These Safety and Pharmacovigilance tips are aimed at improving the understanding of this area of clinical drug and device development. For example, clinical sites are frequently confused about the nuances of adverse event reporting, assessing causality, or the use of proper safety terminology. In addition, some sponsors may not be using the appropriate type of committee to oversee the safety of their clinical trial. See below for the first tip in this series and feel free to reach out to us with any questions: info@medsurgpi.com.

Clinical Investigators and their sites should establish a systematic way of assessing causality when adverse events and serious adverse events occur. The Bradford Hill criteria are an established practical way of determining these events[1]:

Strength of Association: a strong association between a treatment and an adverse event indicates causation. For example, each time the drug was given to a subject, it caused vomiting within a predictable time period.
Consistency: Established adverse event attributions or previous determinations in similar situations indicate causation.
Specificity. An established mechanism of action connecting the treatment and the adverse event indicates causation.
Temporality: exposure to the product must occur before the disease or event, and not after a latency period. However, temporality is not sufficient to establish causation.
Biological Gradient: a dose response effect is a strong argument for causation.
Plausibility: the causal relationship is biologically plausible.
Coherence: the known facts fit the natural history and biology of the disease.
Experiment: Epidemiologic studies indicate causation.
Analogy: a similar agent causes the same type of AE.

[1] Klein, G., Johnson, P. and Morgan R., Medical Monitoring of Clinical Research Studies. J. Clin. Res. Best Practices. 2021: Vol 17 (1)