Faculty Bibliography

Metaplastic breast cancer (MPBC) is a rare subtype that accounts for <1% of all breast cancers. Although these are typically "triple negative," they are relatively chemotherapy-refractory compared to conventional triple negative invasive breast cancers with more aggressive features and an overall poor prognosis. MPBC is a heterogeneous group of tumors that are enriched for TP53 and PIK3CA mutations, and have been found to have high PD-L1 expression though the mechanisms underlying its immunogenicity remain unclear. We perform comprehensive genomic profiling in the largest MPBC dataset (n = 192) to date and assess for other potential biomarkers of immune response.

Background First-line PD-1 checkpoint inhibition (CI) in cisplatin-ineligible advanced UC represents a new treatment standard based on single arm trials [1,2], leaving uncertainty regarding role of chemotherapy. Describing utilization and corresponding outcomes with second-line treatment will provide guidance in this new sequence. We present the outcomes of these patients treated at our institution. Methods 43 patients with advanced UC received 1st-line CI from 6/2014 - 6/ 2018 on or off protocol. Clinical, laboratory and imaging data within 30 days of 1st-line initiation were gathered and clinical outcomes were analyzed including response by RECIST v1.1 and survival (OS). Disposition and treatment post- CI were also analyzed. Clinical outcomes were analyzed for the entire study population as well as known prognostic subgroups. A multivariable analysis was used to determine the prognostic value of baseline factors, and a log rank test was used to compare outcomes in prognostic subgroups. Results 43 patients were treated with 1st-line CI (atezolizumab or pembrolizumab) from 6/2014 until 6/2018. Median age was 77 (range 34 - 89), (74% male) (26% prior BCG), (60% visceral metastases, 19% liver), (reason for cisplatin ineligibility: ECOG PS =2 30%, Impaired renal function 44%, both 21%). ORR to first-line CI was 30.2% (95% CI 28% - 32%), CR 14%. Median OS and PFS was 11.7 mos (95% CI 7.6 - 19.8) and 3.0 mos (95% CI 2 - 11.2), respectively (median follow up 11.7 mos). OS was negatively correlated with visceral metastases at baseline. Of 29 patients who progressed, 17 received 2nd-line treatment (71% chemotherapy (most commonly Gem/Carbo (10 pts)) or 29% immunotherapy). Patients on chemotherapy had an RR of 38.46% while those on immunotherapy had an RR of 20.0%. Combined, 2nd-line treatment resulted in a median OS of 6.2 months (95% CI of 2.9-12.66), an ORR of 11.1% (95% CI of 8.0% to 15.0%) and an RR of 33.3% (95% CI of 28% - 39%). Conclusions In our single institution experience, OS and ORR with 1st-line CI are similar to outcomes reported in single arm trials. RR to 2nd-line chemotherapy is comparable to historical rates with gem/carbo in the first-line, however 12 of 29 progressing patients did not receive 2nd-line treatment, highlighting the importance of patient selection for first- line CI. Outcomes by PD-L1 status will be presented

Importance/UNASSIGNED:Financial incentives shared between physicians and patients were shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in a randomized clinical trial, but it is not known whether these health benefits are worth the added incentive and utilization costs required to achieve them. Objective/UNASSIGNED:To evaluate the long-term cost-effectiveness of financial incentives on LDL-C level control. Design, Setting, and Participants/UNASSIGNED:In this economic evaluation, a previously validated microsimulation computer model was parameterized using individual-level data from the randomized clinical trial on financial incentives, National Health and Nutrition Examination Surveys for model population inputs, and other published sources. The study was conducted from April 15, 2016, to March 29, 2018. Interventions/UNASSIGNED:The following interventions were used: (1) usual care, (2) trial control strategy (increased cholesterol level monitoring and use of electronic pill bottles), (3) financial incentives for physicians, (4) financial incentives for patients, and (5) incentives shared between physicians and patients. Main Outcomes and Measures/UNASSIGNED:Discounted costs (2017 US dollars), lifetime cardiovascular disease risk, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results/UNASSIGNED:The model population (n = 1 000 000 [30.7% women]) had similar mean (SD) age (61.5 [11.9] years) and LDL-C level (153.9 mg/dL) as the observed trial population (n = 1503 [42.7% women]; age, 62.0 [8.7] years; and LDL-C level, 160.6 mg/dL). Using base-case assumptions (including a 10-year waning period of LDL-C level reductions), the usual-care strategy was dominated (higher costs and lower QALYs) by all other strategies. Strategies for physician- or patient-only incentives were dominated by the shared-incentives strategy, which had an ICER of $60 000/QALY compared with the trial control strategy. In a sensitivity analysis regarding the duration of LDL-C level reductions, the shared-incentives strategy remained cost-effective (ICERs <$100 000/QALY and <$150 000/QALY) for scenarios with LDL-C level reductions lasting, with linear waning, at least 7 and 5 years, respectively. In the 1-way sensitivity analysis for the time horizon of the analysis, the ICER of the shared-incentives strategy exceeded $100 000/QALY at 11 years and $150 000/QALY at 8 years. In probabilistic sensitivity analysis, the shared-incentives intervention was cost-effective in 69% to 77% of iterations using cost-effectiveness thresholds of $100 000 to $150 000/QALY. Cost-effectiveness results were also sensitive to the duration of intervention costs. Conclusions and Relevance/UNASSIGNED:This study suggests that the financial incentives shared between patients and physicians for LDL-C level control meet conventional standards of cost-effectiveness, but these results appeared to be sensitive to assumptions about the durations of LDL-C level reductions and years of intervention costs included, as well as to the choice of time horizon.

BACKGROUND:Poor medication adherence is common and limits the effectiveness of treatment. OBJECTIVE:To investigate how social supports, automated alerts, and their combination improve medication adherence. DESIGN/METHODS:Four-arm, randomized clinical trial with a 6-month intervention. PARTICIPANTS/METHODS:A total of 179 CVS health employees or adult dependents with CVS Caremark prescription coverage, a current daily statin prescription, a medication possession ratio less than 80%, and Internet access. INTERVENTIONS/METHODS:Participants were randomly assigned to control, social support (partner), automated adherence alert messages (alert), or both social support and alerts (partner + alert). Participants in the social support arms were asked to name a medication adherence partner (MAP) to help them take their medication. Participants in the alert arms were sent emails, text messages, or automated phone calls if they had failed to adhere on the previous day and on one or both of the 2 days before that. In partner + alert, both participants and fully enrolled MAPs received alerts. MAIN MEASURES/METHODS:Adherence measured by wireless pill bottle opening. KEY RESULTS/RESULTS:Compared to 36.0% adherence in control, adherence was significantly greater in the alert arm (52.9%, difference vs. control of 17.0%, 95% CI for difference 6.3 to 27.6%, P = 0.002) and the partner + alert arm (54.5%, difference vs. control of 18.6%, 95% CI for difference 6.6 to 30.5%, P = 0.003). Adherence in the partner arm was not statistically significantly greater than control (43.2%, difference vs. control of 7.2%, 95% CI of difference - 5.2% to 19.5%, P = 0.25). There were no statistically significant differences among the three treatment arms. Fewer participants invited a MAP in the partner + alert arm than the partner arm (P = 0.02). CONCLUSIONS:Automated alerts were effective at improving medication adherence. Assigning a medication adherence partner did not statistically significantly affect adherence rates. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Number NCT01890018 [ https://clinicaltrials.gov /].

OBJECTIVES/OBJECTIVE:To describe the process of developing a new physician payment system based on value and transitioning away from a fee-for-service payment system STUDY DESIGN: Descriptive. This paper describes a recent initiative involving redesign of primary care provider payment in the State of Hawaii. While there has been extensive discussion about switching payment from volume to value in recent years, much of this change has happened at the organizational level and this initiative focused on changing the incentives for individual providers. METHODS:Descriptive paper. In this paper we discuss the approach taken to shift incentives from fee-for-service towards value using behavioral economics as a conceptual framework for program design. We summarize the new payment system, challenges in its design, and our approach to piloting of different behavioral economic strategies to improve performance. RESULTS:None. CONCLUSIONS:This paper will provide useful guidance to health plans or health delivery systems considering shifting primary care payment away from fee-for-service towards value highlighting some of the design challenges and necessary compromises in implementing such a system at scale.

PURPOSE/OBJECTIVE:To identify whether financial incentives promote improved disease management in Medicaid recipients diagnosed with hypertension or diabetes, respectively. DESIGN/METHODS:Four-group, multicenter, randomized clinical trials. SETTING AND PARTICIPANTS/METHODS:Between 2013 and 2016, New York State Medicaid managed care members diagnosed with hypertension (N = 920) or with diabetes (N = 959). INTERVENTION/METHODS:Participants in each 6-month trial were randomly assigned to 1 of 4 arms: (1) process incentives-earned by attending primary care visits and/or receiving prescription medication refills, (2) outcome incentives-earned by reducing systolic blood pressure (hypertension) or hemoglobin A1c (HbA1c; diabetes) levels, (3) combined process and outcome incentives, and (4) control (no incentives). MEASURES/METHODS:Systolic blood pressure (hypertension) and HbA1c (diabetes) levels, primary care visits, and medication prescription refills. Analysis and Results: At 6 months, there were no statistically significant differences between intervention arms and the control arm in the change in systolic blood pressure, P = .531. Similarly, there were no significant differences in blood glucose control (HbA1c) between the intervention arms and control after 6 months, P = .939. The majority of participants had acceptable systolic blood pressure (<140 mm Hg) or blood glucose (<8.0%) levels at baseline and throughout the study. CONCLUSION/CONCLUSIONS:Financial incentives-regardless of whether they were delivered based on disease-relevant outcomes, process activities, or a combination of the two-have a negligible impact on health outcomes for Medicaid recipients diagnosed with either hypertension or diabetes in 2 studies in which, among other design and operational limitations, the majority of recipients had relatively well-controlled diseases at the time of enrollment.

Background Whether financial incentives, pharmacologic therapies, and electronic cigarettes (e-cigarettes) promote smoking cessation among unselected smokers is unknown. Methods We randomly assigned smokers employed by 54 companies to one of four smoking-cessation interventions or to usual care. Usual care consisted of access to information regarding the benefits of smoking cessation and to a motivational text-messaging service. The four interventions consisted of usual care plus one of the following: free cessation aids (nicotine-replacement therapy or pharmacotherapy, with e-cigarettes if standard therapies failed); free e-cigarettes, without a requirement that standard therapies had been tried; free cessation aids plus $600 in rewards for sustained abstinence; or free cessation aids plus $600 in redeemable funds, deposited in a separate account for each participant, with money removed from the account if cessation milestones were not met. The primary outcome was sustained smoking abstinence for 6 months after the target quit date. Results Among 6131 smokers who were invited to enroll, 125 opted out and 6006 underwent randomization. Sustained abstinence rates through 6 months were 0.1% in the usual-care group, 0.5% in the free cessation aids group, 1.0% in the free e-cigarettes group, 2.0% in the rewards group, and 2.9% in the redeemable deposit group. With respect to sustained abstinence rates, redeemable deposits and rewards were superior to free cessation aids (P<0.001 and P=0.006, respectively, with significance levels adjusted for multiple comparisons). Redeemable deposits were superior to free e-cigarettes (P=0.008). Free e-cigarettes were not superior to usual care (P=0.20) or to free cessation aids (P=0.43). Among the 1191 employees (19.8%) who actively participated in the trial (the "engaged" cohort), sustained abstinence rates were four to six times as high as those among participants who did not actively engage in the trial, with similar relative effectiveness. Conclusions In this pragmatic trial of smoking cessation, financial incentives added to free cessation aids resulted in a higher rate of sustained smoking abstinence than free cessation aids alone. Among smokers who received usual care (information and motivational text messages), the addition of free cessation aids or e-cigarettes did not provide a benefit. (Funded by the Vitality Institute; ClinicalTrials.gov number, NCT02328794 .).

OBJECTIVES/OBJECTIVE:To describe the extent of and longitudinal changes in physician practice variation with respect to implant costs, institutional postacute care (PAC) provider utilization, and total episode payments, as well as to evaluate the association between physician volume and quality and these outcomes. STUDY DESIGN/METHODS:Observational study. METHODS:We combined claims and internal hospital cost data for 34 physicians responsible for 3614 joint replacement episodes under bundled payment at Baptist Health System (BHS). Multilevel multivariable generalized linear models were employed and the intraclass correlation (ICC) was used to quantify between-physician variation. RESULTS:There was significant between-physician variation in implant costs, institutional PAC provider utilization, and total episode payments not explained by observable variables (P <.001 for all). Over 5 years, the ICC decreased from 0.26 to 0.06, 0.15 to 0.13, and 0.12 to 0.10 for implant costs, institutional PAC provider utilization, and total episode payments, respectively, but differences were not statistically significant. Both higher physician case volume and quality were associated with decreased total episode payments and institutional PAC provider utilization, but not with changes in implant costs. CONCLUSIONS:Considerable physician practice variation was observed under bundled payment at BHS and decreased to a greater degree for implant costs than institutional PAC provider utilization or total episode payments. Institutional PAC provider utilization and total episode payments were associated with physician volume and quality. Although some organizational strategies achieve gains by reducing physician practice variation, variation reduction is not an absolute requisite for success under bundled payment.