Atlantic Research Group will be presenting a webinar via Xtalks on Thursday March 11, 2021 at 11am EST. Please register here.
Webinar Content Description:
The drive to expedite arriving at the MTD (Maximum Tolerated Dose) in oncology clinical trials could result in many clear benefits: first and foremost, there will be fewer cancer patients in clinical studies receiving too high or too low of a dose of a given investigational product. Beyond that, there will be a need for fewer overall patients, and there will be a greater chance of success moving into Phase II. In fact, there is literature that takes a theoretical approach that indicates 70% of the time, studies (and therefore patients) are missing the best dose.
A more direct route to the MTD not only benefits patients, but the sponsors as well. Moving dose escalation forward faster equals saved time and money. Large companies trying to determine which of their dozens of compounds they should continue to pursue could make cost-effective R&D decisions. For emerging companies, treating patients at ineffective doses appears to indicate their drug is not working; in reality, it could be the dose and not the compound. A new way of thinking (getting phase II data from a phase I study) could secure an additional round of financing.
All of this begs the question: what is holding back getting to the MTD sooner? The real roadblock is acknowledging the difficulty in getting clinicians over the fear of the complexity of creating a new dose escalation model. Many statisticians and clinicians in clinical trials are apprehensive to try new techniques. In this business, the “KISS” (Keep It Simple Stupid) rule has been in full effect for decades. Looking back, regulatory reviews were already long, with agencies trying to figure out the data. The last thing anyone wanted was for the regulators to have to figure out a new analysis as part of the review process. The idea was that it would take longer for a decision to come from a review–and nobody wanted that. These legacy fears remain today.
Implementing a model-based design requires that the statistician is familiar with the method well enough for a successful implementation, and a clinical team that recognizes the benefits, or better, actually asks for a design that offers the benefits. These designs can be implemented in areas other than oncology as well. Rare diseases often have similar challenges as oncology. It can work as long as the development program has as its objective to find the highest dose possible that causes the least harm.
Another key question is: what is the first step in getting started? We need to be careful to not fall into the classic design trap, which is asking if a study can be done with an innovative design. The better approach is to identify which questions need to be answered on the path to approval, then evaluate which designs are the most efficient (in terms of fewest patients exposed, faster timelines, and less cost). Often, an innovative design has the potential to answer more than one question at a time. Seamless designs do exactly that.
The bottom line in all of this is clinical development programs can be made better without being made more difficult, and that you can do all of this without trepidation.
- Make clinical programs more precise without making them more complicated
- The math is intricate but that should not be a deterrent to the clinician’s decisions
- The best chance at clinical success is correct dosing as soon as possible
- Reaching MTD in a streamlined way can be done without wishful thinking or fear
Who Should Attend:
- Chief Medical Officers
- Medical Monitors
- Clinical Leads
- Clinical Operations
John Friend, MD
Chief Medical Officer
Cellectar Biosciences, Inc.
Ed Shnipper, MD
Head of Clinical Development
Michael Wisniewski, Ph.D.
Vice-President of Biostatistics and Informatics
Atlantic Research Group