OBJECTIVES/GOALS: This project seeks to understand how personalized medicine can optimize care for patients with colorectal cancer. It identifies opportunities for personalized medicine to improve clinical outcomes, and uses cost-effectiveness analysis to assess the clinical and financial impact of this approach. METHODS/STUDY POPULATION: This project uses two methods to understand the impact of personalized medicine. First, this project has used SEER-Medicare data in conjunction with Clinical Pharmacogenetics Implementation Consortium guidelines to identify medications used by patients with colorectal cancer that can be impacted by genetic variants. This data will then be combined with population genetic variant rates to understand the likely impact screening for a given variant will have on medication response and adverse events. Medication use frequencies and genetic variant rates are then used to populate cost-effectiveness models that simulate the clinical and financial outcomes, identifying optimal genes to screen. RESULTS/ANTICIPATED RESULTS: The first result will be a comprehensive overview of treatment patterns for patients with colorectal cancer in the United States, as well as the treatments used for disease-induced comorbidities. The second result will be the identification of genetic variants based on population rates and medication utilization that should be screened in this patient population. The final result will be a breakdown of the clinical and financial outcomes associated with implementing screening for the identified genes. Preliminary results from a two-gene cost-effectiveness analysis demonstrates that screening for variants in those genes improves both clinical and financial outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: This project demonstrates how current treatment approaches can be optimized via personalized medicine. It uses epidemiological methods to identify opportunities to integrate genetic findings from other diseases, and uses cost-effectiveness analysis to understand the impact of transforming care. CONFLICT OF INTEREST DESCRIPTION: Stocks-Aurinia, Syndax, Adaptimmune, Rigel pharma

Objectives: Genetically-guided dosing of anti-cancer agents for mCRC presents the opportunity to improve patient outcomes and reduce direct patient costs, but the impact of this approach from the perspective of a health care system is uncertain. This project examines the budgetary impact of DPYD and UGT1A1 guided dosing for patients receiving FOLFIRI+bev for mCRC. Methods: We conducted a budget impact analysis following the recommendations of the joint ISPOR-SMDM taskforce. This analysis was conducted from the perspective of a US health care system, with a time horizon of 5 years after implementation. The model assumed that 100 new cases of mCRC were treated at this system with FOLFIRI+bev each year. Patients were dosed either based on their genetic variant status and anthropometrics or based on their anthropometrics alone. We included costs for genetic testing, medications and administration costs incurred to treat the disease, medications and administration costs to manage adverse events, clinic and hospitalization costs, and the salaries of providers needed to interpret and implement the genetic dosing approach. Costs were discounted at a 3% per annum rate and reported in 2018 dollars. Sensitivity analyses were conducted to test the impact of assumptions on the validity of the model. Results: The expected total cost over five years was $12,974,000 for a health care system that did not adopt genetic dosing. When 100% of the patients within the system received genetic dosing, the expected cost incurred by the system was $12,819,000, which is a savings of $155,000 or 1.2%. Conclusions: Implementation of genetically-guided dosing for FOLFIRI+bev in patients with mCRC is cost-saving from the perspective of the health care system over a 5-year time horizon. Further work should be done to determine how to implementation, and the impact of improved outcomes due to a reduction of avoidable adverse events.

INTRODUCTION AND OBJECTIVE:Intravesical chemotherapy has been demonstrated to delay recurrence in low-risk non-muscle invasive bladder cancer (LR NMIBC). Mitomycin C has been the most commonly util...

168Background: Variants in DPYD and UGT1A1 impact toxicities experienced by patients being treated with FOLFIRI+bev. Testing allows providers to preemptively adjust dosing, reducing the toxicity th...

Background: Relapsing-onset multiple sclerosis (MS) typically starts in early- to mid-adulthood, yet the trajectory of disease activity over the subsequent lifetime remains poorly defined. Previous studies have not quantified the age-specific portion of decreases in annualized relapse rates (ARR). Objective: The aim of this article is to determine, under a range of disease-related assumptions, the age-specific component of decreases in ARR over time among adults with relapsing-onset MS. Methods: We used a simulation modeling approach to examine a range of assumptions about changes in ARR due to age versus disability status. Scenarios included variations in initial ARR and rate of worsening on the Expanded Disability Status Scale. Model parameters were developed through analysis of MS patients in British Columbia, Canada, and literature review. Results: We found a substantial age-specific decrease in ARR in all simulated scenarios, independent of disability worsening. Under a range of clinically plausible assumptions, 88%–97% of the decrease was attributed to age and 3%–13% to disability. The age-specific decrease ranged from 22% to 37% per 5 years for a wide range of initial ARR (0.33–1.0). Conclusion: Decreases in ARR were due mostly to age rather than disability status. To facilitate informed decision making in MS, it is important to quantify the dynamic relationship between relapses and age.

BACKGROUND: Following the recent publication of results from randomized trials that have demonstrated a survival benefit for the addition of docetaxel or abiraterone acetate to androgen deprivation therapy (ADT) in the treatment of metastatic prostate cancer, it is important to assess whether the benefits of treatment with these agents outweigh their costs. OBJECTIVE: To perform a cost-effectiveness analysis of immediate docetaxel or abiraterone acetate treatment in addition to ADT in men with metastatic hormone-sensitive prostate cancer (PC). DESIGN, SETTING, AND PARTICIPANTS: We developed a state-transition model to simulate the natural progression of metastatic PC. Model parameters were derived from the published literature and through calibration to observed epidemiological data. Following diagnosis, a hypothetical cohort of men with metastatic hormone-sensitive PC could be treated with docetaxel+ADT, abiraterone+ADT, or ADT alone. Once disease progresses to castration-resistant PC, treatment with one of the approved therapies in this setting was initiated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were quality-adjusted life years (QALYs) and costs from a US private payer, health sector perspective. RESULTS AND LIMITATIONS: Compared to treatment with ADT alone, docetaxel and abiraterone resulted in a discounted quality-adjusted survival gain of 3.6 and 22.0mo, respectively. Using standard cost-effectiveness metrics, treatment with docetaxel and ADT provides high value for money (ie, is cost effective) with an incremental cost-effectiveness ratio (ICER) of $34723, compared to an ICER of $295212 for abiraterone. The monthly cost of abiraterone would have to be less than $3114 for it to be cost effective. CONCLUSIONS: Docetaxel+ADT is likely the most cost-effective treatment option for men with metastatic hormone-sensitive PC. Although potentially more effective than docetaxel, the costs of abiraterone would have to be considerably lower to match the cost effectiveness of docetaxel+ADT. PATIENT SUMMARY: This study evaluated the balance of costs and benefits for treatment of metastatic hormone-sensitive prostate cancer with docetaxel plus androgen deprivation therapy (ADT), abiraterone plus ADT, or ADT alone. We found that treatment with docetaxel plus ADT likely represents the most cost-effective option in this setting.

Background In 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be. Methods We use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models. Results Compared to no screening, triennial mtSDNA screening resulted in 82 (range: 79–88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71–89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6–18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option. Conclusions Compared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option.

Background:Relapsing-onset multiple sclerosis (MS) typically starts in early- to mid-adulthood, yet the trajectory of disease activity over the subsequent lifetime remains poorly defined. Previous ...

BACKGROUND Active surveillance (AS) has become the recommended management strategy for men with low-risk prostate cancer. However, there is considerable uncertainty about the optimal follow-up schedule in terms of the tests to perform and their frequency. OBJECTIVE To assess the costs and benefits of different AS follow-up strategies compared to watchful waiting (WW) or immediate treatment. DESIGN, SETTING, AND PARTICIPANTS A state-transition Markov model was developed to simulate the natural history (ie, no testing or intervention) of prostate cancer for a hypothetical cohort of 50-yr-old men newly diagnosed with low-risk prostate cancer. Following diagnosis, men were hypothetically managed with immediate treatment, watchful waiting, or one of several AS strategies. AS follow-up was performed either with transrectal ultrasound-guided biopsy or magnetic resonance imaging (MRI) which was scheduled annually, biennially, every 3yrs, according to the PRIAS protocol (yrs 1, 4, 7, and 10, and then every 5yr) or every 5yr. Diagnosis of higher-grade or -stage disease while on AS resulted in curative treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We measured discounted quality-adjusted life years (QALYs), discounted lifetime medical costs (2017 US$), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS Compared to WW, MRI-based surveillance performed every 5yr improved quality-adjusted survival by 4.47 quality-adjusted months and represented high-value health care at the Medicare reimbursement rate using standard cost-effectiveness metrics. Biopsy-based strategies were less effective and less costly than the corresponding MRI-based strategies for each testing interval. MRI-based surveillance at more frequent intervals had ICERs greater than $800000 per QALY and would not be considered cost-effective according to standard metrics. Our results were sensitive to the diagnostic accuracy and costs of both biopsy modes in detecting clinically significant cancer. CONCLUSIONS Incorporation of MRI into surveillance protocols at Medicare reimbursement rates and decreasing the intensity of repeat testing may be cost-effective options for men opting for conservative management of low-risk prostate cancer. PATIENT SUMMARY Our study modeled outcomes for men with low-risk prostate cancer undergoing watchful waiting, immediate treatment, or active surveillance with different follow-up schedules. We found that conservative management of low-risk disease optimizes health outcomes and costs. Furthermore, we showed that decreasing the intensity of active surveillance follow-up and incorporating magnetic resonance imaging (MRI) into surveillance protocols can be cost-effective, depending on the MRI costs.