The value of risk-factor ("black-box") epidemiology.

Risk-factor epidemiology has been denigrated by some as an empty search for associations, unguided by underlying theory. It has been defended for occasionally identifying useful (if poorly understood) potential interventions. We further defend risk-factor epidemiology as a valuable source of seemingly unrelated facts that await coherent explanation by novel theories and that provide empiric tests of theories. We illustrate these points with a theory that invokes lipid peroxidation as an explanation of an apparently incoherent accumulation of facts about renal-cell carcinoma. The example illustrates the value of viewing epidemiologic, laboratory, and clinical observations as a body of facts demanding explanation by proposed causal theories, whether or not those observations were collected with any hypothesis in mind.