OPTION 3

֍ Consistency of association
When measured associations are consistent in their direction among many different studies performed by various investigators in a range of settings with different methods, this strengthens the evidence of there being a causal association. If this criterion is satisfied, it further supports that a statistical association is real.

֍ Specificity
Specificity of association means as exposure is associated with only one disease or that the disease is associated with only one exposure. If the biological response to the exposure varies, it is less likely to be causal. While this criterion can support a causal hypothesis, failure to satisfy it cannot rule out causality. For example, increased risk of lung cancer is associated with cigarette smoking, diet, radon gas, and asbestos. On the other hand, cigarette smoking has been associated with several cancers, heart disease, and stroke.

֍ Temporal relationship of association
This is a very important criterion because in order for an exposure to cause a disease, the exposure must precede the disease. Temporality can be established in cohort and experimental studies, but it is often difficult or impossible to verify in other types of study designs

֍ Biological gradient
This exists if an increasing amount of exposure increases the risk of the outcome. However, a threshold value may exist and the biological gradient may not be linear.

֍ Biological plausibility
Of interest is whether the association is biologically supported. Biological assessment often involves experiments in controlled laboratory environments involving animals.

֍ Coherence
Causal inference is consistent with known epidemiologic patterns of disease.