A Closer Look At Precision Medicine Clinical Trials

By Dan Schell, Chief Editor, Clinical Leader

Each December, our sister publication, Life Science Leader, publishes its outlook issue, which includes predictions from various industry execs in articles written by our Life Science Connect team of editors. Shortly after I had completed my article, I received an intriguing (albeit late) response to the question I had posed about new challenges to clinical trial sites in 2024, which prompted me to ask even more questions and get on a Zoom call with Jatin Shah, MD, chief oncology development officer at Sumitomo Pharma America (SMPA).

CLARIFICATION OF 2 KEY QUESTIONS

The full question I asked was: As we approach 2024, what are some challenges (or one) clinical trial sites will face that are relatively new or different from the traditional ones like recruitment, retention, and diversity? In other words, is there anything new that has popped up in the last year or so that has really affected how sites operate?

There were two parts of Shah’s answer that I wanted to explore further. The first was the following statement:

There has been an increase in trials that employ precision medicine, targeting smaller focused patient populations. This requires sites to open more trials to provide options for all patients, which changes the efficiency of trials in ways we haven’t seen previously.

For context, SMPA is a sponsor currently conducting clinical trials in psychiatry, urology, neurology, regenerative medicine, and oncology. Shah, who is focused on the latter area, says the company is starting to focus more on precision medicine, which creates a new set of challenges when it comes to running clinical trials. For example, say you’re developing a new medicine for a specific type of leukemia. Traditionally, you would design a trial for every type of AML (acute myeloid leukemia) that likely would involve some type of chemotherapy that a percentage of patients in your clinical trials may not respond well to. Thus, you’re able to enroll a large group of patients, but the side effects and the efficacy are going to vary significantly depending upon the patient’s biology.

“Now that we have a better understanding of the biology of a disease, we know, in the case of leukemia, that there’s going to be a subset of patients who have FLT3 mutations, for example,” explains Shah. “Those patients are more likely to respond well to a FLT3 inhibitor, so you design a trial just for those specific patients. But you could also do the same thing for various other mutations, so you end up with multiple trials for small subsets of leukemia patients.”

The next part of Shah’s answer that I wanted more information on was:

To continue meeting patient needs and realizing the full potential of precision medicine, sites and sponsors will need to explore ways to alter approaches or cost models to help support these changes.

That part about altering approaches and cost models intrigued me and reminded me of his previous statement about “efficiency” of trials. I figured all of that adds up to some significant changes that will need to be made all the way from trial design down to site-level operations. He concurred, explaining that with precision medicine trials, early in the process there is more testing and diagnostics coupled with associated time limits for patients before enrollment. Because there are going to be fewer patients who qualify for a specific type of precision medicine, sponsors need to utilize more sites, which increases costs for the sponsors and sites. “There’s more homework to do when you tackle a precision medicine clinical trial,” says Shah. “We know that on average, historically, 20% of sites never enroll a single patient. And that's without precision medicine where those numbers may increase. That's a lot of wasted time and effort for sites and sponsors. So we have to be much more selective when evaluating potential sites.” Part of that selection process involves being willing to expand beyond the sites a sponsor is used to working with, but doing so takes more time and may require more ClinOps staffing.

Time and staffing are also additional burdens to the sites that take on these kinds of targeted therapies trials. More protocols to learn, more contracts to sign, and more budgets to adhere to all equate to those “ways to alter approaches” that Shah referred to.

SEARCHING FOR EFFICIENCIES

As a former principal investigator (PI), Shah knows how difficult it can be to justify opening a trial that will enroll maybe one or two patients when you have limited resources. There's a lot of overhead and infrastructure you need to consider in these decisions. As such, he says it’s often best to focus on one niche. For example, if site A has a trial for NPM 1 mutation in AML and site B has a trial for patients with IDH1 mutations in AML, the two can develop a relationship for referring patients back and forth. “That’s one of the ways people are trying to find efficiencies when running these trials,” Shah says.

He adds that it is important when signing up a site for a precision medicine trial that site staff — and the patient — are well educated on what to expect, not just from a protocol standpoint, but from some of the basic logistics issues. “Say I’m a PI seeing about 20 patients a day in an office with two or three rooms,” Shah posits. “There’s the time it takes to get the patient into the room, take their vitals, and then, if they are receiving the standard of care drug and don’t have any questions, I could be done in 10 minutes. But if I suggest they get enrolled in a clinical trial, it’s going to take an additional hour of their time — and mine — to do things like have the study coordinator review with them a multipage informed consent document or get extra blood work and any required screening tests completed. If you're not absolutely invested in it, you can see how those little things really add up, especially from the patient's perspective.”

Every clinical trial requires careful planning and coordination. But do those that include precision medicine need more? Perhaps. If anything, Shah stresses that you avoid the “templatized” approach to protocol design. Do you really need this lab or that lab for this subset of patients? Do patients have to come back to the site as many times as traditional non-precision medicine trials? Those are the types of questions he suggests asking early in these trials. “There’s no doubt that when it comes to targeted therapies and precision medicine, it’s a complex issue. You’ve got increased complexity, increased costs, increased resources and all the other issues surrounding trial design and execution. But the upside of these therapies is tremendous for patients, and that’s what we need to keep in mind in all of this planning,” concludes Shah.