What question did this study set out to answer?

To identify consistent quantitative patterns in clinical dose–response relationships across diverse therapeutic compounds and indications to improve the design of future dose-finding studies.

May 27, 2014Statistics in Biopharmaceutical ResearchOpen Access

Meta-Analysis of Clinical Dose–Response in a Large Drug Development Portfolio

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Authors

NTNeal ThomasPfizer (United States)KSKevin SweeneyLynn University VSVeena SomayajiPfizer (United States)

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Implication

Meta-analysis reveals consistent Emax dose-response patterns across clinical drug development programs, suggesting Bayesian priors can optimize future dose-finding trial designs.

Key Points

To identify consistent quantitative patterns in clinical dose–response relationships across diverse therapeutic compounds and indications to improve the design of future dose-finding studies.
Extracted efficacy endpoints from clinical dose–response trials across all efficacious compounds developed by a large pharmaceutical company between 1998 and 2009.
Evaluated trial design characteristics and fitted standard parametric Emax models to individual compounds.
Applied Bayesian hierarchical modeling to characterize Hill parameter distributions and compared early pharmacometric potency predictions against final trial estimates.
The Emax model adequately captured clinical dose–response curves across all analyzed compounds except for a single compound demonstrating a nonmonotone profile.
Bayesian hierarchical modeling demonstrated that dose–response trajectories for the vast majority of compounds conform to Emax functions with Hill parameters centered near 1.0.
Pre-trial pharmacometric predictions of drug potency fell within a 0.1- to 10-fold window of final clinical estimates for 90% of evaluated compounds.

Cite This Study

Thomas et al. (2014) studied this question.

synapsesocial.com/papers/6a7ddb6de37ea741e699a670 https://doi.org/10.1080/19466315.2014.924876

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Implication

Meta-analysis reveals consistent Emax dose-response patterns across clinical drug development programs, suggesting Bayesian priors can optimize future dose-finding trial designs.

Meta-Analysis of Clinical Dose–Response in a Large Drug Development Portfolio

Discussion

Member takes

Implication

Key Points

Cite This Study

Meta-Analysis of Clinical Dose–Response in a Large Drug Development Portfolio

Discussion

Member takes

Implication

Key Points

Cite This Study

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