Developing a Quantitative Interface for Evaluating the Effect of Dosage Modification on Safety and Efficacy
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Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Introduction
To balance benefit risk, drug effects and toxicity are evaluated to optimize the dosage. While these are generally explored during the early phase of drug development, the dosage often needs to be modified to help patients manage adverse reactions. This is very common, particularly for some oncology products in which drugs are prescribed at the maximum tolerated dose. Using lorlatinib and talazoparib as an example, dose reductions/interruptions are recommended at the occurrence of adverse events such as central nervous system effects and acute myeloid leukemia, respectively. However, given that dose interruptions and modifications are post-treatment outcomes, its impacts on treatment effectiveness and safety mitigation have rarely been systematically evaluated.
Objective
When adverse events occur during the use of a drug, dosage modifications are recommended to resolve these occurrences. We are building a dashboard to visualize dosing history and the effects of dosing modifications and pharmacokinetic (PK) changes on safety and efficacy with the goal to facilitate decision making.
Method
An R Shiny application is built to compile a variety of tabulation data of dosing records, PK data, responses to drugs, and adverse events: longitudinal dosing level data and concentration profile (if available) for each patient, adverse reactions of interest from onset until resolution or censoring, and dynamic changes in biomarkers as a measure for clinical benefit. Population profiles will be generated to overview dosing history and its impact on safety and efficacy. The application provides a visual output to easily access and comprehend the data.
Results
The application is expected to streamline the process of data visualization for dosage modifications and their impact on safety and efficacy with a friendly graphical user interface. Conclusion: The application is an accessible tool that provides data regarding the effects of dosage modifications during adverse reactions for a variety of drugs. It allows the data to be visualized and understood easily to evaluate the efficiency of dosage modifications for safety management of the patients and if efficacy is adequately maintained during this process.