The best patient outcomes come when individuals receive the preferred therapy for their clinical situation. But sometimes barriers to optimum care get in the way.
"We have a growing number of cancer therapy options for our patients; but for a variety of reasons, they are not equally accessible to everybody," said Zachary Frosch, MD, MSHP, Assistant Professor in the Department of Hematology/Oncology, and a primary member of the Cancer Prevention Control research program at Fox Chase Cancer Center in Philadelphia.
Frosch, married and father of a toddler son, is a 2022 National Comprehensive Cancer Network Young Investigator Award recipient and has undertaken a research project to develop patient-centered strategies aimed at improving equitable access to cellular therapies.
This interest is a natural progression for Frosch, whose father is a doctor and whose mother is a former research psychologist. Having spent his childhood in Boston, home to many elite medical institutions, Frosch recalled an early interest in all things science.
"Boston is a great science and medical town, so there were really great options to accommodate my probably painfully frequent requests to my parents to do activities set around my interests," he quipped. "As I grew older, I became interested in the social sciences and human behavior. I found the medical field has the perfect blend of science and human elements. After working as an EMT during my undergraduate years [at Wesleyan University in Connecticut], I knew I would go on to medical school."
As an undergraduate, Frosch did a research project as the basis for a senior thesis, which was ultimately published (Addict Behav 2009; doi: 10.1016/j.addbeh.2009.04.007). He examined smoking trajectories over the lifetime of patients and their relationships to health outcomes.
"It was my first foray into a research project that I felt I was driving myself; my mentors provided the balance of guidance and independence that allowed me to take responsibility for moving a project forward," he said. It was also that mix of biological sciences and human behavior that would carry him through medical training and beyond.
Following medical school at the University of Pennsylvania, Frosch returned to Boston for a residency at Brigham and Women's Hospital, served a year as a hospitalist at Dana-Farber Cancer Institute, and completed a fellowship back at Penn where he also earned a master's degree in the science of health policy research before moving to Fox Chase.
Lymphoma Specialization
Today, Frosch's clinical specialty is in lymphoma, "...a very satisfying field because of the rapid pace of innovation and expanding treatment options," he said. "However, there is also a lot of variation in lymphoma types and presentations. There's always something new to consider."
In this specific medical area, despite the aforementioned rapid pace of therapeutic development, "it is also extremely important to have great patience and to help our patients have it, too," stressed Frosch, "because we often spend years observing patients who have indolent lymphomas and currently do not need treatment. But that patience is balanced with a nod to instant gratification. We can very quickly help patients who feel terrible due to an aggressive, uncontrolled lymphoma by starting therapy."
And yet there is still a fly in the ointment. Sometimes patients cannot access the therapy best suited to their disease. "We need to take a step back, think deeply about the problems of access, and ask where the gaps are. Are we doing everything in the best possible ways?" asked Frosch, while explaining the thought process behind his research.
"We have this growing number of effective therapy options for patients, but none of them work if patients cannot receive them," Frosch reflected. "Lack of access can be tied to a lot of factors, including geographic, socio-demographic, and socioeconomic reasons. Patients may live too far away from a treatment center or have limited transportation options even if they are close to a center. Age, social circumstances, and finances are all possible barriers to care. Ultimately, we want only clinical considerations and patient preferences to direct therapy, but we aren't nearly there yet. The question I am asking in my research is: 'How do we get effective therapies to patients more easily?'"
Frosch's line of inquiry started back at Penn with a type of study called a choice-based conjoint analysis. "We presented patients with potential choices between treatment options based on clinical factors, such as efficacy and toxicity, along with the travel they'd have to do to receive treatment, how often they'd have to travel, and whether they could maintain continuity with their current oncologist," Frosch detailed. "Basically, we were boiling down the complex options people face when making treatment decisions into a few factors of particular interest. We wanted to know what the priorities are for patient decision-making."
Unsurprisingly, efficacy and lower toxicity were desirable, as were treatments requiring less travel. "We also found patients have a very strong preference to maintain continuity with their current oncologist; I was surprised by the magnitude of the preference," Frosch noted. "We also looked at preference differences by race and ethnicity. We found that Black patients had a stronger desire to maintain their relationship with their oncologists, and they were less willing to travel than White respondents. We hypothesized that historically based trust issues and resource limitations could be a major driver of that difference."
Research Design
"The clinical scenarios in that earlier research work at Penn were modeled from bone marrow transplants and CAR T-cell therapies, both of which are used for relapsed lymphoma and relate to my clinical interest," Frosch explained. "So now I want to dig much deeper into those issues and hear more directly from patients in interviews. While the choice-based conjoint is a wonderful method to boil down complex decisions and quantify priorities, it doesn't give as much depth as qualitative work does. I think the patient voice has been under-represented in the literature here and I hope we can help to change that."
Working with patients with lymphoma and multiple myeloma whom both have and have not received these therapies, Frosch and the team employ an interview guide they developed based on prior literature, preliminary data, and hypotheses built on theoretical models. "We are conducting semi-structured interviews to determine what patients perceive as barriers and facilitators to receiving treatment," Frosch explained. "We want to hear from patients with a variety of perspectives and experiences."
Also being used within the confines of his research are implementation science techniques. "Basically, implementation science asks: 'What's getting in the way of us using the most evidence-based therapy?' It tries to look at the individual behavior, the context for that behavior at each expanding level starting with the patient, then small systems, and then larger care systems," explained Frosch. "It asks: 'How adaptable is the best treatment? What is the relative advantage compared to other possible interventions? How complex is it to administer? How much does it cost? What can we do to accelerate and increase the use of this evidence-based treatment or intervention? How can it be tailored or refined to the individual context and local needs?"
Still in the early phases of the study, Frosch was asked to pinpoint his hypothesis as to barriers, particularly relating to CAR T-cell therapy. "I think travel, finances both of the treatment itself and expenses of getting to a treatment center, are likely barriers. Also, I suspect trust issues and the willingness to see a different oncologist will be barriers. Prior work in this area shows there are a number of multi-level, interacting barriers which makes access a really complex problem to solve and yet a very interesting one to consider."
Another of Frosch's projects looks at delays to treatment, yet another access-related issue. "I think you can see a theme developing," he said, through a chuckle. "This project is funded by ASCO's Conquer Cancer Foundation and is directed toward facilitating timely cancer treatment. We are using secondary data to look at predictive modeling for treatment delays and an implementation science framework to guide semi-structured interviews to gain both the patients' and clinical teams' perspectives on delays."
As other studies and clinical trials continue to assess when and how cellular therapies should be used, recent findings suggest CAR T-cell therapy might be well-suited to second-line therapy in relapsed patients with aggressive lymphoma, and the potential pool of clinically eligible patients is expanding.
"We really want to make this treatment as accessible and as easy to receive as possible," Frosch stressed. "But the first step has to be identifying the issues, really understanding the complex problems, and all of the dynamics around access. Only then can we design theory-based or evidence-based interventions to overcome access issues, test them, and see if they work."
Asked if there is an overarching message he'd want Oncology Times' readers to absorb about his work, Frosch paused in thoughtful consideration and then answered, "The barriers that patients face are varied, individualized, and complex; they all interact with each other and they're not easy to overcome. There really isn't a 'one-size-fits-all' solution. But the more we understand them from multiple perspectives-between the patient's perspective, the clinical team, and the broader setting-the more tools we'll actually have in our toolbox to make improvements and get patients to where they need to be.
"The real challenge is taking complex circumstances and making potential solutions as simple to implement for patients and their care team as they can possibly be. That is what will lead to patients getting those essential, potentially life-saving treatments. While it's not an easy task, I really believe it's one that is worth pursuing."
Valerie Neff Newitt is a contributing writer.