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

Ponego Lloyd Ponatshego, David Stephen Lawrence, Nabila Youssouf, Sile F. Molloy, Melanie Alufandika, Funeka Bango, David R. Boulware, Chimwemwe Chawinga, Eltas Dziwani, Ebbie Gondwe, Admire Hlupeni, Mina C. Hosseinipour, Cecilia Kanyama, David B. Meya, Mosepele Mosepele, Charles Muthoga, Conrad K. Muzoora, Henry Mwandumba, Chiratidzo E. Ndhlovu, Radha Rajasingham & 18 others Sumaya Sayed, Shepherd Shamu, Katlego Tsholo, Lillian Tugume, Darlisha Williams, Hendramoorthy Maheswaran, Tinevimbo Shiri, Timothée Boyer-Chammard, Angela Loyse, Tao Chen, Duolao Wang, Olivier Lortholary, David G. Lalloo, Graeme Meintjes, Shabbar Jaffar, Thomas S. Harrison, Joseph N. Jarvis, Louis Niessen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere026288
JournalBMJ open
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Fingerprint

Cryptococcal Meningitis
Africa South of the Sahara
Cost-Benefit Analysis
Randomized Controlled Trials
Amphotericin B
Health Expenditures
Therapeutics
Economics
Botswana
Tropical Medicine
Monte Carlo Method
Malawi
Zimbabwe
Phase III Clinical Trials
Research Ethics Committees
Proxy
Informed Consent
Hygiene
Ethics
Health Services

Keywords

  • clinical trials
  • cryptococcal meningitis
  • health economics
  • tropical medicine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Ponatshego, Ponego Lloyd; Lawrence, David Stephen; Youssouf, Nabila; Molloy, Sile F.; Alufandika, Melanie; Bango, Funeka; Boulware, David R.; Chawinga, Chimwemwe; Dziwani, Eltas; Gondwe, Ebbie; Hlupeni, Admire; Hosseinipour, Mina C.; Kanyama, Cecilia; Meya, David B.; Mosepele, Mosepele; Muthoga, Charles; Muzoora, Conrad K.; Mwandumba, Henry; Ndhlovu, Chiratidzo E.; Rajasingham, Radha; Sayed, Sumaya; Shamu, Shepherd; Tsholo, Katlego; Tugume, Lillian; Williams, Darlisha; Maheswaran, Hendramoorthy; Shiri, Tinevimbo; Boyer-Chammard, Timothée; Loyse, Angela; Chen, Tao; Wang, Duolao; Lortholary, Olivier; Lalloo, David G.; Meintjes, Graeme; Jaffar, Shabbar; Harrison, Thomas S.; Jarvis, Joseph N.; Niessen, Louis.

In: BMJ open, Vol. 9, No. 4, e026288, 01.04.2019.

Research output: Contribution to journalArticle

Ponatshego, PL, Lawrence, DS, Youssouf, N, Molloy, SF, Alufandika, M, Bango, F, Boulware, DR, Chawinga, C, Dziwani, E, Gondwe, E, Hlupeni, A, Hosseinipour, MC, Kanyama, C, Meya, DB, Mosepele, M, Muthoga, C, Muzoora, CK, Mwandumba, H, Ndhlovu, CE, Rajasingham, R, Sayed, S, Shamu, S, Tsholo, K, Tugume, L, Williams, D, Maheswaran, H, Shiri, T, Boyer-Chammard, T, Loyse, A, Chen, T, Wang, D, Lortholary, O, Lalloo, DG, Meintjes, G, Jaffar, S, Harrison, TS, Jarvis, JN & Niessen, L 2019, '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', BMJ open, vol. 9, no. 4, e026288. https://doi.org/10.1136/bmjopen-2018-026288
Ponatshego, Ponego Lloyd ; Lawrence, David Stephen ; Youssouf, Nabila ; Molloy, Sile F. ; Alufandika, Melanie ; Bango, Funeka ; Boulware, David R. ; Chawinga, Chimwemwe ; Dziwani, Eltas ; Gondwe, Ebbie ; Hlupeni, Admire ; Hosseinipour, Mina C. ; Kanyama, Cecilia ; Meya, David B. ; Mosepele, Mosepele ; Muthoga, Charles ; Muzoora, Conrad K. ; Mwandumba, Henry ; Ndhlovu, Chiratidzo E. ; Rajasingham, Radha ; Sayed, Sumaya ; Shamu, Shepherd ; Tsholo, Katlego ; Tugume, Lillian ; Williams, Darlisha ; Maheswaran, Hendramoorthy ; Shiri, Tinevimbo ; Boyer-Chammard, Timothée ; Loyse, Angela ; Chen, Tao ; Wang, Duolao ; Lortholary, Olivier ; Lalloo, David G. ; Meintjes, Graeme ; Jaffar, Shabbar ; Harrison, Thomas S. ; Jarvis, Joseph N. ; Niessen, Louis. / 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. In: BMJ open. 2019 ; Vol. 9, No. 4.
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abstract = "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.",
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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

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.

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.

KW - clinical trials

KW - cryptococcal meningitis

KW - health economics

KW - tropical medicine

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U2 - 10.1136/bmjopen-2018-026288

DO - 10.1136/bmjopen-2018-026288

M3 - Article

VL - 9

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 4

M1 - e026288

ER -