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Dose banding – Weighing up benefits, risks and therapeutic failure

AIMS: Dose banding is a method of dose individualisation in which all patients with similar characteristics are allocated to the same dose. Dose banding results in some patients receiving less intensive treatment which risks a reduction in therapeutic benefit (iatrogenic therapeutic failure) because...

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Autor principal: Duffull, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314939/
https://www.ncbi.nlm.nih.gov/pubmed/35277993
http://dx.doi.org/10.1111/bcp.15307
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author Duffull, Stephen
author_facet Duffull, Stephen
author_sort Duffull, Stephen
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description AIMS: Dose banding is a method of dose individualisation in which all patients with similar characteristics are allocated to the same dose. Dose banding results in some patients receiving less intensive treatment which risks a reduction in therapeutic benefit (iatrogenic therapeutic failure) because of variability not predicted by dose banding. This study aims to explore the effects of dose banding on therapeutic success and failure. METHODS: This was a simulation study. Virtual patients were simulated under a simple pharmacokinetic model where the response of interest is the steady‐state average concentration. Clearance was correlated with a covariate used for dose banding. Dose individualisation was based on: one‐dose‐fits‐all, covariate‐based dosing, empirical dose banding, dose banding optimised for net therapeutic benefit and optimised for both benefit and minimising iatrogenic therapeutic failure. RESULTS: The lowest and highest probability of target attainment (PTA) were 44% for one‐dose‐fits‐all and 72% for covariate‐based dosing. Neither dosing approach would result in iatrogenic therapeutic failure as lower dose intensities do not occur. Empirical dose banding performed better than one‐dose‐fits‐all with 59% PTA but not as good as either optimised method (64–69% PTA) while carrying a risk of iatrogenic therapeutic failure in 25% of patients. Optimising for benefit (only) improved PTA but carried a risk of iatrogenic therapeutic failure of up to 10%. Optimising for benefit and minimising iatrogenic therapeutic failure provided the best balance. CONCLUSION: Future application of dose banding needs to consider both the probability of benefit as well the risk of causing iatrogenic therapeutic failure.
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spelling pubmed-93149392022-07-30 Dose banding – Weighing up benefits, risks and therapeutic failure Duffull, Stephen Br J Clin Pharmacol Original Articles AIMS: Dose banding is a method of dose individualisation in which all patients with similar characteristics are allocated to the same dose. Dose banding results in some patients receiving less intensive treatment which risks a reduction in therapeutic benefit (iatrogenic therapeutic failure) because of variability not predicted by dose banding. This study aims to explore the effects of dose banding on therapeutic success and failure. METHODS: This was a simulation study. Virtual patients were simulated under a simple pharmacokinetic model where the response of interest is the steady‐state average concentration. Clearance was correlated with a covariate used for dose banding. Dose individualisation was based on: one‐dose‐fits‐all, covariate‐based dosing, empirical dose banding, dose banding optimised for net therapeutic benefit and optimised for both benefit and minimising iatrogenic therapeutic failure. RESULTS: The lowest and highest probability of target attainment (PTA) were 44% for one‐dose‐fits‐all and 72% for covariate‐based dosing. Neither dosing approach would result in iatrogenic therapeutic failure as lower dose intensities do not occur. Empirical dose banding performed better than one‐dose‐fits‐all with 59% PTA but not as good as either optimised method (64–69% PTA) while carrying a risk of iatrogenic therapeutic failure in 25% of patients. Optimising for benefit (only) improved PTA but carried a risk of iatrogenic therapeutic failure of up to 10%. Optimising for benefit and minimising iatrogenic therapeutic failure provided the best balance. CONCLUSION: Future application of dose banding needs to consider both the probability of benefit as well the risk of causing iatrogenic therapeutic failure. John Wiley and Sons Inc. 2022-03-24 2022-07 /pmc/articles/PMC9314939/ /pubmed/35277993 http://dx.doi.org/10.1111/bcp.15307 Text en © 2022 The Author. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Duffull, Stephen
Dose banding – Weighing up benefits, risks and therapeutic failure
title Dose banding – Weighing up benefits, risks and therapeutic failure
title_full Dose banding – Weighing up benefits, risks and therapeutic failure
title_fullStr Dose banding – Weighing up benefits, risks and therapeutic failure
title_full_unstemmed Dose banding – Weighing up benefits, risks and therapeutic failure
title_short Dose banding – Weighing up benefits, risks and therapeutic failure
title_sort dose banding – weighing up benefits, risks and therapeutic failure
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314939/
https://www.ncbi.nlm.nih.gov/pubmed/35277993
http://dx.doi.org/10.1111/bcp.15307
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