The document discusses severity assessment of adverse drug reactions (ADRs). It describes several scales used to assess the causality and severity of ADRs, including:
- The WHO-UMC Causality Assessment Scale which categorizes ADR causality as certain, probable, possible, unlikely, conditional/unclassified, or unassessable.
- Scales that categorize ADR severity as mild, moderate, severe or lethal based on factors like treatment required and effects on hospitalization.
- The Naranjo Algorithm/ADR Probability Scale which assigns a probability score to determine if an ADR is definite, probable, possible, or doubtful based on responses to 10 questions.
Pharmacovigilance is science of detection,
assessment, reporting and prevention of adverse
reactions to drug(s).
Major aims of pharmacovigilance are:
1. Early detection of hitherto unknown adverse
reactions and interactions
2. Detection of increases in frequency of (known)
adverse reactions
3. Identification of risk factors and possible
mechanisms underlying adverse reactions
4. Estimation of quantitative aspects of benefit/risk
analysis and dissemination of information needed to
improve drug prescribing and regulation.
Pharmacovigilance is science of detection,
assessment, reporting and prevention of adverse
reactions to drug(s).
Major aims of pharmacovigilance are:
1. Early detection of hitherto unknown adverse
reactions and interactions
2. Detection of increases in frequency of (known)
adverse reactions
3. Identification of risk factors and possible
mechanisms underlying adverse reactions
4. Estimation of quantitative aspects of benefit/risk
analysis and dissemination of information needed to
improve drug prescribing and regulation.
detection methods of Adverse drug reactions, postal survey method, Reporting of Adverse drug reactions, Preventability assessment, predictability assessments
pharmacovigilance, adverse effects, causality assessment,methods, who-umc method with case study, FOR DOWNLOAD PPT MAIL ME ON iamgauravchhabra@gmail.com
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
complete description of causality assessment with the definition of basic terminologies.& relation with an adverse event and adverse drug reaction, causality terms & assessment criteria.
Adverse drug reaction , types ,Detection and Reporting,severity and seriousness(Hartwig'severity assessment), preventibility(Schumock and thornston) and predictability, causality assessment Naranjo"s algotithm, WHO UMC causality scale
detection methods of Adverse drug reactions, postal survey method, Reporting of Adverse drug reactions, Preventability assessment, predictability assessments
pharmacovigilance, adverse effects, causality assessment,methods, who-umc method with case study, FOR DOWNLOAD PPT MAIL ME ON iamgauravchhabra@gmail.com
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
complete description of causality assessment with the definition of basic terminologies.& relation with an adverse event and adverse drug reaction, causality terms & assessment criteria.
Adverse drug reaction , types ,Detection and Reporting,severity and seriousness(Hartwig'severity assessment), preventibility(Schumock and thornston) and predictability, causality assessment Naranjo"s algotithm, WHO UMC causality scale
This slide contains the description of ADR, its dissimilarities with Side effects and toxic effects, types of ADRs, risk Factors and the description of Pharmacovigilance program.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
How to Give Better Lectures: Some Tips for Doctors
Causality assessment scales
1. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 1
1) WHO–UMC CAUSALITY ASSESSMENTSCALE
Causality term Assessment criteria(all points shouldbe
reasonably complied)
Certain
Event or laboratory test abnormality, with
plausible time relationship to drug intake
Cannot be explained by diseaseor other
drugs
Responseto withdrawalplausible
(pharmacologically, pathologically)
Event definitive pharmacologically or
phenomenologically (ie. an objective and
specific medical disorder or a recognized
pharmacologic phenomenon)
Rechallenge satisfactory, if necessary
Probable/likely Event or laboratory test abnormality, with
reasonabletime relationship to drug intake
Unlikely to be attributed to diseaseor other
drugs
Responseto withdrawalclinically reasonable
Rechallenge not required
Possible Event or laboratory test abnormality, with
reasonabletime relationship to drug intake
Could also be explained by disease or other
drugs
2. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 2
Causality term Assessment criteria(all points shouldbe
reasonably complied)
Information on drug withdrawalmay be
lacking or unclear
Unlikely Event or laboratory test abnormality, with a
time to drug intake that makes a
relationship improbable(but not impossible)
Diseaseor other drugs provideplausible
explanation
Conditional/unclassified Event or laboratory test abnormality
More data for proper assessmentneeded,
or
Additional data under examination
Unassessable/unclassifiable Report suggesting an adversereaction
Cannot be judged because information is
insufficient or contradictory
Data cannot be supplemented or verified
3. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 3
2) The term severity is often used to describe the intensity of a medical
event, as in grading ‘mild’, ‘moderate’ and ‘severe’. Severity assessment
categorizes the ADRs as mild, moderate, or severebased on the based on
the steps taken for the management of the ADRs.
Karch and Lasagna classified severity into minor, moderate, severeand
lethal as defined below:
i. Minor: no antidote, therapy or prolongation of hospitalization required.
ii. Moderate: requires a changein drug therapy, specific treatment or an
increase in hospitalization by at least 1 day.
iii. Severe: potentially life threatening, causing permanent damage or
requiring intensive medical care.
iv. Lethal: directly or indirectly contributes to the death of the patient.
The USFDA classifies an ADR as serious when it resultsin death, life-
threatening causes, or prolongshospitalization, causesa significant
persistent disability, resultsin a congenital anomaly, or requires
intervention to prevent permanent damage.
4. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 4
3) Hartwig et al categorized ADRs into seven levels as per their severity.
Level 1 & 2 fall under mild category, level 3 & 4 under moderate and level
5, 6 & 7 fall under category severe.
ADR severity assessmentscale
(ModifiedHartwig andSiegel)
Mild
Level 1: The ADR requires no change in treatment with the suspected drug.
OR
Level 2: The ADRrequires that the suspected drug be withheld,
discontinued or otherwisechanged. No antidote or other treatment is
required, and there is no increase in lenght of stay.
Moderate
Level 3: The ADR requires that the suspected drug be withheld,
discontinued or otherwisechanged, and/ or an antidote or other treatment
is required. There is no increase in lenght of stay.
OR
Level 4 (a): Any level 3 ADRthat increases lenght of stay by at least one day.
OR
Level 4 (b): The ADR is the reason for admission.
Severe
Level 5: Any level 4 ADR that requires intensive medical care.
OR
Level 6: The ADR causes parmanentharm to the patient.
OR
Level 7: The ADR either directly or indirectly leads to the death of the
patient.
5. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 5
4) Adverse Drug ReactionProbability Scale (Naranjo)
The AdverseDrug Reaction (ADR) Probability Scale was developed in 1991 by
Naranjo and coworkers fromtheUniversity of Toronto and is often referred to as
the Naranjo Scale. The scale was also designed for use in controlled trials and
registration studies of new medications, rather than in routine clinical
practice. Nevertheless, it is simple to apply and widely used. Many publications
on drug induced liver injury mention results of applying the ADRProbability Scale.
The ADR Probability Scale consists of 10 questions that are answered as either
Yes, No, or “Do not know”. Differentpoint values (-1, 0, +1 or +2) are assigned to
each answer. A simplified version of the 10 questions is provided below:
Are there previous conclusivereports of this reaction?
Did the adverseevent appear after the drug was given?
Did the adversereaction improve when the drug was discontinued or a
specific antagonistwas given?
Did the adversereaction reappear upon readministering the drug?
Were there other possiblecauses for the reaction?
Did the adversereaction reappear upon administration of placebo?
Was the drug detected in the blood or other fluids in toxic concentrations?
Was the reaction worsened upon increasing the dose? Or, was the reaction
lessened upon decreasing the dose?
Did the patient have a similar reaction to the drug or a related agent in the
past?
Was the adverseevent confirmed by any other objective evidence?
The actual ADRProbability Scale formand instructions on how it is completed are
provided below. Total scores rangefrom -4 to +13; the reaction is considered
definite if the scoreis 9 or higher, probable if 5 to 8, possible if 1 to 4, and
doubtful if 0 or less.
6. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 6
While this scale includes all of the usual features that are important in assessing
causality, the scale is not weighted for the mostcritical elements in judging the
likelihood of drug induced liver injury, such as specific time to onset, criteria for
time of recovery, and list of critical diagnoses to exclude, making the scale of
limited use in assessing hepatotoxicity. The Naranjo scale also relies upon testing
for drug levels, which is rarely helpful in idiosyncratic drug induced liver
disease. Finally, the scalewas designed for use in clinical trials, and points are
subtracted if the reaction reappears with administration of placebo, which does
not apply to the usualcase of drug induced liver disease. Direct comparisons to
the RUCAM system haveshown that the ADRProbability Scale is easier to apply,
but has less sensitivity and specificity in assigning causality to cases of drug
induced liver injury.
Naranjo Algorithm - ADR Probability Scale
The Naranjo Algorithm, or AdverseDrug Reaction Probability Scale, is a method
by which to assess whether there is a causalrelationship between an identified
untoward clinical event and a drug using a simple questionnaire to assign
probability scores.
7. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 7
Adverse Drug Reaction Probability Scale
Question YesNo
Do Not
Know
Score
1. Are there previousconclusivereportsonthisreaction? +1 0 0
2. Did the adverse eventappearafterthe suspecteddrugwasadministered? +2 -1 0
3. Did the adverse eventimprovewhenthe drugwasdiscontinued oraspecific
antagonistwasadministered?
+1 0 0
4. Did the adverse eventreappearwhenthe drugwasreadministered? +2 -1 0
5. Are there alternativecausesthatcouldontheirownhave causedthe
reaction?
-1 +2 0
6. Did the reactionreappearwhen aplacebowasgiven? -1 +1 0
7. Was the drug detectedinbloodorotherfluidsinconcentrationsknownto
be toxic?
+1 0 0
8. Was the reactionmore severe whenthe dose wasincreasedorlesssevere
whenthe dose wasdecreased?
+1 0 0
9. Did the patienthave a similarreactiontothe same or similardrugsinany
previousexposure?
+1 0 0
10. Was the adverse eventconfirmedbyanyobjective evidence? +1 0 0
Total Score:
8. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 8
Naranjo Algorithm - ADR Probability Scale
Score Interpretationof Scores
Total
Score
>9
Definite. Thereaction (1) followed a reasonabletemporal sequence
after a drug or in which a toxic drug level had been established in body
fluids or tissues, (2) followed a recognized responseto the suspected
drug, and (3) was confirmed by improvement on withdrawing the drug
and reappeared on reexposure.
Total
Score
5 to 8
Probable. The reaction (1) followed a reasonabletemporal sequence
after a drug, (2) followed a recognized responseto the suspected drug,
(3) was confirmed by withdrawalbut not by exposure to the drug, and
(4) could not be reasonably explained by the known characteristics of the
patient’s clinical state.
Total
Score
1 to 4
Possible. Thereaction (1) followed a temporal sequence after a drug, (2)
possibly followed a recognized pattern to the suspected drug, and (3)
could be explained by characteristics of the patient’s disease.
Total
Score
≤0
Doubtful. The reaction was likely related to factors other than a drug.
9. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 9
Instructions for Using the ADR Probability Scale
The response“Do not know” should be used sparingly and only when the quality
of the data does not permit a “Yes” or “No” answer. “Do notknow” can be
applicable if the information is not available and also if the question is
inapplicable to the case. When more than one drug is involved or suspected, the
ADR Probability Scale is usually applied separately to each of the possibleetiologic
agents, and the drug with the highest scoreshould be considered the causative
agent. In addition, the potential of interaction should be evaluated.
Question1. Arethere previous conclusive reports on this reaction? The answer
“Yes” (+1) applies if there have been two or more published reports in which the
adversereaction has been described in detail or if the adversereaction is listed in
a reliable source, such as a medical textbook, review article on the medication or
on adversedrug reactions, or the productpackage insert. The response“No”
applies when the adverseevent has not been described previously or if only one
reporthas been published, or if published reports wereconsidered inconclusive
or unconvincing. The answer “Do not know” is applicable only when there is no
information, because the agent has not been available for an adequate period of
time or has not been previously evaluated for this adversereaction. The scores
given for “No” and “Do not know” are the same (0), so it is not critical to decide
between these two answers.
Question2. Did the adverseevent appear after the suspected drug was
administered? This question evaluates the temporal relationship between the
reaction and administration of the medication. The answer “Yes” (+2) applies if
there is definitive evidence that the adverseevent occurred after the medication
was started. “No” (-1) applies when the adverseevent developed before the first
doseof the drug. “Do not know” (0) applies if the information is not available or
is unclear.
Question3. Did the adverseevent improvewhen the drug was discontinued or a
specific antagonistwas administered? This question evaluates the responseto
10. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 10
dechallenge or stopping the medication. The answer “Yes” (+1) applies if the
adverseevent diminishes or disappears at any time after stopping the medication,
or if the reaction disappears upon administration of a specific pharmacologic
antagonist(for example, an anticholinergic given for a cholinergic reaction to
physostigmine). Theanswer “No” (0) applies if the adverseevent does not
improveor improves in responseto a nonspecific therapy or an antidote to
another medication or treatment of the underlying disease. The answer “Do not
know” (0) applies if the medication was not stopped or the subsequentcourse
was unknown, inconclusiveor unclear.
Question4. Did the adverseevent reappear when the drug was
readministered? This question evaluates the responseto rechallenge or
reexposure. An answer of “Yes” (+2) indicates that the medication was stopped,
the adverseevent resolved or improved, and there was an unequivocal
reappearanceor worsening of the reaction when the medicine was restarted in a
similar doseand by the same route. The Naranjo scale also allows for a “Yes” if
the causalassociation is well known and rechallenge cannot be done for clinical or
ethical reasons. An answer of “No” (-1) only applies if rechallenge was done, but
the adverseevent did not reappear or worsen. The answer “Do not know” (0)
applies if rechallenge was not done or information on rechallenge is not available
or the reaction was ambiguous.
Question5. Arethere alternative causes that could on their own have caused the
reaction? This question assesses alternativeexplanations for the adverse
event. Because adverseevents are often nonspecific and can be manifestations
of the disease being treated or an unrelated, concurrentdiseaseor condition,
other diagnoses need to be considered and excluded. The answer “No” (+2)
applies if alternative causes havebeen excluded, based upon a systematic and
complete evaluation, thus implicating the drug morestrongly. A risk or
susceptibility factor is not an alternative cause. The answer “Yes” (-1) applies
when there is an alternative cause or explanation. “Do not know” (0) applies if
the investigation of other causes is incomplete, inconclusiveor was not done.
11. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 11
Question6. Did the reaction reappear when a placebo was given? This question
applies to clinical research studies in which a placebo was administered. The
answer “Yes” (-1) applies if the medication was stopped and the adversereaction
resolved or improved conclusively, and there was an unequivocal reappearanceof
the adverseevent after administration of placebo (single or double blind). The
answer “No” (+1) applies if the reaction did not reappear or worsen after
administration of placebo. “Do not know” (0) applies if placebo challenge was not
done or the results were inconclusive.
Question7. Was the drug detected in blood or other fluids in concentrations
known to be toxic? This question applies specifically to dosedependent adverse
reactions when blood, urine, tissueor other specimen concentrations of the
medicine are available. The answer “Yes” (+1) applies if the concentration is in
the accepted toxic or supratherapeutic range. “No” (0) applies if the
concentration is below the toxic range. The answer “Do not know” (0) applies if
drug levels are not available or are inconclusive.
Question8. Was the reaction more severe when the dosewas increased or less
severewhen the dose was decreased? This question evaluates the doseresponse
relationship of medication and the adversereaction. “Yes” (+1) applies if the
adverseevent was more severeor worsened when the dose of the medication
was increased, or was less severeand improved when the dose was
decreased. “No” (0) applies if there was no appreciable change in the severity of
the adverseevent with dosemodification. “Do not know” (0) applies if the dose
or regimen was not altered or the information was not available or inconclusive.
Question9. Did the patient have a similar reaction to the sameor similar drugs in
any previous exposure? This question is directed at past medical history of
adversereactions to the same or a structurally related drug. “Yes” (+1) applies
when there is documentation of a previous similar reaction to the specific drug or
a related medication. “No” (0) applies when the patient does not havea previous
exposureto the same medicine or when the patient did not develop the adverse
reaction in a previous exposureto the same or related drugs. “Do not know” (0)
12. SEVERITY ASSESSMENT OF ADRs – Dr.Renju.S.Ravi
Page 12
applies when there is no information on previous reactions or the information is
inconclusive.
Question10. Was the adverseevent confirmed by any objective evidence? The
final question assesses thequality of the data on which the adverseevent is
assessed. “Yes” (+1) indicates that there is laboratory test documentation of the
adverseevent or that the event was directly observed by a qualified person (for
example, a skin rash described in nursing or physician notes). The answer “No”
(0) applies when neither laboratory tests nor direct clinical documentation can
verify the reaction. “Do not know” (0) applies if there is no specific information
available (no laboratory testing and no clinical description) or the information is
inconclusive. The scores given for “No” and “Do not know” are the same (0), so it
is not critical to decide between these two answers.