Oncology modeling for fun and profit! Key steps for busy analysts in health technology assessment

In evaluating new oncology medicines, two common modeling approaches are state transition (e.g., Markov and semi-Markov) and partitioned survival. Partitioned survival models have become more prominent in oncology health technology assessment processes in recent years. Our experience in conducting and evaluating models for economic evaluation has highlighted many important and practical pitfalls. As there is little guidance available on best practices for those who wish to conduct them, we provide guidance in the form of 'Key steps for busy analysts,' who may have very little time and require highly favorable results. Our guidance highlights the continued need for rigorous conduct and transparent reporting of economic evaluations regardless of the modeling approach taken, and the importance of modeling that better reflects reality, which includes better approaches to considering plausibility, estimating relative treatment effects, dealing with post-progression effects, and appropriate characterization of the uncertainty from modeling itself

Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial.

BackgroundPrimary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care.MethodsPragmatic two-way factorial cluster RCT with Primary Care Physicians' practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians' rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored 'prevention prescription'. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted.Results789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P < 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95$16 to $44) per additional action met.ConclusionsA Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of$61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and$110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug

Developing a framework to incorporate real-world evidence in cancer drug funding decisions : The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration

Background Oncology therapy is becoming increasingly more expensive and challenging the affordability and sustainability of drug programmes around the world. When new drugs are evaluated, health technology assessment organisations rely on clinical trials to inform funding decisions. However, clinical trials are not able to assess overall survival and generalises evidence in a real-world setting. As a result, policy makers have little information on whether drug funding decisions based on clinical trials ultimately yield the outcomes and value for money that might be expected. Objective The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration, consisting of researchers, recommendation-makers, decision makers, payers, patients and caregivers, are developing and testing a framework for Canadian provinces to generate and use real-world evidence (RWE) for cancer drug funding in a consistent and integrated manner. Strategy The CanREValue collaboration has established five formal working groups (WGs) to focus on specific processes in the generation and use of RWE for cancer drug funding decisions in Canada. The different RWE WGs are: (1) Planning and Drug Selection; (2) Methods; (3) Data; (4) Reassessment and Uptake; (5) Engagement. These WGs are acting collaboratively to develop a framework for RWE evaluation, validate the framework through the multiprovince RWE projects and help to integrate the final RWE framework into the Canadian healthcare system. Outcomes The framework will enable the reassessment of cancer drugs, refinement of funding recommendations and use of novel funding mechanisms by decision-makers/payers across Canada to ensure the healthcare system is providing clinical benefits and value for money

Should Hepatitis B Screening Be Added to the United States Immigration Medical Exam? A Cost-utility Model

Hepatitis B virus (HBV) infection is a global leading cause of death as a result of its role in the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). In industrialized nations such as the United States, chronic hepatitis B infection represents a significant and disproportionate disease burden among the foreign-born population. A Markov cohort decision model was developed to determine the cost-effectiveness of HBV screening among new immigrants for the purposes of early detection and treatment, as compared to usual care. The incremental cost-effectiveness ratio for the screening strategy was $45,570 per quality adjusted life year saved. Given the potential for health gains for the immigrant cohort as well as the economic attractiveness of the intervention, some consideration should be given to the addition of a universal HBV screening program to U.S. immigration policy.MAS

The need for improvement in innovativeness development and entrepreneurship training in high school and university science education

The author addresses the need for improvement in innovativeness development and entrepreneurship training in high school and university science education, and suggests some strategies. This topic has been identified as a priority by both government and industry in Canada.The Science Education program at UTM; Director: Professor John Percy

Methodological Issues in Economic Evaluations Submitted to the Pan-Canadian Oncology Drug Review (pCODR).

BACKGROUND:Public drug plans are faced with increasingly difficult funding decisions. In Canada, the pan-Canadian Oncology Drug Review (pCODR) makes funding recommendations to the provincial and territorial drug plans responsible for cancer drugs. Assessments of the economic models submitted by pharmaceutical manufacturers are publicly reported. OBJECTIVES:The main objective of this research was to identify recurring methodological issues in economic models submitted to pCODR for funding reviews. The secondary objective was to explore whether there exists any observed relationships between reported methodological issues and funding recommendations made by pCODR's expert review committee. METHODS:Publicly available Economic Guidance Reports from July 2011 (inception) until June 2014 for drug reviews with a final funding recommendation (N = 34) were independently examined by two authors. Major methodological issues from each review were abstracted and grouped into nine main categories. Each issue was also categorized based on perception of the reviewer's actions to manage it. RESULTS:The most commonly reported issues involved costing (59% of reviews), time horizon (56%), and model structure (36%). Several types of issues were identified that usually could not be resolved, such as quality of clinical data or uncertainty with indirect comparisons. Issues with costing or choice of utility estimates could usually be addressed or explored by reviewers. No statistically significant relationship was found between any methodological issue and funding recommendations from the expert review committee. CONCLUSIONS:The findings provide insights that can be used by parties who submit or review economic evidence for continuous improvement and consistency in economic modeling, reporting, and decision making