Chapter 16 - Balanced Placebo Design, Active Placebos, and Other Design Features for Identifying, Minimizing and Characterizing the Placebo Response

Abstract

Different methods have been developed over the last 50 years of placebo-interested research to identify, characterize and modulate the placebo response in individuals, but also to minimize it in randomized controled trials (RCTs). Among the design features that manipulate information, the balanced placebo design (BPD) and the balanced cross-over design (BCD) are not applicable to patients without authorized deception. Manipulating the timing of the drug, such as in the ‘hidden treatment’ paradigm and the delayed response test (DRT), may be more acceptable but is still limited to experimental settings. In RCTs, ‘active placebos’ and sham controls for non-drug therapy are feasible but are difficult to develop, and their effectiveness in blinding is yet to be evaluated. Waiting list (WL), ‘no-treatment’ controls and treatment-as-usual (TAU) are inappropriate control strategies unless combined with novel approaches such as the Zelen design.