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Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer.We developed a decision model to simulate a hypothetical cohort of 65-year-old patients with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative under 2 different interventions: (1) test for the absence of CDX2 expression followed by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no adjuvant chemotherapy for any patient. We derived disease progression parameters, adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Sensitivity analyses were conducted.Testing for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797 discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients remains cost-effective for hazard ratios of0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence.Testing tumors of patients with stage II colon cancer for CDX2 and administration of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions.

The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful.A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy.For all 3 trials, the model predicted a mortality reduction of ≤5% and power of10%. The FACS recurrence imbalance likely led to a large relative bias (2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients.Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

PDF file - 149K, Appendix containing detailed model description, estimates of survival by race, age and gender over time and Formulas for Calculation of Disparities and Proportion of Disparities Explained by Screening and Survival

Editorial for This Article from Contribution of Screening and Survival Differences to Racial Disparities in Colorectal Cancer Rates

Background: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival.Methods: We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks, aged 50 years and older, from 1975 to 2007 assuming they had: (i) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); (ii) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and (iii) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates.Results: Differences in screening accounted for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. Thirty-six percent of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little more than 50% of the disparity in CRC mortality between blacks and whites.Conclusion: Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites.Impact: Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. Cancer Epidemiol Biomarkers Prev; 21(5); 728–36. ©2012 AACR.

PurposeTo calibrate Cancer Intervention and Surveillance Modeling Network (CISNET) ‘s SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets.MethodsWe used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANN) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models’ parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets.ResultsThe optimal ANN for SimCRC had four hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had one hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 hours for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN.ConclusionsUsing ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, like the CISNET CRC models.

Introduction: Guidelines for routine antibiotic prophylaxis (AP) before dental procedures to prevent periprosthetic joint infection (PJI) have been hampered by the lack of prospective clinical trials. Objectives: To apply value-of-information (VOI) analysis to quantify the value of conducting further clinical research to reduce decision uncertainty regarding the cost-effectiveness of AP strategies for dental patients undergoing total knee arthroplasty (TKA). Methods: An updated decision model and probabilistic sensitivity analysis (PSA) evaluated the cost-effectiveness of AP and decision uncertainty for 3 AP strategies: no AP, 2-y AP, and lifetime AP. VOI analyses estimated the value and cost of conducting a randomized controlled trial (RCT) or observational study. We used a linear regression meta-modeling approach to calculate the population expected value of partial perfect information and a Gaussian approximation to calculate population expected value of sample information, and we subtracted the cost for research to obtain the expected net benefit of sampling (ENBS). We determined the optimal trial sample sizes that maximized ENBS. Results: Using a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the PSA found that a no-AP strategy had the highest expected net benefit, with a 60% probability of being cost-effective, and 2-y AP had a 37% probability. The optimal sample size for an RCT to determine AP efficacy and dental-related PJI risk would require approximately 421 patients per arm with an estimated cost of $14.7 million. The optimal sample size for an observational study to inform quality-of-life parameters would require 2,211 patients with an estimated cost of $1.2 million. The 2 trial designs had an ENBS of approximately $25 to $26 million. Conclusion: Given the uncertainties associated with AP guidelines for dental patients after TKA, we conclude there is value in conducting further research to inform the risk of PJI, effectiveness of AP, and quality-of-life values. Knowledge Transfer Statement: The results of this value-of-information analysis demonstrate that there is substantial uncertainty around clinical, health status, and economic parameters that may influence the antibiotic prophylaxis guidance for dental patients with total knee arthroplasty. The analysis supports the contention that conducting additional clinical research to reduce decision uncertainty is worth pursuing and will inform the antibiotic prophylaxis debate for clinicians and dental patients with prosthetic joints.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations. Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer. Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies. Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clin...

Robotic surgery is increasingly used for proctectomy, but the cost-effectiveness of this approach is uncertain. Robotic surgery is considered more expensive than open or laparoscopic approaches, but in certain situations has been demonstrated to be cost-effective. We examined the cost-effectiveness of open, laparoscopic, and robotic approaches to proctectomy from societal and healthcare system perspectives. We developed a decision-analytic model to evaluate one-year costs and outcomes of robotic, laparoscopic, and open proctectomy based on data from the available literature. The robustness of our results was tested with one-way and multi-way sensitivity analyses. Open proctectomy had increased cost and lower quality of life (QOL) compared with laparoscopy and robotic approaches. In the societal perspective, robotic proctectomy costs $497/case more than laparoscopy, with minimal QOL improvements, resulting in an incremental cost-effectiveness ratio (ICER) of $751,056 per quality-adjusted life year (QALY). In the healthcare sector perspective, robotic proctectomy resulted in $983/case more and an ICER of $1,485,139/QALY. One-way sensitivity analyses demonstrated factors influencing cost-effectiveness primarily pertained to the operative cost and the postoperative length of stay (LOS). In a probabilistic sensitivity analysis, the cost-effective approach to proctectomy was laparoscopic in 42% of cases, robotic in 39%, and open in 19% at a willingness-to-pay (WTP) of $100,000/QALY. Laparoscopic and robotic proctectomy cost less and have higher QALY than the open approach. Based on current data, laparoscopy is the most cost-effective approach. Robotic proctectomy can be cost-effective if modest differences in costs or postoperative LOS can be achieved.

For older adults with relapsing-onset multiple sclerosis (MS), limited information is available to inform if, or when, disease-modifying drugs (DMDs) may be safely discontinued. The aim of this study was to project the outcomes of DMD discontinuation among older adults with relapsing-onset MS. We projected the 10-year outcomes of discontinuation of a DMD (interferon-β, fingolimod, or natalizumab) among older adults (aged 55 or 70 years) who were relapse-free for 5 or more years and had not reached an Expanded Disability Status Scale (EDSS) score of 6. Outcomes included the percentage of people who had at least one relapse or reached EDSS 6, and quality-adjusted life-years (QALYs), which incorporated both relapses and disability. We used a simulation modeling approach. With increased age, relapses decreased and the effectiveness of DMDs for disability outcomes also decreased. We found lower projected benefits for DMD continuation at 70 years of age than at 55 years of age. Compared with discontinuation, the projected benefit of DMD continuation ranged from 0.007 to 0.017 QALYs at 55 years of age and dropped to 0.002–0.006 at 70 years of age. The annual projected benefits of DMD continuation (0.1–3.0 quality-adjusted life-days) were very low compared with typical patient preferences regarding treatment burden. The benefits of DMDs may not be substantial among older adults with relapsing-onset MS. Direct clinical evidence remains limited and the decision of whether to discontinue a DMD should also take into account patient preferences. It is important to gain a better understanding of how age-related changes in the trajectory of relapsing-onset MS affect treatment effectiveness among older adults.

Microsimulation models are often used to predict long-term outcomes and guide policy decisions regarding cancer screening. The United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial examines a one-time intervention of flexible sigmoidoscopy that was implemented before a colorectal cancer (CRC) screening program was established. Long-term study outcomes, now a full 17 years following randomization, have been published. We use the outcomes from this trial to validate three microsimulation models for CRC to long-term study outcomes. We find that two of three models accurately predict the relative effect of screening (the hazard ratios) on CRC-specific incidence 17 years after screening. We find that all three models yield predictions of the relative effect of screening on CRC incidence and mortality (i.e., the hazard ratios) that are reasonably close to the UKFSS results. Two of the three models accurately predict the relative reduction in CRC incidence 17-years after screening. One model accurately predicted absolute incidence and mortality rates in the screened group. The models differ in their estimates related to adenoma detection at screening. While high-quality screening results help to inform models, trials are expensive, last many years, and can be complicated by ethical issues and technological changes across the duration of the trial. Thus, well-calibrated and validated models are necessary to predict outcomes for which data are not available. The results from this validation demonstrate the utility of models in predicting long-term outcomes, and in collaborative modeling to account for uncertainty.

United States clinical practice guidelines for metastatic colorectal cancer recommend use of medications impacted by genetic variants but do not recommend testing. We analyzed real-world treatment using a cancer registry and claims dataset to explore pharmacogenomic (PGx) medication treatment patterns and characterize exposure. In a cohort of 6957 patients, most (86.9%) were exposed to at least one chemotherapy medication with PGx guidelines. In a cohort of 2223 patients with retail pharmacy claims available, most (79.2%) were treated with at least one non-chemotherapy (79.2%) medication with PGx guidelines. PGx-associated chemotherapy exposure was associated with age, race/ethnicity, educational attainment, and rurality. PGx-associated non-chemotherapy exposure was associated with medication use and comorbidities. The potential impact of PGx testing is large and policies aimed at increasing PGx testing at diagnosis may impact treatment decisions for patients with metastatic colorectal cancer as most patients are exposed to medications with pharmacogenomics implications during treatment.

Background The natural history of human papillomavirus (HPV)-induced cervical cancer (CC) is not directly observable, yet the age of HPV acquisition and duration of preclinical disease (dwell time) influences the effectiveness of alternative preventive policies. We performed a Cancer Intervention and Surveillance Modeling Network (CISNET) comparative modeling analysis to characterize the age of acquisition of cancer-causing HPV infections and implied dwell times for distinct phases of cervical carcinogenesis. Methods Using four CISNET-cervical models with varying underlying structures but fit to common US epidemiological data, we estimated the age of acquisition of causal HPV infections and dwell times associated with three phases of cancer development: HPV, high-grade precancer, and cancer sojourn time. We stratified these estimates by HPV genotype under both natural history and CC screening scenarios, because screening prevents cancer development that affects the mix of detected cancers. Results The median time from HPV acquisition to cancer detection ranged from 17.5 to 26.0 years across the four models. Three models projected that 50% of unscreened women acquired their causal HPV infection between ages 19 and 23 years, whereas one model projected these infections occurred later (age 34 years). In the context of imperfect compliance with US screening guidelines, the median age of causal infection was 4.4–15.9 years later compared with model projections in the absence of screening. Conclusions These validated CISNET-CC models, which reflect some uncertainty in the development of CC, elucidate important drivers of HPV vaccination and CC screening policies and emphasize the value of comparative modeling when evaluating public health policies.

BACKGROUND. Clinical trials often report intervention efficacy in terms of the reduction in all-cause mortality between the treatment and control arms (i.e., an overall hazard ratio [oHR]) instead of the reduction in disease-specific mortality (i.e., a disease-specific hazard ratio [dsHR]). Using oHR to reduce all-cause mortality beyond the time horizon of the trial may introduce bias if the relative proportion of other-cause mortality increases with age. We sought to quantify this oHR extrapolation bias and propose a new approach to overcome this bias. METHODS. We simulated a hypothetical cohort of patients with a generic disease that increased background mortality by a constant additive disease-specific rate. We quantified the bias in terms of the percentage change in life expectancy gains with the intervention under an oHR compared to a dsHR approach as a function of the cohort start age, the disease-specific mortality rate, dsHR, and the duration of the intervention’s effect. We then quantified the bias in a cost-effectiveness analysis (CEA) of implantable cardioverter-defibrillators based on efficacy estimates from a clinical trial. RESULTS. For a cohort of 50-year-old patients with a disease-specific mortality of 0.05, a dsHR of 0.5, a calculated oHR of 0.55 and a lifetime duration of effect, the bias was 28%. We varied these key parameters over wide ranges and the resulting bias ranged between 3% and 140%. In the CEA, the use of oHR as the intervention’s effectiveness overestimated quality-adjusted life expectancy by 9% and costs by 3%, biasing the ICER by-6%. CONCLUSIONS. The use of an oHR approach to model the intervention’s effectiveness beyond the time horizon of the trial overestimates its benefits. In CEAs, this bias could decrease the cost of a QALY, overestimating interventions’ cost-effectiveness.

Background Cost-effectiveness acceptability curves (CEACs) and the cost-effectiveness acceptability frontier (CEAF) are the recommended graphical representations of uncertainty in a cost-effectiveness analysis (CEA). Nevertheless, many limitations of CEACs and the CEAF have been recognized by others. Expected loss curves (ELCs) overcome these limitations by displaying the expected foregone benefits of choosing one strategy over others, the optimal strategy in expectation, and the value of potential future research all in a single figure. Objectives To revisit ELCs, illustrate their benefits using a case study, and promote their adoption by providing open-source code. Methods We used a probabilistic sensitivity analysis of a CEA comparing 6 cerebrospinal fluid biomarker test-and-treat strategies in patients with mild cognitive impairment. We showed how to calculate ELCs for a set of decision alternatives. We used the probabilistic sensitivity analysis of the case study to illustrate the limitations of currently recommended methods for communicating uncertainty and then demonstrated how ELCs can address these issues. Results ELCs combine the probability that each strategy is not cost-effective on the basis of current information and the expected foregone benefits resulting from choosing that strategy (ie, how much is lost if we recommended a strategy with a higher expected loss). ELCs display how the optimal strategy switches across willingness-to-pay thresholds and enables comparison between different strategies in terms of the expected loss. Conclusions ELCs provide a more comprehensive representation of uncertainty and overcome current limitations of CEACs and the CEAF. Communication of uncertainty in CEA would benefit from greater adoption of ELCs as a complementary method to CEACs, the CEAF, and the expected value of perfect information.

Objective Evaluate the cost-effectiveness of open, laparoscopic, and robotic colectomy. Background The use of robotic-assisted colon surgery is increasing. Robotic technology is more expensive and whether a robotically assisted approach is cost-effective remains to be determined. Methods A decision-analytic model was constructed to evaluate the 1-year costs and quality-adjusted time between robotic, laparoscopic, and open colectomy. Model inputs were derived from available literature for costs, quality of life (QOL), and outcomes. Results are presented as incremental cost-effectiveness ratios (ICERs), defined as incremental costs per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to test the effect of clinically reasonable variations in the inputs on our results. Results Open colectomy cost more and achieved lower QOL than robotic and laparoscopic approaches. From the societal perspective, robotic colectomy costs $745 more per case than laparoscopy, resulting in an ICER of $2,322,715/QALY because of minimal differences in QOL. From the healthcare sector perspective, robotics cost $1339 more per case with an ICER of $4,174,849/QALY. In both models, laparoscopic colectomy was more frequently cost-effective across a wide range of willingness-to-pay thresholds. Sensitivity analyses suggest robotic colectomy becomes cost-effective at $100,000/QALY if robotic disposable instrument costs decrease below $1341 per case, robotic operating room time falls below 172 minutes, or robotic hernia rate is less than 5%. Conclusions Laparoscopic and robotic colectomy are more cost-effective than open resection. Robotics can surpass laparoscopy in cost-effectiveness by achieving certain thresholds in QOL, instrument costs, and postoperative outcomes. With increased use of robotic technology in colorectal surgery, there is a burden to demonstrate these benefits.

BACKGROUND The Kidney Allocation System (KAS) includes a scoring system to match transplant candidate life expectancy with expected longevity of the donor kidney, and a backdating policy that gives waitlist time credit to patients waitlisted after starting dialysis treatment (post-dialysis). We estimated the effect of the KAS on employment among patient subgroups targeted by the policy. METHODS We used a sample selection model to compare employment after transplant before and after KAS implementation among patients on the kidney-only transplant waitlist between December 4, 2011 and December 31, 2017. RESULTS Post-dialysis transplant recipients aged 18-49 were significantly more likely to be employed 1-year post transplant in the post-KAS era compared to the pre-KAS era. Transplant recipients aged 35-64 with no dialysis treatment were significantly less likely to be employed 1 year after transplant in the post-KAS era compared to the pre-KAS era. CONCLUSIONS This study provides the first assessment of employment after DDKT under the KAS and provides important information about both the methods used to measure employment after transplant and the outcome under the KAS. Changes in employment after DDKT among various patient subgroups have important implications for assessing long-term patient and societal effects of the KAS and organ allocation policy.

Background: Population-based metastatic recurrence rates for patients diagnosed with nonmetastatic colorectal cancer cannot be estimated directly from population-based cancer registries because recurrence information is not reported. We derived population-based colorectal cancer recurrence rates using disease-specific survival data based on our understanding of the colorectal cancer recurrence-death process. Methods: We used a statistical continuous-time multistate survival model to derive population-based annual colorectal cancer recurrence rates from 6 months to 10 years after colorectal cancer diagnosis using relative survival data from the Surveillance, Epidemiology, and End Results Program. The model was based on the assumption that, after 6 months of diagnosis, all colorectal cancer–related deaths occur only in patients who experience a metastatic recurrence first, and that the annual colorectal cancer–specific death rate among patients with recurrence was the same as in those diagnosed with de novo metastatic disease. We allowed recurrence rates to vary by post-diagnosis time, age, stage, and location for two diagnostic time periods. Results: In patients diagnosed in 1975–1984, annual recurrence rates 6 months to 5 years after diagnosis ranged from 0.054 to 0.060 in stage II colon cancer, 0.094 to 0.105 in stage II rectal cancer, and 0.146 to 0.177 in stage III colorectal cancer, depending on age. We found a statistically significant decrease in colorectal cancer recurrence among patients diagnosed in 1994–2003 compared with those diagnosed in 1975–1984 for 6 months to 5 years after diagnosis (hazard ratios between 0.43 and 0.70). Conclusions: We derived population-based annual recurrence rates for up to 10 years after diagnosis using relative survival data. Impact: Our estimates can be used in decision-analytic models to facilitate analyses of colorectal cancer interventions that are more generalizable.

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...

Background: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. Methods: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years). Results: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. Conclusions: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening. National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network (CISNET) [U01CA152959] This work was supported by the National Cancer Institute (grant number U01CA152959) as part of the Cancer Intervention and Surveillance Modeling Network (CISNET), with a supplement from the Evaluation of Genomic Applications in Practice and Prevention (EGAPP). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or Centers for Disease Control and Prevention.

We performed a cost-effectiveness analysis using the PHI (Prostate Health Index), 4Kscore®, SelectMDx™ and the EPI (ExoDx™ Prostate [IntelliScore]) in men with elevated prostate specific antigen to determine the need for biopsy.We developed a decision analytical model in men with elevated prostate specific antigen (3 ng/ml or greater) in which 1 biomarker test was used to determine which hypothetical individuals required biopsy. In the current standard of care strategy all individuals underwent biopsy. Model parameters were derived from a comprehensive review of the literature. Costs were calculated from a health sector perspective and converted into 2017 United States dollars.The cost and QALYs (quality adjusted life-years) of the current standard of care, which was transrectal ultrasound guided biopsy, was $3,863 and 18.085, respectively. Applying any of the 3 biomarkers improved quality adjusted survival compared to the current standard of care. The cost of SelectMDx, the PHI and the EPI was lower than performing prostate biopsy in all patients. However, the PHI was more costly and less effective than the SelectMDx strategy. The EPI provided the highest QALY with an incremental cost-effectiveness ratio of $58,404 per QALY. The use of biomarkers could reduce the number of unnecessary biopsies by 24% to 34% compared to the current standard of care.Applying biomarkers in men with elevated prostate specific antigen to determine the need for biopsy improved quality adjusted survival by decreasing the number of biopsies performed and the treatment of indolent disease. Using SelectMDx or the EPI following elevated prostate specific antigen but before proceeding to biopsy is a cost-effective strategy in this setting.

Introduction: Routine antibiotic prophylaxis (AP) to prevent prosthetic joint infection remains controversial. The lack of prophylaxis guideline consensus from the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) contributes to clinician confusion. Objectives: This cost-effectiveness decision model informs the AP debate and guideline development by comparing the benefits, harms, and costs of alternative prophylaxis strategies. Methods: A Markov state-transition model was developed comparing lifetime health outcomes and costs of alternative AP strategies for dental patients aged 65 y with a history of total knee arthroplasty (TKA). Based on our interpretation of AP recommendations from the AAOS and ADA, incremental cost-effectiveness ratios were calculated to compare the following strategies: no AP, AP for the first 2 y after a TKA, and lifetime AP. Results: The no-AP strategy had the lowest average lifetime costs ($17,119) and quality-adjusted life years (11.2151). Compared with a no-prophylaxis strategy, the 2-y AP strategy had incremental costs of $56 and 0.0006 QALYs gained and was cost-effective (incremental cost-effectiveness ratio = $95,100) when a willingness-to-pay threshold of $100,000 per quality-adjusted life year was used. Based on the results of 1-way sensitivity analysis, the no-AP strategy was cost-effective when we modestly increased base case amoxicillin adverse event estimates that were substantially lower than estimates reported in previous models. When plausible combinations of important model parameters were varied, model results suggested that there may be clinical scenarios when AP may be appropriate for some medically at-risk patient populations. Conclusion: The results of cost-effectiveness decision modeling generally support questioning routine AP for dental patients with TKA. Sensitivity analyses suggest that prophylaxis may be cost-effective for patient populations with a higher medical risk of infection. This finding is consistent with the recommendations of the 2015 ADA practice guideline and the appropriate use criteria jointly developed by the AAOS and the ADA. Knowledge Transfer Statement: The results of this decision modeling research support the contention that routine AP before invasive dental procedures to prevent prosthetic joint infection may not be cost-effective for patients without medical conditions, potentially conferring a higher infection risk. Model sensitivity analyses suggest that there may be clinical situations when medically at-risk patients benefit from AP.

Background. Calibration is the process of estimating parameters of a mathematical model by matching model outputs to calibration targets. In the presence of nonidentifiability, multiple parameter sets solve the calibration problem, which may have important implications for decision making. We evaluate the implications of nonidentifiability on the optimal strategy and provide methods to check for nonidentifiability. Methods. We illustrate nonidentifiability by calibrating a 3-state Markov model of cancer relative survival (RS). We performed 2 different calibration exercises: 1) only including RS as a calibration target and 2) adding the ratio between the 2 nondeath states over time as an additional target. We used the Nelder-Mead (NM) algorithm to identify parameter sets that best matched the calibration targets. We used collinearity and likelihood profile analyses to check for nonidentifiability. We then estimated the benefit of a hypothetical treatment in terms of life expectancy gains using different, but equally good-fitting, parameter sets. We also applied collinearity analysis to a realistic model of the natural history of colorectal cancer. Results. When only RS is used as the calibration target, 2 different parameter sets yield similar maximum likelihood values. The high collinearity index and the bimodal likelihood profile on both parameters demonstrated the presence of nonidentifiability. These different, equally good-fitting parameter sets produce different estimates of the treatment effectiveness (0.67 v. 0.31 years), which could influence the optimal decision. By incorporating the additional target, the model becomes identifiable with a collinearity index of 3.5 and a unimodal likelihood profile. Conclusions. In the presence of nonidentifiability, equally likely parameter estimates might yield different conclusions. Checking for the existence of nonidentifiability and its implications should be incorporated into standard model calibration procedures.

Helicobacter pylori(H. pylori)is present in the stomach of half of the world's population. The force of infection describes the rate at which susceptibles acquire infection. In this article, we estimated the age-specific force of infection ofH. pyloriin Mexico. Data came from a nationalH. pyloriseroepidemiology survey collected in Mexico in 1987–88. We modelled the number of individuals withH. pyloriat a given age as a binomial random variable. We assumed that the cumulative risk of infection by a given age follows a modified exponential catalytic model, allowing some fraction of the population to remain uninfected. The cumulative risk of infection was modelled for each state in Mexico and were shrunk towards the overall national cumulative risk curve using Bayesian hierarchical models. The proportion of the population that can be infected (i.e. susceptible population) is 85.9% (95% credible interval (CR) 84.3%–87.5%). The constant rate of infection per year of age among the susceptible population is 0.092 (95% CR 0.084–0.100). The estimated force of infection was highest at birth 0.079 (95% CR 0.071–0.087) decreasing to zero as age increases. This Bayesian hierarchical model allows stable estimation of state-specific force of infection by pooling information between the states, resulting in more realistic estimates.

Objective Cerebrospinal fluid (CSF) biomarkers are shown to facilitate a risk identification of patients with mild cognitive impairment (MCI) into different risk levels of progression to Alzheimer’s disease (AD). Knowing a patient’s risk level provides an opportunity for earlier interventions, which could result in potential greater benefits. We assessed the cost effectiveness of the use of CSF biomarkers in MCI patients where the treatment decision was based on patients’ risk level. Methods We developed a state-transition model to project lifetime quality-adjusted life-years (QALYs) and costs for a cohort of 65-year-old MCI patients from a US societal perspective. We compared four test-and-treat strategies where the decision to treat was based on a patient’s risk level (low, intermediate, high) of progressing to AD with two strategies without testing, one where no patients were treated during the MCI phase and in the other all patients were treated. We performed deterministic and probabilistic sensitivity analyses to evaluate parameter uncertainty. Results Testing and treating low-risk MCI patients was the most cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of US$37,700 per QALY. Our results were most sensitive to the level of treatment effectiveness for patients with mild AD and for MCI patients. Moreover, the ICERs for this strategy at the 2.5th and 97.5th percentiles were US$18,900 and US$50,100 per QALY, respectively. Conclusion Based on the best available evidence regarding the treatment effectiveness for MCI, this study suggests the potential value of performing CSF biomarker testing for early targeted treatments among MCI patients with a narrow range for the ICER. Electronic supplementary material The online version of this article (doi:10.1007/s41669-017-0054-z) contains supplementary material, which is available to authorized users.

Objective Positive HLA-B*5801 carriers are at greater risk of experiencing rare but severe allopurinol hypersensitivity syndrome (AHS) [i.e., Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)]; however, HLA-B*5801 prevalence and AHS risk vary by race/ethnicity. We evaluated the cost-effectiveness of HLA-B*5801 testing according to race/ethnicity in the United States. Methods We determined the cost-effectiveness of universal testing for HLA-B*5801 compared to no testing prior to the initiation of allopurinol per US major race/ethnicity groups. Using US-specific data, SJS/TEN risks and HLA-B*5801 prevalences were modeled per race/ethnicity (i.e., 1/3846 and 0.7% among Caucasians and Hispanics, 1/735 and 3.8% among African Americans, and 1/336 and 7.4% among Asians, respectively). Those who tested positive for HLA-B*5801 received febuxostat. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime. Results Compared to no testing, universal testing for HLA-B*5801 costs more and was more effective for all races/ethnicities. The ICERs varied substantially across racial/ethnic groups, following their HLA-B*5801 prevalences . HLA-B*5801 testing was cost-effective for African Americans (ICER $83,450) and Asians (ICER $64,190), but not for Caucasians or Hispanics (ICER $183,720), using accepted US willingness-to-pay threshold ($109,000/QALY). Results were robust in sensitivity analyses, except that reducing the risk of SJS/TEN by a half made testing not cost-effective for all races/ethnicities. Conclusion Testing for HLA-B*5801 prior to allopurinol initiation is cost-effective for Asians and African Americans, but not for Caucasians or Hispanics in the United States. Reducing AHS risk by other predictive measures could make HLA-B*5801 testing not cost-effective even among Asians and Blacks.

Evidence about treatment efficacy and long-term toxicities for adjuvant chemotherapy in patients with early-stage breast cancer is often presented in different formats and studies. This leads to challenges for patients and their physicians to adequately weigh the trade-offs between effectiveness and long-term cardiac toxicity when making decisions about adjuvant chemotherapy. We used a decision-analytic framework to quantify these trade-offs by combining the available evidence into a single, comparable metric. We developed a Markov model to simulate a hypothetical cohort of newly diagnosed breast cancer patients under three scenarios: no treatment, anthracycline (AC)-based adjuvant chemotherapy (more effective but also more cardiotoxic), and non-AC-based adjuvant chemotherapy. We derived the model parameters from medical literature (e.g., clinical trials). Our primary outcome is 10-year mortality, and other metrics such as cause of death; life years (LYs) and quality-adjusted LYs over 10 years were evaluated in sensitivity analysis. For 55-year-old women with a 10-year risk of metastatic recurrence

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

Robotic surgery is increasingly used for proctectomy, but the cost-effectiveness of this approach is uncertain. Robotic surgery is considered more expensive than open or laparoscopic approaches, but in certain situations has been demonstrated to be cost-effective. We examined the cost-effectiveness of open, laparoscopic, and robotic approaches to proctectomy from societal and healthcare system perspectives.We developed a decision-analytic model to evaluate one-year costs and outcomes of robotic, laparoscopic, and open proctectomy based on data from the available literature. The robustness of our results was tested with one-way and multi-way sensitivity analyses.Open proctectomy had increased cost and lower quality of life (QOL) compared with laparoscopy and robotic approaches. In the societal perspective, robotic proctectomy costs $497/case more than laparoscopy, with minimal QOL improvements, resulting in an incremental cost-effectiveness ratio (ICER) of $751,056 per quality-adjusted life year (QALY). In the healthcare sector perspective, robotic proctectomy resulted in $983/case more and an ICER of $1,485,139/QALY. One-way sensitivity analyses demonstrated factors influencing cost-effectiveness primarily pertained to the operative cost and the postoperative length of stay (LOS). In a probabilistic sensitivity analysis, the cost-effective approach to proctectomy was laparoscopic in 42% of cases, robotic in 39%, and open in 19% at a willingness-to-pay (WTP) of $100,000/QALY.Laparoscopic and robotic proctectomy cost less and have higher QALY than the open approach. Based on current data, laparoscopy is the most cost-effective approach. Robotic proctectomy can be cost-effective if modest differences in costs or postoperative LOS can be achieved.

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.

Value of information (VOI) analysis quantifies the opportunity cost associated with decision uncertainty, and thus informs the value of collecting further information to avoid this cost. VOI can inform study design, optimal sample size selection, and research prioritization. Recent methodological advances have reduced the computational burden of conducting VOI analysis and have made it easier to evaluate the expected value of sample information, the expected net benefit of sampling, and the optimal sample size of a study design ( $$n^{*}$$ ). The volume of VOI analyses being published is increasing, and there is now a need for VOI studies to conduct sensitivity analyses on VOI-specific parameters. In this practical application, we introduce the curve of optimal sample size (COSS), which is a graphical representation of $$n^{*}$$ over a range of willingness-to-pay thresholds and VOI parameters (example data and R code are provided). In a single figure, the COSS presents summary data for decision makers to determine the sample size that optimizes research funding given their operating characteristics. The COSS also presents variation in the optimal sample size given variability or uncertainty in VOI parameters. The COSS represents an efficient and additional approach for summarizing results from a VOI analysis.

Background. Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model’s predictive accuracy is important. Methods. We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions. Results. All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy. Conclusion. Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications.

Objective To evaluate the cost-effectiveness of a diagnostic protocol for appendicitis in children, the use of a validated clinical decision rule (CDR) and a staged imaging protocol, compared with usual care. Methods We estimated the cost-effectiveness of the three competing strategies using parameters from existing literature as well as a Markov model developed to simulate the effects of exposure to ionizing radiation from a single computed tomography (CT) study in the course of diagnosis. The simulation model was applied to a hypothetical cohort of 100,000 boys and girls, age 10 years, presenting with acute abdominal pain to emergency departments in the United States. Results The integrated strategy, the CDR followed by staged imaging, was found to be the most cost-effective approach. Cost savings accrued from the reduction in CT utilization for low-risk patients compared with the other two strategies. The addition of ultrasound (US) to the CDR strategy reduced CT utilization by an additional 10.9%, its main cost advantage, with negligible change in net health benefits from false-negative US results, and associated morbidity or mortality. Conclusions Results suggest that the integration of staged imaging with the CDR for the diagnosis of appendicitis in children is a cost-effective and cost-saving approach. The model estimates a further 10.9% reduction in the number of CTs from the incorporation of US for patients scoring high or medium risk, in excess of the 19.5% reduction estimated in the CDR validation study.

ObjectiveSurveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test.DesignWe developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year.ResultsFor persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression.ConclusionIn a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

168 Background: 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 that patients experience. We assessed the cost-effectiveness of pre-treatment testing for variants in DPYD and UGT1A1 in patients with mCRC receiving FOLFIRI+bev. Methods: We developed a six-state Markov model to compare pre-treatment genetic testing to no testing. The genetic testing arm screened for UGT1A1 and DPYD using a multi-gene panel. Patients were dosed per proposed guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group) and allowed dose reductions based on toxicity. In the no-test arm, patients received full doses of FOLFIRI+bev, and dose reductions based on toxicity. Costs included medications, clinic visits, and hospitalizations to treat the disease and adverse events, and were obtained from the literature, adjusted to 2019 $US. Quality-adjusted life years (QALYs) were used to assess effectiveness. We used a US health care system perspective with a 16 week horizon, the average length of time patients were exposed to FOLFIRI+bev in clinical trials. We conducted sensitivity analyses to determine the impact of uncertainty on outcomes. Results: Genetic testing cost $25,563, generating 0.21 QALYs. Standard of care cost $25,515, generating 0.20 QALYs. This resulted in an incremental cost-effectiveness ratio (ICER) of $4963 per QALY gained. Results were sensitive to costs of post-progression care, the probability of carrying UGT1A1 variants, and the impact of low-functioning DPYD variants on side effects. Conclusions: Pre-treatment testing for DPYD and UGT1A1 in patients receiving FOLFIRI+bev for mCRC is cost-effective, well below typical oncology ICERs of $50,000-100,000 per QALY. Further work is needed to characterize the impact of post-progression treatment and supportive care medications.

BackgroundIn 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.MethodsWe 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.ResultsCompared 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.ConclusionsCompared 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 Spinal pain is a common and disabling condition with considerable socioeconomic burden. Spine pain management in the United States has gathered increased scrutiny amidst concerns of overutilization of costly and potentially harmful interventions and diagnostic tests. Conservative interventions such as spinal manipulation, exercise and self-management may provide value for the care of spinal pain, but little is known regarding the cost-effectiveness of these interventions in the U.S. Our primary objective for this project is to estimate the incremental cost-effectiveness of spinal manipulation, exercise therapy, and self-management for spinal pain using an individual patient data meta-analysis approach. Methods/design We will estimate the incremental cost-effectiveness of spinal manipulation, exercise therapy, and self-management using cost and clinical outcome data collected in eight randomized clinical trials performed in the U.S. Cost-effectiveness will be assessed from both societal and healthcare perspectives using QALYs, pain intensity, and disability as effectiveness measures. The eight randomized clinical trials used similar methods and included different combinations of spinal manipulation, exercise therapy, or self-management for spinal pain. They also collected similar clinical outcome, healthcare utilization, and work productivity data. A two-stage approach to individual patient data meta-analysis will be conducted. Discussion This project capitalizes on a unique opportunity to combine clinical and economic data collected in a several clinical trials that used similar methods. The findings will provide important information on the value of spinal manipulation, exercise therapy, and self-management for spinal pain management in the U.S.

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.

Objectives. In 2016, the Second Panel on Cost-effectiveness in Health and Medicine updated the seminal work of the original panel from 2 decades earlier. The Second Panel had an opportunity to reflect on the evolution of cost-effectiveness analysis (CEA) and to provide guidance for the next generation of practitioners and consumers. In this article, we present key topics for future research and policy. Methods. During the course of its deliberations, the Second Panel discussed numerous topics for advancing methods and for improving the use of CEA in decision making. We identify and consider 7 areas for which the panel believes that future research would be particularly fruitful. In each of these areas, we highlight outstanding research needs. The list is not intended as an exhaustive inventory but rather a set of key items that surfaced repeatedly in the panel’s discussions. In the online Appendix , we also list and expound briefly on 8 other important topics. Results. We highlight 7 key areas: CEA and perspectives (determining, valuing, and summarizing elements for the analysis), modeling (comparative modeling and model transparency), health outcomes (valuing temporary health and path states, as well as health effects on caregivers), costing (a cost catalogue, valuing household production, and productivity effects), evidence synthesis (developing theory on learning across studies and combining data from clinical trials and observational studies), estimating and using cost-effectiveness thresholds (empirically representing 2 broad concepts: opportunity costs and public willingness to pay), and reporting and communicating CEAs (written protocols and a quality scoring system). Conclusions. Cost-effectiveness analysis remains a flourishing and evolving field with many opportunities for research. More work is needed on many fronts to understand how best to incorporate CEA into policy and practice.

Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for ≥6 mm or ≥10 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator’s institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for ≥6 mm (0.043 ≥10 mm), CTC_S would miss 779 ≥6 mm actionable polyps per 10,000 patients (≥10 mm: 173 per 10,000). Cost to detect an additional ≥6 mm polyp in this cohort is $5,700 (≥10 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion. At an action threshold of ≥6 mm, OC costs at least $5,700 per extra polyp detected relative to CTC_S in patients undergoing surveillance after colorectal cancer surgery, on the order of incremental cost-effectiveness ratios found for other clinical problems involving short-term events.