(063) Causality assessment of adverse drug reactions in post-authorization settings: An analysis from four different countries to find out the most comprehensive and easy-to-use tool

Publication Number: 1059

Background: An adverse drug reaction (ADR)s generally predict hazard from future administration and warrant prevention, or alteration of the dosage regimen, or withdrawal of the product. However, investigating whether a prescribed drug has caused an ADR remains a major challenge as no standardized tool permitting the causality assessment of ADRs has been universally accepted until now.

Objectives: The aim of this work is to provide an up-to-date overview of the different causality-assessment tools that have been published and find out the easiest to use.

Methods: Study design: This is a literature review.
Study period: All the tools published from the year 1976 to 2020 were included in our study.
Study population: Human population treated with drugs worldwide.
Source of data: Electronic search was carried out in MEDLINE (through PubMed), EMBASE, and the Cochrane database. A thorough search on google scholar was conducted.
Variable assessed: We conducted electronic searches using keywords like adverse event, adverse drug events, ADRs, drug side effect, causality, causality algorithm. The pertinence of each causality assessment tool was screened by three reviewers. Each tool deemed pertinent was then scrutinized for its domains (the reported specific set of questions used for calculating the likelihood of an ADR). Five reviewers from four different countries (R1 and R2 from Canada, R3 from India, R4 from Hungary, and R5 from Brazil) then objectively assessed each tool’s exhaustivity and comprehensiveness, as well as easiness of use in each country respective clinical context.
Statistical analysis: The percentage was calculated to check the number of domains covered by each tool. The mean value was calculated to check the easiness of each tool in different clinical context.

Results: A total of twenty-one pertinent tools used for causality assessment of ADRs were retrieved, covering from 1 and 16 domains. The 1981 Naranjo’s tool stand among the most exhaustive/comprehensive, covering 10 domains: plausibility, temporality, dechallenge, rechallenge, co-factors, measurement of the toxicity, dose-response, response to placebo, susceptibility of the patient and objectivity of the ADR. Regarding easiness of use: 17 tools had a mean score >1 (16 with a score of 2 [i.e.: complex] and 1 with a score of 4 [complex and time consuming]). Considering its 10 domains (63%) and easiness of use (score of 1), the Naranjo’s 1981 tool found to be the most exhaustive and easy to use from four different countries’ perspectives.

Conclusions: Among many tools identified, the 1981 Naranjo’s probability scale remains the most comprehensive and easy-to-use for performing causality assessment of ADRs in Canada, India, Hungary, and Brazil clinical contexts.