J Appl Biomed 21:59-66, 2023 | DOI: 10.32725/jab.2023.010

Causality assessment of adverse drug reaction: A narrative review to find the most exhaustive and easy-to-use tool in post-authorization settings

Pallavi Pradhan^{1, 2}, Maude Lavallée^{2, 3}, Samuel Akinola⁴, Fernanda Raphael Escobar Gimenes⁵, Anick Bérard^{6, 7}, Julie Méthot^{2, 3}, Marie-Eve Piché^{2, 8}, Jennifer Midiani Gonella⁵, Lyne Cloutier⁹, Jacinthe Leclerc^{2, 3, 9, *}

¹ University of Quebec at Trois-Rivieres, Department of Anatomy, Trois-Rivieres, Canada

² University Institute of Cardiology and Pulmonology of Quebec - Laval University, Centre of Research, Laval, Canada

³ Laval University, Faculty of Pharmacy, Laval, Canada

⁴ University of Pecs, Faculty of Health Sciences, Department of Nursing, Pecs, Hungary

⁵ University of Sao Paolo, Nursing School of Ribeirão Preto, Sao Paolo, Brazil

⁶ University Hospital Center, Research Center of Sainte-Justine, Montreal, Canada

⁷ University of Montreal, Faculty of Pharmacy, Montreal, Canada

⁸ Laval University, Faculty of Medicine, Laval, Canada

⁹ University of Quebec at Trois-Rivieres, Department of Nursing, Trois-Rivieres, Canada

Background: The core motive of pharmacovigilance is the detection and prevention of adverse drug reactions (ADRs), to improve the risk-benefit balance of the drug. However, the causality assessment of ADRs remains a major challenge among clinicians, and none of the available tools of causality assessment used for assessing ADRs have been universally accepted.

Objective: To provide an up-to-date overview of the different causality assessment tools.

Methods: We conducted electronic searches in MEDLINE, EMBASE, and the Cochrane database. The eligibility of each tool was screened by three reviewers. Each eligible tool was then scrutinized for its domains (the reported specific set of questions/areas used for calculating the likelihood of cause-and-effect relation of an ADR) to discover the most comprehensive tool. Finally, we subjectively assessed the tool's ease-of-use in a Canadian, Indian, Hungarian, and Brazilian clinical context.

Results: Twenty-one eligible causality assessment tools were retrieved. Naranjo's tool and De Boer's tool appeared the most comprehensive among all the tools, covering 10 domains each. Regarding "ease-of-use" in a clinical setting, we judged that many tools were hard to implement in a clinical context because of their complexity and/or lengthiness. Naranjo's tool, Jones's tool, Danan and Benichou's tool, and Hsu and Stoll's tool appeared to be the easiest to implement into various clinical contexts.

Conclusion: Among the many tools identified, 1981 Naranjo's scale remains the most comprehensive and easy to use for performing causality assessment of ADRs. Upcoming analysis should compare the performance of each ADR tool in clinical settings.

Keywords: Adverse drug reactions; Adverse events; Causality assessment; Healthcare quality; Pharmacovigilance

Grants and funding:

This research was funded by the Department of Nursing of Université du Québec à Trois-Rivières, and the Fondation de l’Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval.

Conflicts of interest:

The authors have no conflict of interests to declare.

Received: December 14, 2022; Revised: May 25, 2023; Accepted: December 21, 2023; Prepublished online: June 21, 2023; Published: June 27, 2023  Show citation