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Follow-up must be longer for any given number of cases.
6. The distribution of smoking habits varies considerably with age, as does cancer incidence.
Therefore, age adjustment or age-specific comparisons are needed.
7. To demonstrate that disease diagnosis was not based not only on clinical judgment but
documented by examination of tissue specimens. Particularly with a rare disease, like lung cancer,
false positives can readily distort the observed association, leading to information
(misclassification) bias.
9. Yes: Prevalent cases may have failed to respond initially, and therefore been deleted from the
cohort; short period of follow-up of disease with long induction; doctors may receive better
medical care, thereby reducing mortality.
12. Ultimately, it is not possible to exclude all possible alternate explanations except by conducting
an experiment in which smoking (or stopping smoking), can be randomly allocated in sufficiently
large groups with sufficient adherence to the experimental regimen. For ethical and practical
reasons, such an experiment cannot be conducted with smoking onset as the experimental
variable. Smoking cessation programs have not been sufficiently effective to serve as an alternate
intervention. If they were, it is doubtful that they could be used in a lung cancer trial, since the
evidence for the harmful effects of smoking is so abundant that ethical considerations would
probably preclude such a trial.
Though "absolute" proof requires human experiments, the weight of observational and animal
evidence is convincing. Any particular factor proposed as an alternate explanation (e.g., exercise,
diet) can be examined simultaneously with smoking, to see which factor is associated with lung
cancer when the other factor is controlled. There are no serious contenders. Traditional criteria
for causal inference are well satisfied:
a. strong association (RR about 8 for smokers overall);
b. dose-response effect exists;
c. replication in many studies;
d. cohort studies demonstrate that exposure precedes disease;
e. biologic explanation (animal and tissue culture models, autopsy studies);
f. experimental confirmation available in animal models;
g. analogy to other carcinogen-cancer associations.
Smoking and lung cancer is one of the strongest of epidemiologically-established relationships.
Controversy remains, but that should not paralyze policy planning (see M.A. Ibrahim, The
cigarette smoking/ lung cancer hypothesis. Editorial. Am J Public Health 1976; 66:131-132).
Nevertheless, the debate has continued even into recent years (see references in Bibliography).
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www.sph.unc.edu/EPID168/ © Victor J. Schoenbach 8. Analytic study designs - Assignment solutions - 268
rev. 8/31/1998, 9/5/1999