To inform our understanding of the costs and barriers that patients might face when participating in a clinical trial, as well as the impact of COVID-19 on those costs and barriers, we gathered related literature for this environmental scan. Our findings are listed in Exhibit VI.I. One key finding was that Black and Hispanic patients, patients over age 65, and rural patients have lower clinical trial participation, which might be driven in part by lower socioeconomic status. Below we summarize the literature that suggests strategies to address barriers to clinical trial enrollment.

Some strategies in the literature that may help address some key barriers to clinical trial enrollment include nurse navigators and decentralized approaches to trials. The use of decentralized or remote trials may help to reduce barriers to enrollment like travel and time commitment (Raciborski et al. 2023, Sehrawat et al. 2023). A study at the University of Southern California found that nurse navigators increased the recruitment rate of Black patients with breast cancer into clinical trials and enrolled 86 percent of eligible patients into clinical trials (Holmes et al. 2012). Guerra et al. (2022) wrote a commentary article on approaches to advance equity in cancer clinical trials. Some of these approaches include the use of patient or nurse navigators to increase understanding of trial benefits and provide decision-making support. The authors also stressed the need for financial and social needs assistance to cover out-of-pocket trial expenses like transportation. Duke Cancer Institute’s Health Disparities & Equity Program implemented a patient navigator program to help patients through both routine cancer care and a Community Health Ambassador Program to promote awareness about clinical trial opportunities (Barrett et al. 2016).

Several studies argued that financial support or reimbursement during trials may help to overcome financial barriers and improve representation (Unger and Fleury 2019, Largent and Lynch 2018, Winkfield 2020). In a nationally representative survey of US adults, Hispanic respondents requested higher amounts of compensation to participate in clinical research than non-Hispanic White or Black respondents (Walter et al. 2013). The authors found that a payment of approximately $350 would yield proportional representation, or willingness to participate, in clinical research. A cancer prevention trial increased the proportion of Black participants from 27.2 percent to 31.5 percent, and the number of total recruits for the trial at sites that received Minority Recruitment Enhancement Grants (MREGs) (Cook et al. 2010). The MREGs were $50,000 grants to trial sites that funded salary support for a minority outreach coordinator, reimbursement for parking and gas for participants, and other recruitment materials. A financial reimbursement program focused on increasing the number and diversity of participants at a cancer clinical trial site in Dallas, Texas (Gerber et al. 2022). The reimbursement program, funded by Lazarex Cancer Foundation, provided funding to patients for non-clinical costs associated with trial participant, including travel and lodging, for patients with household incomes up to 700 percent of the Federal poverty rate. Financial support will be up to $1,500 per month for patients at 400 percent of the Federal poverty rate, up to $1,125 per month for patients between 401 and 550 percent of the Federal poverty rate, and up to $750 per month for patients between 551 and 700 percent of the Federal poverty rate. Another financial reimbursement program funded by the Lazarex Cancer Foundation at two cancer centers in California found that implementing the reimbursement program was feasible at a comprehensive cancer center; however, there was no evidence of improved clinical trial enrollment rates for those receiving reimbursement. The biggest barrier to clinical trial enrollment reported in the study was ineligibility due to screening procedures (Borno et al. 2022b). Finally, an open-label, phase IV trial among Black and Hispanic patients with multiple sclerosis was specifically designed to promote retention and decrease burden by providing reimbursement for childcare, transportation, earnings loss, and travel and by providing more flexibility in visit windows (Williams et al. 2023).

In Exhibit IV.1, we summarize the topic areas for the environmental scan and the key findings for each topic. We also detail the areas where there are gaps in the literature. Based on these findings, topics for future work could include the following (additional detail offered in the right column of Exhibit IV.1):

• Estimates of direct and indirect costs to patients, including out-of-pocket medical spending, travel costs, and lost work productivity, in by trial phase and type.
• Patient’s experience with insurance coverage during the clinical trial, including instances of denied coverage for clinical trial monitoring tests or clinical trial sites that were out-of-network or types of care that were not considered ‘routine care costs’ during the trial.
• The impact of eligibility barriers on clinical trial participation and approaches to adapt trial inclusion and exclusion criteria to reduce eligibility barriers for underrepresented groups.
• Patient’s experience and comfort-level with remote monitoring, telehealth, or other remote technology.

Exhibit IV.1

Environmental scan findings by topic area.

Our environmental scan concludes that there is limited research that quantifies direct or indirect costs to patients during clinical trials and no studies on the impact of the COVID-19 pandemic or clinical trial innovations on these costs. Among the available literature, travel costs and patient-reported financial toxicity are most often studied, and much of the literature focused on cancer clinical trials. There were also limited findings on what type of care is considered routine care by insurers during the course of a clinical trial and limited findings on the impacts of COVID-19 on this coverage or associated costs. However, we did find evidence that routine care coverage policies did not address other insurance-related barriers to clinical trial participation like clinical trial sites being considered out-of-network. Finally, we found literature that indicates that Black and Hispanic patients, patients over age 65, and rural patients are less likely to participate in clinical trials. Because differences in socioeconomic factors, like education level, income, and insurance type, may be an underlying cause of these disparities, addressing the cost of participating in clinical trials might have a downstream effect of improving clinical trial participation among these groups. Further information on estimates of direct and indirect costs to patients by clinical trial type (phase and disease) and on differences for underrepresented groups is needed, including among people with disabilities and older adults. Research to estimate the impact of certain clinical trial innovations like the shift to remote monitoring prompted by the COVID-19 pandemic on these costs could inform whether increased uptake of a decentralized trial approach could address financial and nonfinancial barriers to clinical trial participation.

Footnotes

4

See Exhibit III.2 for a breakdown of the different types of costs covered in the literature and the number of articles that discuss each type of cost.