Fair comparisons of cause-specific and relative survival by accounting for the systematic removal of patients from risk-sets.

BACKGROUND: In population-based cancer studies it is common to try to isolate the impact of cancer by estimating net survival. Net survival is defined as the probability of surviving cancer in the absence of any other-causes of death. Net survival can be estimated either in the cause-specific or relative survival framework. Cause-specific survival considers deaths from the cancer as the event of interest. Relative survival incorporates general population expected mortality rates to represent the other-cause mortality rate. Estimation approaches in both frameworks are impacted by the systematic removal of patients from the risk-set, commonly referred to as informative censoring in the cause-specific framework. In the relative survival framework, the Pohar Perme estimator combats the effect of this systematic removal of patients through weighting. When the two frameworks have been compared, informative censoring is rarely accounted for in the cause-specific framework. METHODS: We investigate the use of weighted cause-specific Kaplan-Meier estimates to overcome the impact of informative censoring and compared approaches to defining weights. Individuals remaining in the risk-set are upweighted using their predicted other-cause survival obtained through various model-based approaches. We also compare weights derived from expected mortality rates. We applied the approaches to US cancer registry data and conducted a simulation study. RESULTS: Using weighted cause-specific estimates provides a better estimate of marginal net survival. The unweighted Kaplan-Meier estimates have a similar bias to the Ederer II method for relative survival. Weighted Kaplan-Meier estimates are unbiased and similar to the Pohar Perme estimator. There was little variation between the several weighting approaches. CONCLUSION: In comparisons of cause-specific and relative survival, it is important to compare "like-with-like", therefore, a weighted approach should be considered for both frameworks. If researchers are interested in obtaining net measures in a cause-specific framework, then weighting is needed to account for informative censoring.

Using threshold analysis to assess the robustness of public health intervention recommendations from network meta-analyses: application to accident prevention in households with children under five.

BACKGROUND: In the appraisal of clinical interventions, complex evidence synthesis methods, such as network meta-analysis (NMA), are commonly used to investigate the effectiveness of multiple interventions in a single analysis. The results from a NMA can inform clinical guidelines directly or be used as inputs into a decision-analytic model assessing the cost-effectiveness of the interventions. However, there is hesitancy in using complex evidence synthesis methods when evaluating public health interventions. This is due to significant heterogeneity across studies investigating such interventions and concerns about their quality. Threshold analysis has been developed to help assess and quantify the robustness of recommendations made based on results obtained from NMAs to potential limitations of the data. Developed in the context of clinical guidelines, the method may prove useful also in the context of public health interventions. In this paper, we illustrate the use of the method in public health, investigating the effectiveness of interventions aiming to increase the uptake of accident prevention behaviours in homes with children aged 0-5. METHODS: Two published random effects NMAs were replicated and carried out to assess the effectiveness of several interventions for increasing the uptake of accident prevention behaviours, focusing on the safe storage of other household products and stair gates outcomes. Threshold analysis was then applied to the NMAs to assess the robustness of the intervention recommendations made based on the results from the NMAs. RESULTS: The results of the NMAs indicated that complex intervention, including Education, Free/low-cost equipment, Fitting equipment and Home safety inspection, was the most effective intervention at promoting accident prevention behaviours for both outcomes. However, the threshold analyses highlighted that the intervention recommendation was robust for the stair gate outcome, but not robust for the safe storage of other household items outcome. CONCLUSIONS: In our case study, threshold analysis allowed us to demonstrate that there was some discrepancy in the intervention recommendation for promoting accident prevention behaviours as the recommendation was robust for one outcome but not the other. Therefore, caution should be taken when considering such interventions in practice for the prevention of poisonings in homes with children aged 0-5. However, there can be some confidence in the use of this intervention in practice to promote the possession of stair gates to prevent falls in homes with children under 5. We have illustrated the potential benefit of threshold analysis in the context of public health and, therefore, encourage the use of the method in practice as a sensitivity analysis for NMA of public health interventions.