Patient Navigation Improves Cancer Diagnostic Resolution: An Individually Randomized Clinical Trial in an Underserved Population Free

Patient navigation programs are being increasingly adopted across the United States, although the evidence for their effectiveness is not well established (1). Patient navigation can potentially impact cancer care across the entire continuum, including screening rates, resolution of screening abnormality, diagnosis to initiation of treatment, treatment adherence and completion, survivorship, and end-of-life care.

Most of the reported studies have assessed the impact of patient navigation on screening rates for breast, cervical, and colorectal cancer (2–8). Fewer studies have been published on the effect of patient navigation on diagnostic resolution, treatment outcomes, survivorship, and end-of-life (9).

The Patient Navigation Research Program (PNRP) was initiated in 2005 through funding from the National Cancer Institute's Center to Reduce Cancer Health Disparities. PNRP is a cooperative effort of 9 health care institutions across the United States, serving medically underserved populations, including racial and ethnic minorities and those of low socioeconomic status (1, 10). PNRP enrolled subjects with either an abnormal cancer screening finding or an incident diagnosis of breast, cervical, colorectal, and prostate cancer. In this publication the authors describe the results of the individually randomized clinical trial conducted at the Denver PNRP, addressing subjects with abnormal screening findings.

Denver Health is the public safety net for the City and County of Denver and has a long and distinguished record for serving as the health care provider for Denver's underserved populations. One quarter of Denver residents, or approximately 160,000 adults and children receive their care at Denver Health, of whom 57% are Hispanic, 18% Black, and 20% White. In terms of insurance status, 46% of Denver Health patients are uninsured, 36% have Medicaid, 6% Medicare, 10% commercial, and 2% are covered by the State Children's Health Insurance Program.

Denver PNRP conducted a prospective randomized clinical trial, one of 2 individually randomized trials within the National PNRP. The aims of the overall program were to (1) reduce the time from abnormal screening for breast, colorectal, and prostate cancer to diagnostic resolution, (2) reduce the time from breast, colorectal, and prostate cancer diagnosis to start of treatment, (3) increase adherence to cancer treatment, (4) increase patient satisfaction with care, and (5) determine the cost effectiveness of patient navigation. Patient enrollment began at Denver Health in October 2006 and 1,249 screening and treatment patients were enrolled in the study through June 2010. In this manuscript we report our findings for aim 1.

Eligibility for Denver PNRP included an abnormal breast, colorectal, or prostate screening test or a new diagnosis of these cancers. Breast screening tests included an abnormal clinical breast examination that resulted in a referral to a specialist or an abnormal mammogram that resulted in further diagnostic examination. Colorectal screening included a positive fecal occult blood test, an abnormal rectal examination, history of bright red blood in the stool among those 40 and over, or an abnormal sigmoidoscopy. Men enrolled with an abnormal prostate screening test had an abnormal prostate finding on digital rectal examination or an elevated prostate-specific antigen (PSA; ≥4 ng/mL). Individuals with a prior history of cancer (excluding nonmelanoma skin cancer) within the past 5 years, prior receipt of patient navigation, pregnancy, or incarceration were not eligible for this study.

Potentially eligible patients were identified through weekly electronic lists of patients meeting the criteria from the referral systems and laboratory and radiology results. The recruiter verified eligibility through the electronic medical record. Informational study materials were sent to patients by mail, and a follow-up call was made to obtain verbal consent and baseline information from all patients. Eligibility was confirmed during the initial telephone contact. Patients providing verbal consent and Health Insurance Portability and Accountability Act (HIPAA) authorization were then randomly assigned to either navigation or control groups, using a computer-generated algorithm stratified by cancer type. Navigated patients provided written consent and HIPAA authorization; a waiver for written consent and HIPPA authorization was obtained for the control subjects. Study Institutional Review Board approval was provided by the Colorado Multiple Institution Review Board (COMIRB) before study initiation.

Participants assigned to the control group received a letter informing them of their group assignment status and then received usual care with no additional contact until the postintervention survey administration. Those assigned to the navigation group received an introductory call from a patient navigator within 3 days of assignment.

The Charlson comorbidity index is widely used and was developed to identify 18 comorbid illnesses that increase the risk of 1-year mortality in a cohort of internal medicine inpatients (11).

Time to resolution was determined from the date of abnormal screening test to the date of definitive diagnosis. Study subjects without diagnostic resolution were censored at 365 days. Definitive diagnosis of a cancer was defined as the pathologic diagnosis of an invasive cancer on biopsy.

The conceptual framework used for this intervention is an expansion of Wagner's Chronic Care Model (CCM) first implemented at Denver Health in 1999 (12). The CCM has 3 main themes: evidence-based, population-based, and patient-centered care. It is operationalized through 6 components: (1) Health System and Organization Change, (2) Delivery System Redesign, (3) Decision Support for Health Care Professionals, (4) Clinical Information Systems, (5) Self-Management Support, and (6) Community Resources. The CCM model has been expanded to the Comprehensive Care Model, and is used to guide care throughout Denver Health's Community Health Centers. This model includes the innovative use of patient navigators to promote diagnostic follow-up and to enhance patient/provider interactions. Within this model, the navigators use a strengths-based approach in navigator/patient interactions to identify assets available to patients while traversing the cancer diagnostic and treatment experience.

Patient navigator contact with patients was by phone (63%), email (8%), or in person (29%), depending on patient needs and preferences. A common patient log for navigators was developed to document their work and to capture each patient contact and the activities completed for the patient, along with the duration of each encounter. Patient navigators documented barriers to care from a predefined list, as well as actions taken to address these barriers.

During the initial patient contact, the navigator provided an introduction to navigation services and to the navigator's role. Next, the navigator elicited from the patient their potential and current barriers to completing the diagnostic test or treatment. The navigator monitored the patient during the entire diagnostic phase through resolution or, if a cancer diagnosis occurred, continuing through active cancer treatment. The navigator maintained contact with the patient by phone, home visits, and in-person meetings at the medical center. Through ongoing patient contacts, the navigator continued to assess practical barriers, social support, and intention to complete the recommended course of care.

Within the health care system, the patient navigator ensured that the required examinations were scheduled and communicated with clinic staff about patient needs and concerns. The navigator accompanied patients to their appointments when fear, social support, and language barriers were identified, or if requested.

After each diagnostic test or examination, the patient navigator assessed patient understanding of results and linked the participant to clinic staff as needed for further explanation and to address concerns. If additional examinations were required, the navigator scheduled the appointments and ensured that the appointments were convenient for the patient. If the initial abnormal screening test was resolved with a noncancer diagnosis, the navigator verified patient understanding of surveillance recommendation and terminated navigation services.

Denver Health PNRP used 3 patient navigators. Navigator demographic and training information, including any personal experience with cancer, were collected from each navigator for identification of specific characteristics of navigators associated with successful navigation. All navigators attended an annual training conference designed and delivered by the American Cancer Society and the PNRP (13). In addition, frequent institution-based training sessions were conducted on clinical and psychosocial topics. Patient navigators met with the program manager on a weekly basis initially and then continued to meet monthly throughout the research program. Patient navigators also met with clinical staff for training and feedback on medical questions and patient care. A clinical psychologist met regularly with the patient navigators to assist them in working with patients with various behavioral health conditions, as well as in motivating patients and maintaining professional boundaries.

Demographic and clinical characteristics were compared using a Cochran–Mantel–Haenszel statistics for ordinal variables, Pearson χ² test of independence for nominal variables, as well as independent t tests for continuous variables.

The effect of navigation on the time to resolution of screening was compared using a stratified log-rank test. The 6 strata were abnormal clinical breast examination, BIRADS 0 (additional imaging required), BIRADS 3 (short interval recommended for follow-up mammogram), BIRADS 4 (suspicious abnormality found requiring biopsy follow-up), or BIRADS 5 (highly suspicious for malignancy), colorectal and prostate. The log-rank test was specified a priori; the strata were later identified based on sample size, location, and typical recommendations (e.g., immediate or 6 month follow-up). Test of effect modification used a Cox regression model with separate baseline hazards for the same 6 strata. Visual inspection of Kaplan–Meier plots suggested that the hazard associated with navigation was not constant over time. Time-varying indicator variables were defined for 0 to 90, 90 to 180, and 180+ days; and testing confirmed the hazard was not constant across these intervals (Wald χ² (2df) = 21.1, P < 0.001). Effect modification was tested based on interactions of centered covariates with the 3 time-varying indicators in models that included the covariate as a main effect.

A total of 3,000 abnormal screening subjects were identified as potentially eligible from laboratory and radiology lists and on initial review. Of these, 1,924 were excluded, 1,162 because of not meeting study inclusion criteria, 327 declined to participate, and 435 were unable to be contacted. A total of 1,076 eligible abnormal screening subjects entered into the Denver PNRP from October 2006 through June 2010 were equally randomized to either the navigation intervention (n = 538) or the control (no navigation) arm (n = 538). Among the subjects in the intervention group, 38 did not receive the intervention because of identification of ineligibility (5 subjects) or refusal to submit written consent and authorization (33 subjects). In the control group, 25 subjects did not receive the intervention because of ineligibility (8 subjects) and refusal to provide consent and authorization (18 subjects). Only one navigated subject revoked consent and authorization.

The final analytical sample (993 subjects) included 485 navigated and 508 control subjects. Fourteen navigated and 4 control subjects were excluded in the final group because of issues related to medical records data and data collection. See CONSORT diagram (Fig. 1) for screening subject allocation and follow-up.

Results of the time to resolution of abnormal screening tests for breast (n = 628), colorectal (n = 235), and prostate cancer (n = 130) are described in this report. Of the 628 randomized subjects with abnormal breast screens analyzed, 66 had abnormal clinical breast examinations and 304 had BIRADS 0, 200 BIRADS 3, 58 BIRADS 4 or 5 mammographic abnormalities. Results for the impact of patient navigation on newly diagnosed cancer patients will be reported separately.

The baseline characteristics for the enrolled subjects are shown in Table 1.

Overall demographics were notable for high minority representation (53% Hispanic, 24% White, 19% Black), a high percentage of primarily Spanish speakers (30%), low education attainment (40% with some high school or less); low annual household income (less than $10,000 in 49%), high unemployment (65%), and high uninsured rate (36%). These and other baseline subject characteristics were well balanced between the control and intervention arms.

Time to resolution for all cancer screening combined was significantly shorter in the navigated group, (stratified log rank test, P < 0.001). From visual inspection of Kaplan–Meier plots (Figs. 2 and 3), navigation especially improves adherence to 6-month follow-up for the breast screening population, as shown most clearly in the BIRADS 0 and BIRADS 3 groups, whereas the impact of navigation in colorectal and prostate screening was most pronounced in the 3- to 6-month period. Details for each stratum are described below.

Figure 2 shows the Kaplan–Meier plots for time to resolution by navigation versus control arms for the mammographic abnormalities BIRADS 0 and BIRADS 3 at time of enrollment. Benefit was found especially in subjects presenting with mammographic BIRADS 3 (P = 0.0003), was of borderline significance for patients with mammographic BIRADS 0 (P = 0.09), but was not significant for those with BIRADS 4/5 or abnormal clinical breast examinations (not shown).

Figure 3 shows the Kaplan–Meier plot for time to resolution of abnormal screening test for colorectal cancer by navigation versus control arms. Navigation significantly shortened the time for colorectal screening resolution (P < 0.002).

Figure 3 also shows the Kaplan–Meier plot for time to resolution of abnormal screening for prostate cancer by navigation versus control arms. There is a strong trend for navigation to shorten the time for prostate cancer screening resolution (P < 0.01), although the confidence intervals for point estimates more than the entire range of follow-up displayed in Fig. 3 do overlap.

Effect modification was tested using interactions of covariates with the 3 time-varying indicators of time in models that included the covariate as a main effect. There were no significant main effects by age, language, marital status, insurance, gender (for colorectal), number of baseline barriers, and comorbidity; nor was there evidence that these patient characteristics modified the effect of navigation.

Patients in the navigated group were more likely to complete diagnostic follow-up and resolution of initial abnormal screening tests as compared with the control patients. As can be seen in Table 2, with all 3 cancer screening sites combined, diagnostic resolution was achieved in 88% versus 70% in the navigated versus control groups, respectively (P < 0.001). For the abnormal breast screening group, 92% of the navigated patients reached diagnostic resolution of the initial abnormal test, as compared with 77% for the control patients (P < 0.001). For the abnormal colorectal screening group, 79% reached diagnostic resolution in the navigated group versus 58% in the control group (P < 0.002), and for the abnormal prostate screening group, diagnostic resolution for the navigated group was 84% as compared with 64% in the control group (P = 0.01).

The number of cancers diagnosed for each cancer screening group was similar (Table 2), and the stage at which these cancers were diagnosed did not differ significantly between navigated and control groups (not shown). Although there were more cancers diagnosed in the navigated prostate screening group (23 patients) as compared with the control group (17 patients), this was not statistically significant due to the lower number of prostate screening patients.

Although study designs differed among the 10 PNRP participating institutions, the major aims and outcomes were the same. For assessing time to resolution of an abnormal screening finding, the Denver PNRP was the only one of the participating institutions with an individually randomized study design, although other institutions used group-randomized or prospective cohort controls. The results of our prospectively randomized controlled trial show that patient navigation positively impacts the time to resolution of abnormal screening tests for breast, colorectal, and prostate cancers in a medically underserved population, and significantly improves the percentage of patients reaching diagnostic resolution.

A number of prior studies have reported that patient navigation resulted in improved resolution of mammographic screening abnormality, ranging from 21% to 29% when compared with control subjects [reviewed by Wells and colleagues, 2008 (1) and Paskett and colleagues, 2011 (14)]. However, only 2 of 8 reported studies randomly assigned subjects to a patient navigation and a no-navigation control group (9, 15). The study by Ell and colleagues randomized women with abnormal mammograms to either the navigation intervention group (96 women) or no-navigation control group (108 women). Their results showed that the intervention group was more likely to be adherent through diagnostic resolution than the control group (90% vs. 66%, OR = 4.48, P < 0.001; 15). In the study by Ferrante and colleagues, 55 subjects were randomized to the navigation intervention and 50 to usual care. Women in the navigation group had shorter times to diagnostic resolution (mean of 25 vs. 43 days, P = 0.001) with 94% of navigated patients achieving diagnostic resolution versus 78% in the control group (9).

These results are of similar magnitude to those reported in our study, namely diagnostic resolution rates of 92% for navigated patients with abnormal mammographic findings as compared with 77% for control patients. In our study, the benefits from navigation were especially striking for patients with initial BIRADS 3 mammographic abnormalities, and to a lesser extent in those with BIRADS 0, where we saw a significant improvement in the adherence rates to the recommended 6-month repeat mammogram in the control group (80% vs. 60% resolution at 240 days). BIRADS 4 and 5 patients, on the other hand, saw rapidly rising and high-diagnostic resolution rates in both navigated and control groups (85% and 80%, respectively, at 90 days), most likely driven by the urgency of the serious mammographic abnormalities reflected by this group of patients.

This is among the first publication, to our knowledge, of a randomized controlled trial evaluating the impact of patient navigation on the diagnostic resolution in patients with abnormal screening tests for colorectal cancer (2, 3) and is the first for prostate cancer navigation. As with our patients with abnormal mammograms, we found that patient navigation shortens the time to diagnostic resolution and significantly increased the proportion of patients adherent through diagnostic resolution for colorectal screening abnormalities (positive fecal occult blood, rectal bleeding, abnormal digital rectal examination, or sigmoidoscopy). For patients with prostate cancer screening abnormalities (elevated PSA, abnormal digital rectal examination), navigation led to improvement in time to and in percentage completing diagnostic resolution, although to a somewhat lesser degree than for patients with colorectal cancer screening abnormalities. This is most likely because of the smaller numbers enrolled and a lower sense of urgency in evaluating these abnormalities by both patients and providers.

The populations studied by Ell and colleagues and Ferrante and colleagues included a large proportion of minority patients, as did our study population (9, 15). All 3 populations are notable for low-annual household income, low-education attainment, high unemployment, high uninsured rate, and high comorbidity. These populations encounter numerous barriers to accessing and maintaining health care, including the timely resolution of abnormal cancer screening findings (16, 17). Patient navigation is designed to assist patients to overcome these barriers, provide a safe, nonthreatening forum for deliberation, and lend emotional support to patient decision making and dealing with an adverse screening outcome.

Study strengths include the use of a prospective individually randomized controlled clinical trial design, large number of patients enrolled compared with prior studies, a high-enrollment rate of 77% among subjects able to be contacted, and utilization of a centralized electronic medical record system to identify potential participants and to document study outcomes. We enrolled significant numbers into the breast (628) and colorectal (235) cancer abnormal screening components of the study, with fewer patients with abnormal prostate screening (130). Our results are especially applicable to other safety net health care settings in light of our largely minority, low-income and uninsured study population, with multiple challenges in their ability to adhere to demanding diagnostic evaluations.

An additional strength included consistent interpretation of screening mammograms by 2 mammographers over the 4 years of participant enrollment. The percentage of BIRADS 0 and 3 remained stable over that period, although the percentages of readings falling into these 2 categories were consistently higher than at other participating institutions. We also experienced little staff turnover and were able to retain a cadre of experienced navigators throughout.

Limitations of this study include the delay between identifying eligible patients, contacting them for consent, enrolling them into the study, and initiating the intervention. Our electronic medical record greatly assisted in the identification of potentially eligible patients; however, up-to-date contact information was not always available. In addition, the intervention could not be initiated until consent had been obtained. This delay to enrollment and initiation of the navigation or control intervention was similar for both groups; mean of 36.6 days (SD ± 28.3) for the navigated group versus mean of 34.1 days (SD ± 26.4) for the control group. It is possible that this delay blunted the impact of navigation during the early part of patients' dealing with the abnormal screen results. In future studies, methods need to be explored to shorten this delay, allowing for earlier intervention to further improve outcomes.

A second limitation is the relatively small number of patients entered into the study with abnormal prostate cancer screening findings. Screening practice has undergone changes over the past decade, resulting in fewer men being screened for prostate cancer, especially in the older age groups (18). Although our study still suggests a benefit for the abnormal prostate cancer screening patients, the smaller numbers resulted in borderline statistical significance.

Patient navigation is an effective strategy for improving adherence to diagnostic evaluation and resolution, regardless of ethnicity, insurance status, and education level. Our study provides additional evidence of its effectiveness in patients with abnormal mammographic findings and provides new information in patients with abnormal screening results for colorectal and prostate cancer in an underserved patient population.

No potential conflicts of interest were disclosed.

Conception and design: P.C. Raich, E. Whitley, D. Fairclough

Development of methodology: P.C. Raich, E. Whitley

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): P.C. Raich, E. Whitley, P. Valverde

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): P.C. Raich, E. Whitley, W. Thorland, D. Fairclough

Writing, review, and/or revision of the manuscript: P.C. Raich, E. Whitley, P. Valverde, D. Fairclough

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): P.C. Raich, E. Whitley, W. Thorland, P. Valverde

Study supervision: P.C. Raich, E. Whitley, P. Valverde

The authors thank Denver Health patients and patient navigators, as well as to colleagues Rachel Everhart, MS, Kristin Kilbourn, PhD, MPH, Betsy Risendal, PhD, Al Marcus, PhD, and Sandra Vannice, RN, CNS, AOCN.

Supported by grant 5U01CA6903 from the Center to Reduce Health Disparities of the National Cancer Institute, NIH.