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ENCePP Guide on Methodological Standards in Pharmacoepidemiology


Foreword to the ENCePP Guide on Methodological Standards in Pharmacoepidemiology, Revision 10

The COVID-19 pandemic has had a significant impact on the amount of work performed by pharmacoepidemiologists, due to the need to rapidly evaluate the use, safety and effectiveness of COVID-19 vaccines and therapeutics, not only by collecting and analysing data from large healthcare data sources or setting up primary data collection, but also by screening and appraising the very large amount of published medical literature for a new disease for which knowledge changed at a fast pace.


The time has come to draw lessons to be applied in more routine pharmacoepidemiological practice, or another possible pandemic, and several aspects can already be identified. On the positive side, the level of preparedness achieved through the proactive generation of background incidence rates for adverse events of special interest and the design of template protocols allowed regulators and other stakeholders to very rapidly evaluate and respond to vaccine safety signals, and contextualise the benefit-risk of the vaccines with regards to rare adverse reactions. Moreover, such rapid response was supported by international collaborations, for example with the use of the same protocols for coagulopathy studies applied in Europe, the U.S. and Canada. But several challenges remain. Many researchers were faced with the limited availability of adequate information on vaccine exposure or variant-specific data, the low frequency of data source updates, and lag times to access recent data, which affected the speed of evaluation or its feasibility. These aspects will need to be addressed and ENCePP will continue to evaluate the very rich methodological work done by researchers during the pandemic and support drawing and addressing lessons learned.


Although the height of the pandemic seems to be behind us, we nevertheless expect researchers to be faced soon with another formidable challenge, the long COVID-19 syndrome. Figures of 5 to 20% of COVID-19 patients with persistent symptoms more than 12 weeks after initial diagnosis are cited, but in the absence of widely accepted definitions, diagnostic criteria and coding systems, these figures are uncertain. Even with the lowest estimate, the absolute number of patients presenting with long COVID-19 will nevertheless be high. Moreover, cognitive disorders have been found to be the second most frequent symptom, which has potentially important public health consequences. Many studies will be needed to evaluate the incidence and risk factors of long COVID-19 and identify the possible effects of treatments received during the infection as well as those of existing medicines.


This 10th revision of the ENCePP Methods Guide therefore continues to provide examples of COVID-19 related studies illustrating good practice and methodological developments in pharmacoepidemiology. Such examples are provided in most chapters, and Chapter 15.2 (Vaccine research) was significantly amended on these aspects. Besides the revision of many chapters, this 10th Revision also includes new chapters, on the use of artificial intelligence in pharmacoepidemiology, and on real-world evidence and pharmacoepidemiology; a comprehensive new Annex on the evaluation of medicines in pregnancy and breastfeeding; an extensive revision of the Comparative Effectiveness Research chapter; and considerations on the misuse of statistical significance in Chapter 4.1.


We hope that this 10th revision of the ENCePP Guide will continue to support good practices in pharmacoepidemiology in Europe and elsewhere.


Susana Perez-Gutthann

Catherine Cohet

Co-Chairs of the ENCePP Steering Group



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