In pharmacology, the criteria for causation are quantitative, objective, and numerous: an agonist must reproduce the action of a putative neurotransmitter; the action of neurotransmitter and agonist must be competitively shifted to the right with the same Schild coefficient by an antagonist, with statistical confidence quantitated with P values. For more complex hypotheses, reproducibility, predictive value, and parsimony are the classic criteria of the Scientific Method. However, stepping out of the laboratory, the scientist needs to find common language with non-scientists, which usually means more philosophy and less quantitation.
The so-called “Bradford-Hill Criteria” have been elevated to the status of "Gold Standard” in determining Causation. The reliance on these criteria and especially flawed application of the criteria lead to erroneous conclusions (Phillips and Goodman, 2004). Hill himself (1965) used the term “considerations” rather than “criteria”, and raised numerous cautions concerning their use.
The first consideration, Strength of Association, is a particularly insidious one. The doubling of risk is sometimes considered to be an indication that some factor is causal, and is often used in legal proceedings to determine if a particular cause is “more likely than not”, and even sometimes construed to purport that a cause is established with “reasonable medical certainty”. It is analogous to the doubling of signal over noise to be considered detectable, a rule of thumb for engineers. However, statistically speaking and based on real world experience, the magnitude of an effect is independent of its statistical significance and true causal role. In one case, a ratio* of 1.4 could be highly significant and indicate causation, whereas in another case, a ratio of 5 could be fortuitous and meaningless.
The application of the Bradford Hill Considerations to the adverse reactions putatively attributed to thimerosal by the Institute of Medicine (IOM, 2001) is an example of use of the guidelines. Perhaps it is a telling outcome, however, that no definitive conclusions were reached concerning the ability of thimerosal to cause autism primarily because of failure to satisfy the last (and most subjective) criterion, Biological Plausibility. The Institute of Medicine did however recommend further investigation, and adverse reactions including autism to thimerosal continue to be controversial today.
The Bradford Hill consideration of Dose-Response (#2) should at a minimum be sharpened to take into consideration Exposure - defined as Dose x Duratioin - as the most likely correlate of Adverse Reactions.
Gerneral Causation and Specific Causation.
Specific Causation is the domain of the physician whereas General Causation is the domain of the scientist. When a patient deals with a patient, N=1 and there is no chance uisually to replicate the experiment. Statistics do not apply. Healing is indeed an art and a physician's opinion is influenced by diverse and subjective factors.
*ratio: Risk Ratio or Signal-to-Noise Ratio.