AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.

INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results.

Distribution of chronic disease mortality and deterioration in household socioeconomic status in rural Bangladesh: an analysis over a 24-year period.

BACKGROUND: Little is known about long-term changes linking chronic diseases and poverty in low-income countries such as Bangladesh. This study examines how chronic disease mortality rates change across socioeconomic groups over time in Bangladesh, and whether such mortality is associated with households falling into poverty. METHODS: Age-sex standardized chronic diseases mortality rates were estimated across socioeconomic groups in 1982, 1996 and 2005, using data from the health and demographic surveillance system in Matlab, Bangladesh. Changes in households falling below a poverty threshold after a chronic disease death were estimated between 1982-96 and 1996-2005. RESULTS: Age-sex standardized chronic disease mortality rates rose from 646 per 100 000 population in 1982 to 670 in 2005. Mortality rates were higher in wealthier compared with poorer households in 1982 [Concentration Index = 0.037; 95% confidence interval (CI): 0.002, 0.072], but switched direction in 1996 (Concentration Index = -0.007; 95% CI: -0.023, 0.009), with an even higher concentration in the poor by 2005 (Concentration Index = -0.047; 95% CI: -0.061, -0.033). Between 1982-96 and 1996-2005, the highest chronic disease mortality rates were found among those households that fell below the poverty line. Households that had a chronic disease death in 1982 were 1.33 (95% CI: 1.03, 1.70) times more likely to fall below the poverty line in 1996 compared with households that did not. CONCLUSIONS: Chronic disease mortality is a growing proportion of the disease burden in Bangladesh, with poorer households being more affected over time periods, leading to future household poverty.