An untoward occurrence for which there is some basis for suspicion of an association with the medicinal product of interest but where this association has not been confirmed (see ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal Products in the EU). Examples include:

  • non-clinical toxicological findings that have not been observed or resolved in clinical studies;
  • adverse events observed in clinical trials or epidemiological studies for which the magnitude of the difference, compared with the comparator group (placebo or active substance, or unexposed group), on the parameter of interest raises a suspicion of, but is not large enough to suggest, a causal relationship;
  • a signal arising from a spontaneous adverse reaction reporting system;
  • an event known to be associated with other active substances within the same class or which could be expected to occur based on the properties of the medicinal product (based on ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal Products in the EU).

See also Adverse event, Signal