ENCePP Guide on Methodological Standards in Pharmacoepidemiology
The Guide on Methodological Standards in Pharmacoepidemiology is a longstanding cornerstone of the ENCePP toolkit, as described in Strengthening Pharmacoepidemiology in a Changing Research Environment: The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (Pharmacoepidemiol Drug Saf. 2025;34:e70263).
Since its first edition in 2012, the Guide has provided practical methodological guidance, bringing together international recommendations, key guidelines, scientific literature, and good practice considerations where gaps have been identified.
As the use of real-world data (RWD) in studies on the utilisation, safety and effectiveness of medicinal products is expanding, so has the body of methodological guidance, including but not limited to the Reflection paper on use of RWD in non-interventional studies, ICH M14, Pharmacoepidemiology and Drug Safety’s Core Concepts, guidance documents from international regulators, the International Society for Pharmacoepidemiology (ISPE), the Professional Society for Health Economics and Outcomes Research (ISPOR), the International Society of Pharmacovigilance (ISoP), and peer-reviewed academic and pharmaceutical industry literature.
As these standards continue to rapidly evolve, the Guide has moved to a living resource to continue supporting high-quality pharmacoepidemiological research and the generation of reliable real-world evidence (RWE), serving a broad group of stakeholders including researchers, regulators, healthcare professionals, and marketing authorisation holders and applicants in Europe and globally.
The last full revision, dated July 2023, is available on this page. The Guide is managed by a dedicated Working Group which identifies areas for update and oversees the revision of individual chapters, under the oversight of the ENCePP Steering Group.
The ENCePP network and the wider pharmacoepidemiological research community are encouraged to share with the ENCePP_Secretariat
ema [dot] europa [dot] eu (ENCePP Secretariat) suggestions for improvement and proposals for updates of specific chapters.
Chapters
The increasing ability and expertise to reuse electronic real-world data (RWD) from routine healthcare systems continues to open up opportunities for investigators to conduct non-interventional studies on the utilisation, safety and effectiveness of medicinal products, and stimulate the development.
Epidemiology is the study of the occurrence of health phenomena in the population, their frequency and their relationship with determinants.
Generating adequate evidence involves formulating the right research question(s), identifying and collecting fit-for-purpose data, applying suitable study designs, and conducting the appropriate analyses.
The study protocol is the core document of a study, to be developed as a key step in any study once the research question has been clearly defined.
An epidemiological study measures a parameter of occurrence (generally incidence, prevalence or risk or rate ratio) of a health phenomenon (e.g., a disease) in a specified population and with a specified time reference (time point or time period).
Historically, pharmacoepidemiological studies relied on patient-reported information or paper-based health records.
Self-selection in epidemiological studies may introduce selection bias and influence the validity of study results.
Effect modification and interaction are often encountered in epidemiological research, and it is important to recognise their occurrence.
There are two main approaches for data collection: collection of data to address the specific research question under study or use of data already collected for another purpose, e.g., for clinical management of patients, for reimbursement purposes, or for another research question.
A growing number of pharmacoepidemiological studies use data from networks of databases, often from different countries.
Identification and integration of evidence derived from results from several studies with the same or similar research objective can extend our understanding of the research question.
A general overview of methods for signal detection and recommendations for their application are provided in the report of the CIOMS Working Group VIII Practical aspects of signal detection in pharmacovigilance.
Compared to the protocol that includes a section outlining the analyses, the SAP is a more technical, stand-alone document describing in detail the planned analyses, population definitions and methodology.
Quality in research is a measure of excellence that impacts medicines development and public health. What is quality management system (QMS)? (American Society for Quality, 2022) defines a QSM as a formalised system that documents processes, procedures, and responsibilities.
Aspects of dissemination and communication of study results include, but are not limited to, reports to health authorities and study sponsors, presentations in scientific fora, scientific publications, patient-focused communications, and websites dedicated to publishing study reports.
In the European Union, the conduct of pharmacoepidemiological studies needs to respect applicable Union data protection rules, namely the General Data Protection Regulation (EU) 2016/679 (GDPR) and Member State laws adopted in line with the GDPR
Comparative effectiveness research (CER) is designed to inform healthcare decisions for the prevention, the diagnosis and the treatment of a given health condition.
A systematic review (SR) attempts to collate all empirical evidence that fits pre-specified eligibility criteria to answer a specific research question.
Planning a pregnancy may lead to discontinuation of non-essential medicines before conception