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Home > Standards & Guidances > Methodological Guide

ENCePP Guide on Methodological Standards in Pharmacoepidemiology



Section 8.3. Reporting of adverse events/reactions

The EU obligations to companies sponsoring a post-authorisation study (PAS) are specified in Module VI of the Guideline on good pharmacovigilance practice (GVP) - Management and reporting of adverse reactions to medicinal products. For a non-interventional PAS which is not sponsored by an MAH there are no legal reporting obligations at the European level. Investigators should however enquire whether national obligations exist. In all circumstances, the adverse events/adverse reactions reported during the study should be summarised in the study report. If the study qualifies as an interventional trial, the reporting criteria laid down in Directive 2001/20/EC and Volume 10 of the Rules Governing Medicinal Products in the European Union should be followed.

Obligations or recommendations may also be specified by an ethical committee or a data safety monitoring board. The Guidelines for Submitting Adverse Event Reports for Publication (Pharmacoepidemiol Drug Saf 2007;16(5): 581–7) introduce readers to the key elements that have to be included when someone wishes to publish results about adverse drug events. For a case report (or series), minimum requirements include an account of the patients medical history and disposition, a detailed account of the dispensed product (substances, brand, route of administration) and a detailed account of the adverse event (nature, timing, severity, outcome).


Individual Chapters:


1. General aspects of study protocol

2. Research question

3. Approaches to data collection

3.1. Primary data collection

3.2. Secondary use of data

3.3. Research networks

3.4. Spontaneous report database

3.5. Using data from social media and electronic devices as a data source

3.5.1. General considerations

4. Study design and methods

4.1. General considerations

4.2. Challenges and lessons learned

4.2.1. Definition and validation of drug exposure, outcomes and covariates Assessment of exposure Assessment of outcomes Assessment of covariates Validation

4.2.2. Bias and confounding Choice of exposure risk windows Time-related bias Immortal time bias Other forms of time-related bias Confounding by indication Protopathic bias Surveillance bias Unmeasured confounding

4.2.3. Methods to handle bias and confounding New-user designs Case-only designs Disease risk scores Propensity scores Instrumental variables Prior event rate ratios Handling time-dependent confounding in the analysis

4.2.4. Effect modification

4.3. Ecological analyses and case-population studies

4.4. Hybrid studies

4.4.1. Pragmatic trials

4.4.2. Large simple trials

4.4.3. Randomised database studies

4.5. Systematic review and meta-analysis

4.6. Signal detection methodology and application

5. The statistical analysis plan

5.1. General considerations

5.2. Statistical plan

5.3. Handling of missing data

6. Quality management

7. Communication

7.1. Principles of communication

7.2. Guidelines on communication of studies

8. Legal context

8.1. Ethical conduct, patient and data protection

8.2. Pharmacovigilance legislation

8.3. Reporting of adverse events/reactions

9. Specific topics

9.1. Comparative effectiveness research

9.1.1. Introduction

9.1.2. General aspects

9.1.3. Prominent issues in CER Randomised clinical trials vs. observational studies Use of electronic healthcare databases Bias and confounding in observational CER

9.2. Vaccine safety and effectiveness

9.2.1. Vaccine safety General aspects Signal detection Signal refinement Hypothesis testing studies Meta-analyses Studies on vaccine safety in special populations

9.2.2. Vaccine effectiveness Definitions Traditional cohort and case-control studies Screening method Indirect cohort (Broome) method Density case-control design Test negative design Case coverage design Impact assessment Methods to study waning immunity

9.3. Design and analysis of pharmacogenetic studies

9.3.1. Introduction

9.3.2. Identification of genetic variants

9.3.3. Study designs

9.3.4. Data collection

9.3.5. Data analysis

9.3.6. Reporting

9.3.7. Clinical practice guidelines

9.3.8. Resources

Annex 1. Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes