ORF NCTN dosing clinical trials FDA

US Government Payer-Funded Trials to Address Oncology's Drug-Dosing Conundrum: A Congressional Call to Action?

by Garth W. Strohbehn, MD, MPhil, Allen S. Lichter, MD and Mark J. Ratain, MD

Feb 13^th 2023
5 mins
Journal of Clinical Oncology Volume 41, Number 14

Share This Article

Summary

Since the mid-20th century, cancer drug development has been driven by the "more is better" assumption, seeking the maximum tolerated dose in early trials.
The FDA's Oncology Center of Excellence (OCE) Project Optimus (2021) requires dose optimization for new oncology drugs, but this does not apply to already marketed drugs.
The 2023 US Senate appropriations bill encourages the FDA to organize dose optimization trials for marketed anticancer agents to reduce waste and toxicities.
Government health care payers, like CMS and the Veterans Health Administration, are key to funding post approval dose optimization trials, which can save money and improve patient safety.
The US Federal Government's Executive Branch can organize and fund these trials, involving government payers, federally funded clinical trial groups (NCTN), and OCE.
A self-sustaining cycle for dose optimization trials involves an initial investment by government payers into an Optimization Research Fund (ORF), which funds trials, generates savings, and reinvests in future trials.
Hypothetical trials for drugs like sotorasib and osimertinib illustrate potential cost savings and the feasibility of ORF-supported studies.
The structure leverages core competencies of involved organizations and focuses on cost-effectiveness, patient safety, and rigorous clinical evidence.
Criticisms include concerns about self-sustainability, patient enrollment, and ethical issues, but these can be addressed through careful trial design and patient collaboration.
In conclusion, Congress has provided a goal and template for safer and more cost-effective cancer care through postapproval dose optimization.
Note: The FDA's draft guidance on optimizing oncology drug dosages applies both premarket and postmarket.

Since the mid-20th century, cancer drug development has been guided by the assumption that more is better.1 Early phase clinical trials of new drugs therefore sought the maximum tolerated dose, which would then be compared with the standard of care in a randomized trial. In nearly all other areas of drug development, a range of doses is evaluated before the pivotal trial is conducted. The US Food and Drug Administration's (FDA) Oncology Center of Excellence (OCE) Project Optimus requires, as of 2021, dose optimization of new oncology drugs.

However, this only applies to new drug applications—What of the cancer drugs developed and marketed before the Project Optimus effort? Postapproval dose optimization clinical trials are required for many drugs to mitigate treatment-related toxicity and potentially reduce drug spending...

Click for Source Download PDF version

ORF, NCTN, dosing, clinical trials, FDA