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A study claims: "Daily aspirin use is associated with 22% lower heart attack risk (HR = 0.78, 95% CI [0.71, 0.86])." This was a large observational study. A cardiologist is still cautious. List the key limitations the cardiologist should consider.
A
p < 0.05 is required; the CI doesn't tell us about significance
B
Confounding (healthy user bias: aspirin users may also exercise and eat well), reverse causality (if sicker patients avoid aspirin), selection bias in who takes aspirin, and absence of RCT confirmation
C
HR < 1 always indicates a beneficial drug effect in observational studies
D
Large CIs mean the result is unreliable — [0.71, 0.86] is too wide
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