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Table 1 Hill's viewpoints or considerations for epidemiological causation

From: Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?

Consideration

Explanation

Strength

Strong associations are intuitively considered more compelling. However, weak associations do not rule out causation.

Consistency

The association is found in different experiments, with different populations, and with varied circumstances.

Specificity

The most controversial consideration. A cause leading to a single effect (and vice versa) offers more support for the causation argument than one cause leading to multiple effects (and vice versa).

Temporality

The cause must happen before the effect.

Biologic gradient

A dose–response pattern is present, or incremental amounts of exposure should lead to corresponding increments in the effect.

Plausibility

The proposed association seems reasonable or probable as a cause. Most subjective consideration.

Coherence

A causative effect is not in conflict with current knowledge about the pathophysiology of the disease.

Experimental evidence

The effect can be reduced or altered by reducing or eliminating the proposed cause.

Analogy

Alternative explanations for the causative effect are evaluated and considered less likely than the one proposed.