Traditional clinical trials have four phases. Each phase plays an important, unique role in testing whether new drug products are safe and effective as well as how they compare to the standard of care.
Today in the stem cell field across the globe, the Phase III is under fire including what some might call friendly fire from some academics even.
For instance in Japan and now in the US, there has been pressure to drop the requirement for Phase III in certain cases.
Japan has raced ahead on implementing this change.
The idea behind this move is to accelerate getting new treatments such as regenerative medicine therapies to patients. However, there is a point to having Phase III trials so reducing the requirement for them could pose risks in addition to the potential benefit of speeding up the process. Stem cell clinics have generally not even bothered to do real clinical trials at all. See diagram from Figure 1 of my recent paper.
Bypassing Phase III may be appropriate in rare compassionate use cases and that is now permitted via discussion with the FDA here in the US, but what I’m talking about in this post is the broader idea of not requiring Phase III even in non-compassionate use cases.
The NIH summarizes the four clinical trial phases this way:
- Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
- Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
- Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
- Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use.
The Pancreatic Cancer Network has a nice summary of why Phase III trials are important:
“Q: What is the importance or significance of Phase III trials?
A: Phase III trials are the best way to find a new standard for treatment. Once a Phase III study is completed, the groups of patients can be directly compared to one another to evaluate outcomes. (In other words, researchers can see if one group did better than the other group.) If the patients on the new treatment did better, a new standard of care may be established.
Therefore, this type of trial may result in drugs gaining approval by the FDA and changing the way doctors treat patients. Promising treatments may emerge in other phases, but those trials are not definitive enough to change standards of care or the way we treat patients.”
In other words, based solely on Phase I and II data, no one can be sure the new drug in question is safe, effective, or better than the standard of care. While this example is regarding cancer, the general points here are applicable to stem cell therapies too.
The idea being floated around of eliminating Phase III trials for stem cell products here in America would be a big change and bring new risks into play.
Is that worth the potential benefit of increased speed of getting stem cells to the bedside?