From Signal to Causality: Evidence-Based Approaches in Drug Safety

This Research Topic is associated with the 24th ISoP Annual Meeting 2025, October 24th-27th 2025 | Cairo, Egypt.

Drug safety evaluation begins with the detection of potential safety signals and extends through signal confirmation, characterization, and causality assessment. At every step, different methodologies and data sources contribute unique insights, but also bring their own limitations, creating challenges for drawing consistent and transparent conclusions. This Research Topic explores how principles of evidence-based medicine (EBM) can strengthen drug safety by systematically appraising and integrating diverse evidence streams. We invite contributions that highlight methodological advances, case studies, regulatory perspectives, and innovative approaches to evidence synthesis across the continuum of safety assessment.

Submissions may address statistical signal detection, randomized and observational study designs, translational and mechanistic investigations, patient-reported outcomes, real-world evidence, and novel tools such as Bayesian models or artificial intelligence-driven assessment. By examining the strengths and weaknesses of each evidence source, this collection aims to chart a path toward more rigorous, transparent, and credible approaches to causality assessment in pharmacovigilance. This Research Topic aims to provide a comprehensive platform for discussing how evidence-based principles can transform drug safety evaluation—from the earliest signal detection activities to the final determination of causality. We encourage submissions from researchers, clinicians, epidemiologists, statisticians, regulatory scientists, and other stakeholders in pharmacovigilance.

By bringing together diverse perspectives and methodologies, this collection will map the current landscape of evidence use in drug safety, critically examine the strengths and limitations of each source, and highlight integrative approaches that can support more transparent and scientifically robust decision-making.

We welcome contributions that address conceptual, methodological, empirical, and regulatory aspects of utilizing evidence-based approaches in drug safety. Submissions may include original research, reviews, perspectives, case studies, and methodological papers. Suggested themes include:

• Novel statistical and artificial intelligence-based approaches for signal detection
• Regulatory perspectives on best practices in signal detection and on evidence-based causality assessment across various regions of the world
• Best practices in reporting results of signal detection approaches
• Role of longitudinal healthcare databases for safety evaluation
• Utility of novel study designs in drug safety including strengths in assessing rare or long-latency outcomes
• Use of distributed data networks and multi-regional large-scale real-world studies in drug safety
• Patient-reported outcomes and digital health tools in signal validation
• Data quality, representativeness, and interoperability challenges across regions given cultural differences
• Transparency and reproducibility in safety decision-making
• Case studies of regulatory actions guided by evidence synthesis
• Research priorities for advancing EBM in pharmacovigilance


Topic Editor Dr. Tarek Hammad, is Vice President, Global Head of Medical Safety at Takeda Pharmaceutical Co Ltd. Topic Editor, Dr. Salvatore Crisafulli, declares no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: ISoP, pharmacovigilance, drug safety, signal detection, causality assessment, evidence-based medicine, drug safety evaluation, artificial intelligence in drug safety

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.