Abstract
In the last 15 years the annual number of clinical trials registered worldwide increased from 5635 to 202,210. Almost half are currently recruiting in the United States. 1 The growing number is reflected in the diversity in clinical interventions being investigated. Despite such tremendous growth in biomedical research in the USA, the problem of representativeness of trial participants persists.
According to the Food and Drug Administration, in 2011 African Americans and Hispanics comprised 12% and 16% of the US population, respectively, but accounted for only about 5% and 1% of trial participants. 2 In contrast, 67% of the white population accounted for 83% of participants. 2 This rises to 88% for publicly funded cancer phase I–III trials.3,4 In cancer care, where individual characteristics including race and sex, may affect therapeutic potency, pharmacokinetics, and the ultimate effect of a drug, the problem of representativeness is particularly salient.
The National Institutes of Health make it imperative to promote inclusion of women and racial minorities in trials under the 1993 Revitalization Act. 3 However, due to the higher costs associated with including women and racial minority patients, in addition to translation fees required for non-English speaking patients, industry sponsors are not motivated to recruit from these groups.
In addition to establishing a stringent requirement for enrolling women and racial minorities in trials, the Revitalization Act spurred a new field of study that Epstein coined ‘recruitmentology’ or ‘recruitment science’. 6 The field is defined as ‘an empirical body of studies scientifically evaluating the efficacy of various social, cultural, psychological, technological, and economic means of convincing people that they want to become, and remain, human subjects’. While the field of recruitment science has highlighted issues around inequality, representation and health care access, it has largely contextualized barriers to research participation for minorities through frameworks of cultural and therapeutic misconceptions, poor health literacy, mistrust in the health care system, or fears related to experimentation.
Efforts to dismantle barriers to enrollment have focused on these elements, with implementation of initiatives to improve patient awareness of and access to trials. Research centres are developing an online presence through social media and other user-friendly digital platforms for patients to learn about available clinical trials. Concurrently, and in agreement with regulatory standards, studies strive for cost neutrality in order to eliminate the unwanted incentives to participate, such as access to free drugs. While these efforts are important, they do not recognize or address the potential role of additional costs endured by patients who agree to participate. Little attention has been paid to identifying potential direct or indirect financial barriers to participation.
It is clear that health care costs often influence patients’ decisions. Patients consider not only the direct costs of care, such as travel costs, but also indirect costs such as loss of income when attending appointments. Moreover in the context of cancer care, poorer patients are more often overwhelmed by unstable housing and financing which may discourage interest in participating in clinical research. 1
Additional costs may in part explain why lower income patients are less likely to enroll in trials. 7 Unger et al. 7 found income was a statistically significant predictor of clinical trial participation, and the cost of trial participation was a higher concern for lower income groups. This was confirmed by Jimenez et al. 8 who studied clinical trial participation among under-represented populations and found that race and ethnicity was not associated with clinical trial enrollment after adjusting for socioeconomic status. Given that most research centres are located in urban settings, the burden of travel will be greater among rural poor populations.
Health care payment systems may also contribute. There is a dearth of data quantifying difficulty in recruitment to clinical trials due to third-party payment policies. Nationally, policies exist to cover costs associated with standard care received during a clinical trial. The Centers for Medicare and Medicaid Services (CMS) ‘explicitly authorize payment for routine patient care costs… and costs due to medical complications associated with participation in clinical trials’. 9 In order to receive Medicare coverage, clinical trials must also demonstrate ‘desirable characteristics’ as defined by CMS regarding design appropriateness and scientific integrity. 9 In January 2014, the Affordable Care Act mandated private insurers to cover all standard care associated with clinical trial participation. 9 However, as it can be difficult to define standard care and, by extension, designate which costs should be carried by which party (sponsor, research institution, third-party payer), disparities in third-party payment policies continue to affect trials. It is likely that people from lower income groups are more likely to be concerned about payment issues around clinical trials though little research has explored this relationship.
As the costs of clinical trial participation are more significant for poorer populations, measurement of direct and indirect costs is necessary to ensure equitable access. Solutions include prioritizing the implementation of trials in community health care centres and covering the expense of travel through government subsidy or tax incentives. However, in order to promote greater diversity and equality in clinical trial recruitment, researchers and policy makers should be encouraged to work collaboratively to identify, study and eliminate the direct and indirect economic barriers to trial participation.