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Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
JOHN PRESHANTH KUMAR.P
S/O PATHI RAJ. M
39/2 kaveri nagar, beml nagar post.
Kolar gold feilds..563115
01
Name of candidate and address
(in block letters)
02
Name of institution
03
Course of study and subject
M. Pharm
Pharmacy Practice
04
Date of admission to course
6/06/2007
05
Title of the Topic:
Al-Ameen College of Pharmacy,
Hosur Road, Bangalore- 560027
“ To monitor adverse drug reactions under National Pharmacolovigilance
programme, Ministry of Family welfare, Govt of India at select hospitals in
Bangalore.”
06
BRIEF RESUME OF THE INTENDED WORK
6.1
Need for the study:
Indian scenario:
Monitoring of adverse drug reactions started in India about two decades ago
(1982). Under the chairmanship of the Drug Controller of India, five centres were
established with the idea of starting a monitoring programme nationwide. It
consisted of three phases: the first one being monitoring of reactions in the
institutes, second one in governmental bodies like CGHS, and the third phase
proposed to include general practitioners.
A multi-institutional pilot study involving 58,194 cases was done in 1987 under
the aegis of Indian Council of Medical Research. Its nodal centre (National
Pharmacovigilance Centre) is located in the Department of Pharmacology, All
India Institute of Medical Sciences, New Delhi. It is affiliated to WHO
collaborating Centre for ADR Monitoring, Uppsala, Sweden. The others are
located in PGI (Chandigarh), JIPMER (Pondicherry), KGMC (Lucknow), and
Seth GS Medical College (Mumbai) – special centre. It was envisaged to be a
collaborative activity of both clinicians and pharmacologists; now in India, the
pharmacologists with or without the involvement of clinicians usually do it.
Physicians, however, continue to play a meaningful role in the entire monitoring
process, as the co-operation of the clinicians is needed to have an access to the
patient data and at times in interpretation of the reports of suspected adverse drug
reactions. In many other countries, the pharmacists or nurses usually carry it out
under supervision 2.3.
They are specially recruited for this purpose; physicians and pharmacologists are
involved in the interpretation of the collected data or hypothesis testing on the
basis of the reports. These workers may involve a panel of the physicians in
reviewing all the collected reports. Though the pattern of adverse reactions differs
slightly from country to country, adverse reactions to analgesics (mainly, nonsteroidal anti-inflammatory drugs) and antibiotics constitute about half of all such
reports in India 1. This may be partly due to the fact that these are the most
commonly used drugs in therapeutics.
ADR monitoring features outside India.
A number of studies conducted throughout the world have demonstrated that
ADR’s significantly decrease the quality of life,increase hospitalization, prolong
hospital stay and increase mortality. A landmark study by Lazarou in 1998
described ADRs to be 4th- 6th largest cause of death in the USA & ADRs are
estimated to cause 3-7% of all hospital admissions14 . More than half of the
ADR’s are not recognized by the physicians on admission & ADRs may be
responsible for death of 15 of 1000 patient’s admitted15.
Also the financial cost of ADRs to the healthcare system is also huge. With more
new new medicines being approved for marketing more quickly with long-term
safety studies by the regulatory authorities & switching of prescription only
medicines(POM) to over-the-counter(OTC) to be used more widely by patients
for self-medication, the general public is at risk of exposing itself to ADRs.
ADRs reported by health professional occur on a voluntary basis. The Joint
Commission on Accreditation of Healthcare Organizations (JCAHO) requires
hospitals to have written procedures for ADR reporting, evaluating, and
monitoring. Typically, the hospital’s pharmacy and therapeutics (P and T)
committee reviews monthly summaries of ADRs . The reporting of ADRs
occurring in other settings is still unclear. This is the case with ambulatory or
community settings. However, the impetus is to devise means in which to
capture ADRs in non-traditional arenas.
ADR definitions:
 WHO's Definition for ADR: “a response to a medicine 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”.
 What is important in this definition is that a patient experiences an
unwanted and/or harmful (noxious) reaction following drug therapy.
Individual factors may play an important role but the key point is that the
phenomenon experienced is noxious. An ADR is essentially a “bad”
reaction suffered by the patient and differs from “side effect” which is
essentially an unexpected therapeutic response – which is related to the
pharmacological properties of the drug and may be “good” or “bad”.
 FDA defines an adverse drug reaction as "an appreciably harmful or
unpleasant reaction, resulting from an intervention related to the use
of a medicinal product, which predicts hazard from future
administration and warrants prevention or specific treatment, or
alteration of the dosage regimen, or withdrawal of the product." Such
reactions are currently reported by use of WHO's Adverse Reaction
Terminology, which will eventually become a subset of the International
Classification of Diseases.
Classifications of ADRs:
Type of reaction
Mnemonics
Features
A: dose related
Augmented
Related to pharmacology (toxic effect or
side effect--for example, digoxin toxicity)
B:
non-dose
Bizarre
related
Unrelated to pharmacology (idiosyncratic
for example, malignant hyperthermia, or
immunological--for example, penicillin
rash)
Related to cumulative drug use--for or
C: dose and time
Continuous or chronic chronic example, NSAID induced renal
related
failure
D: delayed effect Delayed
Apparent only some time after use of drug-for example, thalidomide in first trimester
and phocomelia limb defects
Delayed
Apparent only some time after use of drug-for example, thalidomide in first trimester
and phocomelia limb defects
E: Withdrawal
Results
treatment
F: Failure
therapy
of
Failure
from
(previously excluded
according
to WHO definition)
the
ineffective
from
e.g: accelerated hypertension
of inefficient control
analysis
because
Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and
management. Lancet 2000; 356:1255-9.
Based on severity
Severity
Description
Mild
No antidote or treatment is required; hospitalization
is not prolonged
Moderate
A change in treatment (e.g., modified dosage,
addition of a drug), but not necessarily
discontinuation of the drug, is required;
hospitalization may be prolonged, or specific
treatment may be required
Severe
An ADR is potentially life threatening and requires
discontinuation of the drug and specific treatment of
the ADR
Lethal
An ADR directly or indirectly contributes to a
patient's death
Common Terminology for Adverse Events (CTCAE)
National Cancer Institute,
Grading adverse events
By this grading scale, all adverse events are classified as follows:
0=No adverse event or within normal limits 1=Mild adverse event 2=Moderate
adverse event
3=Severe and undesirable adverse event 4=Life-threatening or disabling adverse
event
5=Death related to adverse event
Monitoring of adverse drug reactions is an ongoing, ceaseless, and continuing
process. Though pharmacovigilance is still in its infancy in India, this is likely to
expand in the times to come. This is because, as the newer and newer drugs hit
the market, the need for pharmacovigilance grows more than ever before.
Therefore, monitoring of the adverse effects of newer drugs particularly of
serious nature is mandatory. Physicians should report death due to drugs,
lifethreatening complications, hospitalisation (initial orprolonged), disability if
significant, persistent, or permanent, congenital anomalies, a reaction which
requires medical intervention to prevent damage, such as the administration of Nacetylcysteine following acetaminophen overdose. It is important to remember
that most adverse drug reactions would subside once the offending agent is
discontinued or dosage reduced; however, many result in permanent damage. The
need is to spread awareness about using minimal doses of the drugs, at least in the
beginning of the treatment.
Who can report? How to report? Whom to report to?
These are among the most frequently asked questions by a novice in
pharmacovigilance. Health professionals working in the field of delivering the
health care (both conventional and unconventional) like physicians,dentists,
nurses, pharmacists, can report suspected adverse drug reactions by letter, phone,
fax, e-mail, or by personal contact to any of the five adverse drug reaction
monitoring centres located across the country.
In India, the clinicians working in the tertiary care hospitals usually do the
spontaneous monitoring. A recent study from a large tertiary care hospital from
north India showed that in most instances, such reports are sent by the nonfaculty
postgraduate students (junior doctors)1.There are many problems associated with
this kind of monitoring. The most important among them being under-reporting
or biased reporting. For that matter, all the suspected ADRs should be reported
and lack of the evidence of proof or certainty of causality should not be the
reason for not reporting. This is because the reports sent by the clinicians are
evaluated in a wider perspective, i.e., with the causality assessment criteria and
the detailed assessment is done, with the help of all the available
pharmacoepidemiological tools14,15.
What can be done to decrease ADRs?
The simplest way to prevent most adverse drug reactions is to use the minimum
dosages of drugs17. The simple principle of ‘start low and go slow’ should be
followed. Dosages should be individualised to the patients and drugs should be
tailored to patient’s need and not the vice versa. Health professionals should
periodically be educated about adverse reactions and should be encouraged to
report the same. Students should be taught principles of drug safety and rational
drug use in their undergraduate and postgraduate curriculum. History of drug
allergy should be elicited, and renal and hepatic status of the patient should be
known before drug use. This is because failure to adjust drug dosages results in
adverse drug reactions in cases with renal/hepatic impairment18.
6.2
REVIEW OF LITERATURE
A retrospective study was carried out to evaluate the frequency, severity and
preventability of Adverse drug reactions (ADRs) in pediatric patients during a
six-year period. Data on patient demographic, documented allergies, suspected
drugs, American Health Formulary Service drug classification and dosage
regimen were collected and categorized by severity, preventability and casuality.
The study showed that ADRs resulted in treatment intervention or temporary
patient discomfort in >50% of patients. Opoids, Anticonvulsants and Antibiotics
were the most common drug classes associated with ADRs and thus strategies
targeting these drug classes and intervention during the medication ordering and
administration processes may reduce the number of ADRs and possibly the
associated costs.1
The impact of ADRs on health care costs were studied and showed that these
costs are essentially hospital costs, in particular arising from an increase in length
of stay caused by an ADR.It is therefore necessary to implement preventive
programmes with different strategies consisting of educational programmes,
identifying risks groups, implementing good drug practice and clinical and
laboratory monitoring for ADRs.Promoting pharmacoeconomic studies and cooperation between clinicians, medical pharmacologists and pharmacists remains
the key factor for preventing ADRs and decreasing their costs.2
A pilot study was carried out to assess the feasibility of, establish the
methodology for, conducting a large prospective study to assess the impact of
Adverse drug reactions on In-Patients and the National Health Service (NHS).
Results showed that almost one-fifth of patients suffered an ADR as an impact
and almost two-third of reactions were potentially avoidable and interventions
were required in all ADRs, and reactions indirectly contributed to the death of
two patients. Methodology tested using this pilot will enable the design of a
larger study, which will allow the ADR burden and vulnerability patient groups,
to be more accurately characterized.3
A Postal Questionnaire Survey of ADR reporting by hospital pharmacists to the
Committee on Safety of Medicines was studied, objectives included how ADR
reporting by hospital pharmacists is managed, the education of pharmacy
personnel on ADR reporting, the number of ADR reports send to the Committee
and also the barriers to reporting. Results concluded that the role played by the
pharmacy department in the area of Hospital Pharmacist ADR reporting varied
considerably but in most cases was insufficiently developed.4
A Pharmacovigilance study done to monitor ADRs associated with
Antihypertensive drugs was conducted in medicine outpatient department by way
of one- to -one patient interview by the pharmacist based on a questionnaire
(ADR monitoring form) drafted according to World Health Organization (WHO)
ADR monitoring guidelines. Calcium Channel Blockers was the prescribed drug
category associated with maximum ADRs, followed by Beta-blockers,
Angiotensin Converting Enzyme Inhibitor and Diuretics.5
A Prospective, observational study was carried out in the Dermatology outpatient
department of a hospital for a period of one year to assess Adverse Cutaneous
Drug Reactions (ACDR). The study revealed that the incidence of drug induced
adverse skin reactions was 2.6% and urticaria and fixed drug reactions were the
most common morphological reaction types. Despite the limitations of
spontaneous reporting of ADRs, it can still be considered as an effective tool in
Pharmacovigilence.Only if clinicians recognize and foster a culture for reporting
such reactions to regulatory authorities drug safety measures can be taken. 6
A study was conducted to provide data about the type and incidence of ADRs in a
Neurological department and to compare two different methodological
approaches to collecting information on ADRs.The two methods used were
intensified surveillance of neurological wards by daily ward rounds and computer
assisted screening for ADRs by means of pathologic laboratory parameters. But
the study showed that by measuring pathologic laboratory parameters majority of
ADRs couldn’t be detected in Neurological parameters. 7
The effect of the periodical distribution of a bulletin on drug safety issues and of
including yellow cards in prescription pads on the rate of ADR reporting was
studied. The study revealed that ADR bulletins elicit a temporal increase of ADR
reporting rate and including a yellow card in prescription pads was followed by
even greater increase in the reporting rate, possibly because it guarantees that
yellow cards are available at the workplace.8
A study was carried out to assess the development of monitoring schedule
approach to medication management and also to review and compare the
instruments available for monitoring the adverse drug reactions of Antipsycotic
medications. The UKU (Udvalg for Kliniska Undersogelser) scale and the West
Wales ADR profile showed to assess a broader range of physiological parameters
and potential problems than other instruments and such instruments must achieve
a balance between clinical gain and practical costs, including the time spent in
administration. The study concludes that further work was needed to explore the
translation of formalized ADR surveillance programmes into clinical gains and
improve outcomes for clients.
Materials and methods
7.0
7.1
Source of data
Data will be collected from:
a) Prescribers written spontaneous ADRs reports encountered across the
selected hospitals on prescription charts or case sheets.
b) From the “Yellow Forms” (ADR notification forms) provided to all the
departments of the study hospitals.
Inclusion criteria
 Randomly selected in-patients & out-patients.
 All suspected ADRs that conforms WHO’s definition.
Exclusion criteria
The ADRs which is reported as a result of :
a)
b)
c)
d)
7.2
7.3
Unintended Overdose.
Intended drug abuse.
Improper administration.
Medication errors.
Method of collection of data:
 From the inpatients’ case reports & outpatients’ cards or from the
“Yellow forms” issued to all departments for spontaneous ADR reporting
where a drug(s) is reported or suspected.
 The clinical pharmacist also will participate in ward rounds of the study
hospitals & the spontaneous ADR report would be collected voluntarily
from the prescribers & residents.
 A comprehensive medical history will collected through the medication
charts, the patient &/or the attendant would be quizzed orally w.r.t the
dose cum administration of the prescribed & suspected drug which
would have eventually manifested in the ADR.
 The causality assessment of the reported ADR will be done using
“Naranjo’s causality assessment scale” & WHO’s probability scale.
 Assessment of the severity will be carried out using Hartwig’s scale.
Duration of study
The study will be conducted for a period of 6 months.
7.4
Does the study require any investigation or intervention to be conducted on
patients, other humans or animals?
The study involves collection of data from the patients medication history,
patient’s case sheets, reported Yellow forms duly filled by the prescriber or
residents. The study would include investigation of the reported ADR from the
primary secondary & tertiary sources. The intervention would constitute an
appropriate comment after a thorough search from the sources.
7.5
8.0
Has ethical clearance been obtained from your institution in case of 7.5?
The protocol has been submitted for ethical committee clearance. Ethical
clearance certificate will be submitted to the university as soon as the ethical
committee of the study hospital grants them.
References:
1.
Uppal R, Jhaj R, Melhotra S. Adverse drug reactions among inpatients in
a north Indian referral hospital. Natl Med J Ind 2000; 13: 16-9.
2. Taylor D, Clark DW, Dovey SM, Tilyard MW. The prescribing and
adverse reactions of non-steroidal anti-inflammatory drugs in general
practice. A Dunedin study. NZ Med J 1994; 107 (981): 263-6.
3. Singh G, Rosen-Ramey D. NSAIDs induced gastrointestinal
complications. J Rheumatol 1999; 56S: 8-16.
4. Frequency and Preventability of Adverse Drug Reactions in Pediatric
Patients. Drug Safety Vol27 No11 2004 819-829(11)
5. The cost of adverse drug reactions.Expert Opinion on Pharmacotherapy,
Vol4 No 3 March 2003, 319-326(8).
6. Adverse drug reactions in hospital in-patients: a pilot study.Journal of
Clinical Pharmacy and Therapeutics.Vol31 Issue4 335 Aug 06
7. A survey of adverse drug reaction reporting by hospital pharmacists to the
Committee on Safety of Medicines- the role of pharmacy departments.Int
J Pharm Pract 1999;7:167-71.
8. A pharmacovigilence study for monitoring adverse drug reactions with
antihypertensive agents at a South Delhi hospital.Int J Pharm Pract Vol 14
No 4 Dec 2006 311-313(3).
9. Adverse cutaneous drug reactions:A one year survey at a dermatology
outpatient clinic of a tertiary care hospital. Indian J
Pharmacol2006;38:429-431.
10. Detection of Adverse Drug Reactions in a Neurological
Department:Comparison Between Intensified Surveillance and a
Computer- Assisted Approach.Drug Safety Vol25 No 10 2002 713724(12).
11. Stimulating Adverse Drug Reaction Reporting:Effect of a Drug Safety
Bulletin and of Including Yellow Cards in Prescription Pads.Drug Safety
Vol26 No14 2003 1049-1055(7).
12. Monitoring
adverse
drug
reactions:scales,
profiles
and
checklists.International Nursing Review Vol 51 No 4 Dec 2004 208221(14).
13. 10. National Pharmacological Protocol, Ministry of Family Welfare, Govt
of India.
14. 15 . Taylor D, Clark DW, Dovey SM, Tilyard MW. The prescribing and
adverse reactions of non-steroidal anti-inflammatory drugs in general
practice. A Dunedin study. NZ Med J 1994; 107 (981): 263-6.
15. Singh G, Rosen-Ramey D. NSAIDs induced gastrointestinal
complications. J Rheumatol 1999; 56S: 8-16.
16. Dhikav V, Gosain R, Gupta SK. Adverse drug reactions in the department
of psychiatry: Incidence and preventability (Abstract). Ind J Pharmacol
2001; 33 (1): 70.
17. Polluck BG. Adverse reactions to antidepressants in elderly patients. J
Clin Psychiat 1999; 20S: 4-8.
9.0
Signature of the candidate
10.0
Remarks of the Guide
11.0
Guide
Mr.Jai Prakash.S.Vastrad
Asst.Professor
Department ofPharmacy Practice
Al-Ameen College of Pharmacy
Bangalore-560027.
Signature
12.0
Head of the Department
Signature
Dr.Shobha Rani R.H
Professor and Head
Department ofPharmacy Practice
Al-Ameen College of Pharmacy
Bangalore-560027.
13.0
14.0
Remarks of the Principal
Recommended for research
Principal
Prof. B.G.Shivananda
Al-Ameen College of Pharmacy
Bangalore-560027.
Signature