The Development and Evaluation of a new Experimental Model of an Active Placebo to Investigate how the Experience of Side Effects Influences the Placebo Effects

Most conventional placebos have no perceptible features and therefore are not likely to mimic a real medication in a RCT or clinical practice. This means that using conventional placebos to understand the placebo effect might not accurately reflect the conditions under which placebo effects occur. This project sought to extend the research on active placebos by developing and evaluating a new experimental model of an active placebo to investigate how perceptible features of a placebo influences its effect. A systematic review and meta-analysis showed that adverse event rates differed statistically significantly between placebo groups of RCTs and that the adverse events experienced in the placebo groups statistically significantly correlated with the adverse events reported by the corresponding medications group. Study 1 demonstrated that the new active placebo model successfully elicited the target side, while being mostly well tolerated. Study 2 showed that most participants receiving a conventional placebo correctly guessed that they had been allocated to the placebo group, while active placebo participants were split evenly between indicating having received a placebo and active medication, suggesting differential blinding as a result of the active placebo. Results from Study 3 indicated no statistically significant effect of message framing on sleep following active placebo administration, nor an overall placebo effect. The findings from this thesis indicated no statistically significant placebo effect on sleep for either conventional or active placebo. Interestingly, however, the results indicate that active placebos can facilitate the maintenance of participant blinding in RCTs and that in such contexts, a lack of side effects might have diminished the placebo response. As such, the active placebo model developed here shed light on how side effects may influence outcomes in RCTs and could help inform the development of techniques to improve blinding in practice