ACORI Research Review: December 2023

Despite the growing contributions to the oncology workforce, APPs have not been fully integrated into cancer research across the clinical landscape. In 2020, ACCC was involved in a benchmarking survey examining APPs and clinical trials which included over 400 APPs.2 Key findings from this survey included that APPs:

• Have clinical trials available at their practice
• Believe clinical trials are important to improve the standards of oncology care
• < 50% were involved in clinical trials as investigators
• <25% were involved in research committees
• Multiple barriers to APP participation exist including
  • Time
  • Policies that limit APP participation
  • Lack of education
  • Not a role expectation
  • Lack of financial support

This survey, subsequent publication, along with APP advocacy have led to policy change within the National Cancer Institute (NCI), allowing for enhanced and more meaningful roles for oncology APPs in NCI sponsored trials. Oncology APPs can order cancer therapy on NCI sponsored treatment trials without a co-signature, and serve as treating and primary investigators on cancer supportive care trials.3,4 Overall, there are no federal regulations requiring the investigator to be a physician, however, different industry sponsors may have different regulations along with state and institutional policy.5 Oncology APPs can add value to clinical research from all aspects of trials including accrual, conduct, review, and leadership.

Accrual

First, in terms of clinical trial accrual, oncology APPs can assist with identifying potential patients and discussing available trials with their patients. They can assist clinical research staff with baseline testing and clarify eligibility criteria to facilitate appropriate and timely patient accrual. Oncology APPs often have excellent relationships with their patients and trust is key to clinical trial participation, making the APP the ideal provider to discuss a potential clinical trial with a patient in addition to the collaborating oncologist.

Conduct

Second, in terms of clinical trials conduct, APPs can serve as excellent investigators. Oncology APPs often provide most of the continuing care for cancer patients, especially patients undergoing active treatment. However, there is education that often needs to happen prior to the APP serving in this role as well as some form of human subjects training. To participate in NCI sponsored trials, APPs need to be credentialed as non-physician investigators (NPIVR).

Review

Third, APP can review trials for scientific merit and feasibility. They can also identify any specific barriers or facilitators that may be factors in getting patients on said trials. Unfortunately, based on recent survey results,2, 6 APPs do not typically review trials in this manner. This is definitely an area where APPs can grow their practice in clinical research.

Leadership

Finally, APPs can also serve as primary investigators on trials, taking ownership for and serving as study champions by encouraging other providers and staff members to help promote and recruit patients for trials. They are a key presence in the clinic and are often more available than their physician counterparts. Beyond cancer treatment trials, APPs can take leadership roles on supportive care trials which align with their expertise of symptom management and cancer survivorship issues.

As the oncology provider landscape grows and changes, it makes a lot of sense to engage oncology APPs fully into the clinical trials realm. Not only are they important providers on the oncology care team, but they also enhance value along the spectrum of oncology care and clinical trials are a very important part of that spectrum. Fully integrating oncology APPs into clinical research will only help the oncology workforce to provide better care and to work towards the goal of offering clinical trials to all patients as part of the standard of care.

References

1. Vogel, W. (2021). “Knowing Your Worth: Key Facts About Fair Market Value” The JADPRO Podcast: Episode 35. https://www.advancedpractitioner.com/episode-35-knowing-your-worth-key-facts-about-fair-market-value.aspx
2. Braun-Inglis C, Boehmer LM, Zitella LJ, et al. Role of oncology advanced practitioners to enhance clinical research. J Adv Pract Oncol. 2022;13(2):107-119. doi:10.6004/jadpro.2022.13.2.2
3. Good, M. (2020). NCI DCP & DCCPS NCORP Guidelines: Advanced practice nurse roles in DCP trials & DCCPS studies. Presented at NCORP Administrator Webinar.
4. National Cancer Institute. (2021). The Investigator. In A Handbook for Clinical Investigators Conducting Therapeutic Clinical Trials Supported by CTEP, DCTD, NCI. https://ctep.cancer.gov/investigatorResources/investigators_handbook.htm
5. CFR - Code of Federal Regulations Title 21. (n.d.). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=312
6. Braun-Inglis, C, Dressler, E, Myers, J, Berenberg, J, et al, "Defining the Role of the Advanced Practice Provider within the NCI Community Oncology Research Program, JCO Oncology Practice, in press

One of the primary objectives of SCRS is to advocate for its members. Clinical research is impossible without active collaboration from trial sites, and in order for sites to be successful in working with industry partners, their needs must be met. In the words of SCRS, “sites have long been the silent partner in the research enterprise, and SCRS ensures they are no longer passive participants by catalyzing dialogue with industry leaders and working to find solutions through collaboration.”

According to Jimmy Bechtel, vice president of site engagement at SCRS, some of the major ongoing challenges with research sites include financial burdens, diversity/equity/inclusion concerns, and optimization of remote clinical trial services. In regard to financial challenges, SCRS’ recent advocacy efforts are working to establish monthly payments for sites to conduct trials as part of its new Site Payment Initiative. This Initiative aims to “create a fair state where sites are paid 100% of earned revenue, payment terms are monthly rather than quarterly, and clinical trial volunteers are not penalized through tax”.

Other advocacy efforts consist of the Diversity Awareness Program, created in 2016, to promote more diverse patient recruitment into trials. The awareness program consists of 2 important initiatives: the Digital Innovation Initiative, representing the needs of trial sites in relation to digitalization of clinical trials, and the Workforce Task Force, which addresses the current staffing challenges plaguing many sites. SCRS also hosts 2 different types of advocacy workshops—Sites NOW and Site Advocacy Groups—to help sites operate at their best and facilitate dialogue between sites and industry leaders on topics regarding patient recruitment, technology, operational processes, and more.

The second overarching principle of SCRS is to educate its members on how to conduct clinical trials and carry out research in an efficient and meaningful way. Bechtel notes that many sites “don’t know what they don’t know,” and SCRS serves a significant purpose by sharing best practices and strategies for more efficient operations. SCRS has an incredibly robust “learning campus,” which houses a slew of resources for trial sites. There is a weekly webinar series, featuring topics such as “What Does Disability Look Like? Site Strategies for More Inclusive Patient Recruitment,” and “Giving Site Staff Superpowers – Embracing AI To Affect the Metrics That Matter.” There are also training modules for principal investigators on how to oversee a trial and courses specifically reviewing RECIST and iRECIST criteria. There is even an initiative—called CLEAR (Common Language Evaluation and Reconciliation)—to streamline contract negotiations and accelerate site initiations through the use of easily understandable language.

Moreover, SCRS has established a subgroup specifically dedicated to cancer research and care, given that oncology trials account for a large majority of clinical research. The SCRS Oncology Program strengthens relationships between cancer trial sites, industry sponsors, and research organizations through its networking opportunities and educational resources. The annual Oncology Site Landscape Survey gathers information from sites to inform stakeholders on the current climate of site challenges. For instance, this year’s survey found that when approached by a sponsor or CRO to conduct a decentralized trial, 44% of sites did not participate, largely due to discomfort in conducting this type of trial along with budget constraints. Furthermore, 45% of sites indicated  they needed additional resources to support diversity, equity, and inclusion processes, primarily in the form of internal cultural adjustments and education for staff, external and community engagement best practices, and funding to implement grass-root programs and procedures.

The third major focus of SCRS is to foster relationships and promote networking between trial sites and industry partners. Every year, SCRS hosts several different summits around the world for its membership. Most recently, the European Site Solutions Summit took place in Lisbon, Portugal, from November 13th through the14th, where clinical research professionals, sponsors, clinical research organizations (CROs), and solution providers, were able to engage in innovative discussions, develop meaningful connections, and earn contact hours for educational sessions. Similarly, the Australia-New Zealand Site Solutions Summit covers the Asia-Pacific region, and the Global Site Solutions Summit occurs in the US. There are also specialty summits focusing on oncology research, diversity efforts, and clinical technology. These conferences give stakeholders the opportunity to come together and work on solutions for ongoing site challenges.

All of the members of SCRS are listed in its online directory, which is organized by therapeutic area, geographical location, or demographic data. When SCRS was first initiated, it gained nearly 300 members from 11 countries in 3 months. Since its inception, more than 10,500 research sites across 52 countries have joined the society. Most of its representation comes from members in the US, UK, European Union, Australia, and New Zealand. Although there are hospital and academic centers in SCRS, the large majority of members are free-standing research sites and practices. Sites join with varying levels of research experience, but most of the current members have at least 10 years of research under their belt, according to Bechtel. One of the most compelling reasons for sites to join the trade organization is the ability to contribute to the collective voice to promote change in the field. Even the most experienced sites cannot solve global research challenges on their own; being a part of SCRS empowers sites to work together and move solutions forward.

For new or inquiring members, Bechtel recommends starting with the membership section to understand the benefits and associated costs, and reviewing the publications and advocacy efforts to learn what type of work SCRS produces. In general, member sites find that educational materials and networking opportunities are some of the most impactful resources provided by SCRS. Many members attribute their business growth to connections made through SCRS. To continue fostering these industry connections, mentorship is a core value and intention of SCRS. Much of the current mentorship in the society has developed organically, with sites naturally gravitating towards those who operate similarly or have comparable needs. Of note, SCRS is currently developing a more robust mentorship program that will incorporate mentor/mentee matching.

Along with the many aforementioned benefits of joining SCRS, another unique perk is the ability to gain recognition through its site awards. One of the impactful ideas to come out of the SCRS Site Tank award was Kits4Life, a company that delivers unused medical supplies to developing countries. This year, the winner of Site Tank was a mobile application called AlzWell that uses AI technology to collect data for patients with dementia or Alzheimer’s and matches them with appropriate clinical trials. SCRS members are able to submit for several annual awards focused on patient-centricity, inclusion, innovation and more. Announced at the annual Global Site Solutions Summit, recipients are celebrated all year and have several opportunities to share more information about their groundbreaking initiatives with industry stakeholders through SCRS publications and events.

In its 11 years of activity, SCRS has already made a monumental impact on the global research community by helping practices around the world learn what it means to conduct clinical research and serving as a collective voice for sites to work towards solutions and improve clinical care for all patients. It will be interesting to see how else SCRS continues to change the world of clinical research over the next 10 years and beyond.

The workshop is an exclusive opportunity offered to recipients of the Robert A. Winn Career Development Award (Winn CDA), which is awarded to early-stage investigators who are from diverse or underrepresented backgrounds and/or have demonstrated commitment to enhancing diversity in clinical research. In the words of Dr. Robert A. Winn, director and Lipman Chair of Oncology at VCU Massey Comprehensive Cancer Center and chair of the Winn Award Program National Advisory Committee, “It is our duty as physicians to…ensure [that clinical trials] represent the diverse communities and backgrounds of our patients. Without that representation at the forefront, we are failing the very people we are seeking to serve. By training the next generation of clinical trialists with these commitments, we are moving one step closer to making sure all people can benefit from medical innovation”.

During the workshop, investigators explored strategies to bridge the gap between underrepresented communities and clinical trials. They were empowered to devise innovative ways to reach their communities and transform the current landscape of clinical research. As part of the workshop, participants completed ACCC/ASCO’s Just ASK! Increasing Diversity in Cancer Clinical Research Training Program, a 60 – 90-minute online course pertaining to implicit bias and how it contributes to health care disparities. After the workshop, Winn CDA scholars will continue to participate in a 2-year curriculum consisting of routine scholars’ forums, community engagement assignments, and a capstone project to develop a mentored research protocol.

Since the inception of the Winn CDA in 2020 with a $100 million pledge by BMS, 114 early-stage investigators have been trained in the program, with another 65 physicians to join that total for 2023. By 2027, the Winn Award Program, now with additional funding from Gilead Sciences and Amgen, aims to train and mentor more than 308 clinical trial investigators, and 308 medical students who are diverse or committed to improving clinical trial diversity.

As part of its annual agenda, the NOC conference highlights winners of the ACCC Innovator Awards, which have taken place every year since 2011 to honor cancer programs for their innovative ideas that improve access, quality, and value in cancer care delivery.

This year, there were 6 winners:

• Duke Cancer Institute - e-Consults for Immune-Related Toxicities Improve Patient Access and Reduce Costs
• Mount Sinai - An Advanced Practice Radiation Therapist Role Improves Quality, Efficiency, Wellness and Administrative Outcomes
• Oncology Hematology Care, Inc - Closing the Testing Gap: Standardization of Comprehensive Biomarker Testing in NSCLC
• Orlando Health Cancer Institute - Leveraging Technology to Develop an Express Symptom Management Program and Prevent ED Visits
• Rochester Regional Health - Collaborative Care: A Model for Embedding Counseling in Oncology and Palliative Care
• St. Elizabeth Cancer Center - A Model for Demonstrating Sustainable Outreach for Cancer Screening.

At Duke Cancer Institute, Dr. Afreen Shariff, director of the Duke Endo-Oncology Program, noticed that endocrine oncology patients were waiting an average of 3 months to see an endocrinologist after a referral was made from their oncologist. This long wait time prompted Dr. Shariff and her team to develop an electronic consult service for patients experiencing endocrine immune-related adverse events (irAEs). With this new platform, oncology providers submit an e-consult referral, and the case is triaged by an endocrine provider within 24 to 48 hours. The endocrine provider will recommend diagnostic tests and/or treatments and determine if the patient needs immediate attention. Since its initiation in 2020, the service has reduced the time to appointment from 61 to 39 days and the rate of endocrine-related hospitalizations from 11% to 2%.

The Radiation Oncology department at Mount Sinai won a 2023 Innovator Award for piloting the first advanced practice radiation therapist (APRT) role in the US. The APRT works with the radiation oncologists to screen and assess patients for simulation and treatment, liaise with palliative care team members, and assist with care coordination between inpatient teams and treatment delivery teams. The APRT team at Mount Sinai has enhanced the quality of patient care, reduced physician burnout, and enabled both advanced practice providers and physicians to practice at the top of their licenses.

Oncology Hematology Care, Inc., a large community oncology practice in Ohio, sought to improve their rate of biomarker testing for metastatic non-small cell lung cancer patients by creating standardized templates for new diagnoses, automating biomarker testing, and incorporating interactive learning videos to review the workflow. After one year of the program, rates of biomarker testing at the practice increased significantly from 68% to 92%. The electronic health record template and order set are now being scaled through the US Oncology Network to other institutions as a best-practice initiative.

The team at Orlando Health Cancer Institute identified a substantial need to reduce emergency department (ED) visits of active cancer patients and improve timely handling of acute symptomatic needs. To enhance patient triage and evaluation, the institution developed an Express Symptom Management (ESM) program to help manage adverse side effects of chemotherapy/radiation, conduct infectious workups, address pain issues, and provide other types of supportive care and monitoring. The electronic health record was cleverly utilized to remind patients about accessing the ESM after their infusions: a post-treatment algorithm gives instructions for self-management of symptoms with information to call the ESM if symptoms persist. The establishment of the ESM program has significantly reduced ED visits for patients at Orlando Health Cancer Institute as most patients have been able to receive symptom management over the phone or through a virtual or in-person visit.

Rochester Regional Health - Lipson Cancer Institute adapted a collaborative care model for counseling services that increases access to therapy for their cancer patients across six clinic locations. In this model, patients are able to see a licensed therapist typically within a week and the services are usually at the clinic, thus patients do not have to spend extra time and effort to go to therapy. Embedding these services into the patients' treatment visits helps to reduce access barriers to mental health counseling.

Lastly, St. Elizabeth Cancer Center in Kentucky won a 2023 Innovator Award for implementing an outreach team, known as the Population Health Support Services (PHSS), to help boost screening efforts for lung, breast, and colon cancers. The PHSS team is responsible for identifying and prioritizing patients for screening, reaching out to patients to complete screening, providing patient education, and placing referrals. In 2022, the outreach efforts accounted for 38% of completed lung cancer screenings and 15% of completed breast screenings for the healthcare system.

What complicates the issue even further, is that there is considerable variation across state lines in how private insurance companies are governed and what their coverage entails. These disparities continue to exist despite the enactment of the Patient Protection and Affordable Care Act (ACA) in 2010, which became the first federal law to mandate that private insurers cover routine costs (“all items and services consistent with the coverage provided in the plan that is typically covered for a qualified individual who is not enrolled in a clinical trial”) for patients participating in cancer clinical trials.

After the ACA went into effect, MacKay et al. reported on its impact for cancer patients in Kansas who were potential candidates for clinical trials. They found that the ACA changes helped expand insurance coverage to include trial participation for nearly 55,000 adults, accounting for a 3% absolute increase in coverage throughout the state. Despite these gains, however, a large proportion of patients in the state—nearly 500,000—remained without access to insurance coverage for clinical trials. While the ACA provisions have been able to expand access for many patients, they have several major limitations that differ across states: the laws for clinical trials coverage do not apply to “grandfathered” employer plans, Medicaid plans, or uninsured individuals.

A “grandfathered” plan is one that was in existence on March 23, 2010 and has not made any significant changes to its benefits and coverage since then. Once a grandfathered plan adjusts any of its costs or benefits, then it would have to comply with all ACA provisions, including clinical trials coverage. Since the enactment of the ACA, the number of grandfathered plans have declined throughout the country, but many employers continue to utilize grandfathered plans. Unfortunately, it is hard to tell not only how many grandfathered plans still exist in each state, but also what type of coverage each plan may have regarding clinical trial participation. The inconsistencies among these grandfathered plans from state-to-state contribute to the ongoing geographical disparities in access to clinical research.

Another substantial difference in state-to-state insurance coverage of clinical trials is the varying scope of Medicaid throughout the country. With the ACA, Medicaid was broadened to encompass individuals earning up to 138% of the federal poverty level, and states could choose to adopt the new provisions and receive enhanced federal support accordingly. This expansion inspired Dr. Joseph Unger and colleagues to investigate the question: how did the Medicaid expansion affect cancer clinical trial enrollment? Their recent study, which compared the post-expansion period (January 2014 to February 2020) to the pre-expansion period (April 1992 to December 2013), found an overall increase of 19% per year in the odds of trial patients using Medicaid after the expansion.

Notably, there was a significant difference between the odds of Medicaid use among female patients who were enrolled for trials compared to male patients (27% vs. 8%), a trend that reflects typical Medicaid use patterns as women more commonly meet its eligibility criteria. The results also demonstrated a clear impact on trial participation in states that adopted the expansion: the odds of trial participants using Medicaid increased by 26% annually in these states, compared with 8% for states that did not adopt the expansion. These results imply that access to clinical trials can be enhanced by broadening Medicaid coverage. Moreover, not only can better coverage boost the quantity of patients on trials, but it can also bring greater diversity to research by increasing access to research for patients who are more socioeconomically vulnerable.

At the time of this research, Medicaid was not required to cover routine costs associated with clinical trials, although some states still covered these costs. However, in 2020, Congress passed the Clinical Treatment Act, which mandated that “all states and territories cover and reimburse routine costs of care for treating a Medicaid enrollee who is participating in a qualifying clinical trial.” This law took effect in January 2022, and as of July of this year, all 50 states and the District of Columbia have approved plans to comply with the new requirements. As these changes are implemented over time, the hope is that we see more patients covered by Medicaid enrolling in clinical trials across the country. Of course, there is still a long way to go in our quest of providing equitable cancer care to all patients, but the recent policy changes are steps in the right direction.

One of the more recent developments from a systems standpoint has been the implementation of the Clinical Trial Navigator (CTN) role. The functionality of CTNs can differ from institution to institution, but in general, they play a role in helping patients understand how clinical trials work and matching patients to appropriate trials. In Canada, a CTN program was established in 2019 by the Canadian Cancer Clinical Trials Network. Patients, family members, and providers can refer patients to this program, wherein a CTN will perform a personalized clinical trial search and discuss these results with the patient and their health care team.

The use of this program was analyzed in a publication by Hamm et al. They assessed the patterns of 118 patients who used the Canadian CTN between March 2019 to March 2020. Nearly all (94%) of the referred patients had stage 4 or relapsed/refractory disease and had received a median of 2 prior lines of treatment. The median age of referred patients was 46.5 years, and there was a similar number of male and female patients. Eighty-six percent (86%) of referrals came from small to medium-sized cancer centers and the most common cancers referred included hematologic malignancies, breast cancer, and lung cancer. However, proportionally speaking, patients with rare cancers, such as glioblastoma multiforme, sarcoma, and pancreatic cancer, had greater representation in referrals compared to more common cancers.

Of the 118 patients who were referred to the program, 93 had follow-up information, while 25 did not. The investigators found that 31% of the patients were subsequently referred to a matching clinical trial, of which 7.5% ultimately enrolled. In nearly 40% of cases, no appropriate trials were identified, whereas in one-quarter of cases, potential trials were discovered, but the patient did not end up being referred to the trial. This could have been due to patient or physician choice or identification of other therapies. Twenty-eight percent of patients had passed before they could participate in a clinical trial and nearly 25% were referred to the CTN program within 3.5 months of their death. All in all, the Canadian CTN program provided modest benefit in enrolling patients onto clinical trials, but there are clear areas of opportunity, most notably in finding more available trials.

Other investigators have looked into using patient navigators (PN)—similar to clinical trial navigators—to enhance the recruitment and retention of underrepresented patient populations into clinical trials. The University of Alabama at Birmingham employed patient navigators to help provide education about clinical trials specifically to African American patients with cancer and to help address barriers to trial participation for eligible patients. The PNs assisted with transportation and lodging needs, made reminder calls for appointments, connected the patient with community services and resources, offered emotional and psychosocial support, and more.

In a 7-year time span, 432 African American patients were referred to use patient navigation services at the cancer center (otherwise known as the “IMPaCT program”). Of these patients, 63% accepted PN services; those who did not participate were deemed ineligible for a trial (42%), declined to participate in a trial (22%), did not need assistance (22%), or had other reasons (14%). The IMPaCT program provided a total of 5,152 social support services (reminder calls, paperwork assistance, resource referrals, counseling, etc.), 927 transportation services, 71 lodging services, and 8 insurance services. Throughout the course of the program, referrals of African American patients to cancer clinical trials increased three-fold (5.5% to 16.6%) and overall participation nearly doubled (9% to 16%).

Patients referred to the IMPaCT program (378 patients) were found to be eligible for a clinical trial; of these, 80% enrolled in a trial and 72% agreed to receive PN services – in fact, approximately 90% of clinical trial participants consistently received IMPaCT services over the course of the program. Perhaps the most impressive finding was that those who received PN services were almost 5 times more likely to complete the clinical trial than those who did not. 75% of patients in the IMPaCT program completed the trial whereas only 38% did who opted out of PN support.

Services that help patients navigate through research studies can be an effective way to expand access and increase accrual to clinical trials. Whether these services are geared more towards identifying trials or addressing barriers to participation, they have been shown to make a difference in research recruitment and retention. Clinical research sites are encouraged to consider the implementation of trial navigators to enhance the overall patient research experience.