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.