A published trial testing a vitamin supplement reported subjective improvement in symptoms only in the treatment arm but did not use a placebo and participants were aware of their assignment. Which bias is most likely inflating the reported treatment effect, and how would introducing a placebo and blinding change interpretation?

• A. Selection bias will be solved by adding a placebo because placebos automatically re-randomize participants into groups
• B. Confounding by indication is the sole issue here, which blinding cannot affect, so placebo use is irrelevant to improving inference
• C. Observer bias cannot influence subjective outcomes, so blinding and placebo are unnecessary for symptoms-based trials
• D. Placebo effect and expectation bias are likely inflating observed benefits; introducing a matched placebo and blinding participants (and ideally assessors) would reduce expectation-driven reporting and allow a clearer estimate of the supplement’s physiological effect

Answer: (D)