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Adverse Drug Reaction-Causality Assessment: International Journal of Research in Pharmacy and Chemistry
Adverse Drug Reaction-Causality Assessment: International Journal of Research in Pharmacy and Chemistry
ISSN: 22312781
INTRODUCTION
Adverse drug reactions (ADRs) are considered when drug is stopped or dose is reduced,
as one among the leading causes of morbidity others are more serious and last longer.
and mortality1. .The epidemiological Therefore there is a little doubt that ADRs
importance of ADR is justified by its high increase not only morbidity and mortality but
prevalence rate – they cause from 3% to 6% of also add to the overall health care cost 6, 7.
hospital admissions at any age, and up to 24%
in the elderly population; they rank fifth Adverse drug reaction (ADR)
among all causes of death and, moreover, they Definitions of ADRs exist, including those of
represent from 5 to 10% of hospital costs2. and the World Health Organization (WHO)8.
is a great cause of concern to the medical Karch and Lasagna9 and the Food and Drug
profession. Every occasion when a patient is Administration (FDA)10.
exposed to a medical product, is a unique
situation and we can never be certain about WHO
what might happen. A good example for this Any response to a drug which is noxious and
is thalidomide tragedy in late 1950s and unintended, and which occurs at doses
1960s.Thalidomide prescribed as a safe normally used in man for prophylaxis,
hypnotic to many thousands of pregnant diagnosis, or therapy of disease, or for the
women caused severe form of limb modification of physiological function.
abnormality known as phocomelia in many of
the babies born to those women. It was a Karch and Lasagna
seminal event that led to the development of Any response to a drug that is noxious and
modern drug regulations aimed to identify, unintended, and that occurs at doses used in
confirm and quantify ADRs. An adverse drug humans for prophylaxis, diagnosis, or therapy,
reaction (ADR) is any undesirable effect of a excluding failure to accomplish the intended
drug beyond anticipated therapeutic effects purpose.
occurring during clinical use14. Hence every
health care professional who give advice to FDA
patients need to know the frequency and For reporting purposes, FDA categorizes a
magnitude of the risks involved in medical serious adverse event (events relating to drugs or
treatment along with its beneficial effects. devices) as one in which “the patient outcome
Recent epidemiological studies estimated that is death, life-threatening (real risk of dying),
ADRs are fourth to sixth leading cause of hospitalization (initial or prolonged), disability
death3. It has been estimated that (significant, persistent, or permanent),
approximately 2.9-5% of all hospital admission congenital anomaly, or required intervention
are caused by ADRs and as many as 35% of to prevent permanent impairment or damage.
hospitalised patients experience an ADR
during their hospital stay4. An incidence of Classification of Adverse Drug Reactions
fatal ADRs is 0.23%-0.4%. 5 Although many of ADRs can be divided schematically into two
the ADRs are relatively mild and disappear major categories:
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II. Causality Assessment Between Drug and III. Documentation of ADRs in Patient’s
Suspected reaction23 Medical Records
Causality assessment is the method by which This aids as reference for alerting clinicians
the extent of relationship between a drug and and other health care professionals to the
a suspected reaction is established. possibility of a particular drug causing
It is often difficult to decide if an adverse suspected reaction.
clinical event is an ADR or due to
deterioration in the primary condition. IV. Reporting Serious ADRs to
Furthermore, if it is an ADR, which medicine Pharmacovigilance Centres / ADR
caused it, as many patients are on multiple Regulating Authorities
new medications when ill, particularly if According to FDA, a serious reaction is
admitted to hospital. In spite of these classified as one which is fatal, life threatening,
problems, the decision that a particular drug prolonging hospitalisation, and causing a
caused an ADR is usually based on clinical significant persistent disability, resulting in a
judgment alone. Studies have shown that there congenital anomaly and requiring intervention
is a lot of variation in between rater and to prevent permanent damage or resulting in
within rater decisions on causality of ADRs; death 35 Hatwig SC, Seigel J and Schneider PJ
this applies both to pharmacologists and categorised ADRs into seven levels as per their
physicians25,26 . severity. Level 1&2 fall under mild category
There are various approaches in the first whereas level 3& 4 under moderate and level
approach an individual who is an expert in 5, 6&7 fall under severe category .36(fig:2). Karch
the area of ADRs would evaluate the case. In and Lasanga classify severity into minor,
the process of evaluation, he or she may moderate, severe and lethal. In minor severity,
consider and critically evaluate all the data there is no need of antidote, therapy or
obtained to assess whether the drug has prolongation of hospitalisation. To classify as
caused the particular reaction. A panel of moderate severity, a change in drug therapy,
experts adopts a similar procedure to arrive at specific treatment or an increase in
a collective opinion. using algorithms hospitalization by at least one day is required.
including standardization of methods. Severe class includes all potentially life
Algorithms being structured systems threatening reactions causing permanent
specifically designed for the identification of damage or requiring intensive medical care.
an ADR, should theoretically make a more Lethal reactions are the one which directly or
objective decision on causality. As such indirectly contributes to death of the patient.
algorithms should have a better between and Different ADR regulatory authorities are -
within rater agreement than clinical judgment. Committee on safety of medicine (CSM),
A number of algorithms or decision aids have Adverse drug reaction advisory committee
been published including the Jones’ (ADRAC),37 MEDWATCH, Vaccine Adverse
algorithm, 28 the Naranjo algorithm,27 the Event Reporting System38 WHO-UMC
Yalealgorithm,29 the Karch algorithm,30 the international database maintains all the data of
Begaud algorithm,31 the ADRAC,32 the WHO- ADRs.
UMC,33 and a newer quantitative approach
Algorithm.34 Each of these algorithms has CONCLUSION
similarities and differences. And the most India has more than half a million qualified
commonly used algorithms; the Naranjo doctors and 15,000 hospitals having bed
algorithm (Fig :1) is shown below strength of 6, 24,000. It is the fourth largest
The Naranjo Algorithm is a questionnaire producer of pharmaceuticals in the world. It is
designed by Naranjo et al for determining the emerging as important clinical trial hub in the
likelihood of whether an ADR (adverse drug world. Many new drugs are being introduced
reaction) is actually due to the drug rather every year and so every health care
than the result of other factors. Probability is professional must have knowledge about
assigned via a score termed definite, probable, importance of ADR monitoring and
possible or doubtful. Values obtained from the pharmacovigilance. Every health care
algorithm are sometimes used in peer reviews professional should see it as a part of his/her
to verify the validity of author’s conclusions professional duty keeping in mind about
regarding adverse drug reactions. It is also Hippocrates admonition” at least does no
called the Naranjo Scale or Naranjo Score. harm”.
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2) Did the adverse event appear after the suspected drug was Given?
3) Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given?
4) Did the adverse reaction appear when the drug was Re-administered?
5) Are there alternative causes that could have caused the reaction?
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8) Was the reaction more severe when the dose was increased or less severe when the dose was decreased?
9) Did the patient have a similar reaction to the same or similar drugs in any previous exposure?
SCORING
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