What is the role of negative controls in cohort studies?

• A. They help detect unmeasured confounding.
• B. They adjust for confounding automatically.
• C. They estimate the effect size.
• D. They measure exposure accuracy.

Answer: (A)

Negative controls in cohort studies act as a check for bias, especially unmeasured confounding. The idea is to pick an outcome (or exposure) that should not be causally affected by the exposure of interest. If you observe an association between the exposure and this negative control outcome, it suggests there are unmeasured factors influencing both the exposure and the outcome, meaning the main association you’re studying may be biased. Negative controls are diagnostic tools rather than methods to automatically adjust confounding or to estimate the true effect size. They help reveal when results could be distorted by hidden factors, rather than provide a direct corrective value for the effect estimate.