Negative controls and E-values: what is the purpose of negative controls in cohort studies?

• A. They quantify the magnitude of effect sizes.
• B. They help detect unmeasured confounding.
• C. They automatically adjust for confounding.
• D. They replace outcome data.

Answer: (B)

Using negative controls to detect unmeasured confounding. In cohort studies, a negative control outcome (an outcome that the exposure should not plausibly affect) or a negative control exposure (an exposure that should not influence the outcome) serves as a diagnostic check for hidden bias. If you observe an association with a negative control, that signals that unmeasured confounding or other systematic bias may be distorting the main exposure–outcome result. This helps researchers gauge the plausibility that observed effects are real rather than artifacts of confounding, rather than providing a direct estimate of effect size, automatically adjusting for confounding, or replacing the actual outcome data.