Methods for causality assessment of adverse drug reactions: a systematic review

Drug Saf. 2008;31(1):21-37. doi: 10.2165/00002018-200831010-00003.


Numerous methods for causality assessment of adverse drug reactions (ADRs) have been published. The aim of this review is to provide an overview of these methods and discuss their strengths and weaknesses. We conducted electronic searches in MEDLINE (via PubMed), EMBASE and the Cochrane databases to find all assessment methods. Thirty-four different methods were found, falling into three broad categories: expert judgement/global introspection, algorithms and probabilistic methods (Bayesian approaches). Expert judgements are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality. Algorithms are sets of specific questions with associated scores for calculating the likelihood of a cause-effect relationship. Bayesian approaches use specific findings in a case to transform the prior estimate of probability into a posterior estimate of probability of drug causation. The prior probability is calculated from epidemiological information and the posterior probability combines this background information with the evidence in the individual case to come up with an estimate of causation. As a result of problems of reproducibility and validity, no single method is universally accepted. Different causality categories are adopted in each method, and the categories are assessed using different criteria. Because assessment methods are also not entirely devoid of individual judgements, inter-rater reliability can be low. In conclusion, there is still no method universally accepted for causality assessment of ADRs.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Causality*
  • Databases as Topic / statistics & numerical data
  • Decision Support Techniques
  • Humans
  • Outcome Assessment, Health Care / methods*
  • Reproducibility of Results
  • Risk Assessment / methods