Patients and caregivers allocated to the Wawokiya Health Advocate arm will receive a palliative intervention consisting of regular needs assessments and home visits. After the first 2 visits, visits will occur bi-weekly, though a WHA may increase or decrease frequency of visits pending patient and caregiver needs and cancer status. The first two study visits will follow the same broad structure-structure of follow up visits will be flexible based on patient and caregiver needs. The location of study visits will vary and may include the local IHS site, cancer centers, and the patient's home depending on health status. Patients will be randomized to either receive home visits upon enrollment or be placed on a waitlist.

Patients enrolled into the waitlist group will not receive any additional services beyond what is available to them in their standard course of care. Patients randomized to the waitlist group will be asked to identify a primary caregiver upon enrollment. Data collection procedures will occur as described below. While on the waitlist, any services available for patients and their families will be according to the standards of their local providers and primary cancer providers.

Study visits 1 and 2 will follow the same broad procedures. Subsequent visits will be structured around needs. WHAs will cover multiple domains of assessment utilizing a visit guide.

Visit 1: Specific topics covered in this visit will include; 1) an explanation of palliative care, study, and WHA role and 2) mapping of providers/family/caregivers The WHA will arrange dates and times for future visits.

Visit 2: Occurs 1 week after the first visit. WHAs will begin to assess patient needs utilizing a needs assessment tool. Specific topics covered will include: 1) Documentation of disease history 2) Needs assessment screen

Following Visits: After visit 2, activities will be based on needs assessed. Activities may entail: 1) Review of palliative care and WHA role, 2) Assessment of needs, 3) Addressing needs 3) Exploring goals of care.

We anticipate patients will receive an average of 2-3 WHA visits per month. Investigators will hold regular supervisory meetings with the WHA.

Wawokiya Health Advocate

Sara J Purvis, MPH

Bethany-Rose Daubman, MD

Michele Sargent

Informed by a Community Advisory Board (CAB) and community assessments performed in the first phase of work funded through R01CA240080, this study will test a wawokiya (one who helps) health advocate (WHA)-based palliative care intervention that aims to improve the wellbeing of patients with cancer. In alignment with community guidance, patients will be allocated to an intervention arm or a waitlist arm as dictated by capacity. For those patients receiving the intervention, palliative care trained WHAs will perform regular home visits to assess the needs of patients seriously ill with cancer (as defined by a referring provider) and their caregivers, and work to address those needs using their training and identified community resources. The frequency of visits / calls will be determined based on level of need. The specific aims are listed below.

Specific Aim 1: To examine the impact of a wawokiya health advocate (WHA) palliative care intervention on patient health outcomes including quality of life, symptom burden, and psychosocial wellbeing.

H1: Compared to patients in the waitlist group, patients enrolled in the WHA intervention will have a better quality of life, greater psychosocial wellbeing, and lower symptom burden.

Specific Aim 2: To assess the impact of a WHA palliative care intervention on patient healthcare utilization including emergency room visits, hospitalizations, telehealth visits, and concordance of services with goals of care.

H2: Patients enrolled in the WHA intervention will have fewer ER visits and hospitalizations and a greater number of telehealth visits than patients enrolled in the waitlist group.

H3: A greater proportion of patients enrolled in the WHA intervention will die in their preferred location.

Specific Aim 3: To examine the impact of a WHA palliative care intervention on caregiver outcomes including coping, caregiver burden, and quality of life.

H4: Compared to caregivers in the waitlist group, caregivers enrolled in the WHA intervention will have a better quality of life, better coping, and decreased caregiver burden.

Specific Aim 4: To explore moderators and mediators of a WHA as a palliative care navigator on rural reservations in South Dakota.

H5: Adherence to protocols will moderate the effectiveness of a WHA as a PC navigator.

.

One of the greatest areas of need in cancer care for American Indians in the Northern Plains is palliative care.Defined as the services needed to live well with serious illness, access to palliative care services by this population is almost non-existent, particularly in areas like western South Dakota where many tribal lands are located. Because of the distance to the nearest cancer care facility, the lack of transportation, and the lack of community-based palliative care, the great majority of American Indians with cancer living on Reservations are separated from their families during inpatient cancer care and die either alone in a hospital or at home suffering unnecessarily from symptoms such as pain, shortness of breath and anxiety. While this would be unacceptable for any group, it is particularly detrimental for Tribal Nations in the Northern Plains given the US governmental responsibility for providing their health care, the poverty experienced by the tribes, and the importance the people of these Nations place on spiritual preparation and community support at the end of life.

The past decade has witnessed substantial advances in the delivery of palliative care in other settings, particularly urban areas. Early application of palliative care services has been demonstrated to improve outcomes for patients with cancer, and new models of palliative care delivery are being developed, tested and implemented. Key features of these models, including the use of primary palliative care education, patient navigators and telemedicine for palliative care, have clear applications in the delivery of palliative care to American Indians in the Northern Plains.

Over the last 7 years, investigators have developed a multidisciplinary, Native-driven collaboration to advance the health of Lakota tribes that brings together multiple organizations in South Dakota (Great Plains Tribal Leaders Health Board \[GPTLHB\], Avera Health, Walking Forward, South Dakota State University School of Nursing, Indian Health Service \[IHS\]), the three largest tribes in western South Dakota (Cheyenne River, Oglala, and Rosebud Sioux tribes) and Mass General/Harvard. Initially developed to support clinical care for the Rosebud Sioux tribe, the Great Plains Lakota Health Research Collaboration (GPLHRC) has expanded to address critical health care issues affecting tribal communities across the region.

In the initial phase of the current project, the GPLHRC engaged with community members from each of the three tribes to better understand the existing palliative care landscape. We held 19 talking circles with cancer patients and their caregivers and conducted 12 interviews with local tribal leaders and traditional healers. In addition, we interviewed 38 health care providers both on and off the reservations. In holding open discourse with these key stakeholders, the GPLHRC identified many of the needs and concerns held within the South Dakota provider and patient community regarding palliative care for reservation-dwelling individuals and several challenges providers and their patients face to accessing and/or delivering palliative care.

Our work revealed that the fragmentation of services between the IHS and the urban or semi-urban cancer centers, as well different cultural backgrounds of providers and American Indian patients significantly influence the delivery of palliative services. The need for better coordination between providers and improved navigation of palliative care resources for patients was highlighted across the community. Additionally, providers expressed a desire for additional knowledge about Lakota culture as well as additional knowledge about existing resources and health infrastructure on the reservations.

Informed by Community Advisory Board (CAB) and the qualitative data described above, the investigators have developed a wawokiya health advocate (WHA)-based palliative care navigation intervention that aims to improve the wellbeing of patients with cancer. After receiving a specialized training curriculum through the Harvard Medical School Center for Palliative Care (HMS CPC), WHAs will make regular home visits to patients suffering from cancer to assess needs and locate resources to appropriately address the issues assessed. In alignment with community feedback, patients and their caregivers will be allocated to a waitlist group or the intervention as dictated by WHA patient panel capacity. By evaluating the impact of the intervention on patients and caregivers compared to usual oncologic care, investigators aim to provide evidence for the long-term implementation of a sustainable approach to palliative care delivery for Reservation-dwelling American Indians in the Northern Plains and generate data to improve the quality of cancer care in rural settings across the US.

A novel model will be used in alignment with community feedback on study design. Patients will be allocated to the intervention arm as dictated by interventionist panel capacity. Patients will be added to a waitlist "control" arm as dictated by intervention arm capacity.

Living Well With Serious Illness "Wicokuje Sica Tuha Akisniya Wiconi": Wawokiya Health Advocate Intervention

Advancing Palliative Care in Northern Plains American Indians: Living Well With Serious Illness "Wicokuje Sica Tuha Akisniya Wiconi" - Wawokiya Health Advocate Intervention

IPD will not be shared with researchers who are not involved in this study.

Adherence to protocol will be evaluated via semi-structured interviews with patients

Change from baseline in patient-reported quality of life measured by the Functional Assessment of Cancer Therapy - General 7 (FACT-G7) through study completion (we anticipate an average of 1 year). FACT-G7 is a 7-item Likert scale (range 0-4). Scores range from 0-28, higher scores indicate better quality of life.

Change from baseline in patient-reported symptom burden as measured by the Edmonton System Assessment System - revised (ESAS-r). The ESAS-r is a 9-item scale that measures a total of 9 symptoms on a continuous scale of 0 (no symptoms present) to 10 (most severe level). Scores range from 0-90. Higher scores indicated greater symptom burden.

Change from baseline in patient-reported loneliness as measured by the University of California-Los Angeles (UCLA) three-item loneliness scale. The UCLA loneliness scale is a 3-item likert scale (range 1-3). Scores range from 3-9. Higher scores indicate greater loneliness.

Change from baseline in patient-reported hope as measured by Herth Hope Index (HHI). The HHI is a 12-item Likert scale (1-4). Scores range from 12-28. Higher scores indicate higher levels of hope.

Number of times patient is hospitalized overnight

Number of separate trips to Emergency Room

Number of visits with a provider over video or phone call

Number of home visits with a health care professional (not a wawokiya/study interventionist)

Change from baseline in caregiver-reported quality of life across 10 domains as measured by the CareGiver Oncology Quality of Life questionnaire (CarGOQOL). The CarGOQOL is a 29-item Likert scale (1-5). Scores range from 29- 145. Higher scores indicate a higher quality of life.

Change from baseline in caregiver-reported burden measured by the Montgomery Borgatta Caregiving Burden (MBCB). The MBCB is a 14-item Likert scale (15) subdivided into 3 scales(objective burden, subjective stress burden, subjective demand burden). Scores on the objective subscale range from 6-30 and scores on the stress and demand burden subscales range from 4-20. Higher scores across sub scales indicate higher burden.

Change from baseline in caregiver-reported loneliness as measured by the University of California-Los Angeles (UCLA) three-item loneliness scale. The UCLA loneliness scale is a 3-item Likert scale (range 1-3). Scores range from 3-9. Higher scores indicate greater loneliness.

Change from baseline in caregiver-reported hope as measured by Herth Hope Index (HHI). he HHI is a 12-item Likert scale (1-4). Scores range from 12-28. Higher scores indicate higher levels of hope.

South Dakota State University

Avera McKennan Hospital & University Health Center

Massachusetts General Hospital

Physician-In-Chief

Cancer patients and survivors undergo collection of tissue, blood, saliva, and stool samples on study for genomic sequencing and microbiome analysis. Cancer patients and survivors also complete surveys and interviews on study pre and post intervention.

Undergo collection of tissue, blood, saliva, and stool samples

Biospecimen Collection

Return of Results

Survey Administration

Ursa Brown-Glaberman, MD

Kelsey Ayers, BS

Koby Blackwater

Cheryl Willman, MD

Andrew Sussman, PhD

Shiraz I Mishra, MCCS, PhD

This clinical trial studies engagement strategies for recruiting American Indians (AI) of Southwestern Tribal Nations for cancer genome sequencing. American Indians in the Southwest have higher rates of some types of cancer, such as cancers that arise in the liver, kidney, breast, and colon. American Indians with cancer may also live for less time than people from other population groups who have been treated for the same cancer. Damage to the cells of the body, acquired as people live, grow older, and are exposed to the environment, causes genetic changes in cells that can lead to cancer. This study may help researchers learn how these genetic changes in cells cause cancer and understand how and why cancer is arising in American Indians in the Southwest. This may help better prevent and treat cancer in the future.

PRIMARY OBJECTIVES:

The overall objective of the PE-CGS Research Center is to develop culturally appropriate, respectful, trusted, and collaborative means to engage and recruit American Indians affected by cancer (newly diagnosed cancer patients, patients undergoing cancer treatment, and cancer survivors) for molecular characterization of their tumors.

The clinical trial is embedded in the Patient Engagement Unit (PEU) jointly with the Engagement Optimization Unit (EOU)

The specific objectives for the PEU are to:

1. Conduct direct participant engagement with cancer patients/survivors, community advisors, and partners to refine and optimize methods/processes;
2. Identify, recruit and consent eligible AI cancer patients/survivors;
3. Implement tissue acquisition, epidemiologic, behavioral, and clinical data collection, conduct continuous assessment of performance benchmarks;
4. Return clinical grade and clinically useful genomic data to participants with navigation to counseling and clinical resources as warranted and as they select.

The specific objectives of the EUO are to:

1. Finalize consenting process and informed consent by direct engagement of AI cancer patients, survivors, healthcare providers, genetic counselors, consenting staff, tribal and spiritual leaders and tribal governance;
2. Determine AI cancer patients' and survivors' knowledge, attitudes, cultural beliefs, information needs, and communication preferences and practices regarding clinical genomics testing;
3. Determine AI cancer patients' and survivors' perspectives on strategies to engage and recruit participants for clinical genomics testing.

Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing

Participant Engagement - Cancer Genome Sequencing (PE-CGS) Research Center: Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing

Number and percent of eligible participants enrolled and consented

Number and percent of eligible participants who complete, or partially complete, baseline and follow up data collection of epidemiological assessments and follow up data collection of epidemiological assessments

Number and percent of enrolled participants for whom biospecimens are collected and processed for genomic analysis

Number and percent of participants/samples that undergo successful comprehensive genomic and bioinformatic analysis

Number and percent of participants who elect to receive clinical genetic/genomic results and incidental findings

Number and percent of participants/patients whose clinical genomic data facilitates therapeutic intervention

Successful completion of the Preparatory and Optimization Phases

National Cancer Institute (NCI)

New Mexico Cancer Care Alliance

Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Participants randomized to the intervention group will view the AI culturally-adapted CRC screening decision aid in a private room at a RHCC clinic. The video will be viewed on an electronic tablet or laptop computer.

Participants randomized to the control group will view an attention-control video about food safety in a private room at a RHCC clinic. The video will be viewed on an electronic tablet or laptop computer. The investigators chose the attention-control video so that the structure of the control arm mirrors the intervention arm. The food safety topic was chosen to provide information that is reasonably salient to the control arm participants but that would not be likely to affect encounters with healthcare providers.

Information previously discussed in arm/group descriptions. There will be baseline, post-encounter, and 5-month follow-up assessments.

Colorectal Cancer Screening Decision Aid

Information previously discussed in arm/group descriptions. There will be baseline, post-encounter, and 5-month follow-up assessments. Information previously discussed in arm/group descriptions. There will be baseline, post-encounter, and 5-month follow-up assessments.

Control Group

Leah Frerichs, PhD

Experts note that in order to continue reducing the US cancer burden, it is critical that investigators "more completely apply discoveries in cancer prevention we have already made." Thus, it is important to research strategies that aim to improve application of effective colorectal cancer (CRC) prevention and screening tests among underserved populations like American Indians (AI).CRC is the 2nd leading cause of cancer death among AI; yet, one of the most preventable and treatable cancers when detected early. Increased use of recommended CRC screening tests among men and women ages 50-75 have contributed to nearly 50% declines in US CRC mortality since 1990. However, recent evidence indicates AI have not observed equitable improvements. The investigators propose to build upon our experience addressing CRC screening in underserved populations and strong partnerships with North Carolina tribal partners to gain new insight about a patient-centered, culturally appropriate strategy to increase AI CRC screening.

Colorectal Cancer (CRC) Screening Options. CRC is a unique cancer due to the multiple screening options including stool-based (fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT)), and direct visualization (colonoscopy) options. Healthcare providers tend to recommend colonoscopy, although evidence indicates that many patients, especially low-income and racial and ethnic minorities, prefer stool-based testing for a variety of reasons. In our formative work with North Carolina tribes, the investigators found evidence of low awareness of stool-based tests among American Indians (AI) and healthcare provider preferences to recommend colonoscopy. The US Preventive Services Task Force (USPSTF) guidelines indicate that evidence does not support favoring one CRC screening test above the others, and that recommendations should be based on patient preferences among the screening options. However, patient's general lack of knowledge of CRC screening modalities, literacy barriers to understanding differences between options, and other communication barriers in the healthcare setting (e.g., limited physician time) make this recommendation difficult to implement in practice without appropriate tools and support. Multimedia decision aids provide a practical solution to overcome communication challenges by providing patients information using easy-to-understand graphics and narratives designed to help them understand options, think through what is important to them, and engage with healthcare providers and family in the decision-making process.

CRC Screening Decision Aids. A recent systematic review and meta-analysis found evidence that average risk patients (aged 50 and over) exposed to CRC screening decisions aids showed greater increases in knowledge, were more likely to be interested in getting screened, and more likely to be screened. Most research on decision aids has been conduct with majority White populations; a few studies have focused on patients with low socioeconomic status. To our knowledge, no CRC screening decision aid studies have focused on AI populations.Our team has expertise in adapting CRC screening decision aids for underserved populations. The investigators have used a rigorous, community- and patient-engaged process to adapt a decision aid previously shown to be effective among majority White populations. The process retains effective elements of the existing version and refines content using messages and messengers that are culturally-sensitive (beyond peripheral packaging of graphics and visual content). A version the investigators adapted for low-income Hispanics significantly improved Hispanic patient's CRC screening knowledge, patient-provider communication, self-efficacy, and intent, and when combined with navigation, significantly improved completion of screening.

AI Barriers to CRC Screening. AI may benefit from decision aids; yet, CRC screening decision aids have not been developed or tested with AI populations. Several studies have found that AI have lower awareness and knowledge about CRC screening options and low perceived susceptibility of CRC than White populations. Many qualitative studies also indicate social and cultural barriers to CRC screening. For example, AIs indicate taboos related to speaking of illness or of certain body parts and fatalistic cultural beliefs influence their attitudes and intentions to obtain preventive medical services. In addition, a history of unethical healthcare practices and mistreatment of AI by the US government has led to issues of mistrust. Recent studies have found that AI report negative perceptions of medical providers and mistrust in healthcare institutions as barriers to obtaining CRC screening. Decision aids can address low awareness of options and improve attitudes and intentions for screening, especially if the content and the messengers of the information are adapted for sensitivity to relevant socio-cultural barriers (e.g., spiritual advisors who are credible to AI endorse screening). For this proposal, the investigators propose to test a novel culturally-adapted decision aid that aims to improve knowledge, attitudes and intentions to obtain CRC screening and uses messaging developed with our tribal community partners to overcome health literacy and socio-cultural barriers.

Conceptual Framework. Our decision aid is informed by the Theory of Planned Behavior and Cultural Identity Theory. The Theory of Planned Behavior posits that individual's attitudes (i.e., how one feels about a behavior and the potential outcomes of the behavior), norms (i.e., the amount of social pressure one feels to perform a behavior), and agency (i.e., the extent that one feels in control and able to perform a behavior) impacts their intentions to and subsequent performance of a behavior. The investigators also draw upon Cultural Identity Theory and posit that one's cultural identity and corresponding values underlie how one receives and interprets communicated messages and how one communicates with others about these messages. Our culturally-adapted decision aid uses messages that address AI-specific attitudes, norms, agency and communication concerns.

Preliminary Studies. With developmental funding from UNC's Lineberger Comprehensive Cancer Center, the investigators followed a rigorous process to adapt a general population version of a CRC screening decision aid for AI. From January to May of 2016, the investigators conducted six focus groups (n=74) with AI (ages 50-75) and interviews with healthcare providers (n=8) from three North Carolina tribal communities. The investigators explored perspectives about cultural, communication, and literacy barriers to CRC screening, and identified critical themes regarding AI cultural identity and socio-cultural values that influence CRC screening. The investigators and our tribal partners have operationalized the themes into adaptations of the existing general population decision aid. The decision aid provides information on stool-based and colonoscopy tests, the two types readily available in the community. The investigators are filming and making edits to the decision aid, which will be completed and ready for pilot testing by December 2016. Themes from AI focus groups and operationalized changes to a culturally-adapted CRC screening decision aid Operationalized Changes Healthcare mistrust - concern that inappropriate medical tests are recommended by providers Religious advisor to provide information and conveys trust in CRC screening options AI collectivism - stronger 'family' and community orientation toward health than individual focus New messages emphasize the benefit of CRC screening to one's family and community Privacy concerns- indication of difficulties and discomfort talking about CRC screening with family Vignette that models family communication around CRC screening Fear of cancer and screening - fear of cancer and screening process reduces motivation for screening AI CRC survivor to share experience of being screened and treated early

Methods A. Setting Our current research is centered in North Carolina tribal communities, primarily with the Lumbee Tribe of North Carolina, a state-recognized tribe that is located in Southeastern North Carolina. There are 62,306 Lumbee tribal members, the majority of whom (48,494) live in Robeson county. As with AI populations across the US, North Carolina AI have high rates of poverty and low educational attainment. One-third (33%) of AI in Robeson County are below the federal poverty level compared to 17% in North Carolina overall.45As a state-recognized tribe, Lumbee are not eligible for services through the federally-funded Indian Health Service,44 and many Lumbee tribal members use safety-net and federally qualified health centers such as the Robeson Health Care Corporation (RHCC), partner on this grant (see letter of support) to obtain health services.Robeson Health Care Corporation is a federally qualified health center with six clinics located in Robeson and neighboring counties. RHCC serves over 14,000 patients per year; 40% are AI. Nearly all, 95.6% of RHCC patients are at or below 200% of the federal poverty line. According to recent reports, 6,295 RHHC patients were not up-to-date with CRC screening following recommended guidelines.RHHC also has a long history of research collaboration on cancer screening projects.

The investigators will use a two-group randomized controlled trial to achieve our aims. Participants (n=120) will be randomized to view the AI culturally-adapted decision aid or an attention-control (i.e., food safety) video. The study flow diagram (Figure 2) indicates the recruitment, randomization, and assessment process.Our research to develop and evaluate the decision aid is approved by the Lumbee Tribal Council and the institutional review board (IRB) at the University of North Carolina at Chapel Hill.

A Culturally-adapted Colorectal Cancer Screening Decision Aid Designed for American Indians

A Randomized Trial of a Culturally-adapted Colorectal Cancer Screening Decision Aid Designed for American Indians

Measure of screening intent from prior CRC screening decision aid studies and assessed using a single categorical item regarding intentions to get CRC screening with four response options.

Assessed by a six-item index (based on decision aid content). Items include 1) the availability of more than one option for CRC screening; 2) the availability of a home screening test; 3) the recommended age to begin CRC screening; 4) FOBT screening test frequency; 5) the need for sedation (and companion driver) for colonoscopy procedure, and 6) the existence of a small but non-zero complication risk associated with having colonoscopy.

Assesses attitudes about how important items are for a participant's decision of whether or not to get CRC screening, including potential pros (e.g., having peace of mind after receiving clear findings) and cons (e.g., being worried or concerned that if you do the test you might find something wrong) with 4-point Likert-scale response options.

Assesses the participant's belief that family, friends, and doctors think he/she should be screened.

Assesses confidence to complete screening with 4-point Likert-scale response options (i.e., not at all confident, not very confident, confident, very confident).

Measures screening preferences from prior studies.

Assessed with a participant-reported measure of having had a CRC screening discussion with a healthcare provider in the prior 5 months based on items used in a national survey.

Assessed using a measured adapted from a study on family communication about cancer screening. Participants asked to enumerate social network members and will be asked to identify members with whom they discussed CRC screening.

Dichotomous indicator of whether or not the participant completed any of the recommended CRC screening tests.

UNC Lineberger Comprehensive Cancer Center

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Uterine Cervical Neoplasms

Colonic Neoplasms

Breast Diseases

Skin Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

The investigators will train Community Health Representatives (CHRs) in interactive group discussions techniques. CHRs will administer 1 session/week, lasting approximately 2 hours, and conducted among 12 men or women ages 21-75 per cluster. The CHRs will distribute the cancer-specific (i.e., breast, colorectal, and cervical) small media during the first session and refer to it during the course of the 4 sessions. During the sessions, the CHRs will function as a facilitator linking information with practical skills. At the end of the 4-week INT, participants will receive a voucher to present to a designated point-person at the health center who would schedule the screening for the age- and gender-specific cancers.

Adult men and women will receive age- and gender-specific interventions. Women age 50-75 years will receive the interventions for breast, colorectal, and cervical cancers screening. Men age 50-75 years will receive the intervention for colorectal cancer screening. Women age 21-49 years will receive the intervention for cervical cancer screening. The 4-week interventions, delivered once a week, will consist of educational sessions that discuss cancer-specific information (i.e., breast, colorectal, and cervical cancer): breast (colorectal, cervical) cancer myths and facts, risk factors and symptoms, screening, and review/action plan. The educational sessions will be complemented by cancer-specific small media (brochure).

Breast, Colorectal, and Cervical Cancer Screening Interventions

Shiraz I Mishra, MBBS, PhD

There are continued disparities in cancer incidence, mortality, and survival between American Indians (AIs) and Whites on cancers responsive to early screening (i.e., breast, colorectal, and cervical) in the US. In New Mexico (NM), AIs compared with other racial/ethnic populations are significantly less likely to adhere to recommended screening guidelines. The purpose of this trial is to develop and pilot test multilevel/multicomponent intervention strategies to enhance screening for breast, colorectal, and cervical cancers.

Enhancing Cancer Prevention and Control Pathways-Native Health Initiative

Percentage of women 50-75 years who obtain a mammogram exam

Percentage of men and women 50-75 years who complete a fecal immunochemical test kit

Percentage of women 21-64 years who complete a Pap Smear test

National Institute of General Medical Sciences (NIGMS)

Pharmaceutical Solutions

All Drugs and Chemicals

The high intensity intervention includes: navigated outreach, with four in-depth education outreach sessions; mailed FIT; education material; and follow-up mailed reminders (Group 1). The navigated outreach includes one-on-one information dissemination about CRC, importance of adhering to CRC screening guidelines, identification and solutions to screening barriers, motivation, self-efficacy and comprehension on how to complete the FIT kit, and gathering (if requested) and return of the completed FIT to the laboratory. The educational material (brochure) is specially developed and culturally tailored for the six Tribes recruited for this study. The FIT kit used is the Polymedco OC FIT-CHECK® OC-Light test, which is a single collection test that meets USPSTF's guidelines.

The medium intensity intervention includes: mailed FIT; education material; and follow-up mailed reminders (Group 2). The educational material (brochure) is specially developed and culturally tailored for the six Tribes recruited for this study. The FIT kit used is the Polymedco OC FIT-CHECK® OC-Light test, which is a single collection test that meets USPSTF's guidelines.

The reference group (Group 3), per IHS guidelines and current standard of care at participating IHS facilities, receives usual care (ie, screening recommendation and a FIT kit at a clinic visit). The FIT kit used is the Polymedco OC FIT-CHECK® OC-Light test, which is a single collection test that meets USPSTF's guidelines.

High Intensity (Group 1)

Medium Intensity (Group 2)

Reference Group (Group 3)

Kevin English, DrPH

Recent improvements in colorectal cancer (CRC) incidence, mortality, stage at diagnosis, and survival in the general U.S. population have been attributed to routine screening with prompt removal of polyps, early detection, and timely and appropriate treatment. American Indians/Alaska Natives (AI/ANs) have not experienced improvements in CRC related outcomes and are significantly less likely than non-Hispanic Whites to receive recommended CRC screening. The purpose of this three-arm randomized controlled trial is to determine the efficacy of interventions designed to enhance CRC screening. The study also uses mixed methods to finalize the intervention and to determine promoters and barriers of screening. The study also conducts process evaluation to determine cost-effectiveness of the interventions, fidelity of study implementation, and to develop plans to sustain and scale-up the intervention model. The study will determine the efficacy of serially implemented interventions of graded intensity for increasing CRC screening using the fecal immunochemical test (FIT) in accordance to recommended guidelines among average risk American Indians (AIs) aged 50-75 residing on reservations in rural Southwestern U.S. Serial implementation refers to offering routine screening, irrespective of response to an earlier invitation, in concordance with guidelines which recommend annual FIT testing between ages 50-75. The FIT is most appropriate because it is an approved, high sensitivity fecal occult blood test and is available at Indian Health Service (IHS) and tribal health facilities where resources to provide screening colonoscopy are limited. The study is a collaborative effort between the Albuquerque Area Indian Health Board (100% Indian-owned and operated), six Pueblo Tribes in rural Southwestern U.S., and the University of New Mexico. Findings from this research could lead to an immediate increase in CRC screening and ultimately reduce CRC burden among AIs, thus addressing national and tribal priorities of reducing CRC disparities among AIs.

Despite the effectiveness of CRC screening tests for average risk adults, these tests are under-utilized by AI/ANs. A recent study of AI/ANs who utilize IHS facilities reported that only about 4.0% of average risk AI/ANs age 50-75, compared with nearly 65% of U.S. adults, were current with CRC screening guidelines. The overall objective is to test the efficacy of serially implemented interventions of graded intensity designed to enhance annual CRC screening using the FIT in AI communities. The aims are to:

Aim 1. Finalize and evaluate the efficacy of serially implemented interventions of graded intensity for increasing annual CRC screening uptake.

Aim 2. Determine promoters and barriers to enhancing annual CRC screening practices.

Aim 3. Conduct process evaluation studies on: cost-effectiveness of the interventions, implementation fidelity, and sustainability and scalability.

Protocol A. Aim 1-Qualitative Research (Intervention Finalization)

1. Research Design: Qualitative design, using focus group methodology.
2. Study Population: Recruited from the project's Community Advisory Council, from the Albuquerque Area Southwest Tribal Epidemiology Center's (AASTEC's) Executive Council, Community Health Representatives, and other tribal stakeholders.
3. Recruitment Target: Up to 30-36 eligible (assuming attrition) persons.
4. Recruitment Methods: Purposive sampling methods.
5. Procedures: Conduct three focus groups, with each group consisting of 6 to 8 participants. Each session will meet for approximately two hours. Before starting the discussion, participants will provide informed consent and complete a survey collecting socio-demographic information. The purpose of these focus groups is to finalize the intervention's educational material, ensuring it is culturally appropriate and contains messages operationalizing various constructs of the theory guiding the study (Health behavior Framework; HBF).

B. Aim 1-Quantitative Research (Efficacy RCT)

1. Research Design: Randomly assigned, three-group, pretest-posttest design.
2. Research Setting: Six Pueblo Tribes in New Mexico.
3. Randomization: Using simple random allocation procedures.
4. Participants Identification and Sampling: Identify eligible participants from the IHS Resource and Patient Management System (RPMS) electronic health record system. We will invite all eligible persons (estimated at 1,700) identified through the RPMS to participate.
5. Interventions: The interventions are graded in intensity: high intensity, medium intensity, and reference group (usual care).
6. Procedures: After randomizing tribes to the three Groups, we will mail a recruitment letter, a consent form for completion of surveys, and a baseline survey. We will mail the first posttest survey 12 months after mailing the baseline survey, with the 2nd and 3rd posttest surveys mailed in successive 12-month intervals. Between the baseline and 1st posttest surveys, participants will receive the group-specific intervention. All eligible adults will be included in the analyses for the primary outcome (ie, completion of the FIT kit) since non-completion of a FIT is a valid response. All eligible participants in Groups 1 and 2 will receive a mailed FIT kit whether or not they return the baseline survey.
7. Implementation of the Intervention: We will simultaneously implement the intervention, over three 12-month cycles. For Groups 1 and 2, we will mail the FIT kit, and the educational material about one month following the initial recruitment letter/baseline survey mailing. For Group 1, navigators will offer up to four education outreach sessions. Group 2 will receive the FIT and education material mailing. Group 3 will receive usual care (screening recommendation and a FIT kit at a clinic visit).
8. Baseline and Posttest Surveys: These surveys will collect data on CRC-related knowledge, attitudes, perceived control, perceived susceptibility and severity, social support, and self-efficacy. The baseline survey will also collect socio-demographic data.
9. Data Management and Analysis: We will summarize categorical and continuous variables using descriptive statistics. For all analyses, the overall type I error rate will be α=0.05. We will use appropriate methods such as Tukey's honest significant difference test or a Bonferroni correction for multiple comparisons.

   For the primary outcome, annual completion of the FIT kit, the primary endpoint is the proportion of participants within each Group who completed and returned 0, 1, 2 or 3 FIT kits. All analyses will be intent-to-treat, since all eligible participants will be included in the analysis. We will compare the primary outcome across interventions via a likelihood ratio test with a multiple comparisons adjustment. To summarize intervention effects, we will report odds ratios and their 95% confidence intervals (CIs) for completing all 3 FIT kits as compared to returning each of 2, 1, or no FIT kits.

   The secondary outcomes are temporal changes in the HBF constructs (eg, knowledge, attitudes, perceived risk) from baseline to 12-month cycles following the baseline survey. We will assess temporal changes in the HBF constructs with repeated measures linear regression modeling to understand the interventions' effects over time. Predictive value of the interventions and the HBF constructs on the yearly FIT uptake will be assessed by refitting the repeated measures logistic regression model described in the primary analysis for the dependent variable of return of completed FIT kit (yes vs. no) at each time point, but also including as a covariate score from all returned surveys measuring HBF constructs. We will report odds ratios (and 95% CIs) for completion by Groups.
10. Sample Size Considerations: We powered our study to measure significant changes by Group in the annual completion of the FIT (primary outcome). With hypothesized proportions of participants with 0, 1, 2 or 3 returned FIT kits that reflect an average of 4%, 14% and 24% completing the FIT each year for the three Groups, respectively, the power of the study is \~99% with 566 participants per Group (total=1,698). We adjusted for multiple comparisons in our power calculation by using a Bonferroni correction.

Aim 2-Qualitative Research (Understanding Behavior Change Context)

1. Research Design: Qualitative design.
2. Study Population: Participants "largely adherent" (completed FIT 2 or 3 of 3 times) and "not adherent" (completed FIT 0 or 1 of 3 times) to guidelines; navigators; providers and medical directors of IHS facilities.
3. Recruitment Target: Up to 120-144 participants (assuming attrition) who took part in the Aim 1 Efficacy RCT; with 60 participants "largely adherent" and 60 participants "not adherent" to the FIT guidelines. All the navigators (n=3) working on the project and medical directors (n=3) of the three participating IHS facilities. One health care provider from each of the three participating IHS facilities (n=3).
4. Recruitment Methods: Purposive sampling methods.
5. Procedures: Conduct 12 focus groups, with each group consisting of 6 to 8 participants. Each session will meet for approximately two hours. Before starting the discussion, participants will provide informed consent. The moderator will explore HBF factors most conducive to being "largely adherent" to screening guidelines. Among participants "not adherent" to CRC screening guidelines, we will inquire about barriers to completing a FIT and their potential solutions. We will also inquire about how we can sustain and scale-up the interventions for broader dissemination.

Conduct interviews with navigators, and health care providers and medical directors of the IHS facilities. Before starting the interview, we will obtain informed consent. Interviews with the navigators will focus on delivery of the intervention, barriers and promoters to providing navigation, participants' reasons for "largely adhering" or "not adhering" to CRC screening guidelines, and strategies to sustain and scale-up the interventions. Interviews with the health care providers and medical directors will focus on systems-level factors that may or may not facilitate delivery of CRC screening services, viability of using navigation for cancer screening in community settings, and strategies to sustain and scale-up the interventions. We will collect baseline socio-demographic information from the participants.

Aim 3-Process Evaluation Studies (Cost-Effectiveness Analysis, Implementation Fidelity, and Sustainability and Scalability)

1. Procedure-Cost-Effectiveness Analysis: We will collect and use primary and secondary data to define parameters for the Markov models of cost-effectiveness. We will include data on CRC epidemiology in New Mexico, screening and treatment costs, and screening compliance rates for each cycle of the serially implemented interventions. We will collect data on all costs including navigation, mailing of FITs, educational material, and follow-up costs by each Group. We will assess direct medical costs through the IHS RPMS, which contains patient encounter-level data by outpatient ICD-9 diagnoses and procedure codes. We will extract data on sensitivity, specificity and efficacy of screening tests from the peer-reviewed literature. We will begin by constructing a decision tree for each of the Groups. We will compute the costs of each decision node (FIT completed/FIT not completed and received colonoscopy/did not receive colonoscopy) based on directly accrued medical and non-medical costs obtained from data sources identified above. The result of the cost-effectiveness analysis will be an incremental cost-effectiveness ratio (ICER) for the three Groups.
2. Procedure-Implementation Fidelity: We will evaluate fidelity of implementation based on standard components, including: reach to potentially eligible participants; recruitment; resources and expertise needed for the research; the broader content (ie, social, physical, cultural, and structural factors); fidelity of delivery of the interventions; amount of the intervention actually delivered; amount of the intervention actually received; challenges encountered in implementing the research; potential contamination; and number and quality of partnerships.
3. Procedure-Sustainability and Scalability: We will operationalize concepts for sustaining and scaling-up efficacious interventions, including: the nature of the interventions; the interventions' efficacy; the cost and cost-effectiveness of the interventions; partnerships; organizational capacity; contextual factors; promoters and barriers; and generalizability to other populations.

Enhancing Prevention Pathways Toward Tribal Colorectal Health

We will assess colorectal cancer related knowledge through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including colorectal cancer related knowledge about risk factors, symptoms, its screening tests, and recommended guidelines for screening. We will aggregate responses on the knowledge-related questions to provide an overall composite knowledge score at each of the time points (baseline and the three posttests). We will compute change in knowledge as the difference in the composite knowledge score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

We will assess colorectal cancer related attitudes through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including colorectal cancer related attitudes about cancer, screening, and prevention. We will aggregate responses on the attitudes-related questions to provide an overall composite attitude score at each of the time points (baseline and the three posttests). We will compute change in attitudes as the difference in the composite attitude score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

We will assess perceived control through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including perceived control in getting colorectal cancer, control over its risk factors, and about screening. We will aggregate responses on the perceived control-related questions to provide an overall composite perceived control score at each of the time points (baseline and the three posttests). We will compute change in perceived control as the difference in the composite perceived control score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

We will assess perceived susceptibility through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including perceived susceptibility for colorectal cancer. We will aggregate responses on the perceived susceptibility-related questions to provide an overall composite perceived susceptibility score at each of the time points (baseline and the three posttests). We will compute change in perceived susceptibility as the difference in the composite perceived susceptibility score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

We will assess perceived severity through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including perceived severity of colorectal cancer. We will aggregate responses on the perceived severity-related questions to provide an overall composite perceived severity score at each of the time points (baseline and the three posttests). We will compute change in perceived severity as the difference in the composite perceived severity score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

We will assess self-efficacy through surveys administered at baseline and at three posttests. The surveys will be mailed 12 months apart. We will utilize validated questions from the NIH PROMIS instrument repository (http://www.nihpromis.org/), national surveys, and from our previous studies to measure the important theoretical constructs including self-efficacy with regarding to controlling risk factors and completing colorectal cancer screening. We will aggregate responses on the self-efficacy-related questions to provide an overall composite self-efficacy score at each of the time points (baseline and the three posttests). We will compute change in self-efficacy as the difference in the composite self-efficacy score at posttest 1 and at baseline, at posttest 2 and at posttest 1, and at posttest 3 and at posttest 2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Living Well With Serious Illness "Wicokuje Sica Tuha Akisniya Wiconi": Wawokiya Health Advocate Intervention	NCT05208606	Cancer	Wawokiya Health...	18 Years -	Massachusetts General Hospital
Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing	NCT06207864	Malignant Neopl...	Biospecimen Col... Return of Resul... Survey Administ...	18 Years -	New Mexico Cancer Care Alliance
A Culturally-adapted Colorectal Cancer Screening Decision Aid Designed for American Indians	NCT03569761	Colorectal Canc...	Colorectal Canc... Control Group	50 Years - 75 Years	UNC Lineberger Comprehensive Cancer Center
Enhancing Cancer Prevention and Control Pathways-Native Health Initiative	NCT04259762	Cancer, Breast Cancer, Colon Cancer, Cervix	Breast, Colorec...	21 Years - 75 Years	New Mexico Cancer Care Alliance
Enhancing Prevention Pathways Toward Tribal Colorectal Health	NCT02882620	Colorectal Neop...	High Intensity ... Medium Intensit... Reference Group...	50 Years - 75 Years	University of New Mexico
A Culturally-adapted Colorectal Cancer Screening Decision Aid Designed for American Indians	NCT03569761	Colorectal Canc...	Colorectal Canc... Control Group	50 Years - 75 Years	UNC Lineberger Comprehensive Cancer Center
Enhancing Cancer Prevention and Control Pathways-Native Health Initiative	NCT04259762	Cancer, Breast Cancer, Colon Cancer, Cervix	Breast, Colorec...	21 Years - 75 Years	New Mexico Cancer Care Alliance

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