A review of the sampling methodology used in studies evaluating the effectiveness of risk minimisation measures in Europe.

PURPOSE: This review aims to describe the sampling methodology used in studies assessing effectiveness of risk minimisation measures (RMMs) in the European Union. METHODS: The European Union electronic Register of Post-Authorization Studies (EU PAS Register) was searched to identify studies that assessed the effectiveness of RMMs and recruited a target population of healthcare professionals (HCPs), sites or patients. Studies with both protocol and report were included and data was extracted from these documents to describe study characteristics and variables involved in the sampling methodology. RESULTS: Out of 1092 studies finalised between June 2017 and May 2019, 17 studies were eligible for review. Thirteen were surveys, three chart reviews and one combined both methodologies. All the 17 studies recruited HCPs/sites and 8 of them also recruited patients. The most common rationale for country sampling was market uptake (10/17), while for HCP/site sampling, it was representativeness of the prescribing practices (14/17). Only a minority of the studies (4/17) provided supporting evidence to inform this theoretical framework. HCP/site sampling frames were mainly network of physicians (5/17) or HCP databases (5/17), with only one study providing a detailed description of the sampling frame. HCPs were selected mainly using probabilistic sampling (10/17) and patients using non-probabilistic sampling (6/8). Only a few studies compared participating with non-participating HCPs/sites (5/17) and patients (3/8). Eight studies reported that their results were generalisable. CONCLUSIONS: Overall, the study documents provided insufficient details to understand the rationale behind the sampling decisions. More standardisation and guidance in reporting the sampling strategy and operational considerations applicable to these types of studies would support transparency and facilitate the evaluation of representativeness of the study results.

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

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.