1) Statistical significance

Could the association have been a result of the play of chance? This has come to be tested by the probability that the result is not random at the statistical level of 95%, 1 in 20 or p = 0.05.

2) Strength of association

Is the association strong enough to define a concern? How many individuals will suffer if the effect is real?

3) Consistency

Is the association found in different studies of the same exposure? However, they must be similar studies involving the same exposures.

4) Specificity and reversibility

Is the effect specific to the putative cause? If the cause is removed, does the effect disappear? For effects which are the result of permanent damage, reversibility cannot occur.

5) Relationship in Time

Does the cause precede the effect?

6) Biological gradient

Does increasing the exposure increase the effect? This may only exist over a defined range, if high exposures cause death, gradient cannot be constant.

7) Mechanism: biological plausibility

Is a mechanism known? Do cell studies or animal studies support a plausible mechanism? Hill made clear that this was not a necessary requirement since the true mechanism may not be known.

8) Alternative explanation

Is there a confounding explanation? Could there be some other cause that is responsible for the effect?