Methods
Study design, duration and sampling: This was a prospective cohort study conducted over a period of one-year duration from May 2012 to April 2013 in the Department of Internal Medicine, University College Hospital, Ibadan. The University College Hospital is an 850-bed tertiary centre located in Ibadan, Oyo State in the South Western part of Nigeria. It serves as a referral centre for patients within Nigeria and neighbouring West African countries.
The study was conducted among all consented adult patients admitted to all the medical wards of the hospital during the study period. The medical wards of the University College Hospital consist of six wards with 162 beds. Inclusion criteria included all newly admitted adult patients who gave informed consent while exclusion criteria involved patients who were on admission before the commencement of the study and refusal to give informed consent.
For the purpose of this study, ADRs were defined according to World Health Organization definition [16]. The evaluation method employed included examination of the medical and nursing records, reviewing prescription charts and patients’ interview.
On each day of admission, a specific questionnaire was completed for all newly admitted medical patients. Information obtained included demographics, past medical history, drug and allergy history, the reason for admission, medications taken in the last one month including herbal and other alternative care, and whether there were adverse drug reactions at admission. Thereafter, patients were intensely evaluated daily for the presence of ADRs and were monitored until discharge. Data on the particular suspected medicine(s) and reactions were also documented on the pharmacovigilance form. All the medicines the patient has received before the onset of reactions, their respective doses, routes and frequency of administration were recorded on the forms. All available clinical details, treatments and laboratory test results presented in the medical records were noted and updated from the patients in order to assess the causal relationship between medicine and reactions. Causality relationship was determined between suspected ADR and the suspected medicine.
Adverse drug reactions were classified in accordance with the WHO definition [16]. Severity and avoidability of ADRs were assessed. Fatal ADRs were those that resulted in near-death or eventual death for the patient; severe ADRs included those that were directly life-threatening and/or prolonged hospitalisation, associated with organ or system dysfunction and permanent harm; moderate, those that required treatment intervention and patient was temporarily harmed; and mild as uncomplicated primary disease requiring increased patient monitoring but neither required treatment or drug discontinuation. A reaction was considered as avoidable if the medicine involved in the ADR and/or the route or frequency of administration, dose or dosage form was inappropriate for the patient’s condition. The avoidability of the ADRs was assessed with definitions and criteria developed by Hallas et al., into definitely avoidable, possibly avoidable and unavoidable [17]. However, both definitely and possible avoidable were combined to mean “avoidable”. Analysis of causality assessment was done using the causality categories described by the Uppsala Monitoring Centre [18]. Analysis for causality, severity and avoidability were independently done by two of the investigators.
The length of stay was calculated for each admission and was used to determine the total number of bed days and the mean length of stay. The ADR admission rate was determined based on the number of patients admitted at least once with an ADR during the study.
Patients were classified into (1) patients without ADRs (either at admission or during hospitalisation), (2) patients with ADRs at admission, including patients admitted because of this ADR, and patients with ADRs which were not the cause of hospitalisation and (3) patients with ADRs occurring during hospitalisation. ADRs were also classified as type A (dose-dependent and predictable from the known pharmacology) or type B (idiosyncratic, no clear dose-response and not predictable from the known pharmacology), in accordance with the classification of Rawlings and Thompson [19]. A plausible concise classification A, B, C – chronic/continuous, D - delayed, E -end of treatment and “TREND” for Temporal relationship, Re-challenge, Exclusion, Novelty and De-challenge analysis of assessing causality or detecting ADRs was however not used here [20].
Statistical analysis
Data were entered, cleaned and analysed with IBM SPSS Statistical package version 22. Figures were drawn using Microsoft Excel version 2016. Categorical variables were summarised with frequency and proportions. The continuous variables were summarised with means (standard deviation) for those that were normally distributed and median (range) if otherwise. Relative Risk (95% Confidence Interval) was used to assess factors associated with ADRs observed. Student’s t-test was used to determine the relationship between the number of drugs used by the patients and the development of ADRs. The level of statistical significance was set at less than 0.05.