CAUSALITY ASSESSMENT OF ADVERSE DRUG REACTIONS

INTRODUCTION:

Causality assessment essentially means finding a causal association or relationship between a drug and a drug reaction. It is an assessment of the relationship between drug treatment and the occurrence of adverse events. It is also used to evaluate and check whether the particular treatment is the cause of an observed adverse event or not. It is an important part of adverse drug reaction reports conducted by national pharmacovigilance programs in each country.

OBJECTIVES:

1. Relationship: provides a relationship between the drug and the event.

2. Signal detection: A possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously.

3. Benefit/harm: provide a better evaluation of the benefit/harm profiles of drugs.

4. Early warning systems: This plays an essential part in evaluating ADR reports in early monitoring systems and for regulatory purposes.

METHODS OF CAUSALITY ASSESSMENT:

Many researchers developed various methods of causality assessment by using different criteria such as, 

Chronological relationship between the administered drug and the occurrence of adverse drug reaction.

Screening for the drug whether the event was related to the drug or not.

Confirmation of the reaction by conducting in vivo or in vitro studies.

Previous information on similar events.

Causality assessment methods are classified under three broad categories, which are

• Expert judgment or global introspection.

• Algorithms.

• Probabilistic methods.

  EXPERT JUDGMENT OR GLOBAL INTROSPECTION

  Expert judgments are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality.

  Two methods based on expert judgment or global introspection, are,

  • Swedish method by Wilhelm et al.

  • WHO – UMC causality assessment criteria.

  Swedish method by Wilhelm et al

  Evaluates the causal relationship by considering the below points.

  • Dose relationship.

  • Response pattern of the drug.

  • Concomitant drugs.

  • Previous information on the drugs.

  • The temporal sequence.

  • Re-challenge and

  • Alternative etiological candidates.

  A limitation of this method is the small number of categories into which causality can be placed, as there may be overlap and ADRs could be wrongly evaluated.

  WHO – UMC causality assessment criteria

  This method includes the following four criteria. They are,

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

  2. Absence of other competing causes (medications, disease process itself).

  3. De challenge – Response to drug withdrawal and dose reduction.

  4. Re challenge – Re administration of drugs.
     

  • ALGORITHMS:

  • Algorithms are sets of specific questions with associated scores for

  calculating the likelihood of a cause-effect relationship.

  • There are many algorithmic methods of causality assessment but no single algorithm is accepted as the gold standard because of many shortcomings.

  • Important algorithmic methods are:

  1. Dangaumou's French method.

  • The advantage of this method is that allows certain drugs taken at the same time as the suspect drug to be excluded because each drug is imputed separately.

  • However, this method requires more time when compared to other

  algorithms.

  2. Kramer et al method.

  • This algorithm is applied to a single manifestation after applying after administration of a single suspect drug. In case multiple drugs are involved each is assessed separately.

  3. Naranjo et al method (Naranjo scale).

  • It is the most widely accepted method. It determines whether the adverse drug reaction is actually due to the drug or some other factors.

  • It consists of questions that are answered as yes or no or unknown.

  • These answers are assigned via a score termed definite (score greater

  than or equal to 9), probable (score between 5-8), possible (score between 1-4), or doubtful (less than or equal to 0).

  • This method explains only the causality of one individual drug not

  explains the causality that occurs due to other drug interactions.

  4. Balanced assessment method.

  • It evaluates the case reports on a series of visual analog scales (VAS), according to each criterion if fulfilled.

  5. Ciba geigy method (valet et al).

  • This method was updated and replaced with a checklist of 23 questions, split into three sections,

  1. History of patient’s adverse reactions.
     

  2. Patient’s past adverse event reaction history.

  3. Monitoring physician’s experience.

  
  

  6. Loupe et al method.

  • It is developed to assess the teratogenic potential of the drug.

  7. Roussel uclaf causality assessment method (RUCAM).

  • This method is determined for pre-determined disease states such as liver and dermatological injuries.

  • Although this method is quite easy to use and is organ-specific.

  8. Maria and Victorinox scale (M and V scale)

  • Those are developed this scale for diagnosing drug-induced liver injury.

  • Probability is expressed as a score between 6 and 20.

  
  
  

  • PROBABILISTIC METHODS (Bayesian approaches).

  • Bayesian method.

  Bayesian approaches use specific findings in a case to transform the prior estimate of probability into a posterior estimate of the probability of drug causation.

  The prior probability is calculated from epidemiological information and the posterior probability combines this background information with the evidence in the individual case to come up with an estimate of causation.

  • Australian method.

  Conclusions are drawn from internal evidence, such as timing, and internal laboratory information from case reports.

  
  
  

  REFERENCE
  

  1. Gauravchabra,https://www.slideshare.net/gauravchhabra399/causality- assessmentmethodspharmacovigilance.

  2. Sirinoot palapinyo, adverse drug reaction causality assessment, https://www.slideshare.net/AllergyChula/adverse-drug-reaction-causality- assessment.

  3. Williamson pr, Mason JR, causality assessment of adverse drug reactions. https://www.ncbi.nlm.nih.gov/books/NBK262740/#:~:text=Causality%20 assessment%20of%20ADRs%20is,of%20adverse%20reaction(s).

  4. Pedro Pereira, Ana Silva. Causality assessment of adverse drug reactions, https://www.sciencedirect.com/science/article/pii/S0933365717306152#section.

  
  

B. Rama Charan

B. Pharmacy

                         ID:csrpl_int_ofl_wkd_162/0922