Research to determine the cause of disease is a principal aim of epidemiology. As most epidemiological studies are observational rather than experimental, a number of possible explanations for an observed association must be considered before a cause-effect relationship can be inferred. In his 1965 paper The environment and disease: association or causation, Hill proposed the following nine guidelines to help assess if a causal relationship exists:
1. Strength: (effect size): A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal.
2. Consistency: (reproducibility): Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect.
3. Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship.
4. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay).
5. Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence.
6. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge).
7. Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations".
8. Experiment: "Occasionally it is possible to appeal to experimental evidence".
9. Analogy: The effect of similar factors may be considered.
Wikipedia: Bradford Hill criteria 07/07/15