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ENCePP Guide on Methodological Standards in Pharmacoepidemiology

 

Chapter 1: Introduction

Epidemiology is the study of the occurrence of phenomena of interest among people in the health field, their frequency and their relationship with determinants (O. Miettinen. Theoretical Epidemiology: Principles of Occurrence Research in Medicine, Wiley, 1985,vii-viii). Pharmacoepidemiology is the application of epidemiological methods to study the use and effects of medicines in specified populations. Many textbooks describe methodological standards in pharmacoepidemiology, but they cannot incorporate all new developments. ENCePP therefore considered there was a need for a regularly updated resource providing recommendations on the practical implementation of pharmacoepidemiological principles and innovative methods based on published guidance and illustrative examples.

 

The ENCePP Guide aims to offer a dynamic and publicly available web resource for methodological English language guidance in pharmacoepidemiology. For each topic covered, recommendations are provided with links to selected published articles, guidelines and public documents selected by experts in pharmacoepidemiology from the ENCePP. Where relevant, gaps in existing guidance are addressed with what ENCePP considers good practice. The Guide is updated annually by a structured review in order to maintain its dynamic nature. The final text of the revisions is reviewed by the ENCePP WG1 Research Standards and Guidance and approved by the ENCePP Steering Committee. The Guide may also be amended as necessary in response to comments received. For this purpose, any comment and additional relevant guidance document may be forwarded to ENCePP_Secretariat@ema.europa.eu.

 

The Guide only briefly addresses general methods of pharmacoepidemiology as study designs stemming from traditional epidemiological research are already fully described in existing textbooks. It rather discusses important aspects of more recent designs such as self-controlled designs and specific analytical approaches to traditional designs. It also discusses methods that may be used in studies with different objectives, be they safety, effectiveness, drug utilisation or health technology assessment. For some specific topics, recommendations and references are provided where they differ from general principles.

 

Chapter 15 provides guidance on specific topics: comparative effectiveness research, which has been extensively updated in this Revision 10; vaccine safety and effectiveness; pharmacogenetic studies; methods for pharmacovigilance impact research; and, as new chapters, real-world evidence and pharmacoepidemiology; and use of artificial intelligence in pharmacoepidemiology. A new Annex 2 is providing guidance on methods for the evaluation of medicines in pregnancy and breastfeeding.

 

The increasing ability to electronically capture and store data from routine health care systems and transform it into new knowledge have opened up new opportunities for investigators to conduct studies. The concept of real-world data (RWD) and real-world evidence (RWE) has been increasingly used since the early 2000’s to denote use of observational data originating from routine health care systems to generate evidence in the healthcare field. There is, however, no internationally agreed definition of RWD and RWE, and these terms are not used consistently. Chapter 15.6 discusses definitions of RWD and RWE, their role in medicines evaluation, their relation to evidence generated by clinical trials, and why pharmacoepidemiological methods remain essential for the generation and assessment of RWD and RWE.

 

General guidance on the conduct of pharmacoepidemiology studies can be found in the ISPE Good Pharmacoepidemiology Practices (GPP) and the IEA Good Epidemiology Practice (GEP). The GPP guidance is especially useful for its recommendations on aspects rarely covered by guidelines, such as data quality issues and archiving. The Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology (Eur J Epidemiol. 2019;34(3):301-17) provides detailed recommendations for the planning, preparation, execution, analysis, and evaluation of epidemiological research.

 

The Guideline of good pharmacovigilance practices (GVP) Module VIII - Post-authorisation safety studies provides a general guidance on the development, conduct and reporting of post-authorisation safety studies (PASS) conducted by marketing authorisation holders voluntarily or pursuant to the EU legislation (Directive 2001/83/EC). The Scientific guidance on post-authorisation efficacy studies provides general scientific guidance in the context of EU regulatory decision-making with regard to the need for such studies and methodological considerations.

 

Where to begin? Thirty must-read papers for newcomers to pharmacoepidemiology (Pharmacoepidemiol Drug Saf. 2022;31(2):257-9) provides a list of 30 articles that the authors consider touching upon core principles of pharmacoepidemiology and RWE.

 

Textbooks on standard methods in pharmacoepidemiology that are considered useful are listed below. This list is not aimed at being exhaustive, and researchers may find other textbooks more appropriate to their specific needs. Others are cited in specific chapters.

  • Modern Epidemiology, 4th ed. (T. Lash, T.J. VanderWeele, S. Haneuse, K. Rothman. Wolters Kluwer, 2020) is a comprehensive textbook on methods in epidemiology.
  • Epidemiology: Study Design and Data Analysis, Third Edition (M. Woodward, Chapman & Hall, 2014) focuses on the quantitative aspects of epidemiological research.
  • A Dictionary of Epidemiology, Sixth Edition (M Porta, Editor. Oxford University Press, 2014), sponsored by the International Epidemiological Association (IEA), provides a definition and concise explanation of epidemiologic terms and is a key to understanding epidemiological concepts.
  • Clinical epidemiology: practice and methods, Second Edition (PS Parfrey, BJ Barret, Human Press, 2015) focuses on the diagnosis, prognosis and management of human disease using appropriate research design, measurement and evaluation.
  • Causal Inference: What If (Hernán MA, Robins JM, Chapman & Hall/CRC, 2020) aims to help scientists generate and analyse data to make causal inferences that are explicit about both the causal question and the assumptions underlying the data analysis.
  • Pharmacoepidemiology, Sixth Edition (B. Strom, S.E. Kimmel, S. Hennessy, Wiley, 2019) provides a comprehensive guidance on pharmacoepidemiology addressing data sources, applications and methodologies.
  • Pharmacoepidemiology and Therapeutic Risk Management, First Edition (A.G. Hartzema, H.H. Tilson and K.A. Chan, Editors, Harvey Whitney Books Company, 2008) illustrates practical issues with a large number of real-life examples in addition to a general review of drug-specific methodologies.
  • Practical Statistics for Medical Research, Second Edition (D. Altman. Chapman & Hall, 2020) presents a problem-based statistical text for medical researchers.
  • Drug Utilization Research. Methods and Applications (M Elseviers, B Wettermark, AB Almarsdóttir, et al. Editors. Wiley Blackwell, 2016) provides a comprehensive manual of methodology and applications of drug utilisation research.
  • Mann's Pharmacovigilance, Third Edition (EB Andrews, N Moore, Editors, Wiley-Blackwell, 2014) is a reference for the detection, assessment, understanding and prevention of the adverse effects of medicines, including vaccines and biologics.
  • Post-Authorization Safety Studies of Medicinal Products. The PASS Book, 1st Edition (Ayad Ali, Abraham Hartzema, Ed., Academic Press, 2018) covers the use of observational studies in post-marketing drug safety assessment, presents various types of post-authorisation safety studies and discusses challenges and solutions in the design and conduct of these studies.

 

 

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