Perspectives on Barriers and Facilitators to Minority Recruitment for Clinical Trials among Cancer Center Leaders, Investigators, Research Staff and Referring Clinicians

Abstract

Background

The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet, very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, we sought to assess the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment.

Methods

We conducted 91 qualitative interviews at 5 U.S. cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment.

Results

The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) Racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation; 2) Potential minority participants often face multi-level barriers that preclude them from being offered an opportunity to participate in a clinical trial; 3) Facilitators at both the institutional- and participant-level potentially encourage minority recruitment; and 4) Variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities.

Conclusions

Multi-level approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials.

Introduction

To address the longstanding underrepresentation of racial and ethnic minorities in cancer clinical trials, investigators have assessed barriers and facilitators encountered along the trial enrollment pathway from a potential participant’s initial awareness of a clinical trial to his or her acceptance of an offer to participate.¹ National Cancer Institute-designated (NCI) cancer centers potentially serve as unique clinical and research environments, capable of supporting all the steps in the trial recruitment pathway. Success in minority recruitment within cancer centers relies on not only potential minority participants, but also physicians, investigators, other research staff (e.g. nurses, recruiters), and cancer center leaders.^{1, 2} Though these stakeholder groups all play important roles in minority recruitment, the current literature on minority participation in cancer clinical trials relies almost exclusively on the perspectives of potential minority trial participants.^{1, 3–10} Conversely, significantly fewer efforts have been made to gauge the perspectives of cancer center personnel engaged in study design, recruitment and referral of potential trial participants, and institutional policy-making.

Studies focused on non-patient stakeholder groups, have primarily sought physicians’ opinions on minority recruitment in cancer clinical trials.^11–14 In a systematic review, Howerton et al summarized data collected from primary care physicians, oncologists, and other physician specialists, often practicing outside of NCI-designated cancer centers.¹² These studies collectively identified physician-related minority recruitment barriers, such as a fear of losing patients and the laborious effort required for trial referrals.¹² Studies assessing the opinions of cancer clinical researchers have revealed barriers such as their perceptions of minorities’ lack of awareness of the benefits of trial participation and discordance between research priorities and the needs of minority communities.¹⁵ In contrast to these physician- and investigator-focused studies, no prior studies have assessed the opinions of other research staff or cancer center leaders.¹

To address this gap in the literature, we sought to assess the experiences and perspectives among 1) principal investigators, 2) research staff, 3) referring clinicians and 4) cancer center leaders at 5 NCI-designated cancer centers to identify barriers and facilitators to minority recruitment in cancer clinical trials.

Methods

Study Design

The consortium for Enhancing Minority Participation in Clinical Trials (EMPaCT) was established in 2009 among the NCI-designated cancer centers at five institutions: University of Minnesota, University of Alabama at Birmingham, Johns Hopkins University, M.D. Anderson Cancer Center, and University of California, Davis. The goal of the consortium was to systematically address limited enrollment of minorities in cancer clinical trials. In this paper, we present the qualitative research findings from our interviews at the 5 sites to identify barriers and facilitators related to minority trial participation.

Study Population

Qualitative interviews were conducted at each site among four key stakeholder groups: 1) Principal Investigators, 2) Research Staff, 3) Referring Clinicians, and 4) Cancer Center Leaders. Investigators at EMPaCT sites used administrative data on existing oncology studies and personal contacts to identify eligible participants. Participants in each stakeholder group were recruited based on group-specific inclusion criteria (Table 1).

Table 1.

Inclusion criteria for participants in each stakeholder group

Stakeholder Group	Screening Criteria
Cancer Center Leadership	Cancer Center Director or Associate Director Financial Administrators
Principal Investigators (PIs)	Therapeutic and/or non-therapeutic trials for at least 3 years prior to study enrollment
Research Staff	Non-PIs Involved in the ‘day-to-day’ recruitment and/or enrollment of study participants to cancer clinical trials Potentially includes nurses, recruiters, or other research personnel directly involved in recruitment of human subjects
Referring Clinicians	At least 50% of time allocated to clinical duties

Data Collection

Instrument Development

Based on a review of the literature, a specific interview guide for each of the 4 key stakeholder groups was drafted and reviewed by collaborators at each EMPaCT site for content, item clarity, and relevance to minority recruitment in cancer studies. Guides for each stakeholder group included the same content with slight modifications in the wording to fit the corresponding stakeholder group. We also pilot tested each guide with a member of the each corresponding stakeholder group at the UAB Comprehensive Cancer Center and made subsequent revisions based on pilot interviewee feedback. Final interview guides received approval from the respective Institutional Review Boards at all the sites.

Interviewer training and administration of Interviews

Interviewers participated in a 2-day centralized training session, including the fundamentals of qualitative interviewing and mock interviews using the interview guides. Interviewers (n=15) were assigned in a manner to avoid any interviewer collecting data at his or her own institution or from a known acquaintance.

After providing written informed consent, each interviewee participated in a single interview (range = 30–90 min) by a trained EMPaCT interviewer. Interviews were digitally recorded and transcribed. Participants also completed a brief questionnaire which included questions on personal demographics and professional experience.

Data Analysis

Transcripts were coded by a team of 11 coders, trained on the coding process and the 4 interview guides. In Phase I coding, all coders independently reviewed 9 randomly selected transcripts (10% of total sample) and collectively assembled a master codebook comprised of all the codes representing discrete ideas or concepts from the interview transcripts. A subset of 3 more experienced coders (“lead coders”) worked with remaining coders in small groups to reconcile overlapping or discrepant codes. Lead coders then worked with the investigators (RD, MM) to finalize the codebook by adding any novel codes not initially included and agreeing on definitions for each code. All transcripts were coded using grounded theory.¹⁶ To avoid the potential limitations of a priori conceptual framework, we allowed the codes and related themes to be inductively derived from the data. In creating the final codebook, we did rely on the data to establish categories of barriers and facilitators (e.g. participant-, trial-, investigator-, institutional-, and system-level) for ease of organizing the codebook.

Once the final codebook was created, all 91 transcripts were assigned to pairs of coders for independent review in Phase II coding. Paired coders reviewed assigned transcripts independently and were blinded to their partners’ coding decisions. Coding agreement (Kappa analysis) among all pairs of coders was assessed to ensure quality control, and the average level of agreement on coded transcript excerpts was 99.7% between pairs of coders. Codes were consolidated in instances of coder disagreement.

We report only the analysis of those codes categorized as barriers or facilitators of minority recruitment according to the organizational scheme of the codebook. We tallied the frequency of each code within each stakeholder group according to the number of unique interviewees who mentioned that code at least once during his or her interview. For each stakeholder group, we then identified a code as “high frequency” if the code was mentioned by at least 50% of interviewees within that stakeholder group. The interview excerpts associated with the high frequency barrier and facilitator codes for each stakeholder group were reviewed by two investigators (RD, MM) to identify unifying themes. Descriptive statistics were calculated to describe sample demographic characteristics from the questionnaire.

Results

Our sample included 91 interviewees across all 5 sites (Table 2). Principal investigators (n=34) were the largest stakeholder group while cancer center leaders (n=8) comprised the smallest. Men and women were almost equally represented among all interviewees, and over 70% of participants (n=67) were white.

Table 2.

Characteristics of Study Population

Characteristics	Total (N=91)	Principal Investigator (n=34)	Research Staff (n=33)	Referring Clinician (n=16)	Cancer Ctr. Leadership (n=8)
Mean Age (years)	51	46	52	48	60
Gender
Men	43	21	3	12	7
Women	48	13	30	4	1
Race
Caucasian	67	24	26	10	7
African American	11	3	5	3	0
Asian	13	7	2	3	1
Ethnicity
Non-Hispanic	76	29	30	11	6
Hispanic	15	5	3	5	2
Mean number of years cancer trial experience	12	11	10	13	24
Type of trial
Therapeutic	27	4	19	2	2
Non-therapeutic	6	5	1	0	0
Therapeutic and non-therapeutic	56	24	12	14	6
Not indicated	2	1	1	0	0

Among the 4 stakeholder groups, there were both similarities and differences in the high-frequency codes (Figures 1A and 1B). For instance, some barriers (e.g. distrust in research, unmet transportation needs, and the negative connotation of clinical trials) and facilitators (e.g. increasing awareness of opportunities for participation) were high-frequency codes in all 4 stakeholder groups. In contrast, the lack of recruitment training was a high-frequency barrier among only referring physicians and a lack of funding specifically for minority recruitment was mentioned frequently among only cancer center leaders. Among facilitators, the internal referrals were frequently mentioned among principal investigators and research staff, but not by referring physicians or cancer center leadership. The themes emerging from these high frequency codes are listed in Table 3.

Figure 1.

A. High-frequency codes for barriers among 4 stakeholder groups*

*Missing bars for some codes indicate instances when that code was not among the high-frequency codes (mentioned by ≥ 50%) for that stakeholder group.

B. High frequency codes for facilitators among 4 stakeholder groups

*Missing bars for some codes indicate instances when that code was not among high-frequency codes (mentioned by ≥ 50%) for that stakeholder group.

Table 3.

Unifying Themes and representative codes

Theme		Representative Codes
1.	Racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation	Distrust Discomfort with inherent uncertainty of trial participation Negative connotation of clinical trials Low education level Language discordance
2.	Potential minority participants often face multi-level barriers that preclude them from being offered an opportunity to participate in a clinical trial.	Unmet transportation needs Inadequate Insurance coverage Low education level Language Discordance Competing obligations limit time for trial participation
3.	Facilitators at both the institutional- and participant-level potentially encourage minority recruitment	Establishment of rapport (Participant-level facilitators) Tailoring approach to meet specific participant needs Assistance with typical barriers at institutional level
4.	Variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities.	Establish-maintain rapport (External referrals) Feedback important Internal referrals Increasing awareness of opportunities for participation

Theme 1 – Racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation

Participants in all 4 stakeholder groups perceived some skepticism among racial and ethnic minorities about participating in clinical trials. At times, stakeholders in all 4 groups perceived this skepticism to be due to “distrust” in clinical research based on historical research abuses, such as the U.S. Public Health Service Tuskegee Syphilis Experiment, as well as minority populations’ local experiences with discrimination at their respective sites. For example, a principal investigator noted that “there was a real palpable fear in the community around there [cancer center] that, that they [African Americans] had been taken advantage in research”. Interviewees also noted some racial and ethnic variation in the source of distrust. Perceived distrust among African Americans and Native Americans was deemed to have historical origins while distrust among Asians or Latinos was presented as likely to be secondary to more general fears of mistreatment in clinical research.

Interviewees in all 4 stakeholder groups also thought that skepticism among minorities was based on a general negative connotation of clinical trials as well as discomfort with the inherent uncertainty of clinical trials. Interviewees perceived reluctance among minorities to consider trial participation due to “an aversion to the idea of clinical trials”. Stakeholders note that certain buzzwords, such as “experimental”, may trigger some of the negative perceptions among potential participants. Though interviewees noted that these negative perceptions may be present in non-minority groups, the interviewees reported observing this skepticism more frequently in minority groups, such as African Americans. In addition to the negative connotation of clinical trials, multiple stakeholders recalled experiences with potential minority participants seeming to refuse any consideration of participation in blinded randomized controlled trials due to both the random and unknown nature of treatment assignments. Furthermore, stakeholders thought that reluctance to participate based on the inherent uncertainty or negative connotations of clinical trials was more closely correlated with low levels of formal education compared to more firm distrust in clinical research.

Theme 2 - Potential minority participants often face multi-level barriers that preclude them from being offered an opportunity to participate in a clinical trial

Interviewees also perceived that potential minority participants faced barriers, such as lack of insurance and language discordance with providers, that made them fundamentally less likely to be offered an opportunity to participate in a clinical trial. For example, some stakeholders noted that patients without insurance were not offered trial enrollment due to a researchers’ fears of the patients being saddled with a large bill if they were financially responsible for some portion of the care provided in the trial.

That last I want [sic] is someone to enroll in a clinical trial and for them to get a bill in the mail that they’re not expecting (Principal Investigator).

Similarly, many principal investigators noted that often non-English speaking patients are not recruited due to the expense of making consent forms and recruitment materials available in multiple languages. The absence of translated consent forms was notable because “patients who are not able to be consented in English are not enrolled” (Principal Investigator). Though interpreters are available for clinical care, one principal investigator noted that it was “much more of an effort to try and explain a trial to somebody who you either have to do it through a translator [sic]” and described the process as “a barrier for referral of patients to trials”. Principal investigators and referring clinicians suggested that the additional time and effort required with translators could discourage others from even offering trial participation or making referrals to trials among non-English speaking minority patients. In addition, interviewees noted minorities with participant-level barriers such as unmet transportation needs and low levels of formal education, may have limited access to cancer centers even for clinical care, thus, limiting their opportunities for trial participation in studies being conducted in those centers.

Theme 3 – Facilitators at both the institutional- and participant-level potentially encourage minority recruitment

Interviewees in all four stakeholder groups expressed opinions that both participant- and institutional-level facilitators could enhance minority recruitment. The establishment of rapport with minority communities was a primary facilitator mentioned by multiple stakeholders. For example, a referring clinician noted that institutions “need to embrace community activists and community members, church groups, etcetera” to form partnerships with minority communities. Some interviewees even referenced more formalized efforts such as the use of community health advisors who offered education about cancer and clinical research in minority communities to their increase awareness of cancer clinical trials. Once potential minority participants arrive at cancer centers, stakeholders noted that an individual approach with potential minority trial participants was helpful in in buffering any barriers to trial participation. A cancer center leader noted:

Institutions can’t build trust. It’s individuals within that institution that build trust.

A principal investigator added that rapport with potential minority trial participants was established on a participant-level, in a tailored manner, to accommodate an “individual’s particular culture, needs, stated desires, stated biases”. In addition to the establishment of rapport at the individual-level, the availability of cancer center personnel, such as nurse or lay navigators, to address potential minority participants’ more practical needs, including transportation or lodging, may facilitate minority participation in cancer clinical trials.

Theme 4 – Variation between Internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities

Principal investigators and research staff noted that most of the referrals for clinical trials were internal. Stakeholders in all 4 groups noted that these internal referrals were generated by advertisements (e.g. flyers) throughout the cancer centers, the inclusion of potential referring clinicians in research meetings and the use of internal databases listing all active clinical trials. Trial participant screening processes, within the cancer center, were often formalized such that nursing staff could review clinic schedules to identify potentially eligible patients in advance of their clinic visits. Referring clinicians and principal investigators both noted that, ideally, each cancer center patient would be explicitly informed of pertinent clinical trials even if he or she was not eligible, to ensure that all patients, including minorities, would at least be aware of opportunities for trial participation.

I'm educating the patient, too, as we go that if we can put you in a trial that's usually the best care and so that's always discussed as an option even when I know it's not going to be a viable option that we're going to do. (Principal Investigator)

Though potentially talking to all patients about clinical trials may be effective in increasing the proportions of cancer center patients enrolled in clinical trials, multiple principal investigators lamented the fact that the benefit of this approach for minority recruitment was inherently limited by the small numbers of minority patients with access to their respective cancer centers.

Stakeholders noted that the efforts to encourage external referrals were much less formal compared to internal referral processes. In addition to publicly available lists of clinical trials and the formation of clinical and research networks with external providers, interviewees in all 4 groups highlighted the establishment of rapport with individual external physicians as the primary means of encouraging external referrals to clinical trials.

I mean, if you establish relationships, people are going to send you patients. (Principal Investigator)

However, principal investigators also noted that the informal nature of establishing relationships was not necessarily aimed at increasing the recruitment of minorities. Multiple principal investigators also noted the untapped potential to increase access to minority populations through external referrals.

There are certainly different referring doctors that have more of an African American population; another one that has a very large Asian population. So there are certainly ones that have different mixtures of patients. (Principal Investigator)

Some principal investigators expanded on the potential for minority outreach by suggesting that some of the trial procedures should be moved to centers in minority communities to facilitate an increase in the number of external referrals for minority participants.

Discussion

To our knowledge, our study is the first to obtain insights into minority recruitment among four cancer center stakeholder groups across 5 NCI-designated cancer centers. Results indicate that cancer center leaders, principal investigators, research staff, and referring clinicians have some overlapping as well as diverging unique perceptions on the barriers and facilitators of minority recruitment in cancer clinical trials. The study reveals potentially effective approaches to increasing minority enrollment in cancer clinical trials.

Prior studies assessing physicians’ opinions on barriers to minority recruitment have revealed similar perceptions including minority patients’ concerns about being part of an experiment, minority patients’ lack of awareness about available clinical trials, and language discordance between minority patients and researchers.^{2, 13, 17, 18} Our study and prior studies¹³ based, in part, on physicians’ perspectives did not assess opinions of potential minority participants directly. Yet the physician perspectives reflect the same barriers, such as distrust and minorities’ lack of awareness of clinical trials, mentioned following direct inquiries among minority populations.¹ Our study did differ from prior studies based on the perceptions of physicians because we included clinical and research personnel working in a cancer center with a higher likelihood of some exposure or direct involvement in clinical trials.^{1, 2} Furthermore, the inclusion of other non-physician stakeholder groups, such as cancer center leaders and research staff, yielded the full spectrum of perspectives ranging from the global viewpoints of high-level cancer center leaders to the practical experience of staff directly involved in minority recruitment.

Our assessment of multiple viewpoints highlighted significant overlap among the cancer center stakeholder groups. Yet, there were also distinct responses (e.g. lack of recruitment training among referring clinicians) seemingly based on the unique perspective of a single stakeholder group. Consequently, cancer centers should foster communication among all the various stakeholder groups to ensure that minority recruitment needs are being met among all stakeholders and to coordinate, study design, trial referral and policy-making efforts related to minority recruitment.

Similar to prior studies^{1, 2} based on physician and potential minority participants’ perspectives, our interviewees cited minority distrust in clinical research as a frequent barrier to minority participation in clinical trials. However, our study participants also reported wide-ranging minority skepticism about clinical trial participation based not only on distrust in clinical research, but also on the inherent uncertainty of clinical trials as well as the negative connotation of clinical trials. Our findings resemble other studies¹ suggesting that perceived minority skepticism about trial participation may represent other concerns such as a discomfort with being blinded to one’s treatment assignment or simply being averse to being part of an “experiment”. Skepticism about trial participation among potential minority participants may be commonly mistaken for distrust, which many providers feel helpless to address.^{1, 2} However, the recognition of other causes of perceived minority reluctance to consider trial participation, such as uncertainty of trial participation or the negative connotation of clinical trials, may encourage clinical and research personnel to address barriers potentially more amenable to counseling and education.

Though NCI-designated cancer centers often have an abundance of available clinical trials, limited access to these centers may inherently preclude some racial and ethnic minorities from opportunities to clinical trials. If minority patients are less likely to receive care at cancer centers due to multiple barriers including lack of insurance coverage or low educational level, they will also lack access to a significant number of clinical trials limited to these research-intense centers. Even among those minority patients who do gain access to cancer center clinical care, additional barriers such as language discordance may preclude them from receiving care. Given the multi-tiered nature of barriers, cancer centers must address barriers to access to the cancer center at-large as well as more specific barriers to minority trial participation. Targeted efforts to increase external referrals may be one means of increasing access to the cancer center among minority populations. Increasingly, the National Institutes of Health are promoting collaboration of more research intense-centers with minority-serving institutions and providers.¹⁹ Once these partnerships are established, the process of external referrals from outside the cancer center could potentially be formalized and fully integrated into clinical care at other institutions in a similar manner as clinical trial referrals within the cancer center. In parallel, cancer centers may benefit from locating some or all aspects of some clinical trials, when feasible, to sites based in minority communities. The location of clinical trial activities at sites more convenient to minority populations would potentially alleviate those broader barriers minorities face when attempting to access the cancer centers.

Our study results demonstrate multi-level barriers and facilitators at various junctures along the pathway toward minority enrollment. Ford et al presented a conceptual model of minority recruitment in cancer clinical trials highlighting the potential for barriers and facilitators to hinder or promote, respectively, an individual’s 1) awareness of a trial opportunity, 2) receipt of an opportunity to participate, and 3) acceptance of a trial opportunity to participate.²⁰ Our response data exemplifies this conceptual model with barriers and facilitators identified at each of the 3 main junctures of enrollment in the Ford model. For example, a lack of transportation (Theme 1) and less formal external referral procedures (Theme 4) may limit minorities’ access to the cancer center, and thereby, limit their awareness of clinical trial opportunities. Financial (Theme 2) and language barriers (Theme 2) may preclude some potential minority participants from formally being offered opportunities to participate even after they become aware of those opportunities. Finally, patient skepticism of trial participation (Theme 1) may decrease the likelihood of a patient accepting an opportunity to participate in clinical trials. Our data and subsequent themes support the Ford model and reflect the need for interventions to overcome barriers or enhance facilitators at multiple steps along the pathway to minority enrollment.

This study is not without limitations. This is a qualitative study based on interviews at cancer centers, and the data may not be generalizable to other groups, such as community-based physicians and researchers external to cancer centers (e.g. pharmaceutical company investigators). However, we did interview participants in 4 stakeholder groups at 5 different cancer centers in different regions of the U.S. and with different local minority populations to capture a broad range of perspectives. Some of our data are based on clinical and research staff perceptions of potential minority participants’ opinions and behavior. Though the stakeholder data does coincide with an abundance of data in the previous literature based on direct inquiries with minority populations,¹ we cannot rule out the possibility that stakeholders’ views are informed by both their personal experience as well as previously published literature on minority perspectives on clinical trial recruitment.

Conclusion

Cancer center leaders, clinical and research personnel offer unique insight into the barriers and facilitators of minority recruitment. Based on the experiences and opinions of these stakeholder groups, multi-level facilitators are needed to enhance minority trial participation in the face of multi-level participation barriers along the entire trial enrollment pathway. Ideally, these approaches to recruitment could be developed within cancer centers to increase minority trial participation in these research-intense environments.