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Abstract
Introduction Pregnant women are more vulnerable to malaria leading to adverse impact on both mothers and fetuses. However, knowledge on the efficacy and safety of antimalarials in pregnancy is limited by the paucity of randomised control trials and the lack of standardised protocols in this special subpopulation. Pooling individual patient data (IPD) for meta-analysis could address in part these limitations to summarise accurately the currently available evidence on treatment efficacy and risk factors for treatment failure.
Methods and analysis To assess the treatment efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy, seven databases (Medline, Embase, Global Health, Cochrane Library, Scopus, Web of Science and Literatura Latino Americana em Ciências da Saúde) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrial.gov) were searched. Both interventional and observational cohort studies following up for at least 28 days will be included. IPD of the identified eligible published or unpublished studies will be sought by inviting principal investigators. Raw IPD will be shared through the web-based secure platform developed by the WorldWide Antimalarial Resistance Network using the established methodology. The primary objective is to compare the risk of PCR-corrected treatment failure among different treatments and to find the risk factors. One-stage IPD meta-analysis by Cox model with shared frailty will be conducted. A risk of bias assessment will be conducted to address the impact of unshared potential data and of the quality of individual studies. Potential limitations include difficulty in acquiring the IPD and heterogeneity of the study designs due to the lack of standard.
Ethics and dissemination This IPD meta-analysis consists of secondary analyses of existing anonymous data and meets the criteria for waiver of ethics review by the Oxford Tropical Research Ethics Committee. The results of this IPD meta-analysis will be disseminated through open-access publications at peer-reviewed journals. The study results will lead to a better understanding of malaria treatment in pregnancy, which can be used for clinical decision-making and conducting further studies.
PROSPERO registration number CRD42018104013.
- artemisinin
- individual patient data meta-analysis
- malaria
- pregnancy
- quinine
- treatment efficacy
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/.
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Footnotes
Contributors MS, RMc and PJG conceived the idea. MS and RM drafted the manuscript. KK, FN, RMc, PJG and KS critically revised the manuscript. All authors have read and approved the final manuscript.
Funding The WorldWide Antimalarial Resistance Network is funded by the Bill and Melinda Gates Foundation and the ExxonMobil Foundation. SMRU is part of the Mahidol Oxford University Research Unit supported by the Wellcome Trust of Great Britain. MS is supported by the University of Oxford Clarendon Fund.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This individual patient data meta-analysis met the criteria for waiver of ethics review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) since the research consists of secondary analyses of existing anonymous data. Each study included in the analysis will have received local ethics approvals.
Provenance and peer review Not commissioned; externally peer reviewed.