TY - JOUR
T1 - AMBIsome Therapy Induction OptimisatioN (AMBITION)
T2 - High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: Economic evaluation protocol for a randomised controlled trial-based equivalence study
AU - Ponatshego, Ponego Lloyd
AU - Lawrence, David Stephen
AU - Youssouf, Nabila
AU - Molloy, Sile F.
AU - Alufandika, Melanie
AU - Bango, Funeka
AU - Boulware, David R
AU - Chawinga, Chimwemwe
AU - Dziwani, Eltas
AU - Gondwe, Ebbie
AU - Hlupeni, Admire
AU - Hosseinipour, Mina C.
AU - Kanyama, Cecilia
AU - Meya, David B.
AU - Mosepele, Mosepele
AU - Muthoga, Charles
AU - Muzoora, Conrad K.
AU - Mwandumba, Henry
AU - Ndhlovu, Chiratidzo E.
AU - Rajasingham, Radha
AU - Sayed, Sumaya
AU - Shamu, Shepherd
AU - Tsholo, Katlego
AU - Tugume, Lillian
AU - Williams, Darlisha
AU - Maheswaran, Hendramoorthy
AU - Shiri, Tinevimbo
AU - Boyer-Chammard, Timothée
AU - Loyse, Angela
AU - Chen, Tao
AU - Wang, Duolao
AU - Lortholary, Olivier
AU - Lalloo, David G.
AU - Meintjes, Graeme
AU - Jaffar, Shabbar
AU - Harrison, Thomas S.
AU - Jarvis, Joseph N.
AU - Niessen, Louis Wilhelmus
N1 - Publisher Copyright:
© 2019 Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - clinical trials
KW - cryptococcal meningitis
KW - health economics
KW - tropical medicine
UR - http://www.scopus.com/inward/record.url?scp=85063874278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063874278&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2018-026288
DO - 10.1136/bmjopen-2018-026288
M3 - Article
C2 - 30940760
AN - SCOPUS:85063874278
SN - 2044-6055
VL - 9
JO - BMJ open
JF - BMJ open
IS - 4
M1 - e026288
ER -