasibility concerns should raise awareness among PASS stakeholders to design more thoughtful studies according to pharmacoepidemiological principles and existing guidelines.

AB - Aims: To describe and characterize the first cohort of Post-Authorization Safety Study (PASS) protocols reviewed under the recent European pharmacovigilance legislation. Methods: A systematic approach was used to compile all publicly available information on PASS protocols and assessments submitted from July 2012 to July 2015 from Pharmacovigilance Risk Assessment Committee (PRAC) minutes, European Medicines Agency (EMA) and European Network of Pharmacovigilance and Pharmacoepidemiology (ENCePP) webpages. Results: During the study period, 189 different PASS protocols were submitted to the PRAC, half of which were entered in the ENCePP electronic register of post-authorization studies (EU-PAS) by July 2015. Those protocols were assessed during 353 PRAC reviews. The EMA published only 31% of the PRAC feedback, of which the main concerns were study design (37%) and feasibility (30%). Among the 189 PASS, slightly more involved primary data capture (58%). PASS assessing drug utilization mainly leveraged secondary data sources (58%). The majority of the PASS did not include a comparator (65%) and 35% of PASS also evaluated clinical effectiveness endpoints. Conclusions: To the best of our knowledge this is the first comprehensive review of three years of PASS protocols submitted under the new pharmacovigilance legislation. Our results show that both EMA and PASS sponsors could respectively increase the availability of protocol assessments and documents in the EU-PAS. Protocol content review and the high number of PRAC comments related to methodological issues and feasibility concerns should raise awareness among PASS stakeholders to design more thoughtful studies according to pharmacoepidemiological principles and existing guidelines.

KW - ENCePP

KW - new pharmacovigilance legislation

KW - PASS

KW - PRAC

KW - transparency

U2 - 10.1111/bcp.13165

DO - 10.1111/bcp.13165

M3 - Journal article

C2 - 27780289

AN - SCOPUS:85008262679

SN - 0306-5251

VL - 83

SP - 884

EP - 893

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 4

ER -