Background: Evidence suggesting adverse drug reactions often emerges unsystematically and unpredictably in form of anecdotal reports, case series and survey data. Safety trials and observational studies also provide crucial information regarding the (un-)safety of drugs. Hence, integrating multiple types of pharmacovigilance evidence is key to minimising the risks of harm.Methods: In previous work, we began the development of a Bayesian framework for aggregating multiple types of evidence to assess the probability of a putative causal link between drugs and side effects. This framework arose out of a philosophical analysis of the Bradford Hill Guidelines. In this article, we expand the Bayesian framework and add "evidential modulators," which bear on the assessment of the reliability of incoming study results. The overall framework for evidence synthesis, "E-Synthesis", is then applied to a case study.Results: Theoretically and computationally, E-Synthesis exploits coherence of partly or fully independent evidence converging towards the hypothesis of interest (or of conflicting evidence with respect to it), in order to update its posterior probability. With respect to other frameworks for evidence synthesis, our Bayesian model has the unique feature of grounding its inferential machinery on a consolidated theory of hypothesis confirmation (Bayesian epistemology), and in allowing any data from heterogeneous sources (cell-data, clinical trials, epidemiological studies), and methods (e.g., frequentist hypothesis testing, Bayesian adaptive trials, etc.) to be quantitatively integrated into the same inferential framework.Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses.

Today’s surge of big data coming from multiple sources is raising the stakes that pharmacovigilance has to win, making evidence synthesis a more and more robust approach in the field. In this scenario, many scholars believe that new computational methods derived from data mining will effectively enhance the detection of early warning signals for adverse drug reactions, solving the gauntlets that post-marketing surveillance requires. This article highlights the need for a philosophical approach in order to fully realize a pharmacovigilance 2.0 revolution. A state of the art on evidence synthesis is presented, followed by the illustration of E-Synthesis, a Bayesian framework for causal assessment. Computational results regarding dose-response evidence are shown at the end of this article.

Rationale, aims and objectives: The diversity of types of evidence (eg, case reports, animal studies and observational studies) makes the assessment of a drug's safety profile into a formidable challenge. While frequentist uncertain inference struggles in aggregating these signals, the more flexible Bayesian approaches seem better suited for this quest. Artificial Intelligence (AI) offers great promise to these approaches for information retrieval, decision support, and learning probabilities from data.Methods: E-Synthesis is a Bayesian framework for drug safety assessments built on philosophical principles and considerations. It aims to aggregate all the available information, in order to provide a Bayesian probability of a drug causing an adverse reaction. AI systems are being developed for evidence aggregation in medicine, which increasingly are automated.Results: We find that AI can help E-Synthesis with information retrieval, usability (graphical decision-making aids), learning Bayes factors from historical data, assessing quality of information and determining conditional probabilities for the so-called 'indicators' of causation for E-Synthesis. Vice versa, E-Synthesis offers a solid methodological basis for (semi-)automated evidence aggregation with AI systems.Conclusions: Properly applied, AI can help the transition of philosophical principles and considerations concerning evidence aggregation for drug safety to a tool that can be used in practice.