Use of Communication Technology to Improve Clinical Trial Participation in Adolescents and Young Adults With Cancer: Consensus Statement From the Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network

Abstract

Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.

INTRODUCTION

Although cancer is the leading cause of disease-related death for adolescents and young adults (AYAs; age 15-39 years), few AYAs enroll onto cancer clinical trials (CCTs), the main mechanism through which improvements are made in care delivery and health outcomes.^1-3 Numerous challenges impeding AYA enrollment on clinical trials exist and have only marginally improved in the past few decades.^4,5 The worldwide outbreak of the COVID-19 pandemic in early 2020 led to unanticipated challenges, including disruptions in the health and safety of patients with cancer, hospital functioning and priorities, delivery of care, and the economic and personal well-being of patients, resulting in a significant decrease in accrual for National Cancer Institute (NCI)-sponsored CCTs.^6,7 Concurrently, the pandemic created opportunities to leverage and adapt technological innovations to facilitate participation of AYAs in CCTs.

In 2018, the Children's Oncology Group (COG) AYA Oncology Discipline Committee created the AYA Responsible Investigator (RI) Network, with the overarching goal of increasing AYA enrollment onto NCI National Clinical Trials Network (NCTN) CCTs. It includes more than 150 participating RIs, representing 122 demographically and geographically diverse sites. At each site, RIs highlight AYA disparities, facilitate activation of relevant trials, improve recruitment processes, and expand interactions among oncologists. Through a series of monthly national webinars and workshops, participating RIs review local barriers and facilitators to enrolling AYAs and share initiatives aimed at improving AYA CCT accrual.⁸ In this consensus statement, representatives from the COG AYA RI Network review opportunities for technology-enabled approaches to increase AYA CCT enrollment and provide recommendations for their use.

BARRIERS AND FACILITATORS TO AYA CLINICAL TRIAL ENROLLMENT

Enrollment of AYAs on CCTs is a complex and multifactorial process.⁹ Previously reported barriers include regulatory burden of opening trials; ineffective eligibility screening and recruitment procedures; poor communication between medical and pediatric oncologists; and limited time and resources supporting clinical research. Facilitators include optimizing research infrastructure; improving awareness of available CCTs; and enhancing communication between pediatric and medical oncology providers and patients.¹⁰ Health care technology can be used to mitigate these barriers and strengthen facilitators but was significantly underutilized before the COVID-19 pandemic.

OPPORTUNITIES TO INCREASE AYA ENROLLMENT USING TECHNOLOGY

Although the COVID-19 pandemic has posed numerous challenges, it has paved the way for new digital opportunities to boost AYA enrollment (Fig 1).

FIG 1.

Emerging opportunities during the pandemic to improve AYA clinical trial enrollment. AYA, adolescents and young adult; e-Consent, electronic informed consent; e-PROs, electronic patient-reported outcomes.

Telehealth

For years, telehealth was viewed as an unfulfilled opportunity to increase patient access to health care. Despite inclusion of funding in the Affordable Care Act and policy statements by medical organizations, including the American Academy of Pediatrics and American Medical Association, telehealth participation by providers was low: a national survey of pediatricians in the United States conducted in 2016 showed only 15% of pediatricians surveyed participated or referred patients for telehealth services.¹¹ The biggest perceived barrier was provider reimbursement.

However, utilization of telehealth exponentially increased during the COVID-19 pandemic. Financial concerns were overshadowed by the need to promote physical distancing, mitigate the spread of disease, and improve CCT conduct.¹² In response, the federal and many state governments passed legislation to facilitate telehealth service payments for patients with Medicare, Medicaid, and Children's Health Insurance Program coverage. These changes included expanding payments, enabling license portability, and relaxing previous regulations on the delivery of telehealth.¹³

Notably, telehealth has previously been used in clinical trials and other medical fields as a means to enroll and consent patients and remotely monitor them while on study.¹⁴ Patients in these studies reported satisfaction with the telehealth process; furthermore, telehealth boosted enrollment.¹⁵ Given these precedents, the NCI supported remote informed consent, allowed for remote study visits as minor deviations, and permitted NCTN research bases to perform remote auditing.¹⁶ The AYA oncology population has the potential to benefit greatly from the use of telehealth, given its proficiency with and adoption of information and health care technology. Approximately 80-90% of AYA patients have home broadband internet connections, most have smartphones and use social media, and are well positioned to use telehealth.^17-19

Virtual Tumor Boards

Multidisciplinary tumor boards are an essential part of cancer care delivery, facilitating optimal decision making with multidisciplinary input and improving CCT enrollment.²⁰ AYA tumor boards bring together pediatric and medical oncology care teams to (1) foster collaboration and improve communication; (2) identify optimal treatment approaches; (3) improve enrollment within community networks; and (4) overcome operational and regulatory burden by bringing in pediatric drug development expertise during AYA CCT development.²¹ During the pandemic, many institutions transitioned from in-person to virtual tumor boards, overcoming travel as a barrier for providers, decreasing delays in diagnosis and treatment, improving accrual for relevant trials, and improving attendance, particularly from off-site providers.²² As such, virtual tumor boards can facilitate collaboration among satellite campuses within or between health care systems, improving access to CCTs. A pilot study established the feasibility of a virtual central review to encourage discussions for novel targeted therapies and enrollment onto molecularly guided CCTs.²³

Remote Review of Trial Eligibility

The combined use of telehealth and electronic health records (EHRs) allows health care providers to assess clinical trial eligibility remotely. This includes the remote review of pathology and laboratory and radiologic studies, as well as interviewing potential participants to gather health history. These practices allow the remote review of inclusion and exclusion criteria and preliminary determination of trial eligibility. If conducted before the patients' scheduled in-person appointment, coordination of screening tests with necessary in-person clinic appointments can occur, limiting multiple visits and reducing indirect costs, including time needed to take off from school or work. Although these processes were available before the pandemic, they were constrained in scope by limited communication and coordination with treating providers at different locations and diagnostic facilities. As the pandemic encouraged medical care teams to align more with local facilities and teams for patient safety, these processes have become more robust and have become part of standard workflows for many institutions. Thus, remote trial eligibility screening has become more streamlined, breaking down many geographical hurdles that previously existed.

Electronic Informed Consent

Electronic informed consent (e-Consent) is a platform for consenting research participants using a remote, computer-based consent form with an electronic signature rather than traditional in-person, paper consent. e-Consent uses multimedia resources to communicate the procedures, risks, and benefits of a clinical trial.^24,25 The US Food and Drug Administration (FDA) has provided guidance for institutional review boards on how e-Consent can be used.²⁶

There are multiple advantages to e-Consent for both the patient and clinical research office (CRO). Patients can review and sign consent documents at their convenience, often in the comfort of their own home. They do not need to travel or set up additional clinic appointments to review and complete consent documents, saving time and costs associated with travel. Furthermore, referral centers can obtain consent and enroll patients in collaboration with regional and/or satellite centers, allowing physically distant patients to be included in CCTs. This was particularly relevant during the COVID-19 pandemic when the CDC recommended social distancing to decrease spread of the virus.^27-29 There is also evidence suggesting the e-Consent process is more effective than paper consents for helping potential trial participants understand the procedures and risks of the trial.³⁰ Moreover, electronic processes enable more straightforward translation into multiple languages.³¹ For CROs, e-Consent increases the efficiency of obtaining patient consent for trials. Traditionally, research staff spend a significant amount of time tracking patients during their on-site clinic visits and waiting for patients to be available to sign relevant documents. e-Consent allows research coordinators to multitask while awaiting patients' electronic signatures. During the pandemic, many CROs, providers, and patients gained fluency with electronic signature software, increasing comfort and trust in e-Consent technology.

Remote Study Visits and Study Testing

During the COVID-19 pandemic, the FDA issued a set of nonbinding recommendations regarding the continued conduct of clinical trials, with the goal of maximizing patient safety and trial integrity. The recommendations included implementation of alternate approaches to patient monitoring, including increased use of telehealth visits and assessments at local practices rather than the trial site. Standard safety lab work and disease response and surveillance imaging studies were permitted to be obtained outside of the enrolling institution at local centers, presuming adequate data integrity and quality.³² Clinical visits and physical examinations could also be done locally in coordination with the center conducting the CCT. Although the impact of these trial modifications has not yet been studied or reported, there is evidence to suggest the safety and efficacy of integrating both community cancer centers and remote monitoring of patient-reported symptoms into high-quality cancer care.^33,34 Furthermore, institutions introduced courier or drive-through delivery of medications, which could be an attractive option for AYAs who may live a substantial distance from their treatment site.³⁵

Electronic Patient-Reported Outcomes

Previous studies have demonstrated the feasibility of and increased adherence with electronic patient-reported outcomes (ePROs).^36,37 Moreover, given the near-universal use of cell phones by AYAs, mobile text messages could be used to improve compliance with ePROs and CCT requirements.^17,38 The use of wearable digital health products has increased dramatically in the adult population (from 9% in 2014 to 33% in 2018); 90% of adults in a survey reported that they were willing to share health data from a wearable device with their doctor and 66% reported they would be interested in using a device at home that could test their blood for health reasons.³⁹ Few CCTs capture AYA PROs, and the use of remote data collection has the potential to increase the collection of important health outcome data while limiting patient burden. The pandemic limited patients' ability to have on-site, in-person assessments, further underscoring the importance of assessing patients' symptom burden, treatment tolerability, and health-related quality of life remotely.³² Prior studies have reported improved survival for patients who have the opportunity to complete ePROs during routine cancer care, likely because of the medical team's opportunity to respond to and intervene earlier, preempting downstream consequences.”³⁴

Remote Auditing and Study Monitoring

Traditionally, NCI-supported research bases have conducted in-person auditing of sites to ensure study compliance and safety, a costly and time-consuming process that was restricted by the pandemic. A March 2020 memorandum from NCI's Cancer Therapy Evaluation Program and Community Oncology Research Program encouraged remote auditing as an alternative.¹⁶ The recent broad adaptation of EHRs also made it feasible to conduct these audits remotely. However, although feasible, there are a few considerations before this adaptation can become the standard approach in the postpandemic health care environment. Study sponsors must have confidence that remote study monitoring does not compromise the quality of the reviews and should takes steps to optimize these remote assessments. In addition, study sites need to be comfortable with providing sponsors remote access to source data, which would include the ability to access institutions' EHRs.”

Relevance to AYAs

Having grown up with an ever-increasing incorporation of digital media, technology, and internet of things in daily life, AYAs are digital natives and are uniquely positioned to benefit from the digitalization of CCT conduct.⁴⁰ They benefit from having helped their older family members use novel health technology and possess an innate technology-savviness that enables them to efficiently adapt to novel digital health care interfaces. Moreover, remote study participation removes certain hurdles, including travel and lodging and related costs, thereby facilitating a more patient-centric, as opposed to trial-centric, focus on CCTs.⁴¹ In doing so, interruptions to their personal and professional lives can be mitigated as many AYAs see in-person visits and study obligations as interruptions to their daily life. Financial toxicity, a potential barrier to CCT enrollment, has been reported to be higher in older AYAs (age 26-39 years) because of lack of insurance coverage, often timed to employment; younger AYAs may not have stable jobs or may be still completing their education.^42,43 Hence, obtaining their care closer to home using telehealth will minimize travel and disruption to their professional life, allowing them stability in finding and maintaining a career. Furthermore, as health care environments often bring up challenging emotions (eg, post-traumatic stress disorder, situational anxiety and avoidant behavior, and difficulty in process complex decision making) for many AYAs, being in a more comfortable setting, such as their home, may facilitate increased communication and participation.

CHALLENGES TO USING HEALTH CARE TECHNOLOGY TO IMPROVE AYA CCT PARTICIPATION AND STUDY MONITORING

The COVID-19 pandemic also exposed challenges to the use of technology to optimize CCT participation that must be carefully considered (Fig 2).

FIG 2.

Challenges to the utilization of health care technology to increase AYA enrollment onto cancer clinical trials. AYA, adolescents and young adult; EHRs, electronic health records.

Vulnerable Populations

Although use of telehealth increased dramatically between 2013 and 2016 across all population groups, key underserved populations (eg, Medicaid, low-income, and rural populations) had significantly lower use of telehealth.⁴⁴ Telemedicine and e-Consent require the participant to have access to a computer with a reliable and high-fidelity internet connection. Although a large portion of the US population has access to these capabilities, this connectivity is not equitable across all populations. Many AYA patients are from disadvantaged socioeconomic backgrounds and/or Medicaid beneficiaries, and may encounter significant financial barriers to affording health care technology and reliable internet connections. With ongoing investment, however, this socioeconomic digital divide is narrowing, with 62% of individuals of lower socioeconomic status having broadband or smartphone access; even among minorities, smartphone adoption is increasing.²⁵

Additionally, coordinating a telemedicine encounter can be frustrating, especially for those with limited English or technology proficiency. Removing barriers, particularly financial ones, to telehealth is necessary, including waiving copayments for telemedicine visits or implementing waivers to purchase needed equipment.⁴⁵ e-Consent compatibility on smartphones and tablets is often limited; larger computer screens allow for easier navigation and reading of the document text. AYA participants, however, are more accustomed to smaller, mobile devices and may have an easier adjustment to these processes.

Furthermore, AYAs are a dispersed population, including from rural areas where local facilities may lack AYA-specific services, health professionals, and clinical trials. These specialized services are often concentrated in metropolitan centers that may be geographically distant from patients' local institutions. Although increased adoption of telehealth has the potential to narrow the gap in AYA access to CCTs, expanded internet infrastructure in rural communities is needed to maximize the reach of these opportunities.^46,47

Provider and Institutional Limitations

As with any technology, organizations may require institutional approval, training and management resources, and health care technology support to maintain technology standards. These requirements could add a layer of complexity and cost above traditional paper-based consent and study conduct. In addition, providers may not be comfortable using digital hardware and software to obtain consent and monitor patients. They may perceive electronic processes to be more time-consuming, and the constant changes to the technology and support needed may be discouraging to the adoption of telehealth. It can also be more difficult to verify the identity and capacity of consenting individuals.^24,30 The use of multimedia resources may also result in a lengthier consent process.²⁴ Most physicians in small community practices may not receive training for these processes and these services may not be reimbursed by insurances depending on the location and policy. As such discrepancies may not be uniform across large and small practices, this may further polarize AYA care between resource-rich and resource-limited care settings. However, fostering partnerships between centers has the potential to mitigate these hurdles.

Insurance Reimbursement

Although legislation has temporarily allowed increased flexibility and reimbursement for telehealth by various health insurances, the longevity of these allowances is uncertain. Without ongoing government support and appropriate reimbursement, participation in telehealth may decrease, and with it, the opportunity to use this avenue for AYA CCT enrollment. As all states regulate their own providers, there is not yet a federal consensus on practicing across state lines. Moreover, malpractice insurance might not cover out-of-state practices, opening providers to potential litigation. Thus, advocating for making such flexibility permanent is a necessary endeavor at the state and federal levels.

Varying EHR Management Systems

Referrals to out-of-system health care providers must contend with different EHRs; without a universal system, lack of communications between different EHRs can be time-consuming, frustrating, and costly. Because CCTs are closely regulated, patient data must remain accurate and available to all clinical parties. Radiology imaging can be particularly challenging, given potential incompatibility between radiology software systems, thereby requiring physical copies of the images to be obtained and uploaded. Additionally, measures must be taken to ensure that laboratory and radiology evaluations adhere to strict quality assurance standards. Although central review can overcome these barriers, it is resource-intensive, and many trials rely on local institutions to internally audit quality. The creation of standards that span institutions could potentially address these issues; however, such standardization requires a substantial and coordinated effort. Furthermore, hospitals may have reservations about allowing EHRs to be accessed and shared by a sponsoring company; the burden falls on CROs at each site to generate and upload deidentified data to the appropriate platform for review by the respective sponsor.

Privacy and Security Concerns

The security of audiovisual communication must be ensured and Health Insurance Portability and Accountability Act–compliant to avoid breaches in confidentiality. Steps must be taken to evaluate potential areas of vulnerability and ensure cybersecurity. Privacy during virtual visits can also be difficult to ensure. AYA patients may not feel comfortable discussing sensitive issues if household members might be listening. Although it is acceptable for family members to be asked to step out of the room in the doctor's office, this may not be feasible in the virtual setting. Although using computer resources in a public domain may facilitate access, it inherently creates privacy concerns. Thus, although telehealth could help bring AYA patients with cancer closer to novel cancer research studies, it must be deployed in tandem with new policies and programs that focus on related concerns. Learning from privacy and security guidelines from other professions, such as finance and mental health, may help guide how these critical standards can be maintained. For example, the Financial Deposit Insurance Corporation audits financial institutions for the safety and soundness of their information systems and has laid out strict guidelines for the systems.⁴⁸ Similar guidelines should be proposed when approving new health care platforms for use. Social media is increasingly being used by AYA patients with cancer to gather support and exchange ideas.⁴⁹ The Italian Pediatric Hematology and Oncology Association is developing guidelines on use of social media while interacting with AYA patients with special emphasis on awareness of patient confidentiality issues.⁵⁰ For proper and safe use of health care technology, AYA patients need to be educated about privacy settings on their mobile and technology devices and be aware of their health care data being shared with third parties while using a digital health platform for discussing issues with their medical care team.⁵¹

FUTURE DIRECTIONS AND CONCLUSION

Traditional approaches to enrolling AYAs onto CCTs have resulted in limited AYA participation. The incorporation of health care technology to screen, consent, enroll, and monitor AYAs on CCTs has the potential to increase AYA CCT enrollment, decrease patient burden, and increase provider and CRO efficiency in conducting CCTs. In response to these recently identified opportunities to leverage technology and any challenges that they may present, the COG AYA RI Network is developing initiatives to understand the potential of incorporating health care technology to enhance AYA study participation across the diverse settings in which AYAs receive their cancer care. Table 1 outlines the proposed measures for incorporating health care technology to improve AYA enrollment on CCTs. These initial efforts seek to determine sites' capacity for and current utilization of technology to remotely enroll and monitor trial eligible AYAs and conduct virtual tumor boards. Future endeavors will determine the impact of these enrollment technologies on AYA trial participation and adherence. AYA enrollment remains suboptimal, and novel approaches to improve AYA engagement in cancer trials are urgently needed.

TABLE 1.

Recommendations for Incorporating Health Care Technology to Improve AYA CCT Enrollment

AUTHOR CONTRIBUTIONS

Conception and design: Viswatej Avutu, Varun Monga, Nupur Mittal, Aniket Saha, Danielle E. Bell, Douglas B. Fair, Jamie E. Flerlage, Jamie N. Frediani, Jessica L. Heath, Jennifer L. Reichek, Leanne Super, Michael A. Terao, David R. Freyer, Michael E. Roth

Collection and assembly of data: Viswatej Avutu, Varun Monga, Aniket Saha, Jeffrey R. Andolina, Danielle E. Bell, Michael E. Roth

Data analysis and interpretation: Viswatej Avutu, Varun Monga, Aniket Saha, Jeffrey R. Andolina, Danielle E. Bell, Jamie N. Frediani, Justine M. Kahn, David R. Freyer, Michael E. Roth

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Use of Communication Technology to Improve Clinical Trial Participation in Adolescents and Young Adults With Cancer: Consensus Statement From the Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

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