Importance of valid measurements of benefit and risk.

Without good measurement of both the risks and benefits of drugs, perceptions are bound to be distorted. Similarly, interpretations of findings are likely to be inappropriate, thus leading to decisions by regulatory bodies that are less than optimal. When measuring health phenomena in populations, both numerators and denominators must be determined to permit calculation of prevalence (frequency at a given time), incidence (frequency of new events over a specified period of time), mortality and case-fatality rates. Attribution of an adverse drug reaction to a particular drug can be the most demanding challenge for the clinician, the scientific investigator and the regulator. Criteria that must be met to establish a link between an apparent adverse drug reaction and an incriminated product include, biological plausibility, chronological and timing relationships, specificity, and response to dechallenge and to rechallenge. Acceptable chronology requires that a drug be shown to be taken before the onset of the adverse effect, not after symptoms have appeared. The unmet challenge of measuring benefit is more difficult than the measurement of harm. The need for valid measurements of risk and benefit remains compelling and urgent.