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Placebo-adjusted effect (revision 3)

Old revision·08:18, 25 Oct 2024·GramsNotUnitsGil

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Placebo-adjusted effect
Also calledBetween-group difference, treatment difference
Computed asActive-arm change minus placebo-arm change
Why it mattersThe active-arm change alone is not the drug effect
Topic infobox · conventions

The placebo-adjusted effect is the difference between the change observed in a treatment arm and the change observed in the comparator arm. It is the quantity a randomised trial is designed to estimate, and it is what can be attributed to the treatment.[1]

The active-arm change alone conflates the treatment effect with everything else operating during the trial: regression to the mean, the natural course of the condition, the lifestyle intervention both arms received, and the effects of being observed.[2]

What the comparator arm captures

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A placebo arm in a modern obesity trial is not a no-treatment arm. Participants receive the same lifestyle counselling, the same visit schedule and the same measurement, and the difference between the arms is the treatment alone.[2][3]

Several distinct phenomena contribute to the change in a placebo arm. Regression to the mean operates because participants are enrolled at a moment when their measurement was high enough to qualify. The trial's own intervention — diet advice, activity advice, regular weighing — has an effect. Observation changes behaviour. And the natural course of a condition may be towards improvement or deterioration.[2]

References

  1. ^ International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).
  2. ^ a b c Hróbjartsson A, Gøtzsche PC. "Placebo interventions for all clinical conditions." Cochrane Database of Systematic Reviews (1):CD003974 (2010). PMID 20091554.
  3. ^ International Council for Harmonisation, E10: Choice of Control Group and Related Issues in Clinical Trials (2000).