Table 3 Design adjustments used to manage and understand placebo effects in trials for neuropsychiatric symptoms and syndromes
From: New approaches to symptomatic treatments for Alzheimer’s disease
Design Adjustment | Purpose |
|---|---|
Placebo lead-in | Exclude patients who no longer meet trial entry criteria after 2 weeks of placebo treatment Identify non-adherent patients whose participation in the trial would reduce power to observe a drug-placebo difference |
Pre-randomization psychosocial intervention | Exclude patients who no longer meet trial entry criteria after 1–2 weeks of psychosocial treatment |
Participants meet entry criteria at screening and baseline | Reduce chance of score improvement by regression to the mean |
Central review of scales whose scores determine entry to the trial | More reliable review of the data with fewer site influences |
Patients have at least moderately severe symptoms at screening and randomization | More severe symptoms are less likely to respond to placebo |
Longer trials of 12 to 24 weeks | Placebo responses are often greatest at study onset and become gradually less marked |
Two-arm design with 1:1 randomization | Placebo responses are higher in trials with several active treatment arms |
Sequential parallel comparison design (SPCD) | 2nd stage of the SPCD has only placebo non-responders in the placebo (and active) arm of the trials |
Randomized discontinuation design | All participants are on active treatment in the first period of the trial; only responders to active therapy are randomized to drug or placebo |