Exploring the Effects of Early Censoring and Analysis of Clinical Trial Survival Data on Effectiveness and Cost-effectiveness Estimation through a Case Study in Advanced Breast Cancer.

Interim analyses of clinical trial data are frequently used to provide evidence to obtain marketing authorization for new drugs. However, results from such analyses may not reflect true estimates of relative effectiveness when trial follow-up is complete. Survival results, available at 2 time points from a breast cancer clinical trial, were compared to test the hypothesis that using immature data and a widely used right-censoring rule leads to biased survival estimates. Kaplan-Meier progression-free and overall survival data from 2 published CLEOPATRA trial reports (2012 and 2014) were digitized. Overlaying these results highlighted divergent trends. Parametric functions were fitted to both data sets but did not indicate consistent patterns that could be used as a basis for long-term extrapolation. Heavy censoring of patients in the early data cut coincides with sudden changes in hazard trends and survival patterns, supporting the hypothesis of censoring bias. This challenges the validity of estimates of clinical benefit (progression-free survival and overall survival) based on extrapolation of results from interim analyses of trial data, using a commonly employed censoring rule.

Should we invest in environmental interventions to encourage physical activity in England? An economic appraisal.

BACKGROUND: The Department of Health in England asked the National Institute for Health and Clinical Excellence (NICE) to develop guidance on environmental interventions that promote physical activity. The economic appraisals summarized in this study informed the development of that guidance. In view of the difficulties inherent in applying conventional health economic evaluation techniques to public health interventions, the economic appraisal employed a multi-faceted approach. METHODS: The analyses comprised of three components. Two cost-utility analyses; the first used a life-time disease progression model which sought to take into account the long-term benefits of physical activity on health outcomes, whereas the second used data from a regression analysis which captured some of the short-term, process benefits of physical activity which might manifest themselves in terms of improved mental health and wellbeing. The third approach was a cost-benefit analysis that took into account benefits beyond healthcare. RESULTS: The cost-utility approaches generated cost-effectiveness estimates ranging between £100 and £10 000 per QALY depending on the level of effectiveness of the intervention and the proportion of the intervention cost that was deemed to be attributable to health. The standardized cost-benefit ratio was 11:1. CONCLUSION: The findings present a consistent case to support environmental interventions that promote increased physical activity in the sedentary adult population. However, some degree of caution should be taken in interpreting the findings due to the limitations of the evidence upon which they are based. Further consideration should also be given to the relative merits of alternative approaches to assessing the value of changes to the built environment that might also benefit health as a positive externality.