Table 2

Criteria for causation (Evans 1976)

•  The hypothesised cause should be distributed in the population in the same manner as the disease.
•  The incidence of the disease should be significantly higher in those exposed to the hypothesised cause than in those not so exposed. (The cause may be present in the external environment or as a defect in host responses.)
•  Exposure to the hypothesised cause should be more frequent among those with the disease than in controls without the disease, when all other risk factors are held constant.
•  Temporally, the disease should follow exposure to the hypothesised causative agent.
•  The greater the dose or length of exposure, the greater the likelihood of occurrence of the disease.
•  For some diseases, a spectrum of host responses should follow exposure to the hypothesised agent along a logical biological gradient from mild to severe.
•  The association between the hypothesised cause and disease should be found in various populations when different methods of study are used.
•  Other explanations for the association should be ruled out.
•  Elimination or modification of the hypothesised cause or of the vector carrying it should decrease the incidence of the disease (for example, control of polluted water, removal of tar from cigarettes).
•  Prevention or modification of the host's response on exposure to the hypothesised cause should decrease or eliminate the disease (for example, immunisation, drugs to lower cholesterol, specific lymphocyte transfer factor in cancer).
•  When possible, in experimental settings, the disease should occur more frequently in animals or humans appropriately exposed to the hypothesised cause than in those not so exposed; this exposure may be deliberate in volunteers, experimentally induced in the laboratory, or demonstrated in a controlled regulation of natural exposure.
•  All of the relationships and findings should make biological and epidemiological sense.