Direct costs

Direct out-of-pocket costs for cancer patients in clinical trials or receiving standard of care can reach up to a few hundred dollars per month. Exhibit III.3 provides a list of the articles that include estimates of costs to patients, including direct and indirect costs. In total, five articles provide cost estimates for direct, out-of-pocket medical expenses associated with cancer care or trial participation. Both patients enrolled in clinical trials and those receiving standard care may face significant direct costs. One longitudinal survey found standard care cancer patients pay an average of nearly $400 per month for out-of-pocket expenses related to their care (Chino et al. 2018). In a separate cross-sectional study, researchers found cancer patients reporting financial distress may pay over $700 per month out-of-pocket average for standard of care (Chino et al. 2017). A 2011 study of stage I and II breast cancer survivors found that patients mean total monthly direct out-of-pocket costs associated with standard of care were $316 per month (Pisu et al. 2011). For cancer patients participating in clinical trials, one survey found that the average monthly out-of-pocket expenses were $742 (Borno et al, 2022a). We did not identify any articles that provide cost estimates for non-cancer care.

Exhibit III.2

Number of studies by cost type.

Exhibit III.3

Type of trial-related cost estimates to patients, by article.

Academic sources disagree on whether clinical trial participants face more direct costs than patients receiving standard care. Some studies that seek to determine the cost burden to patients participating in clinical trials found little to no difference compared with the costs that patients receiving standard cancer treatment face (Kilgore & Goldman 2008, Sidana et al. 2022). Kilgore and Goldman (2008) calculated prescription drug costs and out-of-pocket costs (not defined by the study team) for patients participating in phase III oncology clinical trials and compared them with the costs of patients receiving standard cancer care. Using multivariate regression, the study team estimated that clinical trial participants paid, on average, $131 more for prescription drugs than standard care patients within a six-month period but did not spend significantly more on out-of-pocket expenses. In a survey of patients presenting to a medical oncology clinic from 2018 to 2020, researchers found that a significantly higher proportion of clinical trial patients reported out-of-pocket expenses exceeding $1,000 in the prior month than patients receiving standard care (Borno et al. 2022a). Borno et al. (2022a) found that clinical trial participants may, in fact, pay nearly $500 more per month on average for out-of-pocket costs associated with care compared with standard care cancer patients. We did not identify any articles that attempted to quantify patients’ costs for non-cancer clinical trials.

Indirect costs

Studies on indirect costs to patients in clinical trials focus largely on travel (that is, transportation and lodging). Travel costs in the literature ranged from $200 to $1,000 per month depending on proximity to trial site, phase of clinical trial, and in-state versus out-of-state patients. Nipp et al. (2019a) found that, on average, patients enrolled in cancer trials from 2015 to 2017 spent at least $600 per month on travel (such as gasoline, tolls, parking, flights, and hotels) related to their care. Among those who participated in clinical trials, the study team calculated that patients who lived in-state spent $212 per month on travel, those who lived in the New England region spent $330 per month, and those who lived outside the region spent $795 per month. The study included patients from phase I, II, and III oncology trials, but most were phase I trial participants. Nipp et al. (2019a) also explored the impact of monthly reimbursements for patients’ indirect costs. Participants receiving reimbursement reported greater improvement in their travel-related financial concerns than those who did not receive reimbursement. Although such findings may seem obvious, the study team notes that reducing travel-related expenses for trial participants may have wider impacts on trial participation and outcomes (for example, improving quality of life, symptom burden, or treatment adherence). Prior studies found similar results, although out-of-region patients spent slightly more on average ($900) in 2013–2014 as compared to 2015–2017 (Nipp et al. 2015). Nipp et al. (2016) also reported that offering reimbursement for indirect costs significantly increased the rate of recruitment.

A survey conducted by Huey et al. (2021) found similar travel costs, as a cohort of patients participating in phase I oncology clinical trials from October 2018 and January 2020 reported spending $600 per month on average for travel, hotels, food, and other non-medical costs; nearly half (48 percent) of survey respondents reported spending at least $1,000 per month on costs related to participating in a clinical trial. We also identified literature on a financial reimbursement program that covered travel-related expenses for oncology clinical trial participants and their caregivers. Borno et al. (2022b) found that 22 percent of patients paid $300 to $1,000 and 11 percent paid more than $1,000 per month for travel. Considering cost based on travel distance, Borno et al. (2018) found that low-income patients spent more on travel than middle- or high-income oncology clinical trial participants ($15.82 versus $3.14 and $3.91, respectively, per trip based on $0.10 cost per mile); the authors theorized that the travel cost discrepancy could be attributable to low-income patients having to commute from rural homes to urban trial settings. The same study found that White clinical trial participants spent more on travel than Black or Asian participants ($5.32, $2.36, and $2.77, respectively), though the study noted that these disparities might be based on the demographics of rural California, where the study population was based (Borno et al., 2018).

Lost wages may comprise a significant amount of indirect costs to patients. Gafford et al. (2017) estimated the cost implications of opening the Midwest Cancer Alliance clinical trial sites affiliated with the University of Kansas Medical Center, which provided patients with in-state access to oncology clinical trials. Based on assumptions related to travel costs, the authors estimated that patients enrolled in in-state clinical trials would incur about $3,240 per year in indirect costs on average (~$280 in milage and ~$2,960 in lost wages), which represented a significant savings compared with the estimated $9,200 in indirect costs to patients that had to previously travel out-of-state for clinical trial access (~$1,900 in milage, ~$1,400 in lodging, and ~$5,900 in lost wages). This was the only study we identified that directly estimated lost wages.

Parking costs at appointments vary by site but could be burdensome, depending on the number of appointments required. Finally, although not specific to patients enrolled in clinical trials, Lee et al. (2020) quantified the parking fees from the 63 National Cancer Institute-designated cancer centers and found that only 32 percent of centers offered free parking for all patients and that parking costs varied considerably across sites (median hourly costs = $2, IQR= $0, $5; median daily costs = $5, IQR = $0, $10). The authors estimated based on average number of expected visits that costs for parking during a standard course of outpatient treatment could reach up to $800 for breast cancer and $665 for head and neck cancer.

Financial toxicity

Rather than recording direct or indirect costs, some studies examine composite measures of patient-reported financial toxicity, which is broadly defined as the financial consequences or burden related to medical treatment. Two commentary articles reiterated the importance of addressing the financial toxicity related to clinical trial participation (Gharzai & Jagsi 2023, Winkfield et al. 2018). Many studies measured financial toxicity among clinical trial participants using a survey or overall toxicity score rather than providing estimates of costs to patients. Although authors have used various measures of financial toxicity in the literature, several studies we identified leveraged the Comprehensive Score for financial Toxicity (COST) measure, which was validated by de Souza et al. (2017). The COST measure is an 11-item patient reported outcome measure in which patients report how much they agree with statements about their financial distress on a Likert scale from “Not at all” (0 points) to “Very much” (4 points). Example statements include: “I feel financially stressed,” “My out-of-pocket medical expenses are more than I thought they would be,” and “My cancer or treatment has reduced my satisfaction with my present financial situation.” Other approaches to measuring financial toxicity included multi-item questionnaires with Likert scale responses focused on financial concerns specific to clinical trial enrollment (Wong et al. 2016). Gharzai and Jagsi (2023) argue for incorporating collection of financial toxicity measures, such as COST and information on direct and indirect costs to patients, during the conduct of clinical trials. They also indicate that further development of culturally sensitive measures of financial toxicity is necessary, because the COST measure was developed using a patient population that was overly-representative of non-Hispanic White participants (74 percent) compared to the general population (58 percent). Systematic reviews indicate that financial toxicity is infrequently assessed during the conduct of clinical trials. Olivier et al. 2023 completed a systematic review to assess how financial toxicity was characterized in cancer clinical trials, among trials that reported any quality-of-life outcomes.³ Only 73 cancer trials measured quality-of-life outcomes, of which about half (53 percent) assessed financial burden and only three percent provided any financial compensation or payments to patients. The systematic review identified the following measures of financial toxicity in the literature: the ‘COST’ measure, the Patient-Reported Outcome for Fighting FInancial Toxicity measure, and a single item question in the QLQ-C30 instrument (“Has your physical condition or medical treatment caused you financial difficulties?). The authors also noted that the drug was provided by the sponsor in about 70 percent of the 73 cancer trials that reported quality-of-life outcomes, which helps to limit the potential out-of-pocket costs to patients. Another literature review focused on the extent to which financial toxicity was incorporated as an end point into studies involving radiation (Prasad et al. 2022). The review included both observational studies and clinical trials involving radiation from 2001 to 2020 and found that less than 1 percent of studies included financial toxicity as an end point, increasing from 0.1 percent in 2001 to 1.5 percent in 2020. The authors found that financial toxicity was often measured using the single item question from the QLQ-C30 questionnaire, as identified by Olivier et al. (2023) and suggested incorporating more financial toxicity measures into research. Kunos and Abdallah (2020) reviewed early and late-stage trials for those with ovarian cancer to assess the extent to which trials measure financial toxicity. Among the articles, 27 percent discussed the financial burden of ovarian cancer on patients, but none were in the context of the trials or specific to novel radiopharmaceutical therapies. We also identified two additional studies in which quality-of-life questionnaires and financial toxicity monitoring were introduced into ongoing trials. Among gynecologic malignancy patients, increased financial toxicity was associated with worse quality-of-life among trial patients (Andring et al. 2023). In a trial that incorporated financial toxicity screening among patients undergoing treatment for metastatic cancer, about one third of patients experienced financial toxicity (Blinder et al. 2023).

The few studies examining differences in financial toxicity by clinical trial participation had mixed findings. One study compared patient reported financial toxicity using a set of 10 questions adapted from the Medical Expenditure Panel Survey from the Agency for Healthcare Research and Quality. The authors found no differences in financial toxicity between those enrolled in clinical trials and those receiving standard of care for patients with multiple myeloma or lymphoma (cancer of the plasma cells or lymphatic system) (Sidana et al. 2022). However, Keilson et al. (2022) examined differences in the COST measure of financial toxicity by clinical trial enrollment for patients with cholangiocarcinoma (cancer of the bile ducts) and found that patients in clinical trials reported higher financial toxicity than patients who were not enrolled in a clinical trial, despite having higher reported quality-of-life.

Definitions of routine care

Several commentary articles identified the challenge in defining routine care during trials. Researchers suggest that there is considerable patient confusion about the costs that they might incur while participating in a clinical trial, which could contribute to concern over costs—some patients might not know that routine care costs associated with clinical trials are covered by insurance as a provision of the ACA, and others might not know that they could face out-of-pocket expenses while participating in a clinical trial (Manne et al. 2015). A commentary article by Bierer et al. (2021) highlighted the complexity of defining “routine care coverage,” which could include “ancillary medical care, physician and hospital visits, and treatment of research-related injury.” The authors also highlight that trials that qualify for routine care coverage among Medicaid beneficiaries only represent a small proportion of all trials and that those without insurance have no access to trials. The authors of a different commentary article highlighted some key limitations of the ACA legislation on routine care cost coverage, including unclear coverage provisions for experimental or phase I trials, the absence of a clear definition of routine care costs, and unclear coverage of routine surveillance tests during clinical trial follow-up (Martin et al. 2014).

Access barriers despite routine care cost coverage

Despite requirements to cover routine care costs, gaps in policy coverage can limit access to trials for those with insurance. A commentary article assessed what proportion of women with gynecologic malignancies had access to in-network cancer centers accredited by the National Cancer Institute. The authors found that 40 percent of Medicare Advantage plans and 33 percent of private insurance plans did not have in-network cancer centers, which limited their patients’ access to clinical trials because of out-of-network costs despite requirements for routine care coverage (Bodurtha Smith et al. 2022). Martin et al. (2014) also mentioned that a key limitation of the ACA legislation is that plans are only required to cover out-of-network clinical trial costs if the plan already provides coverage for out-of-network services. The American Society of Clinical Oncology issued a policy statement focused on barriers to clinical trial participation that described the limitations for out-of-network care and the financial burden associated with cost-sharing such as coinsurance during clinical trials (Winkfield et al. 2018). The American Society of Clinical Oncology also recommended that payers have clear definitions of routine costs and streamline the prior authorization process.

Other results relevant to routine care costs

Studies found ACA’s routine care coverage legislation had limited impact on trial participation before COVID-19. Mackay et al. (2016) estimated the change in the number of people in Kansas ages 19 to 64 with health insurance coverage for clinical trial participation after the ACA through 2014. The authors found the ACA had limited impact on coverage rates for clinical trial participation because self-funded and Medicaid plans were not subject to the ACA requirements and because most people who were uninsured before the ACA remained uninsured after. Prior to the implementation of the ACA, Ellis et al. (2012) examined the impact of state-level policies requiring insurers to cover patient care costs in clinical trials on the rates of clinical trial enrollment in these states. The authors found no difference in clinical trial participation rates among National Cancer Institute Community Clinical Oncology Program practices in states with and without coverage mandates. The authors suggested that the varying strength of states’ policies may have attenuated the impact, though one study of trial enrollment at a single large cancer center found an increase in insurance clearance for oncology clinical trials for privately insured patients after the implementation of the ACA (Kehl et al. 2017).

Before 2022, state Medicaid policies were complex and restricted access to clinical trials for beneficiaries. Mupfudze et al. (2021) conducted a qualitative analysis with pediatric bone marrow transplant financial coordinators across 10 states in 2019 and found that only 2 states required Medicaid to cover routine medical costs for patients in clinical trials (Florida and Texas). One state (Michigan) provided coverage for transportation and lodging through Medicaid but did not have legislation requiring routine care coverage during clinical trials. Although state coverage of routine care was not prevalent prior to 2022, there was evidence of a growing proportion of clinical trial patients enrolled in Medicaid. Unger et al. (2023) examined the impact of Medicaid expansion on the number and proportion of clinical trial patients covered by Medicaid across the Southwest Oncology Group Cancer Research Network from 1992 to 2020 and observed a 19 percent increase in the odds of patients using Medicaid insurance in clinical trials after expansion. Female Medicaid beneficiaries had a greater increase in clinical trial participation than male beneficiaries during this period, but there were no significantly different trends by race, ethnicity, or age. Starting in 2022, all state Medicaid plans must cover routine care costs during clinical trials, but we did not identify any articles that evaluated the impact of this new policy (Social Security Act §1905(a)(30)).

Financial barriers

The main financial barriers to clinical trial participation cited in the literature were cost concerns (in particular out-of-pocket costs for direct medical costs and indirect costs such as travel, as well as insufficient insurance coverage). Chino and Zafar (2019) reviewed the literature on the impact of financial toxicity on clinical trial participation and found that worries about out-of-pocket expenses and concerns about insurance coverage result in lower-income patients being less likely to participate in clinical trials. In a study of 1,256 cancer patients, worries about health insurance coverage of clinical care costs represented one of the strongest barriers to clinical trial participation (Nipp et al. 2016). Information on actual costs of additional out-of-pocket expenses was limited, with one study reporting a substantial proportion of patients in cancer clinical trial taking on credit card debt and spending more than 10 percent of income on medical expenses, which equated to an estimated $600 a month per participant (Nipp et al. 2019a). For participants receiving Medicaid benefits, there were historically no federal mandates for clinical trial coverage, making it prohibitively expensive for many Medicaid beneficiaries to participate in clinical trials (Winkfield et al. 2018). In addition, lack of transparency of potential trial-related out-of-pocket costs and payers’ clinical trial coverage policies were barriers to participation (Winkfield et al. 2018). Here, we summarize the findings on financial barriers in the literature and review any literature in which financial barriers might differ for underrepresented groups.

Lower socioeconomic status, including lower income, underinsurance, and lower educational attainment, might confound the association between being in an underrepresented group and lower rates of clinical trial participation. We found several articles that suggest that underrepresented groups, such as racial minority patients and younger adult patients, have lower socioeconomic status, which could explain their lower rates of participation. In a survey of clinical trial sites, MacLennan et al. (2023) found that survey respondents at clinical trial sites reported that lack of reimbursement and lack of payment for participation, in addition to lack of translator services, were the biggest barriers to improving diversity and inclusion in clinical trials. Socioeconomic factors, such as underinsurance and having less than a high school education, were found to be the biggest barrier to minority recruitment in multiple papers and were found to be stronger barriers than race (Duma, 2017; Williams et al. 2021; Manne et al. 2016). One study highlighted that populations with historically lower financial resources including uninsured patients and minority patients were found to have lower clinical trial enrollment overall (Nipp et al. 2019b). Perni et al. (2022) found that patients who reported financial burden were younger and more likely to have incomes less than $60,000 USD. In another study Black patients and patients in areas of higher disadvantage had lower odds of enrollment, highlighting the confounding effects of systemic issues and socioeconomic status (Caston et al. 2022).

Two studies, however, found that racial minorities either were no more likely to report financial burden or were less likely to report financial burden than non-Hispanic White patients. Using the Health Information National Trends Survey of U.S. adults, 55 percent of respondents reported at least one cost-related factor that would influence their willingness to participate in a clinical trial (C. Williams et al. 2023). Patients who were “not living comfortably on their current income” were more likely to report a cost-related factor that would influence trial participation, but there was no association with reported annual household income. In this survey, younger age, non-Hispanic White race, and higher education levels were associated with increased reporting of cost-related factors influencing trial enrollment. Among patients with cancer who were enrolled in clinical trials and referred for financial assistance, 57 percent reported financial burden and 41 percent reported cost concerns (Perni et al. 2022). Patients with lower income were more likely to report both financial burden and cost concerns, and there were no significant differences by other sociodemographic or clinical factors (such as sex, race, type of insurance, trial type, or trial phase).

Patients in rural areas or those living farther from the clinic commonly reported financial barriers. In a survey of rural patients with cancer in West Virginia, 53 percent listed monetary burden and 36 percent listed commute as strongly influential factors in their decision to participate in a clinical trial (Virani et al. 2011). Among the approximately 5,500 survey respondents in a survey about factors associated with clinical trial participation, lower income and longer distance to the clinic were both statistically significantly associated with lower rates of clinical trial participation, and lower income patients reported more concerns about how to pay for clinical trials (Unger et al. 2013). In a separate survey of about 1,300 breast, colon, and lung cancer patients at eight Southwest Oncology Group clinical sites, annual household income less than $50,000 was associated with a 32 percent lower odds of clinical trial participation (Unger et al. 2016). The association between income and trial participation was magnified among two subgroups in this study: those living more than 13 miles from the clinic and women, who had significantly lower odds of trial participation (43 percent lower and 36 percent lower, respectively).

Non-financial barriers

Non-financial barriers identified in the literature included lack of patient or provider knowledge about clinical trials, mistrust, complexity of protocol requirements and exclusions, lack of invitation or encouragement from providers to participate, logistical barriers (including the ability to take time off of work, travel, and caregiving coverage), and individual patient factors (Chino & Zafar 2019; Nipp et al. 2019b; Paidipati et al. 2022). These individual level barriers to clinical trial participation include fear of adverse effects, mistrust in science, cultural or religious beliefs, and poor health literacy (Duma et al. 2017, Rocque et al. 2022). These findings were consistent with findings from a survey of 1,256 patients assessing demographic factors and attitudinal barriers that found that the most significant barriers were fear of side-effects, worry about health insurance, and efficacy concerns (Manne et al. 2015). Below we summarize the findings on non-financial barriers in the literature and review any instances in which non-financial barriers might differ for underrepresented groups.

Two studies suggested that lack of information on available clinical trials were barriers for rural patients and racial and ethnic minorities. In a study focusing on barriers to rural patients’ access to clinical trials only 19.6 percent of rural patients surveyed reported that their health care teams discussed clinical trials with them. Among those who did discuss clinical trials with their care team, 59.8 percent said their decision not to participate in a clinical trial was strongly influenced by discouragement from their oncologist, and 49.4 percent cited discouragement from a family physician. Monetary burden, the commute, and lack of information were also cited as highly influential factors in deciding to participate in a clinical trial (Virani et al. 2011). Hamel et al. (2016) also cited medical staff’s awareness of trial availability as a barrier to participation for racial and ethnic minorities with cancer.

Although there was some mixed evidence, studies generally found that racial minorities and rural patients are no less likely to be willing to participate in clinical trials. Using a linkage of patient-reported outcomes, electronic health records, and clinical trial data, Caston et al. (2022) evaluated the association between underrepresented patient populations and clinical trial eligibility, interest, and enrollment for patients with breast or ovarian cancer. After adjusting for age, cancer type, insurance type, living in a rural area, and their zip code’s Area Deprivation Index, Black patients had similar odds of trial eligibility but lower odds of interest (odds ratio [OR]=0.40; 95 percent confidence interval [CI]: 0.18, 0.90) and enrollment (OR=0.56; 95 percent CI: 0.32, 0.98) in clinical trials as compared to White patients. Clinical trial eligibility, interest, and enrollment did not differ for rural versus urban patients. Patients living in areas of high neighborhood disadvantage, as measured by the area deprivation index (ADI) had lower odds of enrolling in clinical trials than those in areas of lower ADI (OR=0.46; 95 percent CI=0.24, 0.89). Similar results were found using data from the Health Information National Trends Survey in 2020, where Williams et al. (2021) detailed the association between history of clinical trial participation and age, race/ethnicity, rural versus urban residence, insurance coverage, and health status. In a multivariate regression, Non-Hispanic Black patients were more likely to be invited to join a trial (OR=1.85; 95 percent CI=1.13, 3.02), but less likely to participate in the trial than non-Hispanic White patients (OR=0.28; 95 percent CI=0.09, 0.87). Rural residents were less likely to be invited to join a trial compared to urban residents (OR=0.33; 95 percent CI=0.17, 0.65). However, one study cited by Hamel et al. (2016) suggested that overall, individuals from minority populations are as likely as White individuals to consent to participate if they are offered a clinical trial. Further, in the National Academies of Sciences, Engineering, and Medicine’s 2022 report on “Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups”, the literature on willingness to participate generally indicated that racial minorities and those in rural areas were no less likely to be willing to participate if asked (NASEM 2022). Some key papers in this report include Langford et al.’s (2014) review of National Cancer Centers Program data, which found that there were no differences in willingness to participate in trials for Asian, Black, and Hispanic Americans as compared with White Americans. Those living in rural areas were also no less likely to be willing to participate in a large study in Arkansas of more than 5,000 individuals (McElfish et al. 2018) and in a small study across several southern states and Puerto Rico (Thetford et al. 2021). In general, most studies did not find differences in willingness to participate in trials for underrepresented groups. One of the two studies with differing results was fielded in one southern state (Caston et al. 2022), and the other was fielded at the beginning of the COVID-19 pandemic (Williams et al 2021), limiting their generalizability.

Availability and proximity of clinical trials were noted as barriers to enrollment that particularly affected under-resourced and rural communities. In a qualitative study of low-income, multiethnic patients with cancer, despite financial reimbursement from the Lazarex Cancer Foundation for expenses associated with trial participation, patients reported significant barriers related to the time commitment required for trial participation, as well as indirect costs such as lodging and travel (Medina et al. 2023). There were a number of studies focusing on barriers to clinical trial participation for rural individuals. In a study of patients enrolled in clinic trials between 1993 and 2014 at the University of California San Francisco the researchers found that patients from lower-income areas (n=5,799) traveled longer distances than patients from higher-income areas (n=5,773; 58.3 vs. 17.8 miles, respectively; p < .001) (Borno et al. 2018). The same study also found that White patients (83 percent) traveled longer distances than Black patients (4.4 percent), with median distances of 29.9 and 13.9 miles, respectively (p < .001); however, the study cited California’s demographic mix in rural areas as the likely main factor in travel distance disparity, as rural areas of the state have a greater number of White residents. In tandem with individual proximity to clinical trials, availability of clinical trials was also cited as a barrier to participation. In addition, Hamel et al. (2016) created a multilevel model to analyze disparities in clinical trials at the system, individual, and interpersonal level. Using their model, the team reported a limited number of trials available both nationally and regionally, as well as inadequate hospital infrastructures and resources to participate in clinical research. These factors were found to disproportionately affect enrollment for minority populations who are more likely to receive their care at under-resourced hospital systems.

Complexity of clinical trial protocols present particular barriers for older adults. Duma et al. (2017) found that because of the aggressive therapies involved in most clinical trials, elderly patients may be unwilling to accept the additional treatment toxicity which may not be aligned with their care goals. Duma and colleagues also mentioned that older adults are more likely to have comorbidities that may make them ineligible for trial participation. In a study conducted by BrintzenhofeSzoc et al. (2022) using focus group interviews of older adults who were patient representatives for the National Cancer Institute’s Community Oncology Research Program, other barriers to enrollment included complex consent forms, not being referred to trials, patient costs, cultural insensitivity, limited accessibility in community setting and transportation issues.

There is some evidence that Black and Hispanic patients are more likely to report logistical barriers to clinical trial participation, such as difficulty being able to secure time off work or obtaining childcare. Qualitative research among Black and Hispanic patients found that in addition to barriers such as trust, logistical barriers such as time conflicts and childcare responsibilities were important factors that precluded participation in research (Calderon et al. 2006).

Several studies found that underrepresented racial and ethnic minorities and rural patients were less likely to meet trial eligibility criteria because of more advanced disease, worse health status, or potentially implicit bias. In an asthma trial, patients from underrepresented racial and ethnic groups were less likely to meet the inclusion criteria of adequate response to the methacholine challenge (Hardie et al. 2010). The authors indicated that the cutoff for adequate response did not account for known differences in methacholine responsiveness for racial and ethnic minorities, indicating a need to account for disparities in exclusion criteria in trial design. Several other studies indicated that racial minorities may not meet eligibility criteria because of more advanced disease or delayed diagnoses, which may be driven by lower rates of cancer screening and confounded by socioeconomic differences (Giuliano et al. 1998; Ward et al. 2004; King et al. 2011). Later stage at diagnosis, which may preclude eligibility, was more common among rural patients (Virani et al. 2011). A pair of companion papers looking at enrollment of pediatric patients in a bronchiolitis trial found that Hispanic patients were less likely to be deemed ‘appropriate’ with vague justifications for their ineligibility (Coon et al. 2022; Popkin et al. 2022).