Precision Dosing Priority Criteria: Drug, Disease, and Patient Population Variables

Abstract

The administered dose of a drug modulates whether patients will experience optimal effectiveness, toxicity including death, or no effect at all. Dosing is particularly important for diseases and/or drugs where the drug can decrease severe morbidity or prolong life. Likewise, dosing is important where the drug can cause death or severe morbidity. Since we believe there are many examples where more precise dosing could benefit patients, it is worthwhile to consider how to prioritize drug-disease targets. One key consideration is the quality of information available from which more precise dosing recommendations can be constructed. When a new more precise dosing scheme is created and differs significantly from the approved label, it is important to consider the level of proof necessary to either change the label and/or change clinical practice. The cost and effort needed to provide this proof should also be considered in prioritizing drug-disease precision dosing targets. Although precision dosing is being promoted and has great promise, it is underutilized in many drugs and disease states. Therefore, we believe it is important to consider how more precise dosing is going to be delivered to high priority patients in a timely manner. If better dosing schemes do not change clinical practice resulting in better patient outcomes, then what is the use? This review paper discusses variables to consider when prioritizing precision dosing candidates while highlighting key examples of precision dosing that have been successfully used to improve patient care.

Keywords: biomarkers; disease states; drug development; individualized dosing; pharmacoeconomics; pharmacokinetics/pharmacodynamics; precision dosing; therapeutic index.

Figure 1

Assessment of candidacy for precision dosing. The considerations to guide the assessment of candidates for precision dosing are outlined. Drug, disease state, patient population, and clinical implementation are all areas that could influence decisions on precision dosing. These categories can be used to help think through both clinical and logistical concerns related to integrating the precision dosing of a drug into practice. PK, pharmacokinetic; PK/PD, pharmacokinetic/pharmacodynamic.

Figure 2

Drug development changes enabling precision dosing. The drug development process approval is generally not designed to facilitate precision dosing. Changes such as studying a target dose range could prime a drug in development for future precision dosing (Maloney, 2017; Peck, 2019), while other changes could facilitate precision dosing in already approved drugs, such as the use of clinical decision support tools to guide dosing. Early drug development encompasses phase I and II clinical trials, late drug development includes phase III clinical trials, and approval – post-approval includes phase IV investigations. Half maximum effective concentration (EC₅₀), Maximum effect (E_max), pharmacokinetic (PK), pharmacokinetic/pharmacodynamic (PK/PD).