Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Cost-effectiveness analysis of varenicline versus existing smoking cessation strategies in Central America and the Caribbean using the BENESCO model.

OBJECTIVES: In Central American countries, the economic burden of tobacco has not been assessed. In Costa Rica, a study demonstrated that tobacco-related diseases represent high costs for the health care system. The aim of this study was to assess the cost-effectiveness of varenicline compared with other existing strategies for smoking cessation within a 10-year time horizon in an adult population cohort from Central American and Caribbean countries using the health care payer's perspective. METHODS: The Benefits of Smoking Cessation on Outcomes simulation model was used for an adult cohort in Costa Rica (n = 2 474 029), Panama (n = 2 249 676), Nicaragua (n = 3 639 948), El Salvador (n = 4 537 803), and the Dominican Republic (n = 6 528 125) (N = 19 429 581). Smoking cessation therapies compared were varenicline (0.5-2 mg/day) versus bupropion (300 mg/day), nicotine replacement therapy (5-15 mg/day), and unaided cessation. Effectiveness measures were: life-years (LYs) gained and quality-adjusted life-years (QALYs) gained. Resource use and cost data were obtained from a country's Ministry of Health and/or Social Security Institutions (2008-2010). The model used a 5% discount rate for costs (expressed in 2010 US$) and health outcomes. Probabilistic sensitivity analyses were conducted and acceptability curves were constructed. RESULTS: Varenicline reduced smoking-related morbidity, mortality, and health care costs in each country included in the study. Accumulatively, mortality in the varenicline arm was reduced by 1190, 1538, and 2902 smoking-related deaths compared with bupropion, nicotine replacement therapy, and unaided cessation, respectively. The net average cost per additional quitter showed that varenicline was cost-saving when compared with competing alternatives. Regarding LYs and QALYs gained in 10 years, varenicline obtained the greatest number of QALYs and LYs in each country, while unaided cessation obtained the fewest. Cost-effectiveness analyses in all 5 countries showed that varenicline was the dominant strategy. Acceptability curves showed that, independent of the willingness to pay, the probability that varenicline is cost-effective was 99% for this region. The results of the probabilistic sensitivity analyses support the robustness of the findings. CONCLUSION: Smoking cessation therapy with varenicline is cost-saving for the Central American and Caribbean countries included. These results could help to reduce the tobacco-related disease burden and align cost-containment policies.

Cost analysis of varenicline versus bupropion, nicotine replacement therapy, and unaided cessation in Nicaragua.

OBJECTIVES: In Nicaragua, 30% of current morbidities are associated with tobacco smoking. Tobacco control policy measures have been initiated in this Central American country; however, the population does not have a complete understanding of the long-term consequences of tobacco use. The aim of this study was to compare the direct medical costs of smoking cessation therapies with varenicline, bupropion, nicotine replacement therapy, and unaided cessation in Nicaragua over 5 time horizons: 2, 5, 10, and 20 years, and lifetime. METHODS: The current annual costs of chronic obstructive pulmonary disease, lung cancer, coronary heart disease, and stroke were estimated based on the current annual incidence for each disease using 1 public hospital database (Hospital Lenin Fonseca, 2010). The Benefits of Smoking Cessation on Outcomes simulation model was used to obtain the projected direct costs for each strategy. An adult cohort (N = 3 639 948) from Nicaragua was used and the assessment was conducted using the health care payer's perspective. Costs were discounted at 5% annually. Probabilistic sensitivity analyses were conducted using a Monte Carlo second-order approach. RESULTS: Varenicline is associated with the highest health care cost-savings compared with the other 3 alternatives at 5, 10, and 20 years, and lifetime. At lifetime, varenicline would result in savings of US$4 545 008, US$5 859 300, and US$11 033 221 when compared with bupropion, nicotine replacement therapy, and unaided cessation, respectively. Varenicline also avoided the highest number of smoking-related deaths in comparison with the alternatives. At year 10, varenicline avoided 96, 124, and 234 more deaths than bupropion, nicotine replacement therapy, and unaided cessation, respectively. The results of probabilistic sensitivity analyses support these findings. CONCLUSION: The use of a smoking cessation therapy with varenicline would generate long-term savings to Nicaragua's health care institutions of > US$11 million in the lifetime time horizon.