Use of case reports and the Adverse Event Reporting System in systematic reviews: overcoming barriers to assess the link between Crohn’s disease medications and hepatosplenic T-cell lymphoma

Table 1 Characteristics of published instruments assessing causal relationship between medication exposure and adverse events

	Naranjo	Kramer	WHO
Numerical range	−4 to +13	−7 to +7	n/a
Format	Ten questions answered ‘yes,’ ‘no,’ or ‘don’t know,’ each with a numerical value; numbers summed for final score. Higher scores indicate greater likelihood of causality.	An algorithm with six separate axes/flowcharts. Each axis contributes points to the final score. Higher scores indicate greater likelihood of causality.	Contains six categories; the user selects the one for which most criteria are met.
Distinguishes irreversible adverse events from other adverse events?	No	Yes	No
Addresses methods used to confirm adverse event?	Yes	No	No
Asks about serum medication levels?	Yes	Yes	No
Considers prior experience with medication?	Yes	Yes	Yes
Considers alternate etiologies?	Yes	Yes	Yes
Questions about rechallenge?	Yes	Yes	Yes
Questions about dechallenge?	Yes	Yes	Yes