Preface: Engaging Older Adults in Cancer Clinical Trials Conducted in the National Cancer Institute Clinical Trials Network: Opportunities to Enhance Accrual

Barriers to the accrual of older adults with cancer onto both therapeutic and cancer control intervention clinical trials are well described in the literature. The reasons for underrepresentation of older adults onto cancer clinical trials are complex because barriers stem from multiple systems that need to interact efficiently to support accrual. These barriers can include oncology and clinician teams (eg, clinician bias), study design (eg, eligibility restrictions), infrastructure (eg, need for extensive travel and/or multiple appointments), and patient and caregiver factors. A comprehensive systematic review by Sedrak et al. (1) on behalf of the Cancer and Aging Research Group (CARG) provided a strong foundation for the workshop. Of 8691 articles screened for eligibility, only 13 met the inclusion criteria for the study questions related to barriers and interventions related to accrual of older adults in clinical trials. The investigators concluded that there is a need for high-quality research that examines barriers to accrual at multiple levels. Further, only 1 of the studies evaluated an intervention to improve accrual to National Cancer Institute (NCI) clinical trials; this trial, conducted in the Cancer and Leukemia Group B network, although negative, did demonstrate a high-priority need to better understand prioritization of cancer clinical trials for the older patient population at the national level (2). In 2021, a study conducted by the NCI demonstrated that a clinical trial screening tool can identify barriers to accrual to cancer clinical trials (3). Patients aged 70 years and older were more likely to not be enrolled onto trials after screening; in addition, older adults were more likely to have comorbidities that prevented accrual because of eligibility restrictions. Two studies have evaluated the perceptions of community oncologists with regard to accrual of older adults to cancer clinical trials. The first, by Freedman et al. (4), reported results from a survey administered to oncologists affiliated with the Alliance for Clinical Trials in Oncology. More than 1000 members participated representing a diverse group of clinicians and staff members across this NCI-funded network. More than one-third of members felt that older adults should represent most clinical trial participants. Strategies to improve accrual included improving study design such as expansion cohorts for older adults, dedicating trials for more vulnerable and frail older adults, reducing exclusion criteria for all trials especially related to comorbidity restrictions, and increasing research to develop system-level improvements for recruitment. A qualitative analysis by Sedrak et al. (5) identified differing perceptions to accrual of older adults by oncologist based on location of practice (community vs academic). Whereas community oncologists were more likely to report barriers related to patient and caregiver hesitation to accrual, academic oncologists reported clinician bias and limited support as the most common barriers.

This prior work highlights the barriers to enrolling older adults to clinical trials and importantly underscores the paucity of interventions to address them. Emanating from the Cancer Moonshot^SM Network for Direct Patient Engagement Implementation Team, a one and a half day workshop was held to develop recommendations to increase accrual of older adults to NCI-supported clinical trials. Participants included oncologists, nurse scientists, advance practice nurses, gerontologists and geriatricians, statisticians, clinical trialists, and patient partners. An emphasis was placed on engaging patient partners to gain a better understanding of their perspective and how medical personnel can facilitate their participation in clinical trials. The goals of the workshop were to

1. engage physicians to address barriers to enrollment of older adults to clinical trials;

2. engage patients to enhance our understanding of the barriers to enrollment of older adults to clinical trials and discuss ways to overcome them;

3. develop consensus regarding the research priorities for the use of geriatric assessment (GA) to enhance precision enrollment and treatment of older adult patients on NCI-sponsored clinical trials; and

4. build consensus around the methods to integrate comprehensive GA in future trials, with the long-term objective of having these trial results provide evidence to use comprehensive GA to inform decision making for cancer treatments in older adults, both in routine care and in future trials.

A planning group comprised of experts in geriatric oncology and clinical trial design and accrual was formed to develop the workshop format and agenda. The group included representation from the NCI Community Oncology Research Program (NCORP) Research Bases, Community Sites, Minority/Underserved Community sites, and CARG Patient Partners (Table 1). The group decided on 4 main areas of focus: stakeholder engagement, clinical trial design, GA, and infrastructure to support accrual. Working groups focused on these 4 areas were formed to review the literature, identify current efforts to avoid duplication, develop approaches to address identified gaps, and suggest speakers and topics (see Table 2 for specific charges of each group). The working groups presented their recommendations at the workshop so the focus could be on the discussion of actionable interventions that could be further studied or implemented to address barriers to accrual to older adults with cancer.

Table 1.

Members of working groups

Study design	Geriatric assessment	Infrastructure	Stakeholders
Rich Little (NCI lead)	Allison Magnusona	Cristina Russo (NCI lead)	Alexis Bakos (NCI lead)
Jennifer Le-Rademacher (lead)	Harvey Cohena	Grace Mishkin (NCI co-lead)	Carol Weil
Efrat Dotan	Stuart Lichtmana	William Dale	Judy Hopkins
Barbara Radziszewska	Aminah Jatoia	Mina Sedrak	Worta McCaskill-Stevens
William Tew	Martine Extermann	Rachel Freedmana	Beverly Canin
Joseph Unger	Melisa Wong	Hyman Mussa	Andrea Denicoff
Heidi Klepin	Tanya Wildes	Grant Williams	Harpreet Singh (FDA)a
	Naom VanderWalde	Nadine McCleary Jacksona	Liz Brem
		Gretchen Kimmicka	Brea Lipp
		Selina Chowa	Karylnn BrintzenhofeSzoca
			Peggy Wishera
			Jeff Berenberga
			Judy Hopkins (co-lead)
			Jim Atkinsa
			Christa Braun-Inglisa

^aExternal to planning committee. FDA = Food and Drug Administration; NCI = National Cancer Institute.

Table 2.

Charge of working groups^a

Study design	Geriatric assessment	Infrastructure	Stakeholders
Consider trial designs that promote enrollment of older adults (eg, cohort designs, extended cohorts, parallel cohorts, less fit older adults), stratification by vulnerability Consider endpoints for fit vs unfit individuals	Use of geriatric assessment in clinical trials; identify research gaps	Develop a roadmap from conceptualization of research question to dissemination of results Necessary resources Consideration of the older adult throughout the processInclusion of a recruitment plan Describe resources available to investigators for how they can access experts with aging expertise	Join Study Design and Infrastructure group calls as able Define stakeholder Identify modifiable accrual barriers from each stakeholder perspective
Describe design approaches for vulnerable individuals (those who cannot be defined as fit or frail)	Identify best approaches and measures to define fitness and frailty to enroll in a clinical trial and methods to develop and validate objective measures	Identify infrastructure needs to perform comprehensive geriatric assessment	Identify interventions that can address the identified barriers to enhance accrual of older adults to NCI-sponsored clinical trials
		Use technology and telehealth to engage older adults in clinical research	Address clinician biases toward enrolling older adults to clinical trials
		Consider approaches to accrue racial and ethnic minority older adults and those from rural areas	Identify patient needs and strategies to develop interventions to address trial accrual

Updated accrual data to NCI treatment trials was provided to the working groups, which provided an understanding of accrual by age group and cancer type. This data was last published 10 years ago by Hurria et al. (6) in a publication that described a conference focused on the design of therapeutic trials for older adults. The updated data, which was also presented at the workshop and is published in this Monograph (Mishkin et al.), demonstrated improvement in enrollment of older adults to NCI-supported therapeutic trials; however, there is an ongoing need for improvement, particularly for individuals aged 75 years and older.

The stakeholder group conducted an evaluation to better understand the perceptions of community oncology teams (clinicians and research staff) to accrual of older adults to cancer control clinical trials offered through the NCORP network. A survey developed by a team of investigators in cancer and aging, community oncologists, and research staff from the University of Rochester Cancer Center NCORP Research Base was administered by the NCI to NCORP Community Affiliate sites. The more than 300 members of the NCORP network that participated in the survey identified unique barriers and solutions and communicated recommendations for interventions to improve accrual. This work by Hopkins et al. (7) was presented at the workshop and is published in this Monograph.

Another major goal of the workshop was to elicit input from patients and caregivers themselves to extend understanding of barriers and possible solutions for improving accrual of older adults to cancer clinical trials. Patients and caregivers who have fostered engagement in NCI-funded cooperative groups as well as in SCOREboard, an older patient with cancer and caregiver group affiliated with the CARG, were key participants in all of the activities to prepare for the workshop and at the workshop itself. Also presented at the workshop and published in this Monograph by BrintzenhofeSzoc et al. are results from focus groups with older patients with cancer and caregivers that elucidated key themes related to accrual barriers.

Building on prior recommendations from the CARG (6) and the American Society of Clinical Oncology (8), the study design working group reviewed study design options that could help increase accrual of older populations and those who have aging-related conditions. To provide recommendations, the group reviewed published trials and those in progress that have used novel designs. These recommendations and trial examples presented and published in this Monograph by LeRademacher et al. can serve as a resource to investigators and reviewers at the cooperative groups and NCI as they consider new concepts. Investigators and reviewers should strive to evaluate and encourage the best options to foster adequate representation of older adults.

The GA working group focused on integration of GA into NCI-funded cancer clinical trials. GA can include comprehensive assessment of health status using validated measures that can guide decision making for cancer treatment and management for aging-related conditions or shorter measurement tools that can capture specific aging-related conditions (eg, comorbidity, disability). A manuscript published in this Monograph was developed by experts in trial design and GA to offer solutions to common concerns and questions related to how to incorporate GA into clinical trials (Klepin et al).

The infrastructure working group organized a framework to address structural barriers that centers on developing and centralizing resources, standardizing data for reporting of NCI clinical trial results, and utilizing strategic approaches to understand and learn from what has previously been executed (Kimmick et al). A short checklist is included in the manuscript that could guide review processes for trial concepts.

Collectively, these manuscripts offer new and innovative solutions to common barriers to accrual. The recommendations will be disseminated to NCORP and NCI’s National Clinical Trials Network stakeholders at meetings and webinars. The NCI and NCORP Research Bases will work collaboratively to actualize the workshop recommendations with the aim to increase accrual of older adults to NCI-supported clinical trials.

Funding

No funding was used for the workshop or to generate this manuscript.

Notes

Role of the funder: Not applicable.

Disclosures: SGM and DSG have no disclosures/conflicts of interest to report.

Author contributions: Both SGM and DSG participated in the conceptualization and drafting of this manuscript.

Acknowledgements: We would like to thank the Cancer Moonshot Implementation Team, Network for Direct Patient Engagement, for their support of the workshop. We would like to thank Dr. Worta McCaskill Stevens for her leadership and support of the workshop and commitment to ensuring underrepresented populations are enrolled to NCI clinical trials. We would like to thank Dr. Margaret Mooney, Dr. Richard Little, Grace Mishkin, and Andrea Denicoff for their support. We also would like to thank the planning committee who devoted hours of planning and their expertise: Alexis Bakos, Elizabeth Brem, Beverly Canin, William Dale, Andrea Denicoff, Efrat Dotan, Martine Extermann, Judith Hopkins, Heidi Klepin, Jennifer Le-Rademacher, Brea Lipe, Richard Little, Worta McCaskill Stevens, Grace Mishkin, Mina Sedrak, William Tew, Joseph Unger, Tanya Wildes, Grant Williams, Melisa Wong, and Noam VanderWalde. In addition, we would like to thank the working group members listed in Table 1 of the Preface.