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  • The effect of dose on the antimalarial efficacy of artesunate-mefloquine against Plasmodium falciparum malaria: a protocol for systematic review and individual patient data (IPD) meta-analysis

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Infectious diseases
Protocol
The effect of dose on the antimalarial efficacy of artesunate-mefloquine against Plasmodium falciparum malaria: a protocol for systematic review and individual patient data (IPD) meta-analysis
  1. Rashid Mansoor1,2,
  2. Prabin Dahal1,2,
  3. Georgina S Humphreys3,
  4. Philippe Guerin1,2,
  5. Elizabeth A Ashley2,4,
  6. Kasia Stepniewska1,2
  1. 1 WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK
  2. 2 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  3. 3 Wellcome Trust, London, UK
  4. 4 Myanmar-Oxford Clinical Research Unit (MOCRU), Yangon, Myanmar
  1. Correspondence to Dr Kasia Stepniewska; kasia.stepniewska{at}wwarn.org

Abstract

Introduction Antimalarial posology based on weight bands leaves patients at the margins vulnerable to receiving either lower or higher weight-adjusted (mg/kg) dosages. This article aims to describe the protocol for systematic review and individual patient meta-analysis (MA) for a study of the distribution of artesunate and mefloquine dosage administered in patients with uncomplicated Plasmodium falciparum malaria treated with an artesunate-mefloquine (AS-MQ) regimen. Relationship between mg/kg dose and therapeutic outcomes will be assessed through a one-stage individual participant data (IPD) MA.

Methods and analysis Therapeutic efficacy studies with the AS-MQ regimen will be identified by searching the following databases: PUBMED, EMBASE and Web of Science. The corresponding authors of the relevant studies will be requested to share the IPD for the purpose of this MA to a secured repository. All available studies will be standardised using a common data management protocol and pooled into a single database. The relationship between mg/kg dosage and treatment failures will be assessed using a Cox regression model with study sites considered as a shared frailty term. Safety parameters will be explored where available.

Ethics and dissemination This IPD MA met the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee as the research consisted of secondary analysis of existing anonymous data. The results of this analysis will be disseminated at conferences, WorldWide Antimalarial Resistance Network website and any peer-reviewed publication arising will be made open source.

PROSPERO registration number CRD42018103776.

  • malaria
  • plasmodium falciparum
  • efficacy
  • IPD meta-analysis
  • mefloquine
  • artemisinin

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2018-027738

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    Footnotes

    • RM and PD contributed equally.

    • Contributors RM, PD, PG, EAA and KS: conceived the idea and wrote the first draft of the protocol. GSH: systematic review of all published antimalarial studies. GSH, EAA and KS: data acquisition and standardisation. All authors read and approved the submission of the final draft of the study protocol.

    • Funding The WorldWide Antimalarial Resistance Network (RM, PD, GSH, PG and KS) is funded by a Bill and Melinda Gates Foundation grant and the ExxonMobil Foundation. The funders did not participate in the study development, the writing of the paper, decision to publish or preparation of the manuscript.

    • Competing interests None declared.

    • Ethics approval The individual patient data meta-analysis met the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee since the research consisted of secondary analysis of existing anonymous data. Each study included in the analysis received local ethics approvals.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Patient consent for publication Not required.