Borah, Bijan J.

395 Background: Patients with BCG-unresponsive carcinoma in situ (CIS) are treated with radical cystectomy (RCx) or salvage intravesical chemotherapy (SIC). Recently, the FDA approved pembrolizumab for BCG-unresponsive CIS +/- papillary tumors. Given the costs and toxicities of pembrolizumab, it remains unclear whether its benefits are sufficient to warrant widespread use for BCG-unresponsive CIS. To that end, we conducted a cost-effectiveness analysis comparing pembrolizumab with RCx and SIC (using gemcitabine-docetaxel as the prototypical regimen) for patients with BCG-unresponsive CIS. Methods: A decision-analytic Markov model compared pembrolizumab, SIC (with gemcitabine-docetaxel), and RCx for patients with BCG-unresponsive CIS +/- papillary tumors who are RCx candidates (index patient 1) or are unwilling/unable to undergo RCx (index patient 2). Each treatment option was a Markov node containing distinct variations of the following health states: surveillance, recurrence, progression to MIBC, progression to metastasis, treatment toxicity, and death. Incremental Cost-Effectiveness Ratios (ICERs) were compared using a willingness-to-pay threshold of $100,000/Quality-adjusted life year (QALY). The model used a US Medicare perspective with a 5-year time horizon for the base case. One-way and probabilistic sensitivity analyses were performed for all model parameters. Results: For index patient 1, pembrolizumab was not cost-effective vs. RCx (ICER $1,403,008) or SIC (ICER $2,011,923). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to RCx with a > 93% price reduction. Relative to RCx, SIC was cost-effective for time horizons < 5 years and nearly cost-effective at 5 years (ICER $118,324). One-way sensitivity analysis revealed that SIC became cost-effective relative to RCx if its risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required > 90% price reduction to be cost-effective vs. RCx (ICER $1,073,240). Probabilistic sensitivity analyses revealed that pembrolizumab was unlikely to be cost-effective even at high willingness-to-pay thresholds. Further sensitivity analyses found that no two-way combination of extrapolated values resulted in pembrolizumab being favored over RCx or SIC for either index patient. Conclusions: Based on decision-analytic Markov modeling of treatment options for patients with BCG-unresponsive CIS, pembrolizumab was unlikely to be cost-effective without a > 90% price reduction. While both RCx and SIC were more cost-effective than pembrolizumab, further studies may validate the cost-effectiveness of gemcitabine-docetaxel relative to RCx if the recurrence and metastasis thresholds are met. Overall, our model supports the preferential use of RCx and SIC over pembrolizumab for BCG-unresponsive CIS.

Abstract Background Real‐world data for patients with positive colorectal cancer (CRC) screening stool‐tests demonstrate that adenoma detection rates are lower when endoscopists are blinded to the stool‐test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow‐up to a known positive stool‐based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow‐up colonoscopies after positive stool‐tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC‐AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow‐up/surveillance colonoscopies. Methods Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt‐sDNA), or annual fecal immunochemical test (FIT) from 50 to 75 years. Outcomes were reported per 1000 individuals without diagnosed CRC at age 40. Base‐case adenoma sensitivity values were identical for screening and follow‐up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios. Results As the differences in adenoma sensitivity for screening versus follow‐up/surveillance colonoscopies became greater, life‐years gained (LYG) and reductions in CRC‐related incidence and mortality versus no screening increased for mt‐sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached >90% with FIT in the base‐case scenario and with mt‐sDNA in a “medium impact” scenario. Conclusions Assuming identical adenoma sensitivities for screening and follow‐up/surveillance colonoscopies underestimate the potential benefits of stool‐based screening strategies.

Abstract Purpose: Among a Latina population in a low resource healthcare setting, to test the effectiveness of bilingual (Spanish/English) written and interpersonal educational interventions in increasing breast density (BD) awareness, knowledge, and conversations with healthcare providers, which are goals of BD notification mandates. Procedures: This randomized trial was conducted at a Federally Qualified Health Center (FQHC) in an urban community of the Southwest U.S. Women ages 40- 74 presenting for screening mammography were recruited and randomized 1:1:1 to usual care (mailed letter with mammogram and BD results), enhanced care (letter plus BD educational brochure), or interpersonal care (letter, brochure, and telephonic promotora education). The baseline survey was administered in person at enrollment prior to the mammogram. Follow-up surveys were by phone or mail after the mammography results letter was mailed and promotora delivery was complete (median days from baseline to follow-up survey = 97 days). Differences between groups at baseline or follow-up were assessed with chi-square tests. Logistic regression using generalized estimating equations to account for repeated data was used to assess differences by time (baseline to follow-up) within group, including a time-by-group interaction. Results: Between October 2016 and October 2019, 1377 women were enrolled. Of these, 1085 (79%) self-identified Latinas completed baseline and follow-up surveys. Median age was 47 years. Most (91%) reported speaking mostly Spanish, and 69.1% had less than a high school degree. At baseline, only 20.9% reported having heard of BD, and only 30.5% of those knew their personal BD category. At follow-up, women in the interpersonal group were more likely to report seeing their BD results in the notification letter compared to the usual care and enhanced groups (70.4% vs. 52.9% and 54.3%, p &lt; 0.001) and to report having spoken with a provider about their BD (27.3% vs. 14.2% and 15.7%, p &lt; 0.001). They also reported higher mean understanding of BD (7.7 on a 0-10 scale vs. 6.3 and 6.6, p &lt; 0.001). There were no significant differences on these outcomes between the usual care and enhanced groups. All groups saw significant improvement in correct responses from baseline to follow-up for questions on the ability of BD to mask tumors on a mammogram and BD as a breast cancer risk factor (p &lt; 0.001 all groups), but the degree of improvement in masking knowledge was significantly higher for the interpersonal vs usual care group [OR for a correct response in follow-up vs baseline: 6.4 (interpersonal) vs 3.7 (usual care), p=0.01]. Conclusion: Among a Latina population in a FQHC, telephonic promotora education was more effective than written notification alone or a mailed brochure on key goals of notification mandates. Adding a brochure does not appear to be more effective than sending a letter alone on key outcomes, but the interpersonal nature of promotora education may prompt attention to mailed information and provide an opportunity for questions. Citation Format: Jennifer L. Ridgeway, Sarah M. Jenkins, Deborah J. Rhodes, Bhavika K. Patel, Edna Ramos, Bijan Borah, Karthik Ghosh, Vera J. Suman, Aaron Norman, Davinder Singh, Celine M. Vachon. Evaluating educational interventions to increase breast density awareness among Latinas: A randomized clinical trial in a Federally Qualified Health Center [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-245.

Abstract Objective: Breast density notification laws aim to increase women’s awareness and knowledge about breast density (BD). This study’s aim was to compare BD knowledge and awareness in two Hispanic populations: a safety-net clinic serving Latina population in Maricopa County, Arizona (AZ) and a national sample of Hispanic women participating in an online research panel. Materials/Methods: Women ages 40-74 were recruited at the AZ clinic from 2016-2019 at a screening mammography appointment as part of a larger clinical trial (AZ cohort). Surveys were completed in person (English or Spanish) at enrollment to assess awareness of BD, understanding of BD risk, and mammography history. The same questions were asked in a nationally representative online panel survey conducted in 2017. All data from the national survey were weighted to adjust for probability of selection into the panel and post-stratified to match known U.S. Hispanic population distributions (NS cohort). Univariate comparisons between the clinic and the national panel were performed using Rao-Scott chi-square tests. Associations with awareness and correct knowledge were examined with multivariable logistic regression. All summaries and analyses are weighted, and were performed with SAS version 9.4 SURVEY procedures (SAS Institute Inc., Cary, NC). Results: The analysis included 1332 Hispanic women from the AZ clinic and 152 Hispanic women who completed the national survey. The AZ cohort was younger (mean age: 48.5 vs 52.8), had less education (less than high school: 68.7% vs 34.8% less than high school), more likely to prefer Spanish (92.3% vs 53.1%) and less likely to have had a prior mammogram as compared NS cohort (82.8% vs 90.4%) (all p≤ 0.03). NS cohort was more likely to have awareness of BD (32.6% vs 20.7%); correct understanding of the masking effect of BD, (67.8% vs 37.0%,) and breast cancer risk (72.2% vs 32.6%,), compared to the AZ cohort (all p &lt; 0.004). When adjusted for differences in education, age, language, and screening mammography history, BD awareness was similar between the two cohorts (adjusted odds ratio [ORadj] 0.95, p=0.83). Awareness was positively associated with more education, previous mammogram history, and English language. However, differences in BD knowledge remained (ORadj=2.8 [p=0.03] and 7.2 [P&lt;0.001] for knowledge of masking and risk, respectively). Conclusions: There were significant differences in BD awareness and knowledge between a nationally-representative sample of Latinas and Latinas in a low-resource setting. The differences in BD awareness, but not knowledge, could be explained by education, screening history and preferred language. These findings suggest that a one-size-fits-all approach to raising BD awareness and knowledge will not work. To ensure equitable dissemination of health care to Latina women undergoing screening mammography, future work should be aimed at developing effective tools and resources for educating Spanish-speaking women about BD and risk-based screening. Citation Format: Jillian Leaver, Bhavika K. Patel, Jennifer L. Ridgeway, Sarah Jenkins, Vera Suman, Deborah J. Rhodes, Aaron Norman, Karthik Ghosh, Bijan Borah, Carrie Hruska, Edna Ramos, Davinder Singh, Matt Jewett, Carmen Radecki-Breitkof, Celine Vachon. Breast density knowledge and awareness among Latinas in a low-resource setting: A comparison nationally-representative sample of Latinas [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-238.

Abstract Purpose To evaluate the impact of a collaborative intervention by pharmacists and primary care clinicians on total cost of care, including costs of inpatient readmissions, emergency department visits, and outpatient care, at 30, 60, and 180 days after hospital discharge in a population of patients at high risk for readmission due to polypharmacy. Methods A retrospective study of cost outcomes in a cohort of adult patients discharged from a single institution from July 1, 2013 to March 25, 2016, was conducted. All patients had at least 10 medications listed on their discharge list, including at least 1 drug frequently associated with adverse events leading to hospital readmission. About half of the cohort (n = 496) attended a postdischarge visit involving both a pharmacist and a primary care clinician (a physician, physician assistant, or licensed nurse practitioner); this was designated the pharmacist/clinician collaborative (PCC) group. The remainder of the cohort (n = 500) attended a visit without pharmacist involvement; this was designated as the usual care (UC) group. Costs were compared using a quantile regression to assess the potential heterogeneous impacts of the PCC intervention across different parts of the cost distribution. All outcomes were adjusted for differences in baseline characteristics. Results At 30 days post index discharge, there was a significant decrease in total costs in the 10th and 90th cost quantiles in the PCC cohort vs the UC cohort, without a statistically significant decrease in the 25th, 50th or 75th quantiles. The difference was significant in the 75th and 90th quantiles at 60 days and in the 25th, 50th, and 75th quantiles at 180 days. There was a nonsignificant cost reduction in all other quantiles. Conclusion Medically complex patients had a significantly lower total cost of care in approximately half of the adjusted cost quantiles at 30, 60, and 180 days after hospital discharge when they had a PCC visit. PCC visits can improve patient clinical outcomes while improving cost metrics.

AbstractBackgroundCompare the cost-effectiveness of 2 recombinant hepatitis B virus (HBV) vaccines in patients with inflammatory bowel disease (IBD).MethodsMarkov models were developed for 2 IBD cohorts: (1) 40-year-old patients prior to starting IBD treatment and (2) 40-year-old patients already receiving therapy. Cohort A received full vaccination series, cohort B had primary vaccine failure and received a vaccine booster. Two vaccines were compared: adjuvanted HEPLISAV-B and nonadjuvanted Engerix-B. Clinical probabilities of acute hepatitis, chronic hepatitis, cirrhosis, fulminant hepatic failure and death, treatment costs, and effectiveness estimates were obtained from published literature. A lifetime analysis and a US payer perspective were used. Probabilistic sensitivity analyses were performed for different hypothetical scenarios.ResultsAnalysis of cohort A showed moderate cost-effectiveness of HEPLISAV-B ($88,114 per quality-adjusted life year). Analysis of cohort B showed increased cost-effectiveness ($35,563 per quality-adjusted life year). Changing Engerix-B to HEPLISAV-B in a hypothetical group of 100,000 patients prevented 6 and 30 cases of acute hepatitis; and 4 and 5 cases of chronic hepatitis annually for cohorts A and B, respectively. It also prevented 1 and 2 cases of cirrhosis, and 1 and 2 deaths over 20 years for each cohort. Cost-effectiveness was determined by vaccination costs, patient age, and progression rate from chronic hepatitis to cirrhosis.ConclusionsHEPLISAV-B is cost-effective over Engerix-B in patients receiving immunosuppressive therapy for IBD. Benefits increase with population aging and lower costs of vaccines. We advocate measuring levels of HBV antibodies in patients with IBD and favor adjuvanted vaccines when vaccination is needed.