This study joins a small but growing body of literature that highlights the importance of access to different SOC types, particularly for novel therapies [41, 42]. We found that expected travel burden was consistently reduced at the national and regional levels by expanding CAR T cell therapy access to additional SOC types. The estimated cost difference was substantial, with the $1630 per-patient savings between scenario A and scenario C comparable to the total patient out-of-pocket expense for lymphoma treatment in the month of diagnosis (~$1200) .
Distance and time to the nearest administering facility are key drivers of cost—variables that can be reduced by expanding care. However, in many cases, increasing access to community hospitals was insufficient to significantly reduce travel burden. This nonsignificant reduction occurred in the northeast and south regions, urban areas, and Black and Native American race groups. In contrast, expanding access to NASONCs significantly reduced travel costs among all groups and regions.
The estimated economic burden was highest among patients residing in the west and rural regions, patients of White or Native American race, and those living below the FPL. For many of these populations, high travel burden may represent a true barrier to accessing therapy. The federal poverty guideline for a household of two in 2019 was an income of $16,910 . In our analysis, mean travel costs for both scenarios were a significant percentage of this income level ($5588 for scenario A [33% of the FPL] and $3970 for scenario C [23% of the FPL]). Thus, cost savings ($1619) between scenario A and scenario C represented 10% of this threshold income level, which is a consequential saving.
Expected travel burden may increase further under scenario A if capacity is restricted for novel therapies. Academic hospitals, while large and reputable, are limited in number. Patients would be expected to travel farther distances and thus incur higher costs if only a small number of centers can gain experience administering novel therapies because of network limitations or other reimbursement restrictions.
Costs to establish a CAR T cell program by setting of care (e.g., in community settings compared with community hospitals and academic centers of excellence) may vary. The investment costs have not been estimated; however, in any setting of care, providers in the CAR T cell therapy unit will require focused education consistent with standards provided by the Foundation for the Accreditation of Cellular Therapy (FACT) [44, 45]. Logistical considerations for CAR T cell therapy administration in any setting would include room design to minimize risk of infection and hours to support infusion, monitoring, and time for potential manufacturing delays.
The CAR T cell therapy process has many steps, including leukapheresis or lymphocyte collection, transportation of the collected cells to a laboratory, cell engineering, patient conditioning with lymphodepleting chemotherapy, followed by infusion, patient monitoring and follow-up. Many of these steps can and currently are being performed at the nearest blood center, clinic, or infusion center; however, considerable unnecessary costs are incurred if the patient must travel to an academic hospital or community multispecialty hospital for the infusion, as shown in the extreme sensitivity analysis in which we excluded lodging costs.
Although economic burden may not be entirely realized by the patient or payer, the value of time spent traveling and costs borne by any entity represent suboptimal resource use and potential barriers to care. Pharmaceutical manufacturers and commercial insurance providers have developed patient assistance programs to alleviate the impact of some travel-related direct costs. Manufacturers and payers may be obligated to compensate higher amounts if, on average, patients are traveling farther distances to receive care at academic hospitals. Moreover, patients may be exposed to higher out-of-pocket costs if the assistance programs do not sufficiently cover the high burden associated with traveling to academic hospitals. In both cases, economic inefficiency is realized by restricted SOC access. Beyond the direct costs borne by any stakeholder, indirect costs generated by unproductive and potentially uncomfortable excessive travel represent an unnecessary fee to society and patients’ overall well-being. Our study attempted to value the total economic burden imposed on patients and caregivers, with a focus on travel burden.
Over time, health care payers and pharmaceutical manufacturers have developed de facto centers of excellence networks that have influenced patient access to novel oncology therapies. Manufacturers have established networks of providers in the clinical trials phase, with the goal of achieving consistent practice and low complication rates. Many large payers have developed language in their coverage plans that restrict or encourage referrals to a select subset of providers or centers of excellence. These networks will expand over time, while patient access will be determined by both payer-defined and manufacturer qualifications for administration of therapies, in addition to potential restrictions imposed by the US Food and Drug Administration and governmental payers, including the Centers for Medicare & Medicaid Services.
This study has several limitations. Not all patients with relapsed/refractory DLBCL would be candidates for or elect to receive CAR T cell therapy. Our study assumed that all eligible patients with relapsed/refractory DLBCL would receive CAR T cell therapy; however, a change in the number of patients receiving care would maintain the relative difference between expected travel costs. Additionally, some nonacademic centers may not be equipped to manage patients with comorbidities or predisposing factors after CAR T cell therapy administration, and these patients may require treatment at an academic center. The current landscape of CAR T cell therapy administration sites may have changed since the beginning of 2019, and some states were not included as noted previously . Furthermore, we cannot unequivocally attribute exact costs to patient travel using modeling methods, though the analysis offers important directional insight into the scale of the impact of SOC access for novel therapies.
The inclusion of SOCs specified by available CAR T cell therapy limits the generalizability of the findings to other cancer types. As a descriptive study, this research did not attempt to make causal inferences between geographic access and receipt of therapy or patient outcomes, yet it provides the foundation for this next logical step. Patient incidence data for NHL and DLBCL incidence was estimated as a proportion of NHL using the literature on DLBCL. We assumed there was no geographic variation in DLBCL as a proportion of NHL, which may not be precise; however, the comparability of the scenarios should not be impacted, as these data were applied to all analyses.