Translation and cultural adaptation were performed in collaboration with the research group responsible for designing and validating the original English language versions of LCAT and LAAT. For an in-depth understanding of the construction and investigation of the psychometric properties of the tools, the corresponding author spent approximately six months based in the Paediatric Medicines Research Unit at Alder Hey Children's Hospital (AHCH) (Liverpool, UK) for study design [15] and practical training.
The validation of the cross-cultural adaptation of tools was obtained by the functional equivalence (given by the degree of agreement between conceptual and item equivalence, semantic equivalence, operational and measurement equivalence) between the original versions and the translated versions of the tools (Figure 1) [15,16].
Conceptual, item and semantic equivalence
A literature review was conducted to identify any new publications about the original instruments, since their development and their use in the target population [16]. Next, a committee of experts, made up of authors of the new (translated) version and the original version, assisted in identifying the concepts of terms and phrases used in the tools, considering the characteristics of the target population and culture [15].
The translation of LCAT and LAAT was performed independently by two professionals (a physician and a pharmacist) fluent in the in the source language and culture, considering the conceptual equivalence and avoiding the literal translation [15,16]. Then, members of the committee of experts conducted a synthesis of translated texts in a single version (v1) of each tool and assessed any linguistic, conceptual, and contextual discrepancies [15,16]. A retranslated version of each tool obtained from the source language (British English) from v1 was used to compare the original text's content and evaluate semantic equivalence and equivalence of items [17].
Application of v1 of each tool consisted of a pre-test performed by a group of 27 Brazilian professionals (24 pharmacists, 1 doctor, and 2 nurses with experience in pharmacovigilance). The objective was to verify the adequacy, structure, and usefulness of each of the tools. Any operational difficulties were recorded and discussed for each item of the tools [15]. Small changes made in response to points raised by the group resulted in version 2 (v2) of both tools.
Operational and measuring equivalence
Martagão Gesteira Child Care and Pediatrics Institute of the Federal University of Rio de Janeiro (IPPMG - UFRJ, Rio de Janeiro, Brazil) was selected as the setting for the introduction of the versions of each tool translated and adapted into Brazilian Portuguese (v2). IPPMG - UFRJ is a medium-sized teaching hospital (80 beds) linked to the Single Health System (SUS) for highly complex pediatric care.
All suspected cases of ADRs related to anti-infectives in children aged 0 to 17 years hospitalized at IPPMG – UFRJ identified from an observational study with prospective data collection (between May and October 2019) were assessed with the exception of ADRs which occurred in the intensive care unit and oncology as these were excluded. Anti-infectives were chosen for this study because they were the main agents responsible for reports of ADRs in Brazilian children [18].
Information on; (a) patient characterization (age, gender, health, and medication history); (b) prescription of all drugs (including dosages), and; (c) details of suspected cases, was collected daily from patient diaries, laboratory results and medical records were used to prepare case reports (6,14,19). The following were also considered: (i) pharmacology, (ii) known history of allergy or similar previous reaction, (iii) known preventative strategies, (iv) other sources of information or information in the history available for prevention of reactions; (v) appropriate measures taken to avoid an ADR, and, (vi) follow-up of ADR prevention strategies and management plan(s) [11,14].
The v2 (in Brazilian-Portuguese) of both tools (LCAT and LAAT) were used to assess twenty-six cases from twenty-two children by two independent reviewers (a pharmacist and a doctor) who worked in the IPPMG - UFRJ. Prior to case assessment, the reviewers participated in a meeting (90 minutes) for structured discussion based on frequently asked questions about ADRs induced by anti-infectives in children and the use of the tools.
Each suspected ADR was evaluated for causality as unlikely, possible, probable or definite, and for avoidability as unassessable, not avoidable, possibly avoidable, and definitely avoidable using the LCAT and LAAT, respectively. This step considered the relevance and adequacy of each tool, and the format of the questions/instructions, the mode and scenario of application, and the categorization mode [16].
The measurement equivalence step was based on psychometric studies with the following approaches: (a) evaluation of dimensional validity and adequacy of component items, (b) reliability assessment, and, (c) criterion validity construct validity assessment [16].
The inter-rater reliability was assessed using Cronbach's alpha. The exact agreement percentages (%EA) were computed to measure the absolute concordances of the evaluator's results. The percentage of extreme disagreement (%ED) (in which the causality and avoidability scores between evaluators of the same case was greater than two) was measured between the pairs. This evaluation was based on an ordinal score of the outcomes for LCAT (unlikely = 0; possible = 1; probable = 2; definite =3) and LAAT (unassessable = 0; not avoidable = 1; possibly avoidable = 2; definitely avoidable = 3 for LAAT), and it allowed %ED between raters to be estimated.
The overall Kappa index which measures the nominal scale agreement among several raters was calculated with 95% confidence intervals (CI) [11,14]. Kappa values were interpreted according to the guidance from Altman (20): poor <0.2; fair 0.21±0.4; moderate 0.41±0.6; good 0.61±0.8 and very good 0.81±1 agreement. The statistical analysis was performed using IBM Statistical Package for the Social programs Statistics in Earth Sciences (SPSS) 19 and Microsoft Excel.
Ethical issues
This study was evaluated and approved by the Research Ethics Committee (REC IPPMG - UFRJ – Number: 3.264.238.