Table 1.
Methodology for establishing a link between a drug and an adverse event
| Methods to link specific drugs with an adverse drug reaction |
| (1) Exclusion of other agents |
| (2) Withdrawal of culprit drug |
| (3) Rechallenge |
| (4) Singularity of drug (i.e., no other potential offending agent used) |
| (5) Consistent pattern of adverse drug reaction |
| (6) Quantitation of drug level (when possible/pertinent) |
| Degrees of certainty for causality of a drug-associated event |
| (1) Causative—ideally would involve a diagnostic test that is specific for a drug-associated event |
| (2) Probable—consistent with a drug event but lacking specific objective evidence for the link between drug and event |
| (3) Possible—the event can be neither confirmed nor excluded as an adverse drug event |
| (4) Coincidental—additional investigation reveals another cause of the event |
| (5) Negative—additional investigation excludes the association (e.g., drug never taken) |
| Quality of evidence for causality of a drug-associated event |
| (1) Excellent—prospective, controlled trials; large case-control series; animal models; large number of reports |
| (2) Good evidence—large case series; separate case reports with consistent pattern of disease and good quality |
| (3) Fair evidence—individual case reports of good quality |
| (4) Poor evidence—individual case reports of poor quality |