Rethinking Clinical Trials and Personalized Medicine with Placebogenomics and Placebo Dose.

Area of Science:

• Variability science
• Personalized medicine
• Social pharmacology

Background:

• Placebo and nocebo effects, historically neglected, have genuine neurobiological underpinnings.
• These effects significantly influence patient outcomes and clinical trial interpretations.
• The COVID-19 pandemic highlights the impact of public expectations and social movements on placebo/nocebo responses.

Purpose of the Study:

• To review the history, biology, and variability of placebo effects.
• To introduce emerging concepts: placebogenomics, nocebogenomics, and augmented placebo.
• To propose a roadmap for placebogenomics and its integration with social pharmacology.

Main Methods:

• Historical review of placebo research.
• Discussion of biological mechanisms and variability factors.
• Introduction of novel concepts and their implications for future research.

Main Results:

• Placebo and nocebo effects possess a neurobiological basis and exhibit significant inter-individual variability.
• These effects are influenced by disease type, symptoms, trial design, and socio-cultural contexts.
• Emerging concepts like placebogenomics offer new frameworks for understanding drug and placebo variability.

Conclusions:

• Forecasting and explaining placebo/nocebo variability are essential for robust clinical trials and personalized healthcare.
• Placebogenomics and social pharmacology offer synergistic approaches to understanding personalized therapeutic responses.
• A new taxonomy for drug and placebo variability is anticipated in the coming decade.