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; 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 Lalloo; Graeme Meintjes; Shabbar Jaffar; Thomas S. Harrison; Joseph N. Jarvis; Louis Niessen

doi:10.1136/bmjopen-2018-026288

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 RajasinghamSumaya 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 Lalloo, Graeme Meintjes, Shabbar Jaffar, Thomas S. Harrison, Joseph N. Jarvis, Louis Niessen

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

TRIAL REGISTRATION

ISRCTN 7250 9687; Pre-results.

Original language	English
Article number	e026288
Pages (from-to)	e026288
Journal	BMJ Open
Volume	9
Issue number	4
DOIs	https://doi.org/10.1136/bmjopen-2018-026288
Publication status	Published - 1 Apr 2019

Keywords

clinical trials
cryptococcal meningitis
health economics
tropical medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/bmjopen-2018-026288

Ambition HE Protocol Manuscript Resubmission 260119Accepted author manuscript, 76.1 KBLicence: CC BY

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Correction: AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: Study protocol for a phase 3 randomised controlled non-inferiority trial
Lawrence, D. S., Youssouf, N., Molloy, S. F., Alanio, A., Alufandika, M., Boulware, D. R., Boyer-Chammard, T., Chen, T., Dromer, F., Hlupeni, A., Hope, W., Hosseinipour, M. C., Kanyama, C., Lortholary, O., Loyse, A., Meya, D. B., Mosepele, M., Muzoora, C., Mwandumba, H. & Ndhlovu, C. E. & 9 others, Niessen, L., Schutz, C., Stott, K. E., Wang, D., Lalloo, D., Meintjes, G., Jaffar, S., Harrison, T. S. & Jarvis, J. N., 14 Jan 2019
Research output: Other contribution

Open Access
2 Citations (Scopus)

Cite this

Ponatshego, P. L., Lawrence, D. S., Youssouf, N., Molloy, S. F., Alufandika, M., Bango, F., Boulware, D. R., Chawinga, C., Dziwani, E., Gondwe, E., Hlupeni, A., Hosseinipour, M. C., Kanyama, C., Meya, D. B., Mosepele, M., Muthoga, C., Muzoora, C. K., Mwandumba, H., Ndhlovu, C. E., ... 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, 9(4), e026288. Article e026288. https://doi.org/10.1136/bmjopen-2018-026288

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title = "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.",

abstract = "INTRODUCTIONCryptococcal 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 ANALYSISCountry-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 DISSEMINATIONThe 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 REGISTRATIONISRCTN 7250 9687; Pre-results.",

keywords = "clinical trials, cryptococcal meningitis, health economics, tropical medicine",

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

year = "2019",

month = apr,

day = "1",

doi = "10.1136/bmjopen-2018-026288",

language = "English",

volume = "9",

pages = "e026288",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "4",

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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, D, 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, pp. e026288. https://doi.org/10.1136/bmjopen-2018-026288

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 et al.
In: BMJ Open, Vol. 9, No. 4, e026288, 01.04.2019, p. e026288.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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.

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

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 - INTRODUCTIONCryptococcal 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 ANALYSISCountry-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 DISSEMINATIONThe 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 REGISTRATIONISRCTN 7250 9687; Pre-results.

AB - INTRODUCTIONCryptococcal 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 ANALYSISCountry-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 DISSEMINATIONThe 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 REGISTRATIONISRCTN 7250 9687; Pre-results.

KW - clinical trials

KW - cryptococcal meningitis

KW - health economics

KW - tropical medicine

U2 - 10.1136/bmjopen-2018-026288

DO - 10.1136/bmjopen-2018-026288

M3 - Article

SN - 2044-6055

VL - 9

SP - e026288

JO - BMJ Open

JF - BMJ Open

IS - 4

M1 - e026288

ER -

Ponatshego PL, Lawrence DS, Youssouf N, Molloy SF, Alufandika M, Bango F et al. 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. 2019 Apr 1;9(4):e026288. e026288. doi: 10.1136/bmjopen-2018-026288

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.

Abstract

Keywords

UN SDGs

Access to Document

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Research output

Correction: AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: Study protocol for a phase 3 randomised controlled non-inferiority trial

Cite this