Controls who experienced hypothetical causal intermediates should not be excluded from case-control studies.
It has been suggested that controls with adenomatous polyps of the colon and rectum should be excluded from case-control studies of cigarette smoking and colorectal cancer. A claim has been made that the presence of such controls creates a bias toward the null. The polyps are an intermediate step in a hypothetical causal pathway between the exposure and the disease. Thus, the recommendation logically extends to the exclusion of all controls who experienced hypothetical causal intermediates from all case-control studies. It is shown, in the simple case of an exposure that acts solely through the pathway involving the intermediate, that such exclusions create a bias away from the null. The rationale for recommending the detrimental exclusions appears to stem from a variant of the "trohoc fallacy": the mistaken view of case-control studies as comparisons between diseased and healthy groups and not as comparisons between groups that differ by exposure.
Poole
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Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, USA.
D000236:Adenoma / Q000150:complications; D015982:Bias; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology; D006801:Humans; D007417:Intestinal Polyps / Q000150:complications; D012107:Research Design; D012907:Smoking / Q000009:adverse effects