A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration
Abstract
A key goal in drug development is optimized dosing for patients. Interactions between drug developers and regulatory scientists throughout development are important for the optimization of dosing and serve as a forum to discuss approaches for optimal dosing, such as precision or individualized dosing. To date, there has not been a systematic assessment of the advice provided by the US Food and Drug Administration (FDA) to drug developers from an individualized dosing perspective. Here, we reviewed FDA recommendations on dose selection for efficacy trials at end‐of‐phase meetings between the FDA and drug developers for 76 new molecular entities approved between 2013 and 2017 that are considered amenable for an individualized dosing method, response‐guided titration. Forty FDA dosing recommendations were identified as specific to dose selection and design of the respective efficacy trials and subsequently: (i) characterized based on if they were supportive of individualized dosing and (ii) compared with dosing regimens used in efficacy trials and labeling at approval to evaluate if FDA recommendations were implemented. Of these 40 recommendations for efficacy trials, 35 (88%) were considered supportive of individualized dosing. Eighteen of these 40 recommendations (45%) were incorporated into efficacy trials and 11 (28%) were incorporated into labeling. Thismore »
- Authors:
-
- Office of Clinical Pharmacology Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1786457
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Clinical Pharmacology and Therapeutics
- Additional Journal Information:
- Journal Name: Clinical Pharmacology and Therapeutics Journal Volume: 109 Journal Issue: 1; Journal ID: ISSN 0009-9236
- Publisher:
- Wiley-Blackwell
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Wang, Lingshan, Maxfield, Kimberly, Guinn, Daphne, Madabushi, Rajanikanth, Zineh, Issam, and Schuck, Robert N. A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration. United States: N. p., 2020.
Web. doi:10.1002/cpt.2068.
Wang, Lingshan, Maxfield, Kimberly, Guinn, Daphne, Madabushi, Rajanikanth, Zineh, Issam, & Schuck, Robert N. A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration. United States. https://doi.org/10.1002/cpt.2068
Wang, Lingshan, Maxfield, Kimberly, Guinn, Daphne, Madabushi, Rajanikanth, Zineh, Issam, and Schuck, Robert N. Sun .
"A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration". United States. https://doi.org/10.1002/cpt.2068.
@article{osti_1786457,
title = {A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration},
author = {Wang, Lingshan and Maxfield, Kimberly and Guinn, Daphne and Madabushi, Rajanikanth and Zineh, Issam and Schuck, Robert N.},
abstractNote = {A key goal in drug development is optimized dosing for patients. Interactions between drug developers and regulatory scientists throughout development are important for the optimization of dosing and serve as a forum to discuss approaches for optimal dosing, such as precision or individualized dosing. To date, there has not been a systematic assessment of the advice provided by the US Food and Drug Administration (FDA) to drug developers from an individualized dosing perspective. Here, we reviewed FDA recommendations on dose selection for efficacy trials at end‐of‐phase meetings between the FDA and drug developers for 76 new molecular entities approved between 2013 and 2017 that are considered amenable for an individualized dosing method, response‐guided titration. Forty FDA dosing recommendations were identified as specific to dose selection and design of the respective efficacy trials and subsequently: (i) characterized based on if they were supportive of individualized dosing and (ii) compared with dosing regimens used in efficacy trials and labeling at approval to evaluate if FDA recommendations were implemented. Of these 40 recommendations for efficacy trials, 35 (88%) were considered supportive of individualized dosing. Eighteen of these 40 recommendations (45%) were incorporated into efficacy trials and 11 (28%) were incorporated into labeling. This research suggests that early FDA‐sponsor interactions can support the study of doses in efficacy trials that may lead to individualized dosing strategies in labeling.},
doi = {10.1002/cpt.2068},
journal = {Clinical Pharmacology and Therapeutics},
number = 1,
volume = 109,
place = {United States},
year = {Sun Nov 15 00:00:00 EST 2020},
month = {Sun Nov 15 00:00:00 EST 2020}
}
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