Major biases that threaten internal validity in clinical trials include which of the following?

• A. Selection bias
• B. Measurement bias
• C. Confounding
• D. All of the above

Answer: (D)

Internal validity in a clinical trial depends on the study design ensuring that the observed effect is due to the intervention and not other factors. Selection bias happens when the way participants are assigned or recruited creates groups that differ in important ways from the start, so differences in outcomes may reflect these pre-existing differences rather than the treatment. Measurement bias occurs when outcome data are collected or interpreted inconsistently across groups—such as when those assessing outcomes know which treatment a participant received and rate results differently. Confounding arises when an external variable is related to both the intervention and the outcome, creating a false impression of a treatment effect; even with randomization, imbalances or unmeasured confounders can still influence results. Because each of these biases can distort the true effect, all of the above are major threats to internal validity in clinical trials.