As of 2019, there were over 3.8 million breast cancer survivors in the United States, with this number projected to increase substantially by 2030 [1]. Excluding skin cancers, breast cancer is the most common cancer type and accounts for 30% of new cancer diagnoses in the United States [2,3]. In 2021, breast cancer incidence was expected to be 284,200 in the United States, with a 0.5% annual increase [3]. Although mortality rates have declined, the projected number of deaths from breast cancer in 2021 was over 44,000, and nearly all these deaths were due to metastatic breast cancer (MBC), which has a median survival of about 3 years [3,4]. Breast cancer incidence is higher in urban populations than among those living in rural settings [5]. However, this rural-urban disparity has been attributed to lower mammography screening rates, due to limited access to health care services in rural settings and low socioeconomic status [6,7], impacting this population’s ability to obtain quality care and making the diagnosis of breast cancer at later stages more likely [8]. When viewed at the population level, these barriers often explain the observed gap in breast cancer incidence between urban and rural populations [7].

Despite significant advances in treatment, there is no cure for MBC [9-12]. Current treatment options are palliative in nature with the goal of extending survival and improving quality of life, but are frequently encumbered by care coordination challenges [9,11,13]. Even with national guidelines for the treatment of MBC and subtype-specific MBC, which encourage participation in clinical trials [14-16], there is not always a clear sequence of treatments or an accessible clinical trial available for patients, particularly those in rural settings [9,17-19]. Additionally, there is often a need for ancillary supportive care services for patients with MBC [17,19]. The complexities involved in the routine care of patients with MBC can lead to underutilization or overutilization of care; missed opportunities to improve cancer outcomes, including cancer-specific survival and treatment-related symptoms; and undue patient and care delivery burden. Therefore, there is a need for coordinated care models that cater to the increasing prevalence of patients with MBC in the United States [20].

Patients with MBC usually choose to receive cancer care near their homes. Treatment may be at a community or academic center. However, while many patients live near academic centers, a considerable number of patients also travel to academic centers for treatment or second opinions, clinical trial options, and ancillary services not available at their local community practice [21]. Effective coordination and communication between the referring provider and oncologists at academic centers are needed to maximize the benefits of these consultations. When coordination is lacking, patients may be seen at an academic center when they are not candidates for a clinical trial or when a relevant trial is unavailable. Treatment plans may also be delayed if certain medical records or up-to-date test results are unavailable. In addition, patients are often not referred due to referring physicians’ lack of access to real-time clinical trial options at an academic cancer center or their concern for patient burden, including financial responsibility, health insurance limitations, and transportation cost [17,19,22]. Given these referral barriers, communication is often limited to a phone call or email between individual physicians, which is not always a secure, reliable, or organized approach. This way of communication also inhibits collaborative consultations for patients who may benefit from a multidisciplinary review of their case. Therefore, existing communication media and channels lack efficiency and create barriers to eliciting a second opinion or screening patients potentially eligible for clinical trials. Ultimately, a lack of consistent uniform coordination and communication among physicians is likely to result in decreased patient satisfaction and potentially missed opportunities to improve patient outcomes [13].

Addressing physician-level barriers to referring patients, such as physicians’ lack of awareness of available trials, concern of losing patients, and lack of time [23], is imperative to adequate patient care. Additionally, current referral practices encompassing preappointment communication regarding available trials, required testing and records, patient functional status, and preferences must be honed among academic and referring community centers. A collaborative care model can improve workflow, minimize patient burden, improve care delivery and communication between physicians, and ultimately enhance the referral process between academic and community cancer centers [22].

In this protocol paper, we describe the implementation science study design of a project for adapting and developing an academic and community practice collaborative care model for MBC care (Project ADAPT). This project evaluates clinical health service utilization (eg, access and utilization of clinical trials, virtual consult/telemedicine, and genomic testing), and the fidelity and adoption of a coordinated care intervention between academic and community settings. This model can then be tested on a larger scale, with a more significant number of community partners, to evaluate its impact on additional outcomes, including quality of life, and progression-free and overall survival, among patients with MBC.

WUSM/SCC received single IRB approval in May 2021 from the Washington University Institutional Review Board (Protocol #202104173-1001). Due to the various characteristics of our 3 partner sites, these sites are in different stages in the administrative and registration processes to obtain single IRB approval through the WUSM IRB. Utilizing the single IRB approval process strengthens the existing executive partnerships to create a sustainable research collaboration [26].

Washington University in St. Louis School of Medicine (WUSM) is partnering with the following 3 community hospitals within the St. Louis region to establish this care model: Missouri Baptist Medical Center (MBMC) in St. Louis County, Missouri; Southern Illinois Healthcare (SIH) in Carbondale, Illinois; and Phelps Health Delbert Day Cancer Institute (DDCI) in Rolla, Missouri. These hospitals are affiliated with broader regional health care organizations that offer the potential to expand and scale-up Project ADAPT. An existing informal referral relationship exists between each of these partner sites and SCC. Therefore, we are building off this foundational relationship to coordinate care for patients with MBC. Specifically, MBMC and SIH are affiliated with The BJC Collaborative, LLC, an organization inclusive of 7 health systems in Missouri and Illinois working together to enhance the quality of care, increase access to health services through meaningful population health benefits, and reduce the total cost of care within the Midwest region. Phelps Health is a county hospital serving South Central Missouri, whose Delbert Day Cancer Institute is affiliated with the Siteman Cancer Network, an affiliation led by SCC committed to improving the health and well-being of people and communities through research, treatment, and prevention. WUSM is the project’s lead/coordinating site.

The lead site, WUSM, has an extensive history of research, education, and patient care, as one of the preeminent medical research institutions in the United States. SCC is the only NCI-designated cancer center in Missouri and is part of the main Washington University Medical Center campus with multiple satellite locations throughout the St. Louis region. SCC brings together over 450 physicians and researchers from WUSM, Barnes-Jewish Hospital, and St. Louis Children’s Hospital (both part of BJC Healthcare). Thus, SCC provides several vital resources for cancer research in the St. Louis area, with extension throughout the SCC catchment area.

MBMC’s Cancer Center is a regional leader in providing care and support to patients throughout their cancer care. This cancer center aims to deliver treatment, comprehensive care, and advanced research to patients receiving care in the surrounding areas. The hospital has over 1700 new cancer cases each year, and the cancer center is staffed with 8 medical oncologists. MBMC has outreach sites in more rural areas in Missouri and Illinois, for example, MoBap Sullivan in Sullivan, Missouri, and is an active partner in this effort to share best practices and recruit women with MBC. In 2019, prior to the COVID-19 pandemic (as this has caused significant disruptions in cancer care), MBMC’s Cancer Center referred 3 out of 41 patients with MBC to SCC.

SIH is a leading health care system serving the people of southern Illinois. SIH offers services in rural clinics in addition to a regional referral center for the 16-county region. SIH aims to provide expertise and advanced treatments tailored for the needs of the rural setting. As the region’s first dedicated cancer treatment center, the SIH Cancer Institute provides surgical and treatment options using evidence-based approaches to advance the care of patients with MBC. There are 5 medical oncologists, 2 radiation oncologists, and 1 breast surgical oncologist in the cancer program serving an estimated 200 breast cancer patients yearly. From 2016 to early 2019, out of the 26 patients with MBC seen at SIH, there were no referrals to SCC.

The DDCI provides cancer care services and continuity of care for patients in a rural 7-county region across South Central Missouri. The DDCI offers radiotherapy, medical oncology, laboratory, clinical research, and imaging services. All cancer treatment and support services are at a single location to ensure the best possible patient experience and to ease the burden of traveling to multiple locations for treatment. In addition, it offers ancillary services, such as patient education and customized counseling services, to achieve the mission to improve the health and wellness of people in the region. The Phelps Health DDCI had 10 patients with MBC, with only 1 referral made to SCC, in 2019.

In the exploration phase, participants must meet the following inclusion criteria: (1) diagnosis of MBC (stage IV); (2) referral to SCC for MBC treatment; and (3) referral before the implementation phase of Project ADAPT. For the implementation phase, the inclusion criteria are (1) histologically or cytologically confirmed MBC (this includes newly diagnosed [de novo] or recurrent metastatic disease); (2) age ≥18 years; (3) self-reported ability to speak and understand English; and (4) willingness to provide written informed consent. There are no participant limitations based on sex.

For this protocol paper, providers recruited for this study are oncologists who primarily manage MBC cases and are involved in the referral process of patients with MBC. We have used the term “provider” throughout the protocol to make it inclusive for other sites that may replicate this study and have clinical buy-in from a variety of health care providers. The inclusion criteria for oncologists are as follows: (1) academic oncologists from SCC and oncologists from participating partner community sites, and (2) willingness to provide written informed consent. Table 1 shows the distribution of participants throughout the study phases.

Project ADAPT has 5 intervention components designed to enhance communication between providers, continue engagement between research and clinical teams, and provide optimal patient care regardless of geographic location. These components are as follows: (1) ADAPT coordinator; (2) Epic communication between providers and research teams; (3) Powerful partnerships with collaborating sites; (4) WUSM clinical trial finder; and (5) Virtual consult/telemedicine.

Several surveys employed within this study explore patients’ and providers’ satisfaction with the referral process and are grouped into patient and provider surveys. Surveys designed for the patient population are as follows: (1) ADAPT patient survey; (2) ADAPT patient sociodemographic survey; (3) Epic data extraction form; and (4) Decision Regret Scale [36] (Multimedia Appendices 1-5).

The ADAPT patient survey (Multimedia Appendix 1) captures patients’ satisfaction and acceptability of the current referral process. There are open-ended and free-response options that offer participants the opportunity to provide insights and experiences valuable to the study. The ADAPT patient sociodemographic survey (Multimedia Appendices 2 and 3) includes baseline characteristics of patients with MBC referred from outside institutions to SCC to gain insights into the backgrounds of our patient sample population. The Epic data extraction form (Multimedia Appendix 4) gathers information on tumor characteristics, treatment history, and receptor status from Epic. The Decision Regret Scale [36] (Multimedia Appendix 5) evaluates patients’ feelings of regret (if any) regarding transferring cancer care from partner sites to SCC.

Surveys for the providers recruited into Project ADAPT are as follows: (1) ADAPT provider survey and (2) Implementation Climate Scale [37] (Multimedia Appendices 6-8). The ADAPT provider survey (Multimedia Appendices 6 and 7) emphasizes providers’ satisfaction and acceptability of the current referral process, and the Implementation Climate Scale [37] (Multimedia Appendix 8) captures the level of application of evidence-based health practices at the partner sites. These surveys also include free-response options that delve deeper into providers’ encounters with the referral system.

Our adapted coordinated care model can enhance relationships among academic and community cancer centers. This model has the potential to improve patient and provider satisfaction and acceptability of the cancer care referral process. We anticipate that patients and providers can help identify limitations with the current MBC referral process to help identify opportunities to improve satisfaction and acceptability. Through Project ADAPT, we aim to positively impact clinical trial enrollment for patients with MBC, improve case discussion among providers, and provide a feasible and sustainable solution for improving care among patients with MBC. Moreover, as the number of women living with MBC continues to grow, our research extends beyond existing advancements in treatment [20,42] to evaluate interventions that have the potential to improve quality of life. We plan to disseminate our findings through academic platforms (eg, conferences and peer-reviewed journal articles), and we plan to make our data publicly available while adhering to IRB protocols. In addition, we will disseminate our findings to our community partner sites in a consumer-friendly plain language format.

There are few studies on the impact of collaborations among different hospitals to improve MBC care coordination. Only the EMBRACE program, to our knowledge, has conducted a multilevel systemic care coordination model for patients with metastatic breast cancer. WUSM received IRB approval in June 2021 and has completed participant recruitment for the exploration phase. WUSM has recruited 21 participants, including patients and providers. The latest community hospital, DDCI, joined the project in March 2021, while MBMC and SIH onboarded in late 2020. All partner sites are going through the single IRB registration in accordance with the current single IRB policy of the National Institutes of Health for multisite nonexempt human research carried out in the United States. The aim is to enhance and standardize the IRB review process among multiple research centers, avoiding duplication of review efforts to allow research to begin promptly [43]. This single IRB infrastructure has the potential to enhance the sustainability of these research partnerships and collaborations.

All communication requires reaching out to key stakeholders at these partner hospitals, presenting our research idea, and requesting collaboration virtually via Zoom meetings. Continued partnership and engagement have remained this way with a digital media platform by scheduling regular monthly meetings with all team members via Zoom to discuss updates on the study, recruitment and planning strategies, and IRB approval status. The research team meets at a time when most, if not all, can attend, and the ADAPT coordinator later sends out meeting minutes to all members of the group via email. During the research team meetings, study process modifications include creating study materials, such as the ADAPT patient flier for distribution to eligible patients at clinics and a page summary of Project ADAPT for providers.

We are approved to conduct virtual consultation for providers to share resources and knowledge among SCC, an NCI-designated cancer center, and our partner sites with NCORP clinical trial resources, creating a bidirectional relationship that improves patient care. This virtual consultation runs concurrently with telemedicine for patients. This platform of providing care to patients with MBC has become even more critical with the current COVID-19 pandemic [35]. This virtual experience also captures patients who would not be able to travel to SCC for whatever reason, but could still receive quality specialist care through this medium.

Patient recruitment for the exploration phase is via telephone calls, and surveys are distributed electronically through REDCap links. Utilizing e-consent for Project ADAPT has made recruitment manageable, especially during the COVID-19 pandemic. It resonates with studies showing that this approach can enhance access to participation among rural cancer patients in clinical trials, which is usually difficult due to geographic location [19,44]. Moreover, through virtual demonstrations via Zoom, the ADAPT coordinator has shown partner sites how to navigate the clinical trial tree finder.

Use of the digital EMR Epic messaging tool for communication among providers streamlines the referral process and allows providers access to real-time information regarding available clinical trials at SCC. Finally, as we prepare for the implementation phase, we strive to improve this design model with input from experts in different fields participating in the study and lessons learned from each stage of this study.

We have buy-in and support from the leadership, oncology teams, and staff at the community partner sites. A minimum commitment of monthly scheduled communication throughout the duration of the project is expected, and continued engagement in the adaptation process will be needed from all sites. It is possible that the initial support and enthusiasm for this project will diminish, but we are using an implementation-science framework to enhance continued engagement. In addition, we are working with sites that use the Epic EMR system. The feasibility data collected in this investigation will give us a sense of the timeline, personnel, and community setting infrastructure, including the EMR system, needed for scaling up this type of study.

WUSM research team members have launched a single IRB Support Network to develop a shared repository of resources and information to help guide partner sites through the single IRB process. We are in the process of creating a toolkit of resources to illustrate, in plain language, the single IRB application process. This toolkit will create a shared database with information about existing single IRB relationships with external partners (eg, key characteristics about the site and the research infrastructure, existing IRB agreements with WUSM, and past/current studies collaborated on with WUSM) and help to determine outreach strategies that best support partner sites throughout the single IRB process. For example, the study team has found that smaller community sites often lack third-party accreditations for their clinical research programs that may be more commonplace for larger academic health centers. In this way, the single IRB application process for studies that include a wide variety of recruitment sites would benefit from a streamlined approach to ensure the protection of human research subjects while accommodating the unique capabilities of each site.

In preparation for a larger trial, our team will complete provider-focused Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) [45]. Evaluating our approach using the 9 PRECIS-2 domains (ie, eligibility, recruitment, setting, implementation resources, provider strategy flexibility, intervention flexibility, data collection, primary outcome, and primary analysis) will facilitate engagement from our care coordination stakeholders to match our research approach with the overall study aims of a future trial. The implementation science methods used throughout Project ADAPT will establish a robust methodological foundation for future trials investigating care coordination across multiple sites.