An adverse drug
reaction is any unintended response to a drug, which includes prescription,
non–prescription, biological, and herbal drug products. Drug abuse, drug
interactions, and overdoses are also monitored using the reporting system. A
possible link between a drug and an adverse reaction is sufficient to file a
The concept of ADR
reporting system is still in its infancy in Pakistan. This study is aimed at
investigating ADR reporting system and to suggest possible ways of improving the
method of reporting. By using questionnaire, the knowledge and attitude of
doctors & pharmacists have been evaluated in different public and private
hospitals of Lahore. The questionnaire sought the demographics of doctors &
pharmacies, their knowledge and attitude to ADR reporting. Provision is also
made for suggestions on the possible ways to improve ADR reporting. Doctors
& pharmacies have not reported ADRs either due to lack of education and
training on ADR reporting & because of lack of tradition. But now they
should be encouraged to a large role in reporting ADRs.
The public health
importance of adverse drug reactions in the hospitals cannot be ignored. It has
long been a principle of practice of medicines, “Premium non-nicer” first of
all be sure you do know harm. In 1955 addressing the American Medical
Association, it was argued that one of the great hazards in the use of potent
drugs is their inherent toxicity e.g. digitalis because its actual ingredients
continue to be implicated in many adverse drug reactions. Most people get far
more benefits from medicine than harm. Some patients experience undesirable
effects by using medicines. These effects are so severe to required hospital
treatment and a few will die e.g. (NSAIDS) cause 12,000 admissions per year due
to GI bleeding and causing about 2000 deaths. They kill (one) 1 in 1200 people
who use them for 2 months or more. From 39 various American Studies, the rate
of serious ADR was calculated as 6.7% and the rate of fatal ADR was 0.3%,
making ADR a serious health issue (1).
ADR reporting is the
cornerstone of drug safety after the release of a drug into the market. It has
been shown over the years that ADR reporting has provided early warning in drug
In Pakistan there are
no proper diagnostic ways to identify ADRs, so chances of ADRs incidences are
greater in hospital out-patient departments. The studies of ADRs system are
very rare. Irrational prescribing is common. Internationally a lot of work has
been done in this sector. In Pakistan actually the environmental and so many
other problems are different therefore the results are different.
It is a formal or
informal process whereby verbal or written accounts of health care related
adverse events are shared with others either internally within an organization
or externally with other interested parties. The purpose of a reporting system
is often to provide a medium for sharing lessons learned and opportunities for
improvement, and to prevent recurrence of similar incidents in future. It is a
reporting system whereby accounts of health care related adverse events are
compelled by law, policy, or by any other formal means. A reporting system
whereby verbal or written accounts of health care related adverse events are
shared without the inclusion of any identifiable details of the patient or care
providers involved. The information contained in anonymous reporting systems is
often less complete than information contained in confidential reporting
Prospective observational study was conducted
to investigate the current ADR Reporting System at Different hospitals of
Lahore and compare it with the ADR system in the developed countries.
Information relevant to the study was accessed by circulating Questionnaire to
the respondents after obtaining ethical clearance from the Hospital. Survey
method involving Doctors, Pharmacists of different hospitals of Lahore was
Inclusion Criteria: All
specialized and tertiary care hospitals in public and private sectors in Lahore
were included in the study.
Exclusion Criteria:The Hospitals
where the health care professionals (Doctors, Pharmacists) were not willing to
participate in the study and the ones who were on leave were excluded from the
study.The hospitals where the Administration was reluctant to provide
information about the ADR System were also excluded from the study.
Sample Size: A total of 84
Doctors and 52 Pharmacists from 30 different hospitals in Lahore participated
in the study.
Sampling technique:A Random
Sampling technique was applied to collect the sample.
Sampling Procedure:The relevant
data or the related information was collected from all the health care
professionals through one-to-one interview.
Study Tool:The initial draft of
the Questionnaires was made by utilizing different ADR systems of developed
countries, Literature evaluation, published research articles. In addition,
this draft circulated to different health care professionals of different
hospitals of Lahore and then finalized after necessary changes keeping in view
the objectives of the study. Different questionnaires were designed to collect
the required information. One of the questionnaires was developed to gather the
general hospital information including ADR systems. Other two questionnaires
were specific for Doctors and Pharmacists.
Pre Testing: Pre Testing is
critical for identifying problems for both respondents and interviewers. No
matter how experienced you are in developing questionnaire or how “routine” the
survey might he considered, it is always important to pre-test your instrument
before it is printed and fielded. Give the questionnaire to a small group of
health care professionals, who preferably know little or nothing about the
research itself. Ask them to read the questionnaire to see if they, too, can
clearly understand what is required and whether the flow makes sense to them. After
Pre-Testing, some changes were made on the basis of responses. There was some
question that didn’t work. I have excluded these questions and modified some
questions in such a manner that might work next time. Order of some questions
was also changed to make it logical and systematic.
Field Experience & Data Collection:After
pre-testing, the next step was data collection. The data collection lasted for
four months. Considering the behavior of the health care professionals and
response from the Hospital Administration, some hospitals were excluded from
the study. Initially, difficulties were faced in collecting the data, but it
was assured that the study is meant for academic purpose only and all information
will be kept confidential. However, the staff of some hospitals was very
Analysis was conducted by using the statistical package – SPSS (statistical
package for social sciences), Version 11.5.This analysis was carried out in two
Arithmetic Mean (Average) was
calculated for quantitative variables, while for qualitative variables,
frequencies and percentages were measured. Histogram was obtained for
quantitative variables, while Pie chart and Bar chart were used to express the
graphical picture of qualitative variables.
Pearson’s Chi-Square test was used to
measure the associations between different Variables in this study. For 2x2
Contingency table, where observed frequency less than 5, Fisher’s Exact test
was used to measure the associations between different variables.
RESULTS AND DISCUSSION
Twenty-two (73.3%) hospitals were acute care / general, while
twenty (66.7%) hospitals were teaching. Fifteen (50.0%) hospitals have more
than or equal to 500 beds and in four (13.3%) hospitals, there were less than
100 beds. eleven (36.7%) hospitals have between 1000-15000 no of admissions and
six (20.0%) hospitals show 45000 – 60000 admissions. In fifteen (50.0%)
hospitals there are 0-150 doctors and eleven (36.7%) hospitals have between
150-300 doctors and one (3.3%) hospital has 750-900 doctors.
Only seven (23.3%) hospitals have ADR reporting policy while in
ten (33.3%) hospitals the pharmacy department has an ADR reporting policy. In
few hospitals, certain reasons have been described for the absence of an ADR
reporting policy e.g; no clinical set-up in the hospital, lack of interest and
absence of separate pharmacy department in the hospital. Majority of hospitals
have no ADR reporting policy. In five
(16.7%) hospitals, all drugs are targeted for ADR reporting. While in one
(3.3%) hospitals, only few drugs and MOH listed drugs are targeted for ADR
Out of 33 doctors, six (18.2%) doctors and out of 35 pharmacists,
three (8.6%) pharmacists suggest that “doctors” should do documentation of ADR.
Similarly seven (21.2%) doctors and ten (28.6%) pharmacists suggest
“pharmacists” to do documentation of ADR.
One (3.3%) hospital respond to drug assays, microbiology and
biochemistry tests for screening of suspected ADRs. No hospital shows response
regarding use of triggers to identify possible ADRs. Five (16.7%) hospitals
respond to “doctors”, while three (10.0%) hospitals respond to “pharmacists”
and two (6.7%) hospitals consider both “doctors & pharmacists” as the
concerned personnel involved in ADR reporting.
In ten (33.3%) hospitals, pharmacy department is involved in ADR
reporting. One (3.3%) hospital responds to formulary alteration, information
bulletins and regular reporting to MOH to prevent ADRs. One (3.3%) hospital
shows that patient is informed through e-mail or verbally. Four (13.3%)
hospitals respond to add information on the discharge slip. Eleven (36.7%) hospitals respond to “No”,
regarding any reward / fee for reporting ADRs in hospitals.
Patient reporting ADR
can be a good solution and can help to improve the ADR reporting program. Six
countries provided information on patient reporting system while summary data
was obtained from four countries. Possible new ADRs were identified by patient
report that had not previously been reported, by health professionals. The
quality of patients reports appeared to be similar to that of health
professional reports. Some evidences showed that patients reported an ADR when
they came to know that their health professional had not listened to their
concerns properly. In the beginning, patient reports might be time consuming to
be processed. All evidences indicated that patients reporting of suspected ADRs
had potential benefits than drawbacks(2).
Thirty three (39.3%) doctors and 35 (67.3%) pharmacists gave
response in this study. Thirty three (39.3%) of doctors and thirty four (65.4%)
of pharmacists know how to report ADRs within the hospital. While nine (10.7%)
of doctors and thirteen (25%) of pharmacists know about ADR reporting to
MOH. In this project, 136 health care
professional participated. Among 84 doctors, sixty two (73.8%) were males and
twenty two (26.2%) were females. Similarly among 52 pharmacists, twenty two
(42.3%) were males and thirty (57.7%) were females. Thirty Nine (46.7%) doctors
have registration period from 7-10 years followed by sixty four (76.2%) doctors
with the registration duration under 7 years. Similarly thirty five (67.3%)
pharmacists have registration duration under 7 years followed by ten (19.2%)
pharmacists between 7-10 years. The working experience of seventy four (88.1%)
doctors is below 7 years and five (6.0%) have between 7-10 years. In the same
way, forty eight (92.3%) pharmacists have working experience under 7 years and
three (5.8%) above 10 years and one (1.9%) between 7-10 years.
Thirty three (39.9%) doctors have knowledge about ADR reporting
within the hospital while nine (10.7%) know how to report ADR to MOH. Similarly
thirty four (65.4%) pharmacists have awareness about ADR reporting within the
hospital and thirteen (25.0%) know report ADRs to MOH. The average awareness
about ADRs is 50.9% and 49.1% for doctors and pharmacists respectively.
involvement of pharmacists in ADR reporting pharmacists actual contributions
were evaluated by using an international questionnaire based survey among
countries participating in the WHO drug monitoring program in September 2002
(3). The respondents showed their assessment for quality and significance of
contributions out of 68 participating countries, 41 responded by returning the
questionnaire. In the countries having more experience and with greater number
of pharmacists ADR reports, the appreciation is high whereas the countries that
received fewer reports from pharmacists gave lower scores to their
contribution. The improvement in the international adverse drug reaction
reporting system was possible by the specific contribution of pharmacists.
The factors that discourage respondents from reporting ADR are
uncertain association (60.6%), awareness (57.6%), report forms not readily
available (57.6%), Concern about legal liability (51.4%). From hypothetical ADR questions, the
respondents liked to report thrombocytopenia with heparin (48.5%), duodenal
ulcer with Diclofenac (45.4%), Neutropenia with ACE-Inhibitors (42.9%). The
average awareness in doctors is 32.5% and in pharmacists 30.4%.
Doctors were Shows un-awareness about ADR of “Headache with
venlafaxine” (87.9%) and information about weight loss with venlafaxine
(81.8%). Similarly pharmacists show more unawareness regarding the following factors
i.e.; Constipation with Montelukast (82.9%), headache with venlafaxine (91.4%).
The average unawareness in doctors is (67.5%) which is less than pharmacists
In Pakistan, people consume drugs at a large scale. In the market,
counterfeit and substandard drugs are available. These drugs belonged to
alternative systems of medicine like Unani, Homeopathy and the drugs which have
been banned in developed countries. These factors indicate that a comprehensive
ADR reporting system should be established in Pakistan. One of the examples of three German departments of clinical pharmacology
Jena, Dresden, Rostock, served as pharmacovigilancecenters in collaboration
with pharmaco-epidemiology Research Group of the University of Munich improved
the spontaneous substantial reporting system (4). It
is possible to remove harmful drugs from the market by using a proper ADR
In Pakistan, the concept of ADR reporting system is in the very
early stages as compared to rest of the world. We are facing the problem of
poor post marketing surveillance. Therefore, Ministry of Health (MOH) should
initiate the National Pharmacovigilance Program and under this program various
peripheral, regional and zonal pharmacovigilancecentres should be established.
Pharmacovigilance is the pharmacological science relating to the detection,
assessment, understanding and prevention of adverse effects of medicines. It is
an important and integral part of clinical research. Developed countries have
done major advancement in this field. In Pakistan not much has been achieved,
so there is an immense need to understand and implement pharmacovigilance.
Pakistan should join World Health Organization (WHO) adverse drug
reaction monitoring program based in Uppsala, Sweden (5). This program is meant
to detect, evaluate, to study ADR and to inform prescribing physicians. There
must be a central drugs standard control body that would launch NPP under the
influence of Directorate General of Health Services, Ministry of Health. The
basic purpose of this program is to analyze and achieve ADR data for making
regulatory decisions regarding drugs marketed in Pakistan. The physicians,
pharmacists and nurses can complete prescribed ADR form and report to the
nearest Peripheral Pharmacovigilance Centre. Then the report may be forward to
the regional center. It can make analysis and then submit to zonal center where
the data will be statistically analyzed and send to the global Pharmacovigilance
database managed by WHO Uppsala Monitoring Centre in Sweden. The National
Pharmacovigilance Advisory Committee (Constituted by MOH) will review the final
report based on analyzed data.
Majority of People in Pakistan visit Government hospitals to get
health care facilities which can be helpful to generate good ADR data.
Initially a culture of ADR reporting has to be created among clinicians,
pharmacists and junior doctors. Further Government has to make it mandatory for
health care providers to report ADRs. Lack of awareness, education and training
and time are potent reasons for showing no interest in reporting ADRs. So
education and training programs will have to carry out for health care
professionals to produce the habit of ADR reporting. There should be strong
collaboration between clinical departments and department of pharmacology. For
postgraduate students, ADR monitoring programs should be taught during
training. Even the undergraduate students and interns should be given lectures
on ADR reporting. Pharmacovigilance programs can be provided to all nurses and
other allied health staff. All Government hospitals as well as medical colleges
should adopt this strategy to generate a real ADR database for the people of
Pakistan. Even a computer based on-line reporting system could be launched as
utilized by many developed countries.
Jason Lazarou, MSc; Bruce H. et al, Incidence of
adverse drug reactions in hospitalized patents Vol. 279 No. 15, April 15, 1998.
The Journal of the American Medical Association.
A Blenkinsopp, P Wikie, M Wang, and P ARoutledge, et
al, Patient reporting of suspected adverse drug reactions: a review of
published literature and international experience. Br J ClinPharmacol. 2007
Kees van Grootheest, MD, Sten Olsson, MSc, Pharm, Mary
Couper, MD, Lolkje de jong van den Berg, PhD, PharmD, et al, Pharmacist, role
in reporting adverse drug reactions in an international perspective.
Pharmacoepidemiology and Drug Safety Volume 13 issue 7, pages 457 – 464
Published Online: 15 Sep 2003.
Hippious M, Humaid B, Sicker T, Hoffmann A, Gottler M,
Hasford J, et al, Adverse drug reaction monitoring – digitoxin over dosage in
the elderly. In J ClinPharmacolTher 2001; 39: 336-43.
Wester K, Jonsson A, Spigset O, Hagg S, et al,
Spontaneously reported fatal suspected adverse drug reactions: a 10-year survey
from Sweden. Pharmacopidemiol Drug Saf. 2007 Feb; 16(2): 173-80.