Which of the following statements is most consistent with a true cause-and-effect relationship between an exposure and disease?

• A. The exposure and disease are observed only in a single cross-sectional study.
• B. The exposure and disease are observed to be associated, but temporality is unclear.
• C. The exposure and disease are never observed together.
• D. The exposure precedes the disease and there is a consistent, plausible mechanism.

Answer: (D)

To infer a true cause-and-effect relationship, the exposure must come before the disease (temporality) and there should be a plausible mechanism linking the exposure to the disease. The statement that the exposure precedes the disease and that there is a consistent, plausible mechanism provides this temporal order plus a biological justification, which strengthens causal interpretation beyond mere association.

The other scenarios fall short because they either cannot establish temporality (observing exposure and disease together in a cross-sectional context), show association without a clear time sequence, or imply no co-occurrence at all, which cannot support causation.