D2 - Joining mechanistic and epidemiological approaches to enhance causal inference of drug effects

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Almut G Winterstein (University of Florida, USA) and Stephan Schmidt (University of Florida. USA)


Mechanistic studies have seen great advances in use of models and modelling to predict drug effects, but inherent in these inductive approaches are concerns about (lack of) translation into real-world situations. In contrast, population-based analyses of real-world data have direct clinical application but are prone to biases. Both approaches are typically executed in isolation and take limited advantage of each other’s strengths when aiming to make causal inferences.

This session will discuss the scientific synergies in joining mechanistic and epidemiologic approaches when making causal inferences about drug effects that are applicable to real world situations, using three examples: (1) a synthesis of cell-based and animal experiments and pharmcoepidemiologic studies to investigate whether toxic effects of systematic quinolones on connective tissue expand to otic application, resulting in permanent tympanic membrane perforation; (2) how a joined pharmacoepidemiologic, cell-based pharmacologic and clinical pharmacokinetic approach was combined to both discover and characterize a novel drug-drug interaction between warfarin and dicloxacillin and its underlying mechanisms; (3) how combinations of pharmacometrics, pharmacoepidemiology, and pharmacoeconomics can enhance research and decision-making for generic drug substitution. The session will close with a discussion of the opportunities and barriers in expanding joint approaches to enhance our understanding of drug safety and effectiveness.


Opportunities and barriers of joint approaches to enhance causal inference on drug effects
Almut G Winterstein (University of Florida, USA)

Linking otic quinolone and tympanic membrane perforations: Validating pharmacoepidemiologic safety signals with laboratory models
Patrick Antonelli (University of Florida, USA)

Dicloxacillin in drug-drug interactions – a translational tale from registries to the bench and back again
Tore Bjerregaard (University of Southern Denmark, Denmark) and Anton Pottegård  (Universtity of Southern Denmark, Denmark)

A multi-disciplinary collaboration using pharmacometrics, pharmacoepidemiology, and pharmacoeconomics for efficacy and safety questions related to generic substitution
Joshua Brown (University of Florida, USA)


Learning Objectives

  1. Describe mechanisms how causal inference can be strengthened through translational collaborations between mechanistic and population-based pharmaceutical sciences
  2. Describe hurdles in developing collaborations, such as learning to “speak each others language”
  3. Analyze and outline opportunities to establish translational collaborations to enhance their own research