FACULTY
M EDIC INE – U NIVERSITY
OF
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
Prevalence of adverse drug reactions: A self-reported random
digit dialing study in the adult population of Porto
Júlia Barbosa,
Ruben Barreto,
Sara Cunha,
med05012@med.up.pt
med05234@med.up.pt
med05090@med.up.pt
Sara Mota,
Sara Nogueira,
Sara Oliveira,
med05087@med.up.pt
med05088@med.up.pt
med05088@med.up.pt
Sérgio Azevedo,
Sílvia Monteiro,
Sílvia Silva
med05093@med.up.pt
med05094@med.up.pt
med05095@med.up.pt
Adviser: Dr. João Fonseca – jfonsecaed.up.pt , Dr Luis Azevedo – lazevedo@med.up.pt,
Class: 21
Abstract
Introduction – Adverse reactions to medicines is the response to a drug, noxious and unintended,
for prophylactics, of diagnosis or therapeutics effects, or for modification of the psychological function that
happens in normal dosage. Multiple factors associated to these side effects as well as a lack of diagnosis methods
to some specific drugs lead to difficult diagnosis.
Aims - To estimate the prevalence of adverse drug reactions in the adult population of Porto; to
identify the most common symptoms; to identify the drugs more usually associated to the symptoms referred.
Methods - In order to obtain, in a certain moment, a sample from the population it was used a
cross-sectional study. Relevant variables are related to the existence of reaction, its durability and symptoms.
The participant selection obeyed to specific rules as in each Porto telephone households only one adult individual
was inquired. Because all telephone numbers were selected at random we analysed a random sample of
households with telephone in the Porto region.
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
Results - Out of 200 phone calls, 103 individuals answered the questionnaire, so the rate of
participation was 51,5%.
Participants ranging from 18 to 85 years (mean 50,6 ± 15,5 years) and the majority were female
(52,5%).
The prevalence of self-reported adverse drug reactions was 26,8%.
The prevalence of self-reported drug allergy was 21,4% from which 51,5% have doctor confirmation.
The most referred drug was penicillin (47,4%).
From 103 subjects 9,7% were submitted to tests in order to confirm the reaction. The most common
were skin and blood tests (60,0% and 20,0%, respectively).
Discussion - After analysing our results we realized that the percentage of subjects who claimed to
have adverse drug reactions was far superior (21,4%),.We believe that the differences were due to vies and the
reduced sample.
Key-words:
Drug allergy, drug hypersensitivity, self-reported drug allergy, adverse drug reactions.
Introduction
Adverse reactions to medicines is the response to a drug, noxious and unintended, for
prophylactics, of diagnosis or therapeutics effects, or for modification of the psychological
function that happens in normal dosage [1]. However, this is an inaccurate definition, so some
authors [2] defined it as "an unpleasant reaction and significantly harmful, as a result of an
intervention related with the use of medical products, which predicts hazard from future
administration and warrants prevention or specific treatment, or alteration of the dosage
regimen or withdrawal of the product". There are two types of adverse drug reactions: drugs
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
hypersensitivity and allergic reactions to drugs. When immunological mechanisms are involved,
that reaction is classified as an allergic reaction to the medicine [3].
Drugs hypersensitivity is difficult to diagnose because there are many factors that can
be associated with the emergence of the symptoms [4]. The identification of the responsible
agent for the reaction is important. That identification [5], should be based “mainly on the
observation of the clinical signs, their durability, eventually answering to anti-allergic
treatments, and, more important, in answer to appropriate tests, like DPT (Drug Provocation
Testing)”. Some epidemiologic studies approach the prevalence of adverse reactions to
medicines, including hypersensitivity, mainly in inpatients, and in pharmacological surveillance
programs. Has been recently reported [6], the goal-analysis of 33 prospective US studies
conducted from 1966 to 1996. Those investigators showed that 15.1% of hospitalized patients
suffer an opposes drug reaction (of which 6.7% plows severe), and that the incidence of drugrelated hospital admissions screech from 3.1 to 6.2%.
A recent French survey [7], conducted over 14 days in a representative sample of both
teaching and general hospitals, support these data; 3.2% patients had been admitted to hospital
because of an adverse reaction. In another study [8], nurses and pharmacists of the Boston
Collaborative Drug Surveillance Program, in USA, collected information about adverse drug
reactions from 4037 patients hospitalized during a six month period. In a a total of 247
identified reactions (incidence of 6,1%), 41,7% were severe and 1,2% lead to death.
According to a different study [9], 0.009% of deaths in USA in 1995 were due to
adverse drug reactions. According to the above author, using Medwath 1995 database, 6,3% of
adverse drug reactions leaded to death.
In 10-20% of hospitalized Patients occur adverse drug reactions [10].
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
On the basis of the data presented by several authors [6, 7, 8, 11, 12], hypersensitivity
drug reactions represent up to one-third of adverse drug reactions, which can affect 10-15%
of hospitalized patients and are, in most cases, not reported.
Some studies [10, 13, 14; 15] about the prevalence of adverse reactions to medicines,
specifically hypersensitivity, esteem that 3-7% of the population presented adverse reactions to
medicines. A Recent study [16], refer that the prevalence of adverse reactions to medicines was
self-reported at 7,8% of the inquired UP individuals. Similar results, obtained by other study
[17], verified that 7,7% of those students referred ADR. The allergic reactions to medicines
have been having an increasing clinical and economical relevance, due to the morbidity and
mortality caused by the reactions. In a marry-control study [11], 1580 patients who suffered
opposes drug reactions that occurred during hospitalization were compared with 20 197
control individuals. The patients were hospitalized goes 1.91 days longer than were the control
individuals, incurring additional costs of US$2262 per patient. Some authors [6], analyzed 33
prospective US studies from 1966 to 1996, and showed that 0.32% of hospitalized patients
died from opposes drug reactions, resulting in an estimated 106 000 deaths goes the year 1994
– the fourth causes of death in the USA.
The purpose of this study was to estimate the prevalence of adverse drug reactions in
the adult population of Porto, the most referred symptoms and medicines frequently
associated.
Participants and Methods
Study design
This is a cross-sectional survey of the general adult population of Grande Porto. We
selected a random sample of participants. A questionnaire about the occurrence of adverse
drug reactions in adults was applied through telephone interviews. Detailed information about
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
the reaction and the clinical history of the participants were used to better characterize the
different types of reactions.
Study population
The study population was every adult (18 years or above) in Grande Porto, with
telephone in their house, and, for each phone call it were interviewed the adult with the nearest
birthday.
Selection of participants
The selection of participants involves 2 phases: (1) the 1st step bases on the selection
of the numbers. Starting from 2 lists, one of prefixes and another of suffixes randomly
chosen, a prefix is combined with a suffix. If the number is not attributed or it is not a
household, we pass for the following prefix of the list; if the number is attributed and if it is a
household, we proceed for to 2nd step. (2) in the 2nd step, having identified a prefix that is a
household, we use the same prefix with the following suffixes of the list until 5 valid numbers
(with or without answering to the questionnaire) are achieved, including the first. When a
suffix is not attributed, the following of the list is used; if it is attributed, but the call is not
assisted, we try for 2 consecutive days considering it not a household (not valid) at the end of
that period; when we have 5 numbers attributed with the same prefix, and at least 1 don't
assist, the process is blocked, until assisting or being considered invalid. After the obtaining of
5 valid numbers with the same prefix, we pass for the following prefix.
At the end, we had forty prefixes, corresponding to two hundred valid numbers.
Data collection methods
We used a structured questionnaire given by the service of biostatistics and medical
informatics of medical faculty of Porto University. This questionnaire was not validated;
however, we applied it according with the suggestions given.
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FACULTY
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M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
It’s composed by questions of closed response and questions of short and objective
answers. It’s divided in six sections:
1.
The first section consist of the interviewer presentation and confirmation of the
interviewed availability to answer the questionnaire;
2.
The second section consists in a brief presentation of the aims of the work, as well
as, the identifications of the existence or not of adverse drug reactions history;
3.
The third section is only to those who reported an adverse drug reaction history. It’s
sub-divided according to the symptoms referred (cutaneous, respiratory, digestive and others),
being each one made by a brief history of the reaction (starting of the symptoms, drugs
related to the symptoms and its evolution);
4. In the fourth section we tried to obtain the medical conformation of the allergy to
the specific drug, as well as the test made to confirm that diagnosis;
5. In the fifth section it is questioned the allergic background of the subject as well as
another non-allergic pathologies;
6. In the sixth and last section of the questionnaire we made some questions about the
subject such as the age, sex and residence.
Statistical analysis
The data processing and the evaluation of the results were made in a SPSS statistical
package (version 13.0). Then, a descriptive analysis was done. Continuous variables were
described as mean and standard deviation (SD) or median and percentiles as appropriate;
categorical variables were described as absolute and relative frequencies (%). Prevalence was
calculated as the proportion of the sample having certain characteristic and 95% confidence
intervals for proportions were calculated using the approximate method of Wald. The
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
prevalence of response was compared among groups using the Pearson 2 test. A level of
significance of 5% (=5%) was used in all the hypothesis tests.
Results
General characteristics of the sample
Out of 200 phone calls, 103 individuals answered the questionnaire, so the rate of
participation was 51,5%. Among the individuals that didn’t answered the questionnaire
28,9% were females so, the difference between sexes for a significance level of 0,05 was
significant (p<0,001) and 14,4% were aged between 51 and 65 years old therefore the
differences between age ranges were also significant (p<0,001) for the same confidence
level. Participants ranging from 18 to 85 years (mean 50,6 ± 15,5 years) and the majority
were female (52,5%). The prevalence of self-reported adverse drug reactions was 26,8%.
(table 1). We can report with 95% of confidence that between the range of 18%-36%
individuals show adverse drug reations The prevalence of self-reported drug allergy was
21,4% (table 2) and18,4% have doctor confirmation (table 3). We can report with 95% of
confidence that between the range of 13%-29% individuals believe to be allergic to drugs,
and we can report with 95% of confidence that between the range of 11%-26% individuals
had doctors confirmation of allergic to drugs. The most referred medicines were penicillin
(47,4%), antibiotics (10,5%) and others non-specified (26,3%) (graphic 1). The most
common tests were skin and blood tests (60,0% and 20,0%, respectively). Rhinitis is the
most frequent allergic disease (36,4%). 34,0% of the subjects had other non-medicine
allergic reactions like dust, animals and food.
Valid
Yes
Frequency
26
Valid Percent
26,8
Table 1 – Self-report about adverse drug reactions
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FACULTY
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M EDIC INE – U NIVERSITY
OF
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Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
Believe that is allergic
Valid
Yes
Frequency
22
to drugs
Percent
21,4
Table 2 - Self-report about adverse drug reaction
With doctor confirmation
Valid
Frequency Percent
Yes
19
18,4
Table 3 - Doctor alergic drug reaction confirmation
Graphic 1 - Drugs confirmed by a doctor
Drugs with doctor's confirmation
penicilina
desconhecido
Drugs
antibiótico
Claudicat
cartia
C-gripe
0
2
4
6
8
10
Count
Subjects with self-reported adverse drugs reactions
Women were significantly more likely to have self-reported adverse drug reactions
(78,9%).
In spite of this difference the proportion of adverse drug reactions, to a 0,05
confidence level, is the same to male and female (p=0,642). We can report with 95% of
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FACULTY
OF
M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
confidence that between the range of 10%-29% female individuals show adverse drug
reations. To the male sex the range is between 10-30%.
15% of the inquired individuals are aged between 18-35 years old; 21,5% between
35-50; 22% between 51-65; above 65 years old only 12%. The proportion between the
adverse drug reactions of different age ranges is equal to a confidence level of 0,05
(p=0,927). Can be reported with 95% of confidence, to a confidence range between 1% and
33%, that people between 18-35 years old show adverse drug reactions; to a confidence
range between 6%-34% the individuals aged between 36-50 have adverse drug reactions; to
individuals with ages between 51-65 can be said, with 95% of confidence, with a
confidence range between 5%-35%, that they show adverse drug reactions; we can also tell,
with the same confidence percentage, with a confidence range between 3%-43% that
individuals with more than 65 years old had adverse drug reactions.
Recalled clinical manifestations were separated into cutaneous, respiratory and
digestive reactions. The most common manifestations were cutaneous and digestive
symptoms (48% both) (table 4).
Cutaneous reactions were more frequent in people 40-50 years old. The most
referred medicines related to this manifestation were penicillin (23,1%) and others nonspecified (30,8%). In 92,3% of these subjects it was the first time they were in contact with
the drug. 30,8% had doctor’s confirmation and 60,0% made tests. 15,4% had the same
reaction without the drug.
Digestive reactions predominate in people 30-40 years old. The most referred
medicines related to this manifestation were brufen (16,7%) and others non-specified
(25,0%). In 75,0% of these subjects it was the first time they were in contact with the drug.
69,2% had doctor’s confirmation and 40,0% made tests. 33,3% had the same reaction
without the drug.
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FACULTY
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M EDIC INE – U NIVERSITY
OF
P ORTO
Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
Respiratory reactions prevalence in 11,5% of the individuals and were more
common in people 18-35 years old. The most referred medicine related to this
manifestation was penicillin (66,7%). In 100% of these subjects it was the first they were in
contact with this drug. None of them had doctor’s confirmation, made tests or had the same
reaction without the drug.
Other diseases like diabetes mellitus and hypertension were recorded in the subjects
(8%) (table 4).
Type of reaction
Cutaneous reaction
Respiratory reaction
Digestive reaction
Other reactions
Valid
Yes
Yes
Yes
Yes
Frequency
12
3
12
2
Valid Percent
48
11,5
48
8
Table 4 - Most common symptoms referred.
Discussion
According to some authors [6, 10, 13, 14, 15] adverse drug reactions affect 3-7% of inpatients or patients that have been admitted in the hospital. Similar results have been obtained
by Portuguese authors who studied adverse drug reactions in the population of Porto [16, 17].
However, after analyzing our results we realized that the percentage of subjects who claimed
to have adverse drug reactions was far superior (26/103, 26,8%), as well as those who claimed
to be allergic to drug (22/103, 21,4%) and that had doctor's confirmation (19/103, 18,4%).
In spite of having more responses from females (52,5%) and from the age range of 5165 years old (22%) these differences do not have significant statistical value according to
Pearson 2 tests (p=0,642).
We believe that the differences were due to bias of information as the information
given by the subjects may be incomplete or even wrong. The differences between the methods
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M EDIC INE – U NIVERSITY
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Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
used by us and the others studies, as well as the different populations studied could be other
reason for the difference between results.
Once our sample is too small when compared whit the study population, we can not
extrapolate this results to the general population.
If we had the chance to repeat this study, we would certainly interview a bigger sample,
using a more specific questionnaire.
Acknowledgments
We thank to Dr Prof. Altamiro, Dr Luís Azevedo and Dr João Fonseca for their help to the
work.
References
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Department of Biostatistics and Medical Informatics
Introdução à Medicina 2005/2006
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