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\begin{document}

\title{Dose Banding -- weighing up benefits, therapeutic failure and risks}



\author[1]{Stephen Duffull}%
\affil[1]{University of Otago}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\begin{abstract}
Aim Dose banding is a commonly used method of dose individualisation in
which all patients with similar characteristics are allocated to the
same dosing group. Dose banding results in some patients receiving less
intensive treatment with the potential for a reduction in therapeutic
benefit (iatrogenic therapeutic failure). This study aims to explore the
effects of dose banding on therapeutic success and failure. Methods This
was a simulation study conducted using MATLAB. Virtual patients were
simulated under a simple pharmacokinetic model with a predefined target
steady-state average concentration (c\_(ss,ave)). Clearance was
correlated with a covariate used for dosing. Dose individualisation was
based on: one-dose-fits-all, covariate based dosing, empirical dose
banding, dose banding optimised for benefit:risk only and dose banding
optimised for both benefit:risk and minimising iatrogenic therapeutic
failure. Results The lowest and highest probabilities of target
attainment (PrTA) were 46\% for one-dose-fits-all and 72\% for fully
individualised 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
once-dose-fits-all with 59\% PTA but not as good as either optimised
method (64-69\% PrTA) while carrying a risk of iatrogenic therapeutic
failure in 25\% of patients. Optimising for benefit:risk (only) improved
PrTA but carried a risk of iatrogenic therapeutic failure of up to 10\%.
Optimising for benefit:risk and minimising iatrogenic therapeutic
failure provided the best balance. Conclusion Future application of dose
banding needs to consider both the probability of benefit:risk as well
the risk of causing iatrogenic therapeutic failure.%
\end{abstract}%



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