21 CFR

               

SCALES USED FOR CAUSALITY ASSESSMENT

INTRODUCTION: 

Causality assessment is the assessment of the relationship between drug treatment and the occurrence of an adverse event.

It is basically used to estimate and investigate whether the particular treatment is the cause of an observed and adverse event.

It is an essential part of the ADR report and an important task, conducted by the National Pharmacovigilance Programme in each country.

OBJECTIVES OF CAUSALITY ASSESSMENT:

• Provides a relationship between the drug and events.

• Provide better evaluation of the benefit/harm profiles of drugs.

• Plays an essential part in evaluating ADR reports in early warning systems and for regulatory purposes.

METHODS OF CAUSALITY ASSESSMENT:

 Three broad categories of various methods of causality assessment:

THE VARIOUS METHODS OF SCALES USED FOR CAUSALITY ASSESSMENT ARE:

WHO causality assessment scale and Naranjo scale are widely used and commonly preferred in most practices.

World health organization [WHO]-Uppsala Monitoring Centre (UMC):

The WHO-UMC causality assessment method includes the following four criteria:

1. Time relationships between drug use and the adverse event.

2. Absence of other competing causes [medications, disease process itself]

3. Response to drug withdrawal or dose reduction

4. Response to drug re-administration

CAUSALITY ASSOCIATION:

1. Certain

2. Probable

3. Possible

4. Unlikely

Certain:

• Event or laboratory test abnormality, with a plausible time relationship to drug intake

• Cannot be explained by disease or other drugs

• Response to withdrawal plausible (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 a reasonable time relationship to drug intake 

• Unlikely to be attributed to disease or other drugs

• Response to withdrawal clinically reasonable

• Rechallenge not required

Possible:

• Event or laboratory test abnormality, with a reasonable time relationship to drug intake

• Could also be explained by disease or other drugs

Unlikely:

• Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible)

• Disease or other drugs provide a plausible explanation

Karch and Lasagna classified severity into minor, moderate, severe, and lethal as defined below:

i. Minor: no antidote, therapy, or prolongation of hospitalization required ii. Moderate: requires a change in drug therapy, specific treatment, or an increase in hospitalization by at least 1 day. ii. Severe: potentially life-threatening, causing permanent damage or requiring intensive medical care.

iv. Lethal: directly or indirectly contributes to the death of the patient.

NARANJO SCALE:

• Naranjo scale assesses the causality using the traditional categories of definite, probable, possible, and doubtful.

• A ten-elemental questionnaire with yes, no, and unknown replies are developed.

• Based on the replies, the score has been determined into categories.

Limitation: The Naranjo Scale does not address the points needed in the assessment of the causality of possible drug interactions.

The ADR Probability Scale consists of 10 questions that are answered as either Yes, No, or "Do not know". Different point values (-1, 0, +1, or +2) are assigned to each answer. A simplified version of the 10 questions is provided below:

• Are there previous conclusive reports of this reaction?

• Did the adverse event appear after the drug was given?

• Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given?

• Did the adverse reaction reappear upon readministering the drug?

• Were there other possible causes for the reaction?

• Did the adverse reaction reappear upon administration of a 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 adverse event confirmed by any other objective evidence?

              Naranjo Algorithm - ADR Probability Scale

The Naranjo Algorithm, or Adverse Drug Reaction Probability Scale, is a method by which to assess whether there is a causal relationship between an identified untoward clinical event and a drug using a simple questionnaire to assign probability scores

CONCLUSION:

An attempt to attribute an event to a cause is a basic principle of monitoring and clinical management in aDSM

• Attributing a relationship requires a systematic < Process and is one of the main reasons why data are collected in aDSM. The exercise is done by experts who are competent in therapeutics and toxicity

• The causality assessment is once done attributes a level of certainty between the event and the exposure, ranging from certain to unrelated

REFERENCES:

https://www.slideshare.net/renjusravi/causality-assessment-scales-54995363

https://www.slideshare.net/drarunsingh4/causality-assessment-scale

Student Name: Rukhayya

Student ID: 014/012023

Qualification: Pharm.D

e-Mail ID: rukhayyashahvez0904@gmail.com