Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

Background: To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods: We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results: Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82%) and 69% (60–77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%. Conclusion: We demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S

Cost-effectiveness of metal stents in pancreatic cancer.

260 Background: American Society for Gastrointestinal Endoscopy guidelines recommend endoscopic metal stent placement for pancreatic carcinoma patients with biliary obstruction and estimated life expectancy of >6 months. Because life expectancy of many such patients has until now been <6 months, plastic stents are frequently placed. Recent phase III trials demonstrated that compared with current standards of care, treatment with chemotherapy regimens FOLFIRINOX and gemcitabine/nab-paclitaxel significantly prolonged overall survival (OS) well beyond the 6-month range. Given this prolonged survival, we evaluated the cost effectiveness of initial metal versus plastic stent placement in pancreatic adenocarcinoma patients with biliary obstruction. Methods: A Markov cohort model was developed to project lifetime health-related outcomes, costs, quality-adjusted life years (QALYs), and cost effectiveness of metal compared with plastic stents. Patients entered the model with locally advanced cancer and underwent endoscopic retrograde cholangiopancreatography with metal or plastic stent placement. Patients were at risk of complications, stent migration or occlusion with subsequent stent placement, progression to metastatic cancer, and death. Published sources were used to estimate clinical, cost, utility, and event rate inputs, and results were presented from the 3 rd party payer perspective in 2012 U.S. dollars/QALY. In sensitivity analyses, overall survival was varied from 6-24 months to assess the impact of uncertainty in estimates on model outcomes. Results: Patients with metal stents had lower costs and greater overall and quality-adjusted survival. Placement of metal stents saved approximately $1,500 per patient over a lifetime, improving OS by 0.07 months and quality-adjusted survival by 0.10 months. These findings were robust in sensitivity analyses varying the length of survival for patients with pancreatic cancer. Conclusions: This model demonstrates that placement of metal biliary stents at initial onset of obstructive jaundice in patients with stage III/IV pancreatic adenocarcinoma is cost saving and improves survival when compared with use of plastic stents