Health Administrator Vol : XIX Number 1: 20-21
CHAPTER - 6
ADVERSE DRUG REACTION MONITORING
*C.H. Shashindran and ** B. Gitanjali
An adverse drug reaction has been defined
as one which is noxious and unintended and which
occurs at doses normally used in man for the
prophylaxis, diagnosis or therapy of disease, or for
the modification of physiological function.
The discovery of the adverse drug reaction
(ADR) profile of a new drug prior to marketing lies
entirely within the sphere of the pharmaceutical
company and therefore, they have the responsibility
for providing adequate information on a new drug.
After a drug is marketed, the responsibility for
extending the knowledge of the adverse reactions
of a new drug spreads to all the prescribers of that
drug, as well as to specific organizations set up for
that purpose.
Before deciding to prescribe a drug to a
patient, a doctor must balance the expected
benefits of the drug against its potential risks. In
other words he must assess the cost/benefit ratio
in that particular situation – where benefits will be
measured in terms of the efficacy of the drug and
the cost in terms of the side effect liability that use
of the drug entails.
Information on adverse reactions is always
incomplete when a drug is first introduced into
clinical practice. Premarketing exposure to the
investigational drug is limited usually to 1000 to
3000 subjects. Therefore the probability of
identifying adverse reactions with a frequency of
less than 1:1000 is remote. The full range of
adverse reactions may not be known until a drug
has been used in hundreds of thousands of people
or in some cases after exposure for prolonged
periods or only long after exposure to the drug.
Proving that a specific drug is responsible for
an adverse event in a patient may be extremely
* Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research
Pondicherry - 605 006
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difficult because of multiple drug exposures and
underlying illnesses. The physician should report
a suspected new, serious, adverse drug reaction
even if considerable uncertainity exists.
There are several algorithms for establishing
casual relationship between drug administration
and an event. All these include the following
criteria:
(1) A temporal relationship between the
suspected drug and the adverse event.
(2) Improvement after removal of the drug i.e.,
positive dechallenge.
(3) Recurrence of the adverse event when
administration of the drug is resumed, i.e.,
positive rechallenge
(4) The lack of confounding effect i.e., the event
is unlikely to be due to concomitant disease.
Based on these an adverse event can be classified
as :
HIGHLY PROBABLE: The event follows a
reasonable temporal sequence from administration
of the drug and is confirmed by positive
dechallenge and positive rechallenge.
PROBABLE: The event follows a reasonable
temporal sequence from administration of the drug:
is confirmed by dechallenge and is not reasonably
explained by the known characterization of patient’s
clinical state.
POSSIBLE: The event follows a reasonable
temporal sequence from administration of the drug
and follows a known response pattern to the
suspected drug but could have been produced by
the patient’s clinical state or other modes of therapy
administered to the patient.
REMOTE: Any event that does not meet the above
criteria especially if the event has no temporal
association with use of the drug.
Ideally an adverse reaction of a drug should
have a profile consisting of the following elements.
(a) Manifestation
(b) Severity and seriousness
(c) Mechanism of action
(d) Frequency of occurrence
(e) Casuality
(f) Predisposing factors
(g) Therapy if any
(h) Reversibility or sequelae
The main sources of ADR data are:
(a) Spontaneous reporting by doctors,
pharmacists nurses etc;
(b) ADR monitoring schemes in hospitals
(c) Clinical trials (all phases including post-
marketing surveillance)
(d) Vital statistics (mortality, morbidity registers,
birth registers for congenital defects)
(e) Special studies (case control studies, cohort
studies)
However it should be stressed that there is no
single effective, fool-proof method for the collection
of ADR data. Clinical experience has demonstrated
that alert clinicians reporting their observations
without hesitation have been repeatedly proven
correct, and have prevented many disasters.
Though excellent reference books on ADRs
are available, the time lag between the reaction
being reported in journals and its inclusion in books
is unrealistic. This problem is partly overcome by
abstracting publications such as ‘Clin-Alert’,
‘Reactions’ which are available fortnightly and deal
exclusively with ADRs. Computerization of ADR
data and the availability of many on-line data bases
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allow retrieval of information literally at one’s
fingertips. The advantages and disadvantages of
the various data bases differ and are beyond the
scope of this paper, but it is obvious that
administrators intending to invest in such a
package should carefully consider factors such as
(a) The requirements and the applications of the
system
(b) The degree of user friendliness
(c) The robustness of the package
(d) Its cost
(e) Performance on existing hardware
Rising costs of patient care, increasing
awareness of patients towards the untoward effects
of drugs and the rise in the frequency of cases of
litigation against doctors and hospitals have made
clinicians, hospital administrators and health care
planners aware of the necessity of closely
monitoring adverse drug reactions. The Govt. of
India in due recongnition of this fact has established
six ADR monitoring centres to collect and classify
ADR data in the Indian population. Though ADR
monitoring has not received the importance
relegated to it in the west, Indian physicians are
becoming increasingly aware of the necessity of
observing the profile of adverse events of a drug
in our population. This may be just the beginning,
but with time and experience ADR monitoring will
become a part and parcel of the comprehensive
health care provided to patients.
References:
1. The detection of new adverse drug reactions,
Stephens MDB, (eds), M Stockton Press, New
York, 1985.
2. Adverse drug reactions – A global perspective
on signal generation and analysis.
Proceedings WHO Anniversary Symposium,
Uppsala, Sweden, 1988.
3. Clinical Pharmacology, Laurence Dr, Bennett
PN (eds), 6t h Edition, ELBS, Longman
Singapore Publishers, 1987.