Developing innovative models of care for cancer survivors: use of implementation science to guide evaluation of appropriateness and feasibility.

PURPOSE: Limited understanding of factors affecting uptake and outcomes of different cancer survivorship care models hampers implementation of best practices. We conducted a formative evaluation of stakeholder-perceived acceptability and feasibility of an embedded primary care provider (PCP) survivorship care model. METHODS: We identified clinical, operational, and patient stakeholders within Kaiser Permanente Southern California and conducted semi-structured interviews. Analyses were guided by the Consolidated Framework for Implementation Research (CFIR), an integrated framework from the field of implementation science. Deductive thematic categories were derived a priori from CFIR domains; thematic sub-categories were developed inductively. RESULTS: We interviewed 12 stakeholders; multiple themes were identified. Acceptability: oncologists and operational leaders perceived that the model was an acceptable solution to issues of capacity and efficiency with the potential to improve quality; however, several oncologists perceived negative consequences including "[loss of] the joy of medicine." Patients were less enthusiastic, fearing the introduction of "[someone] who doesn't know me." Feasibility: confidence was high that this model can succeed, although there was concern about finding the right PCP and investment in training and staff support. Culture/climate: numerous system-level facilitators were identified, including encouragement of innovation and familiarity with developing new models. CONCLUSIONS: Formative evaluation is a critical pre-implementation process. Acceptability and feasibility for this model were high among oncologists and operational leaders but patients were ambivalent. Keys to successful implementation include training and support of engaged PCPs and a patient transition plan introduced early in the care trajectory.

Medication adherence, molecular monitoring, and clinical outcomes in patients with chronic myelogenous leukemia in a large HMO.

OBJECTIVE: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DESIGN: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews. Medication possession ratio (MPR) was used to measure drug adherence. SETTING: A large, community-based, integrated health plan in Southern California. PARTICIPANTS: The cohort consisted of 245 adult patients (≥18 years old) with Philadelphia positive chronic phase CML diagnosed from 2001 to 2012 and followed through 2013. MAIN OUTCOME MEASURES: In survival analyses, we examined the association of TKI adherence (MPR) and polymerase chain reaction (PCR) monitoring test frequency with the composite clinical outcome, progression to accelerated phase disease-blast crisis or mortality (progression-free survival). The cohort was followed for a maximum of 13 years (median 4.6 years). RESULTS: Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and the mean MPR was 88% (SD 18%). Virtually all patients (96%) started on imatinib. The rates of progression to accelerated phase-blast crisis and mortality were lower in patients with greater TKI adherence (20.4/1000 person-years) versus lower adherence (27.0/1000 person-years). Patients who underwent PCR monitoring had a significantly reduced risk of progression or mortality, which was seen in patients with high and low TKI adherence status from both the groups (hazard ratio [HR] 0.07 [95% CI 0.03-0.19 if MPR >90%] and HR 0.70 [95% CI 0.02-0.21 if MPR<90%]). CONCLUSION: Our results suggest that close clinical monitoring, which includes PCR monitoring in patients with high and low TKI drug adherence, is associated with a lower risk of progression or mortality.

Race/Ethnicity and Adoption of a Population Health Management Approach to Colorectal Cancer Screening in a Community-Based Healthcare System.

BACKGROUND: Screening outreach programs using population health management principles offer services uniformly to all eligible persons, but racial/ethnic colorectal cancer (CRC) screening patterns in such programs are not well known. OBJECTIVE: To examine the association between race/ethnicity and the receipt of CRC screening and timely follow-up of positive results before and after implementation of a screening program. DESIGN: Retrospective cohort study of screen-eligible individuals at the Kaiser Permanente Northern California community-based integrated healthcare delivery system (2004-2013). SUBJECTS: A total of 868,934 screen-eligible individuals 51-74 years of age at cohort entry, which included 662,872 persons in the period before program implementation (2004-2006), 654,633 during the first 3 years after implementation (2007-2009), and 665,268 in the period from 4 to 7 years (2010-2013) after program implementation. INTERVENTION: A comprehensive system-wide long-term effort to increase CRC that included leadership alignment, goal-setting, and quality assurance through a PHM approach, using mailed fecal immunochemical testing (FIT) along with offering screening at office visits. MAIN MEASURES: Differences over time and by race/ethnicity in up-to-date CRC screening (overall and by test type) and timely follow-up of a positive screen. Race/ethnicity categories included non-Hispanic white, non-Hispanic black, Hispanic/Latino, Asian/Pacific Islander, Native American, and multiple races. KEY RESULTS: From 2004 to 2013, age/sex-adjusted CRC screening rates increased in all groups, including 35.2 to 81.1 % among whites and 35.6 to 78.0 % among blacks. Screening rates among Hispanics (33.1 to 78.3 %) and Native Americans (29.4 to 74.5 %) remained lower than those for whites both before and after program implementation. Blacks, who had slightly higher rates before program implementation (adjusted rate ratio [RR] = 1.04, 99 % CI: 1.02-1.05), had lower rates after program implementation (RR for period from 4 to 7 years = 0.97, 99 % CI: 0.96-0.97). There were also substantial improvements in timely follow-up of positive screening results. CONCLUSIONS: In this screening program using core PHM principles, CRC screening increased markedly in all racial/ethnic groups, but disparities persisted for some groups and developed in others, which correlated with levels of adoption of mailed FIT.

Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors.

BACKGROUND: Controversy persists about whether certain antidepressants reduce tamoxifen's effectiveness on lowering breast cancer recurrence. We investigated whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. METHODS: We examined 16 887 breast cancer survivors (TNM stages 0-II) diagnosed between 1996 and 2007 and treated with tamoxifen in two California health plans. Women were followed-up through December 31, 2009, for subsequent breast cancer. The main exposure was the percent of days of overlap when both tamoxifen and an antidepressant (paroxetine, fluoxetine, other selective serotonin reuptake inhibitors, tricyclics, and other classes) were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models with time-varying medication variables. RESULTS: Of the 16 887 women, half (n = 8099) used antidepressants and 2946 women developed subsequent breast cancer during the 14-year study period. We did not find a statistically significant increased risk of subsequent breast cancer in women who concurrently used paroxetine and tamoxifen. For 25%, 50%, and 75% increases in percent overlap days between paroxetine and tamoxifen, hazard ratios were 1.06 (95% CI = 0.98 to 1.14, P = .09), 1.13 (95% CI = 0.98 to 1.30, P = .09), and 1.20 (95% CI = 0.97 to 1.49, P = .09), respectively, in the first year of tamoxifen treatment but were not statistically significant. Hazard ratios decreased to 0.94 (95% CI = 0.81 to 1.10, P = .46), 0.89 (95% CI = 0.66 to 1.20, P = .46), and 0.85 (95% CI = 0.54 to 1.32, P = .46) by the fifth year (all non-statistically significantly). Absolute subsequent breast cancer rates were similar among women who used paroxetine concomitantly with tamoxifen vs tamoxifen-only users. For the other antidepressants, we again found no such associations. CONCLUSIONS: Using the comprehensive electronic health records of insured patients, we did not observe an increased risk of subsequent breast cancer in women who concurrently used tamoxifen and antidepressants, including paroxetine.

Trends in Prostate-specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments From 2000 to 2012.

OBJECTIVE: To determine whether the rates of prostate-specific antigen (PSA) screening, related biopsies and subsequent prostate cancer utilization decreased between 2000 and 2012 in a large, managed care organization. METHODS: Male members of Kaiser Permanente Southern California who were aged ≥40 years and had no history of prostate cancer (N = 15,326) were passively followed through electronic health plan files from January 1, 2000, through December 31, 2012 (N = 1,539,469). The rates of PSA testing, elevated PSA tests, prostate biopsies, prostate cancer treatment (surgery and radiation), and urology visits were calculated per year among eligible men and stratified by age group. RESULTS: A 59% decrease in PSA screening occurred among men aged ≥75 years beginning in 2008, followed by 49% in ages 65-74, 20% in ages 50-64, and 33% in ages 40-49 years in 2009. However, the number of elevated PSA tests remained largely unchanged in all groups except in men aged ≥75 years (45% decrease). Prostate biopsy rates and urology visits remained consistent among elderly men. CONCLUSION: Among men in this managed care setting, although there was a sharp decline in PSA testing among men aged ≥75 years after 2008, prostate biopsy rates remained constant, and subsequent prostate cancer treatment remained highest among men in this age group. These results suggest that the guidelines recommending against PSA and the subsequent provider-targeted interventions implemented in this system resulted in decreased screening across age groups and potentially led to more discriminant screening among those aged ≥75 years.

Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model.

IMPORTANCE: Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs. OBJECTIVE: To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection. DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010. EXPOSURES: Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma. MAIN OUTCOMES AND MEASURES: Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis. RESULTS: In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses. CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.