Researchers, regulatory agencies, and the pharmaceutical industry are moving towards precision pharmacovigilance as a comprehensive framework for drug safety assessment, at the service of the individual patient, by clustering specific risk groups in different databases. This article explores its implementation by focusing on: (i) designing a new data collection infrastructure, (ii) exploring new computational methods suitable for drug safety data, and (iii) providing a computer-aided framework for distributed clinical decisions with the aim of compiling a personalized information leaflet with specific reference to a drug's risks and adverse drug reactions. These goals can be achieved by using 'smart hospitals' as the principal data sources and by employing methods of precision medicine and medical statistics to supplement current public health decisions.

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.

Contemporary debates about scientific institutions and practice feature many proposed reforms. Most of these require increased efforts from scientists. But how do scientists’ incentives for effort interact? How can scientific institutions encourage scientists to invest effort in research? We explore these questions using a game-theoretic model of publication markets. We employ a base game between authors and reviewers, before assessing some of its tendencies by means of analysis and simulations. We compare how the effort expenditures of these groups interact in our model under a variety of settings, such as double-blind and open review systems. We make a number of findings, including that open review can increase the effort of authors in a range of circumstances and that these effects can manifest in a policy-relevant period of time. However, we find that open review’s impact on authors’ efforts is sensitive to the strength of several other influences.

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.

The debates between Bayesian, frequentist, and other methodologies of statistics have tended to focus on conceptual justifications, sociological arguments, or mathematical proofs of their long run properties. Both Bayesian statistics and frequentist (“classical”) statistics have strong cases on these grounds. In this article, we instead approach the debates in the “Statistics Wars” from a largely unexplored angle: simulations of different methodologies’ performance in the short to medium run. We used Big Data methods to conduct a large number of simulations using a straightforward decision problem based around tossing a coin with unknown bias and then placing bets. In this simulation, we programmed four players, inspired by Bayesian statistics, frequentist statistics, Jon Williamson’s version of Objective Bayesianism, and a player who simply extrapolates from observed frequencies to general frequencies. The last player served a benchmark function: any worthwhile statistical methodology should at least match the performance of simplistic induction. We focused on the performance of these methodologies in guiding the players towards good decisions. Unlike an earlier simulation study of this type, we found no systematic difference in performance between the Bayesian and frequentist players, provided the Bayesian used a flat prior and the frequentist used a low confidence level. The Williamsonian player was also able to perform well given a low confidence level. However, the frequentist and Williamsonian players performed poorly with high confidence levels, while the Bayesian was surprisingly harmed by biased priors. Our study indicates that all three methodologies should be taken seriously by philosophers and practitioners of statistics.

Real World Evidence (RWE) and its uses are playing a growing role in medical research and inference. Prominently, the 21st Century Cures Act—approved in 2016 by the US Congress—permits the introduction of RWE for the purpose of risk-benefit assessments of medical interventions. However, appraising the quality of RWE and determining its inferential strength are, more often than not, thorny problems, because evidence production methodologies may suffer from multiple imperfections. The problem arises to aggregate multiple appraised imperfections and perform inference with RWE. In this article, we thus develop an evidence appraisal aggregation algorithm called EA³. Our algorithm employs the softmax function—a generalisation of the logistic function to multiple dimensions—which is popular in several fields: statistics, mathematical physics and artificial intelligence. We prove that EA³ has a number of desirable properties for appraising RWE and we show how the aggregated evidence appraisals computed by EA³ can support causal inferences based on RWE within a Bayesian decision making framework. We also discuss features and limitations of our approach and how to overcome some shortcomings. We conclude with a look ahead at the use of RWE.