Work

Drug‐Placebo Additivity in Randomized Clinical Trials

Year: 2019

Type: article

Abstract: In randomized clinical trials (RCTs), it is assumed that nonspecific effects beyond action of pharmacological agents are roughly equivalent in drug and placebo treatment groups. Hence, since the inception of RCTs, drug efficacy is determined by comparing outcomes in active to those in placebo control arms. However, quantitation of efficacy is based on an unproven assumption, that drug and placebo responses are always additive. Response to treatment in RCTs can be differentially influenced by the perturbing effects of patient expectations, side effects, and pharmacogenomic interactions in both drug and placebo arms. Ability to control for these effects requires understanding of when and where they arise, how to mitigate, analyze, and even leverage their impact. Here, we examine three factors that influence additivity: expectation, side effects, and pharmacogenomics. Furthermore, to provide novel insights into nonadditivity and solutions for managing it, we introduce systems pharmacogenomics, a network approach to integrating and analyzing the effects of the numerous interacting perturbations to which a patient is exposed in RCTs.

Source: Clinical Pharmacology & Therapeutics

DOI: 10.1002/cpt.1626

Authors: Kathryn T. Hall, Joseph Loscalzo

Institutions: Brigham and Women's Hospital, Harvard University

Language: English

Topic: Statistical Methods in Clinical Trials

Subfield: Statistics and Probability

Field: Mathematics

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green