Enrolling Older Adults Onto National Cancer Institute–Funded Clinical Trials in Community Oncology Clinics: Barriers and Solutions

Abstract

In April 2021, the National Cancer Institute (NCI) Division of Cancer Prevention collaborated with the NCI Division of Cancer Treatment and Diagnosis to produce a virtual workshop that developed recommendations for enhancing NCI-sponsored clinical trial accrual of older adults. Prior to the workshop, a multidisciplinary group of stakeholders (eg, community oncologists, advanced practice practitioners, clinic and research staff, and patient advocates) gathered information related to accrual of older adults to clinical trials from the literature. Subsequently, a survey was conducted to detail NCI Community Oncology Research Program members’ perspective on accrual barriers for this population; 305 individuals responded to the survey. Barriers to clinical trial accruals included comorbidity-attributed trial ineligibility, transportation and time issues, concern that the proposed regimen is too toxic for older adults, patient or family caregiver declined participation, and lack of trials relevant to older patients. Identified solutions included broadening clinical trial inclusion criteria, increasing the number of clinical trials specifically designed for older adults, simplifying consent forms, improving recruitment materials for older adults and their families, and facilitating transportation vouchers. At the workshop, participants, including stakeholders, used prior literature and survey results to develop recommendations, including interventions to address clinician bias, implement geriatric assessment, and promote clinician and staff engagement as mechanisms to improve accrual of older adults to clinical trials.

Cancer diagnoses occur in 42% of patients aged 70 years and older (1), yet less than 10% of patients in this age group participate in National Cancer Institute (NCI) clinical trials (2). Consequently, care innovations established by clinical trials often lack efficacy and effectiveness in this older population. Gaps in knowledge on how to improve outcomes of older patients with cancer remain, especially for those who are aged 70 years and older and who have aging-related conditions. In April 2021, the NCI Division of Cancer Prevention collaborated with the NCI Division of Cancer Treatment and Diagnosis to produce a virtual workshop that developed recommendations for enhancing NCI-sponsored clinical trial accrual of older adults. A primary goal of the workshop was to identify modifiable barriers to clinical trial participation among older patients, including clinician bias. Prior to the workshop, a multidisciplinary group of researchers, NCI staff, and stakeholders (eg, community oncologists, advanced practice practitioners [APP], clinic and research staff, and patient advocates) convened monthly for 6 months. The group collated evidence from the literature prior to the workshop, and qualitative themes from the literature guided the development of a survey to assess NCI Community Oncology Research Program (NCORP) members’ perspective on accrual barriers of older adults to NCI-funded cancer clinical trials in community oncology clinics. NCORP is a national network that brings cancer clinical trials and cancer care delivery studies to patients where they live in their communities; NCORP sites are community oncology practices, and the network includes more than 9000 physicians, APPs, nurses, and research staff (3). The survey primarily solicited community oncology clinicians and their research staff because community oncology clinics provide care for the majority of older patients with cancer (4). At the workshop, participants reviewed the literature synthesis and survey results and discussed pragmatic recommendations that could guide NCI efforts to improve accrual of older adults to cancer clinical trials. Workshop participants included the multidisciplinary group that convened prior to the meeting; additional National Institutes of Health staff and scientific leaders, leaders of the NCI-funded cooperative groups, and stakeholders also attended the workshop.

In this manuscript, investigators report the literature that was considered to inform the workshop agenda and activities. Survey results detailing NCORP members’ perspective on accrual barriers for this population and potential solutions are also included. The referenced literature and survey results informed pragmatic recommendations to address common oncology team–identified barriers to accrual of older adults to NCI-funded cancer clinical trials.

Overview of Key Manuscripts From the Literature

Tejeda and colleagues (5) reported age disparities in NCI-sponsored cancer treatment trials as early as the 1980s. Trimble et al. (6) later noted older adults were underrepresented in clinical trials, particularly in trials studying the safety and efficacy of treatment for cancers disproportionately impacting this population; prostate cancer, predominantly observed among older men, provided the exception. Kornblith and colleagues’ pilot study (7) assessed provider-perceived accrual barriers to breast cancer clinical trials. Respondents in this pilot study (n = 156; 85% oncologists) noted that transportation needs (68%), comorbid conditions (53%), treatment toxicities (51%), poor compliance due to difficulty understanding complicated trials (50%), and patient ineligibility per study inclusion criteria (36%) presented accrual challenges for older adults. Proposed solutions suggested by the respondents included dedicated clinic personnel to explain clinical trials to older patients (69%), dedicated educational material for older adults (63%), provision of transportation (63%), better educational material for family members (59%), and fewer exclusion criteria (49%).

Kimmick et al. (8) designed and tested a geriatric educational intervention to improve cooperative group–sponsored treatment trial accrual of cancer patients aged 65 years and older. Institutions received standard information (n = 73) or an educational intervention (educational seminar, educational materials, a list of available protocols, e-mail and mail reminders, and a case discussion seminar); the study’s primary endpoint was percentage of older adults accrued to phase II and III trials. Analyses did not reveal any accrual differences between the 2 groups. The investigators concluded that more intense and multifaceted approaches may be necessary to increase accrual. There are no other published randomized controlled trials explicitly striving to increase accrual of older adults to clinical trials (1).

More recent studies affirm that accrual challenges persist. Freedman and colleagues’ (9) investigation of accrual barriers noted that respondents (clinicians enrolling patients onto studies for the Alliance Cooperative Group) most frequently identified the following barriers: inability to meet eligibility criteria (67.5%), treatment regimens were too toxic (44.4%), transportation issues (44%), patient or family preference not to enroll (35%), and concern for limited life expectancy in older patients (28%). Potential recommended strategies included dedicated trials for older adults (36.3%), minimizing exclusion criteria focusing on comorbidity (35.5%), developing specific strategies for those aged 65 years and older separated from those aged 70 years or older (33.2%), requiring expansion cohorts of older patients (30%) and creating standardized educational interventions for family members and caregivers (22.3%).

Sedrak et al. (1) published the most comprehensive systematic review of barriers and interventions for older adult participation in clinical trials to date. Investigators employed PRISMA guidelines (10) to identify 145 full-text articles for review. Investigators subsequently included only 13 studies that identified systemic, provider, patient, and caregiver barriers in the analysis. Systemic barriers included eligibility criteria, consent form language, and trial availability. Provider barriers included toxicity concerns, preference for other treatments, time and burden to enroll on a clinical trial, lack of personnel, preference against research, and lack of awareness of eligible trials. Patient barriers included knowledge of clinical trials, transportation, time and burden, toxicity concerns, financial concerns, belief that they were too old, and emotional burdens. Caregiver concerns included burden and preference against research. Recommendations to expand inclusion of older adults to cancer clinical trials included specific trial design for older adults, measurement of relevant endpoints, broadening of eligibility criteria, addressing specific site and stakeholder barriers, pragmatic clinical trial design, and leverage of real-world data.

More recent reports affirm accrual barriers’ persistence, with the current pandemic exacerbating preexisting roadblocks (11,12). Consequently, investigators surveyed community oncology clinicians and staff within NCORP to clarify current perceptions and solicit recommendations to address barriers in this current climate.

NCORP Survey

Methods

The aforementioned studies informed NCORP survey questions to assess respondent perceptions about barriers and solutions and use a Likert scale of 0-5 (0 = never or the least; 5 = always or the most). The multidisciplinary group adapted survey questions from previously completed studies for this study (7,9). Investigators invited participants to rank their top 5 barriers and solutions and to comment on their own experience or perspective on the noted barriers in open-ended questions, including possible solutions and research gaps. Investigators solicited all NCORP clinicians (physicians, APPs, nurses) and staff (including coordinators and administrators) and collected data anonymously via a web-based platform. The University of Rochester NCORP Research Base received and analyzed the de-identified data in aggregate. To develop qualitative themes, a thematic analysis approach (13) was used, which included 1) quotes from the open-ended questions were pulled from the database into an excel document in a tabular form; 2) using inductive open-coding, 2 reviewers (KM and SG) organized themes into similar categories; 3) themes were reviewed by the authors; and 4) exemplar quotes were identified for themes by the authors.

Results

Respondent Characteristics

A total of 305 individuals responded to the survey; 50% were coordinators, 38% were physicians, 5% were administrators, 3% were APPs, and 5% categorized themselves as other. Of the physicians, 13% self-identified as medical oncologists, 12% as an NCORP principal investigators, 6% as an NCORP physician, 4% as a surgeon, and 3% as a radiation oncologist. Seventy-three percent identified as female. Of the individuals, 76% reported age as between 36 and 65 years, 14% were aged younger than 26 years, and 9% were aged older than 65 years. A total of 58% reported being in practice for 11 or more years, and 20% identified as members of a community cancer center, 37% identified as being in private practice, and 37% worked in academic medical centers. Of the respondents, 33% characterized their practices as 26% to 50% rural, 43% had less than 25% rural patients, 6% of practices were 76% to 100% rural, and 6% were not rural.

Barriers and Solutions

The top 5 barriers to accrual included comorbidity-attributed trial ineligibility (84% chose as a top 5 barrier); transportation issues and the time involved with clinical trial participation (58%), concern that the proposed regimen is too toxic for older adults (56%), patient or family caregiver declined participation (49%), and lack of trials relevant to adult patients (42%). These barriers also had the highest mean scores on the Likert scale for concern (Table 1). Barriers rated relatively less problematic included fear of patient compliance, the time required to discuss or explain a clinical trial to an older adult, physician bias, requirement for some trials to perform geriatric assessment (GA), and lack of knowledge to assess fitness prior to enrollment.

Table 1.

Barriers with most concern

Barrier with most concern	Mean (SD)	Median (IQR)	Range	Exemplar quotes
Failure to meet clinical trial eligibility requirements because of comorbidities	3.34 (0.70)	3 (1)	1-5	“Organ function eligibility requirements may be too strict for older adults eg, creatinine clearance.” “The single biggest barrier is creatinine clearance. I would say that 90% of my patients older than 75 cannot meet the creatinine clearance threshold specified for any study.” “I have a lot of older adults fail because the lab entry criteria are too strict and they are often mildly anemic and in real life I would treat but would not be allowed in trials.” “Comorbidities and specifically previous cancers have been a big issue.”
Transportation issues; distance to the treatment center, time considerations	3.09 (0.89)	3 (2)	1-5	“Lack of payment for hotel and transportation for our rural patients.” “VA insurance.” “Lack of CRA support at remote part time rural clinic sites.” “Time commitment related to a study can be a huge barrier for older adults. They would rather have to spend less time in my setting (hospital).” “Enrollment takes too long.”
Proposed regimen is too toxic for the older adults	3.03 (0.81)	3 (0.75)	1-5	“In some instances, patients themselves opt for less toxic approaches due to age, performance status, quality of life concerns, and perceived life expectancy.” “In elderly or patients with many comorbidities, they are either ineligible or not suitable for aggressive chemotherapy regimens.” “Hearing loss is a major barrier to trial enrollment in the elderly.” “Concerns about cognitive capacity for consent.”
Patient or family and caregiver preferences not to participate in clinical research	2.87 (0.92)	3 (2)	1-5	“Older patients are choosing not to treat their cancer.” “Patients feeling too overwhelmed at new diagnosis.”
Lack of trials relevant to older adult patients	2.85 (1.05)	3 (2)	1-5	“Docs and nurses and clinical staff frequently think supportive care trials are too burdensome for elderly patients and the clinical staff act as barriers and gatekeepers.”

Qualitative themes regarding barriers included eligibility concerns, perceptions that older patients choose less toxic treatments than proposed in the clinical trial and want trial designs for them specifically (vs accrual onto trials open to anyone who meets eligibility), impressions that clinical trials are too burdensome for older adults, and concerns that there is not sufficient family and caregiver support (Table 1). Clinicians and staff reported believing most supportive care trials are too burdensome for older patients and doctors and nurses act as gatekeepers. Respondents expressed concern over technology expectations (eg, smartphone availability) and presumed prospective enrollees desire paper option for questionnaires. Respondents also expressed that family and caregivers are essential and should be included in the research process as much as possible to support patient’s well-being, adherence to trial, and ability to comply. Many respondents reported family members needed to be more involved in trial design owing to their presumed knowledge of the patient or challenges patients face; care navigators also are of great importance to facilitate patient involvement and overcome barriers.

The top 5 rated solutions were as follows: broadening clinical trial inclusion criteria (75% rated in the top 5); increasing the number of clinical trials specifically designed for older adults (70%); simplifying consent forms (56%); improving recruitment materials for older adults and their families (52%); and facilitating transportation vouchers (52%). Table 2 reports mean scores for solutions and exemplar quotes.

Table 2.

Most supported solution^a

Most supported solution	Mean (SD)	Median (IQR)	Range	Exemplar quotes
Real-world exclusion criteria including the usual comorbidities older adults have	4.10 (1.01)	4 (1)	1-5	“Less stringent eligibility criteria related to renal and liver function as well as comorbidities would also make it easier to enroll older adults.” “Definitely need to expand criteria including ECOG to 0-2 or up to 3 if felt to be disease related; CKD and other common comorbidities permitted.” “Number 1 would be to make inclusion exclusion criteria age friendly.”
Create trials specifically for the older adults	4.01 (0.98)	4 (1)	1-5	“Dosage and/or treatment options should be modified to include safer treatment options for elderly participants.”
Simplify consent forms	3.79 (1.10)	4 (2)	1-5	“Simplify things (the consent, provide tools to help patients and their families stay organized or better understand the trial and its activities).”
Targeted trial recruitment material for older adults and their family/caregivers	3.71 (1.03)	4 (1)	1-5	“Have a rundown created for each study, showing exactly what would be expected on the study from the patient’s point of view.” “Support groups—identify other patients who can help ‘mentor’ particularly patients who are widowed and live alone.” “Generic (not study-specific) research recruitment materials noting benefit to future generations.”
Provide transportation voucher or gas card for trial participants 65 years and older	3.64 (1.13)	4 (2)	1-5	“Assistance with insurance issues and co-pays for those on fixed budgets.” “Transportation vouchers should be done for everyone.” “Leverage home health, virtual medicine, or other vehicles to fulfill research requirements and data collection while minimizing patient expense, discomfort and burden on family/support.”

^aCKD = chronic kidney disease; ECS = Eastern Cooperative Oncology Group.

An important theme from the open-ended questions centered on technological barriers. Specifically, providers reported data collection concerns (patient-reported outcomes or virtual visits) requiring an app, smartphone, or internet access may limit accrual of older adults. Respondents advocated researchers retaining traditional data collection media (eg, paper and pencil, with one respondent stating, “ditch the electronic requirements”) (Table 3).

Table 3.

Technology barriers and solutions^a

Barriers

Solutions

“Use of technology to collect data (ePRO or virtual visit).” “Trials require ‘extra work’ that may be considered burdensome or overwhelming to the elderly, including the use of electronic patient reported outcome devices.” “Having required tech/internet access for needed QOLs.” “Having to use ePRO’s or an app.” “Study requires patient to use technology, ie, smartphone apps, computer-generated questionnaires, video conferencing.” “Many elderly are not willing to do electronic questionnaires or study requirements on an app or smartphone, but much prefer paper forms completed during an office visit.” “Also, many older adults do not have electronics or do not have the technical skill level to complete study activities online.”

“Avoid electronic diaries, PROs, etc.” “Provide nontech options for questionnaires, ie, paper forms completed at clinic visit.” “While technology is great, continue to offer QOLs, tutorials, and other patient materials in paper form vs just electronic.” “Please stop creating protocols that require older patients to have and be facile with internet participation and other electronic ideas.” “Offer PROs on paper as opposed to electronically.” “Ditch the electronic requirements.”

^aePRO = electronic patient-reported outcome; QOL = quality of life.

Discussion

The review of the literature and the NCORP survey results highlight important barriers to clinical trial accrual for older adults with cancer in community oncology clinics. Although several of these barriers were reported in previous studies focused on accrual of older adults in academic cancer centers, it is important to understand the impact of the barriers in community oncology clinics where most older adults are cared for. A qualitative analysis of medical oncologists (24 academic and 20 from the community) previously demonstrated differences in perceived barriers; community oncologists were more likely to report that patient understanding and caregiver burden impacted accrual than academic oncologists (14). Given the increasing focus on electronic methods of data capture and clinical service delivery, an important theme that emerged from this analysis was difficulties with having older adults complete electronic requirements for clinical trial data capture. As these requirements grow in an effort to increase access to trials and manage pandemic-related concerns with coming into the office, an unintentional and potentially adverse outcome could be a further disparity in accrual of older adults from community oncology clinics to cancer clinical trials.

Eligibility restrictions in protocols are a long-standing barrier to accrual of older adults in clinical trials. NCORP survey respondents listed broadening eligibility as the top solution for accrual. In one national study of 5499 patients, investigators found that having 1 or more comorbidities was associated with fewer trial discussions and correspondingly less trial participation (15). The American Society of Clinical Oncology and the Friends of Cancer Research have published robust guidelines on how to develop studies to broaden eligibility with regard to comorbidity, prior therapies, concomitant medications, and performance status (16-19). By following this guidance, it is projected that accrual of older adults to clinical trials would increase (15). Further, guidelines included a recommendation to include a more optimal functional status evaluation (such as instrumental activities of daily living) when assessing performance status. A robust evidence base indicates oncologists benefit from objective tools to assess the performance status and fitness of older adults accurately (20). Clinicians may assume fit older adults are at high risk of adverse outcomes because of chronologic age alone. Moreover, many providers mislabel aging-related conditions in older patients who are frailer, leading to undertreatment of fit older adults and overtreatment of older adults (21). Clinicians can employ GA to minimize biased assessment and improve trials assessment and treatment propriety. GA, including shorter screening tools and abbreviated versions (20,22,23), provides 2 benefits. First, the GA encourages providers to utilize established, standardized metrics to assess recruitment propriety. Such metrics may refine or correct clinician biases and minimize their influence on trial solicitation. Second, these standardized metrics can inform protocol revisions expanding or restricting eligibility. Evidence-based protocol revisions, encouraged by reliable and valid GA assessment, may increase solicitation frequency, even if revisions reduce the number of study-eligible patients for trials that are designed for fit patients. These data can guide alternative trials for patients who are more vulnerable and frailer. A recent systematic review demonstrated that one of the most frequent reasons for GA inclusion in clinical trials was the ability to recruit study participants based on frailty level. Use of GA to evaluate frailty as part of trial eligibility will add information that is normally not captured as part of routine oncology performance status evaluations (24). GA information can be used to identify patients who have characteristics that lead to adverse outcomes from treatment (2,20). With GA information, clinicians may more readily, validly, and reliably discern study-eligible patients, thereby allowing more time for clinicians to promote and discuss trials with those truly eligible, and may aid in retention of older adults to clinical trials (24–26). Workshop participants advocated for integrating GA into cancer clinical trials to increase accrual of older adults who have patient characteristics that are more representative of older adults cared for in community oncology clinics. As one example, a NCI-funded trial evaluating a GA intervention for reducing toxicity, conducted in the NCORP network, enrolled a high prevalence of older adults with comorbidities (27,28). These studies provide evidence that studies designed specifically for older adults that integrate GA can be successful and increase accrual of this underrepresented population. Other manuscripts were developed by workshop participants for this supplement review optimal study design for clinical trials and integration of GA into these trials.

The pandemic has increased concerns about the access of vulnerable groups to clinical trials. There were negative consequences to oncology clinical trial participation that led to consideration of the use of technology solutions in an attempt to maintain equitable participation (29). The NCORP survey demonstrated that transportation issues (because of travel time and distance as well as need for caregiver support) remain a serious barrier. In another study, a survey of 1183 patients with cancer demonstrated that although the majority indicated they would be more likely to participate in a trial if remote technology was included, older adults were more likely to say they would participate in trials only if they were closer to home (30). NCORP clinicians and staff noted that requiring internet for studies would remain a barrier for older adults. There have been data supporting feasibility of remote (ie, telemedicine) visits for GA, however, expanding trials into community oncology clinics so that patients have the ability to participate locally in person remains a strong recommendation. Further, in the open-ended questions, NCORP clinicians and staff reported that they had concerns with the ability of older adults to complete electronic requirements for data reporting, especially patient-reported outcomes and quality-of-life questionnaires. Several commented that offering paper-and-pencil approaches is needed for older adults. Although there is data to support feasibility of remote collection of data for older adults (31), the NCORP survey participant recommendations to “continue to offer QOLs, tutorials, and other patient materials in paper form vs just electronic” should be heeded. Trials should be designed with pragmatic design elements and components, offering flexibility and choice whenever possible so older patients can choose where they wish to participate and how they wish to provide information. Engaging patient and caregivers as research partners when developing study procedures can foster feasibility with technology options (32).

In addition to reviewing and discussing the survey results, the workshop provided a forum for participants to discuss additional accrual barriers, notably implicit or unintentional bias, and explored strategies that may mitigate this presumed clinical trial barrier. Workshop participants additionally discussed how engagement of clinical staff could improve clinical trial accrual of older adults.

Bias Related to Accrual of Older Adults to Clinical Trials

Bias is a stereotype that leads to a distorted judgment negatively impacting an already disadvantaged group (33-36). Aspects of clinician bias may reflect well-intended aspirations designed to protect or advance disadvantaged groups. Results from the survey support that respondents believe that clinicians and staff act as gatekeepers for trial enrollment. This “explicit benevolence” may reinforce the very disparity well-intended clinicians aspire to mitigate. For older adults, explicit benevolence manifests during the assessment of patients’ trial eligibility (a clinician-level consideration). Clinicians intend to first, do no harm. Where uncertain about trial propriety (ie, patient fitness and/or concerns about toxicity), clinicians may err toward exclusion, not solicitation. Further, clinicians align both patient care and trial accrual principles on tenets of justice, beneficence, and respect for persons. When contemplating trial recruitment, clinicians consider whether a trial advances or deprives a patient of care that the provider deems essential or asks patients to undergo increased burden (justice). Clinicians commit to securing patients’ well-being, which includes maximizing benefit and minimizing harm (beneficence). Finally, clinicians aspire to affirm patients’ autonomy and to protect those less positioned to act independently (respect for persons). These aspirational classifications potentially motivate an explicit benevolence that blunts trial solicitation and accrual. In addition, the care encounter is fraught with competing demands and perceptions that mitigate trial engagement (1,37,38). Those particularly germane to trial accrual include provider belief that their organization does not value research enough to credit in career advancement considerations, lack of access to research training, perceived inability to influence practice through research, and belief that research teams underestimate the time required to execute research tasks (39,40). Thus, competing care demands and cultural barriers provide a context in which explicit benevolence may mediate trial recruitment and accrual.

In circumstances where there is limited evidence for safety and efficacy, clinicians may more readily rely on clinical experience when considering accrual of older adults to clinical trials. Clinicians relying on erroneous estimates may demonstrate an “insensitivity to prior probability of outcomes” (41). Specifically, clinicians potentially evaluate the likelihood a patient is study eligible or ineligible referencing the degree to which the patient exhibits an exclusion criterion–relevant stereotype. For example, clinicians may unconsciously label all or most older adults as frail because the majority of their frail patients are older. This insensitivity potentially begets the “explicit[ly] benevolent” stance, “I believe older adult patients are frail. I aspire to do no harm and protect my patients. Therefore, I will not subject my older adult patients to [a given] clinical trial and decline to recruit this patient.” Although clinicians intend to do no harm, these beliefs stem from age-related stereotypes (ie, ageism) that perpetuate inequities (35,42). Addressing this perspective is a prerequisite to trial design innovation. Indeed, pragmatic trials may hold promise for increasing accessibility, assuaging resource use, and imposing less patient burden (43). However, study design and inclusion criteria pragmatism, though necessary, may still fail to address the clinician’s interpretation of the inclusion criteria. Consequently, clinicians may employ well-meaning, but flawed, exclusionary defaults, regardless of a study (or inclusion criteria’s) pragmatic qualities.

Addressing explicit benevolence and/or bias is challenging. Systemic modifications to clinical trials, including expansion of inclusion criteria, will not produce change unless individual clinicians acknowledge inherent biases and, once recognized, change behavior. By reflecting on biases, clinicians can critically examine their own opinion of a study’s capacity to advance clinical practice. Clinicians can constructively articulate their concerns to investigative teams, including study sponsors and the principal investigators (PIs). Likewise, study teams can actively engage community oncology stakeholders to co-develop trials prioritizing older adult recruitment. Apart from sponsor and PI education, these discussions also encourage clinician and practice ownership, responsibility, and accountability for accrual effort. Such discussions potentially discourage provider rationalization (eg, “This study is too difficult”) by identifying solutions early in trial development. Clinicians can also communicate their opinions on a study’s value thereby directing sponsor and PI efforts from potentially futile protocol amendments. Information gleaned from this transparency allows PIs to tailor studies, particularly recruitment, to practice and/or organization characteristics to improve recruitment. PIs can use this feedback to transition from patient-focused inclusion criteria (eg, age, disease status) to multilevel inclusion criteria that include matching studies to clinician and practice resources, culture, and goals (40). Such an approach may restrict site availability but maximize recruitment at the sites electing to participate. Multilevel research is needed to rigorously assess the merits of these potential approaches (44).

Clinician and Staff Engagement as a Mechanism to Increase Enrollment of Older Adults to Clinical Trials

The previous 20 years produced an explosion of APPs including nurse practitioners, physician’s assistants, and clinical pharmacists, who more directly participate in oncology patient care, including older adults. APPs report interest in increasing their participation in clinical research and desire inclusion in clinical trials teams (45,46). Therefore, APPs may help address staffing-attributed accrual barriers. Additionally, APPs can facilitate education for older adults and caregivers, and this education may better ensure informed decisions regarding clinical research participation.

Clinicians express concern about extra time required to enroll patients onto trials; however, they may mitigate this barrier by employing a team approach. For example, an oncologist may introduce the study as part of the standard of care, and then the APP subsequently educates the patient on the treatment and describes the clinical trial option. For patients expressing interest, the APP can solicit the clinical research coordinator to more explicitly describe the trial to the patient and family. This team approach can lessen accrual burden among team members and may allay the “time and burden to enroll” (47). APPs and nurses also report routinely providing patient care coordination, follow-up visits, and toxicity checks as part of their daily practice for older patients with cancer (48). Care teams typically include APPs and nurses particularly positioned to address the identified barriers (eg, toxicity management, visit coordination) (49).

Forty years of research reveals suboptimal accrual of older adults in clinical trials, with investigators identifying barriers and proposing solutions. An NCORP survey affirms these challenges persist. The subsequent NCI-sponsored workshop considered strategies to mitigate these strident barriers. Workshop participants identified the need to address clinicians’ assumptions regarding participant inclusion criteria. Participants also considered the merits of GA to mitigate unconscious bias blunting trial accrual and considered the potential benefit of employing team approaches to clinical trial presentation and execution. This latter consideration is a novel approach that may diffuse the additional administrative and counseling burden around the accrual of older adults to clinical trials, encourage stakeholder engagement, and promote informed decisions by older patients and caregivers.

No single intervention will address these long-standing challenges. Today’s clinicians function in a historical context of structural ageism in clinical trial design and conduct, and traditional clinical cultures and assumptions portend suboptimal trial recruitment, enrollment, and retention (35). Consequently, multilevel interventions are necessary to eliminate barriers and capitalize on existing talents and opportunities in clinical practices. Although the workshop discussed long-standing barriers to accrual, we were able to identify solutions that could facilitate accrual of older adults to NCI-funded clinical trials in community oncology clinics; this information will guide interventions and efforts led by the NCI to improve accrual of older adults to clinical trials. Consequently, we encourage interventions targeting patient, providers, families and caregivers, and organizations in which care teams contemplate trial propriety. Ultimately, stakeholders must also consider the community context and sociopolitical landscape that informs, reinforces, and rewards organizational structures, policies, and activities that inherently impede accrual of older adults to NCI-funded cancer clinical trials.

Funding

This study received funding from the National Cancer Institute (UG1CA189961 for the URCC NCORP Research Base and UG1CA189804 for the Hawaii Minority/Underserved NCORP) and the National Institute on Aging (K24AG056589, R33AG059206 to SGM).

Notes

Role of the funder: The funder, the NIH, is a sponsor for the conference and for all the manuscripts in the Monograph. This manuscript is a collaboration between investigators and NIH employees.

Disclosures: There are no disclosures to report for any of the authors.

Author contributions: Conceptualization all; Funding acquisition DS; Data collection DS, SM; Project administration SM, MW; Data analysis SM, SG, KM, MW; Data interpretation all; Writing all except DS; Writing review all.

Data Availability

Data (ie, survey responses) were collected by NIH and reported in aggregate. The University of Rochester NCI Community Oncology Research Program Research Base analyzed the data. No identifiers were collected. Raw aggregate data can be requested by emailing the corresponding author.