Drug Dosing Recommendations for All Patients: A Roadmap for Change

Abstract

Most drug labels do not contain dosing recommendations for a significant portion of real-world patients for whom the drug is prescribed. Current label recommendations predominately reflect the population studied in pivotal trials that typically exclude patients who are very young or old, emaciated or morbidly obese, pregnant, or have multiple characteristics likely to influence dosing. As a result, physicians may need to guess the correct dose and regimen for these patients. It is now feasible to provide dose and regimen recommendations for these patients by integrating available scientific knowledge and by utilizing or modifying current regulatory agency-industry practices. The purpose of this commentary is to explore several factors that should be considered in creating a process that will provide more effective, safe, and timely drug dosing recommendations for most, if not all, patients. These factors include the availability of real-world data, development of predictive models, experience with the US Food and Drug Administration (FDA)'s pediatric exclusivity program, development of clinical decision software, funding mechanisms like the Prescription Drug Users Fee Act (PDUFA), and harmonization of global regulatory policies. From an examination of these factors, we recommend a relatively simple, efficient expansion of current practices designed to predict, confirm, and continuously improve drug dosing for more patients. We believe implementing these recommendations will benefit patients, payers, industry, and regulatory agencies.

Figure 1

Precision drug dosing recommended actions over the investigational new drug (IND) and new drug application (NDA) Life Cycle. There are eight proposed actions over the research and development drug cycle designed to produce more precise dosing recommendations at market approval or soon thereafter and continuously improve dosing based on real‐world data (RWD). CDS, clinical decision support; FDA, US Food and Drug Administration; PD, pharmacodynamic; PK, pharmacokinetic; RWP, real‐world patient.