Better Late Than Never: Fully Incorporating Oncology Advanced Practice Providers Into Cancer Clinical Trials

Advanced practice providers (APPs) represent a growing and critical component of the oncology workforce. By 2017, more than 80% of US oncology practices reported employing APPs—a category that generally includes nurse practitioners, physician assistants, clinical nurse specialists, advanced-degree nurses, and pharmacists.^1,2 These individuals work across practice settings, including private and academic, and ambulatory and inpatient.³ Within these practices, more than 90% of APPs report participating in patient counseling and prescribing, whereas more than 80% report involvement in treatment management and follow-up visits.⁴ Driven by a doubling of the number of Americans age 65 years and older and an 80% increase in people living with or surviving cancer, the increase in demand for oncologists is projected to outpace the increase in supply three-fold.⁵ As the projected shortage of oncology physicians looms, the number of oncology APPs has grown to an estimated 10,000 nationwide.⁶

A Missed Opportunity

Despite the growing contributions and integration of APPs in the oncology workforce, their involvement in clinical research has lagged considerably. In a recent nationwide survey of more than 400 oncology APPs, over 70% reported that their practice participated in National Cancer Institute (NCI) clinical trials. However, only 35% were registered with the NCI as investigators,⁷ which means the majority are not participating in any NCI trial-related activities, such as adverse event review, assessment of performance status, physical examination, and review of concomitant medications. Nonetheless, more than 95% of respondents reported believing that clinical trials are important to advancing oncology care, and more than 80% felt adept at finding information on specific trials and discussing clinical trial options with patients—findings that suggest this discrepancy may reflect lack of opportunity or awareness rather than lack of interest. Further limiting APP involvement in cancer clinical trials are system factors, such as a longstanding NCI Cancer Therapy Evaluation Program (CTEP) policy requiring qualified physician investigators to cosign APP orders for study agents on NCI-sponsored clinical trials—even if state and institutional regulations otherwise permit independent APP prescribing of cancer therapies on non-NCI trials or off protocol.

Restricting APP involvement in cancer clinical trials may represent a major missed opportunity. In response to the increasing complexity, slowing enrollment, and decreasing generalizability of clinical trials, we are witnessing an unprecedented effort to render research protocols practical and accessible.^8,9 The US Food and Drug Administration has made real-world evidence a key priority.¹⁰ Technological advances have ushered in the era of decentralized or virtual-first clinical trials, which allow patients to enroll on study protocols without traveling to a distant clinical site.¹¹ With APPs already thoroughly integrated into standard oncology practice, their inclusion in clinical research directly supports the goal of accessible and representative trials.

An Optimal Workforce for Cancer Clinical Trials

Creating workflows that integrate APPs into the clinical research team could be beneficial on multiple levels. Their involvement in trials could span the four major steps in trial accrual: (1) promote awareness of available trials; (2) identify eligible patients; (3) explain standard treatment and trial options to patients; and (4) complete enrollment.¹² Indeed, we believe that—acknowledging heterogeneity in communication and relationship skills among individual practitioners—APPs may tend to have interests and qualities highly relevant to clinical trial access, participation, conduct, and monitoring (Table 1). Key to clinical trial participation is gaining patient trust and understanding, an area where APPs may be particularly adept. More than 90% of oncology APPs report confidence in communicating empathically.¹³ In oncology or palliative care settings, patients report feeling empowered, at peace, and in control as a result of the support, guidance, and attention given to them by APPs.²¹ In a survey of more than 1,200 oncology patients across 27 sites who had received clinical care from an APP, the overall satisfaction score exceeded 90%.²³ Indeed, some studies suggest that patients feel even more satisfied with care provided by APPs than that provided by physicians, particularly in areas of education and support,^24-27 whereas others report improved patient quality of life and health status with APP-led care.²⁸

TABLE 1.

Potential APP Roles in Clinical Research

APP experiences and characteristics may help connect targeted patient populations with clinical trials. For instance, as the cancer population ages, APPs may bring relevant skills to interactions with geriatric patients considering and enrolling on trials. A 2013 national study found that APPs accounted for 60% of all cancer-related Medicare patient claims, with their proportion of clinical services particularly high in rural regions and the South.^29,30 Additionally, given their focus on holistic patient care, APPs are well poised to address social determinants of health, which may in turn enhance access to and diversity of clinical trials.^15,16

Once participants are enrolled to clinical trials, adequate and accurate documentation represent cornerstones of good clinical practice. APPs appear to provide more informative and complete medical records than do physicians.^17-19 They also appear more compliant with clinical guidelines,²⁰ a trait that seems potentially relevant to trial protocol adherence. Given APPs' close connections with patients and direct involvement in clinical operations,^14,22 incorporating APPs as part of the clinical research team may enhance team communication with clinical research coordinators and personnel as a resource to assist in the management of patients on trial, including provision of oncology-specific education, evaluation of test results, and assessment of treatment modifications. Such participation is likely to address some of the challenges in communication and coordination between clinic and research teams, as well as provide critical continuity of care.^31-33

Oncology APPs serve in key roles in symptom management and coordination of care. These skills add to the team when enrolling in clinical trials involving complex oncology patients who have multiple comorbidities and often require management of multiple simultaneous side effects. Indeed, since August 2020, oncology APPs have been able to serve as enrolling investigators and, in some cases, principal investigators for NCI Community Oncology Research Program cancer prevention, symptom management, behavioral intervention, and cancer care delivery protocols funded by the NCI Division of Cancer Prevention and Division of Cancer Control and Population Sciences.^34-36 As these platforms have for their physician colleagues, such involvement may provide important career development and mentorship opportunities to strengthen the pipeline of oncology nurse and APP scientists.³⁷

Welcome Changes

In response to concerns that not permitting APPs to sign treatment orders independently (1) presented a barrier to trial conduct, (2) differed from approaches of other study sponsors, and (3) restricted APP practice beyond state regulations and some institutional policies, CTEP revised its policy. Effective September 7, 2021, CTEP released new guidance allowing qualified (ie, appropriately privileged and credentialed) APPs to sign treatment orders, including investigational new drug agents and standard-of-care agents, without physician cosignature.

With APPs demonstrating interest in and appropriate skills for clinical research—and policy changes now supporting their participation—what are the required steps to optimizing their inclusion in clinical trial operations? As with routine clinical care, a single model will not fit every practice.³ APP prescribing of investigational therapy may fit only certain centers' operations and state regulations. Some practices may have independent APP visits, whereas others have shared visits with physicians. In certain practices, APPs are already taking the lead on supportive care and cancer care delivery trials.²² And, as is the case for other health care providers, interest in and proficiency with clinical trials is surely to vary widely among APPs. To address workflows and education, the SWOG has launched a 5-year project focusing on APP engagement in cancer clinical trials. This effort—which includes participants from across the NCI's National Clinical Trials Network groups—aims to provide education, assess institutional policies, and examine workflows. Along with recent NCI policy changes, this project represents an important step in integrating APPs more fully into the cancer clinical research team.

In response to growing patient numbers and increasing complexity of care, APPs now serve critical roles in cancer clinical care. To the oncology workforce, they have brought highly relevant and desirable characteristics, including complete and accurate documentation, empathic and supportive communication, adherence to guidelines, and expertise in symptom management and care delivery. Clearly, these same traits ideally fit the entire spectrum of cancer clinical research activities. Adding APPs to the clinical research team is a welcome, logical, and overdue step to enhance the reach, diversity, equity, and quality of care in cancer clinical trials.

AUTHOR CONTRIBUTIONS

Conception and design: All authors

Administrative support: David E. Gerber

Provision of study materials or patients: Christa Braun-Inglis

Collection and assembly of data: Christa Braun-Inglis, Erin L. Williams, Alyssa Macchiaroli, Andrea Denicoff

Data analysis and interpretation: Erin L. Williams, Andrea Denicoff, David E. Gerber

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

Better Late Than Never: Fully Incorporating Oncology Advanced Practice Providers Into Cancer Clinical Trials

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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