Estimating and Extrapolating Survival Using a State-Transition Modeling Approach:A Practical Application in Multiple Myeloma

Objectives: State-transition models (STMs) applied in oncology have given limited considerations to modeling postprogression survival data. This study presents an application of an STM focusing on methods to evaluate the postprogression transition and its impact on survival predictions. Methods: Data from the lenalidomide plus dexamethasone arm of the ASPIRE trial was used to estimate transition rates for an STM. The model accounted for the competing risk between the progression and preprogression death events and included an explicit structural link between the time to progression and subsequent death. The modeled transition rates were used to simulate individual disease trajectories in a discrete event simulation framework, based on which progression-free survival and overall survival over a 30-year time horizon were estimated. Survival predictions were compared with the observed trial data, matched external data, and estimates obtained from a more conventional partitioned survival analysis approach. Results: The rates of progression and preprogression death were modeled using piecewise exponential functions. The rate of postprogression mortality was modeled using an exponential function accounting for the nonlinear effect of the time to progression. The STM provided survival estimates that closely fitted the trial data and gave more plausible long-term survival predictions than the best-fitting Weibull model applied in a partitioned survival analysis. Conclusions: The fit of the STM suggested that the modeled transition rates accurately captured the underlying disease process over the modeled time horizon. The considerations of this study may apply to other settings and facilitate a wider use of STMs in oncology

Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients

In 2008, 249,007 new leprosy patients were detected in the world. It therefore remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. The study is based on a large trial including 21,711 contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to contacts and followed them up for four years. The main outcome measure was the development of clinical leprosy. The cost effectiveness was expressed in US dollars per prevented leprosy case. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total $6,009 was invested and 38 leprosy cases were prevented after 2 years, costing$158 per prevented leprosy case. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world

Life Expectancy and Life Expectancy With Disability of Normal Weight, Overweight, and Obese Smokers and Nonsmokers in Europe

The goal of this study was to estimate life expectancy (LE) and LE with disability (LwD) among normal weight, overweight, and obese smokers and nonsmokers in Western Europe. Data from four waves (1998-2001) of the European Community Household Panel (ECHP) were used; a standardized multipurpose annual longitudinal survey. Self-reported health and socioeconomic information was collected repeatedly using uniform questionnaires for 66,331 individuals in nine countries. Health status was measured in terms of disability in daily activities. Multistate Markov (MSM) models were applied to obtain hazard ratios (HRs) and age-specific transition rates according to BMI and smoking status. Multistate life tables were computed using the predicted transition probabilities to estimate LE and LwD. Significant associations were observed between disability incidence and BMI (HR = 1.15 for overweight, HR = 1.64 for obese, compared to normal weight). The risk of mortality was negatively associated with overweight status among disabled (HR = 0.77). Overweight people had higher LE than people with normal-weight and obesity. Among women, overweight and obese nonsmokers expect 3.6 and 6.1 more years of LwD than normal weight persons, respectively. In contrast, daily smokers expect lower LE but a similar LwD. The same patterns were observed among people with high education and those with low education. To conclude, daily smoking is associated with mortality more than with disability, whereas obesity is associated with disability more than with mortality. The findings suggest that further tobacco control would contribute to increasing LE, while tackling the obesity epidemic is necessary to prevent an expansion of disability

Life Expectancy and Life Expectancy With Disability of Normal Weight, Overweight, and Obese Smokers and Nonsmokers in Europe

The goal of this study was to estimate life expectancy (LE) and LE with disability (LwD) among normal weight, overweight, and obese smokers and nonsmokers in Western Europe. Data from four waves (1998-2001) of the European Community Household Panel (ECHP) were used; a standardized multipurpose annual longitudinal survey. Self-reported health and socioeconomic information was collected repeatedly using uniform questionnaires for 66,331 individuals in nine countries. Health status was measured in terms of disability in daily activities. Multistate Markov (MSM) models were applied to obtain hazard ratios (HRs) and age-specific transition rates according to BMI and smoking status. Multistate life tables were computed using the predicted transition probabilities to estimate LE and LwD. Significant associations were observed between disability incidence and BMI (HR = 1.15 for overweight, HR = 1.64 for obese, compared to normal weight). The risk of mortality was negatively associated with overweight status among disabled (HR = 0.77). Overweight people had higher LE than people with normal-weight and obesity. Among women, overweight and obese nonsmokers expect 3.6 and 6.1 more years of LwD than normal weight persons, respectively. In contrast, daily smokers expect lower LE but a similar LwD. The same patterns were observed among people with high education and those with low education. To conclude, daily smoking is associated with mortality more than with disability, whereas obesity is associated with disability more than with mortality. The findings suggest that further tobacco control would contribute to increasing LE, while tackling the obesity epidemic is necessary to prevent an expansion of disability

Socioeconomic inequalities in life and health expectancies around official retirement age in 10 Western-European countries

Background Discussions on raising pension eligibility age focus more on improvement in life expectancy (LE) and health expectancy measures than on socioeconomic differences in these measures. Therefore, this study assesses the level of socioeconomic differences in these two measures in Western-Europe. Methods Data from seven annual waves (1995-2001) of the European Community Household Panel were used. Health and socioeconomic information was collected using standardised questionnaires. Health was measured in terms of disability in daily activities. Socioeconomic status was determined as education level at baseline. Multi-state Markov modelling was applied to obtain age-specific transition rates between health states for every country, educational level and gender. The multi-state life table method was used to estimate LE and disability free life expectancy (DFLE) according to country, educational level and gender. Results When comparing high and low educational levels, differences in partial DFLE between the ages 50 and 65 years were 2.1 years for men and 1.9 years for women. At age 65 years, for LE the difference between high and low educated groups was 3 years for men and 1.9 years for women, and for DFLE the difference between high and low educated groups was 4.6 years for men and 4.4 years for women. Similar patterns were observed in all countries, although inequalities tended to be greater in the southern countries. Conclusions Educational inequalities, favouring the higher educated, exist on both sides of the retirement eligibility age. Higher educated persons live longer in good health before retirement and can expect to live longer afterwards