Publication Date:
2019
Description:
Abstract
In randomized clinical trials (RCTs), it is assumed that non‐specific 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 influence 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 non‐additivity 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.
Print ISSN:
0009-9236
Electronic ISSN:
1532-6535
Topics:
Chemistry and Pharmacology
,
Medicine
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