Balazs Szigeti

Balazs has a physics degree from Imperial College London and earned a PhD in computational neuroscience from the University of Edinburgh. After graduating, he spent a few years as a biomedical software engineer at the Icahn Institute of Genetics in New York to create tools for whole cell modeling. He became involved with psychedelics science in 2016, when he collaborated with the Global Drug Survey to show that neuroimaging studies consistently overestimate the potential harm of recreational MDMA use.He invented 'self-blinding', a novel methodology that enables self-experimenters to incorporate placebo control into their experimentation without clinical supervision. Using this methodology, Balazs designed and lead the self-blinding microdose study, the largest placebo-controlled study on psychedelics microdosing to-date. Balazs currently researches the intersection of placebo effect and psychedelic medicine, while also continuing to setup new citizen science initiatives using his self-blinding methodology.

Solving the blinding problem in psychedelic trials

Psychedelic trials often face criticism due to functional unblinding, i.e. both patients and assessors can identify who was given the active drug and who was given the placebo due to intense effects of psychedelic drugs. This issue was a major reason for the FDA’s rejection of MDMA-Assisted Therapy for the treatment of post-traumatic stress disorder.

In this talk, I will offer a solution to this problem by considering how blinding changes effect sizes of both treatment and control arms. Generally, unblinding increases effect size in the treatment arms, while decreases effect size in the control arms. Based on a review of the literature, I argue that unblinding effects are significantly stronger in the control arms relative to the treatment arms. In other words, biases associated with unblinding are not driven by positive effects in the treatment arm, but rather by negative effects in the control arm. Therefore, to eliminate biases associated with unblinding, we need to eliminate the disappointment associated with being randomized into the control condition.

The Zelen design can accomplish this objective by altering how information is shared with patients and by randomizing patients prior to obtaining consent. In Zelen trials, patients are randomized immediately upon contacting the study team (i.e. before consent) and the information shared with them pretends it is a single-arm trial where only the given intervention is tested. Therefore, patients in the control arm do not know about the alternative arm, thus, eliminating the disappointment associated with being in the control condition. This design is feasible for trials where the control condition is also active, such as psychedelic trials that use a low dose as control condition. Will consider what a psychedelic Zelen trial would look like, together with some practical challenges and limitations of the design.