The conversations about improving clinical trials to better meet the needs of cancer patients continue, with two noteworthy arguments set forth recently.
Both arguments address the need to rethink the design of clinical trials.
In a Pharma Strategy Blog, the author (MaverickNY) suggested that rather than seeking to find the maximum tolerable dose in clinical trials researchers test for the minimally effective dose. The idea being that an effective dose with less toxic side effects “would potentially lead to better adherence and may even improve overall survival.”
The author writes “Physicians and Pharma companies often forget that in the real world, patients fail to comply with oral cancer medications due to intolerable side effects that make their lives miserable…Even tyrosine kinase inhibitors (TKIs) are not always a piece of cake to take. The constant niggly, but low volume side effects, can wear anyone down.
“With the growing trend to combine two TKIs or a TKI and monoclonal, whether approved or as a novel-novel combination, a fresh approach to testing drug combinations rather than different MTDs starts to look more appealing.”
Jerry Call, the Life Raft Group’s Science Director, reacted to the proposal this way:
“The concept of a minimally effective dose is interesting and a worthy goal. In practice however, it may be complex and difficult to determine. Is the minimal effective dose one that controls the disease at a specific time point or long-term? What if the minimal effective dose will control the disease for 12 months, but a higher dose will control it for 36 months? Determining control at one time point does not necessarily equate with long-term disease control. How response is measured and duration of response will have to be considerations in any trial designed to explore minimal effective doses.”
In a New York Times Week in Review piece earlier this month, Clifton Leaf argued that “for subtypes of disease that are already known, it may be feasible to design small clinical trials and enroll only those who have the appropriate genetic or molecular signature.”
He points out that this is beginning to happen. At Genentech/Roche, 60 percent of the new drugs in the works are being developed with a companion diagnostic test to identify the patients who are most likely to benefit.
Previously, the Life Raft Group has mentioned its plans to work on developing a new clinical trial model that would harness resources such as our Patient Registry and Tissue Bank to make these kinds of trials possible.
Clearly, the clinical trials process needs to be improved. We will keep you posted as the conversations on this topic develop.