Equitable Design

Background

WWARN was established in 2009 to understand and curtail the threat of antimalarial resistance. Key to the delivery of WWARN's aims was engaging with global malaria researchers and encouraging them to share their data with the central WWARN repository, at a time before data sharing was required by any funders, publishers or regulatory agencies. The real and perceived challenges to data sharing were many and diverse, so WWARN developed a number of strategies to enable and encourage equitable sharing of robust data to inform malaria treatment policies and practices9. This case study will focus on efforts to promote equity in sharing of data by, and with, researchers from malaria-endemic countries.

Malaria is a poverty-related disease, and its control and eventual eradication are threatened by the spread of parasite resistance to all currently available antimalarials, including the pivotal artemisinins that have played a central role in global decreases in malaria burden since 2000. Promptly sharing reliable data on the efficacy of antimalarial medicines has the potential to prevent or slow antimalarial drug resistance. However, requests to share data to address this critical global health threat have resulted in expressions of concern from researchers, including that the quality of data may be scrutinised or study outputs challenged by external researchers, and that researchers in low-resource malaria-endemic settings are less able to benefit from the fruits of data sharing than researchers in better resourced settings.

Over the past decade WWARN has worked with collaborators in over 280 institutions globally to develop and update its scientific, technical, ethical and governance frameworks to promote equity in data sharing. Key aspects of these efforts which address the primary concerns of the malaria research community are capacity strengthening and technical support in data standardisation and quality, as well as inclusion of primary data generators in secondary analyses.

The impact of these efforts is demonstrated by the size of the WWARN platform which, thanks to the contributions of the global malaria research community, now holds over 80% of the world's individual patient clinical trial data on artemisinin-based combination antimalarials. These data on factors affecting the efficacy of antimalarial medicines have been used to optimise treatment regimens for high-risk groups including pregnant women, young and malnourished children, and provides evidence to inform the development of new antimalarial drugs.

Selected ethical issues and suggestions for ways forward

1. In order to address the concerns of many researchers, and not just those based low-resource settings, that their raw data may not be entirely ready for international scrutiny and their study outputs challenged, WWARN has invested heavily in providing researchers with the resources needed to feel more confident in the quality of data that they share.

a) WWARN developed and continues to expand its tools and resources to enhance the efficiency and quality of planning, executing, analysing and reporting primary data collection (see WWARN Tools and Resources page).

b) This is supported by WWARN's external quality assurance and proficiency testing programme, to enhance data quality and comparability for laboratories conducting antimalarial drug assays.

c) The WWARN Informatics platform accepts data submitted in almost any format, with the related protocol / case report forms / metadata / data dictionaries needed to ensure that data are useable for secondary analyses. The contributed data are curated and standardised using established data and statistical management plans. The "data contributor" receives a study report which includes a list of changes made during curation and processing and a list of any outliers or unexpected results. The original data files and the resultant data set that complies with the Clinical Data Interchange Standards Consortium (CDISC) standards (where applicable) are stored in the WWARN repository, which is an re3data registered repository. These outputs are all available to the contributor or designee, enhancing the quality of their datasets for their own future use.

2. In order to address the concerns of many researchers, primarily in low-resource settings, that they may be less able to benefit from the fruits of data sharing than researchers in better resourced settings, WWARN has developed a number of strategies.

a) In order to give data contributors more choice about how their data can be accessed, WWARN has recently changed its governance frameworks. Data contributors can now choose between "contributor controlled access" where the contributor will review each individual request, or for this to be done through the WHO hosted independent Data Access Committee.

b) WWARN also organizes study groups to bring together data contributors conducting individual participant data meta-analyses to answer important research questions that cannot be answered as reliably or efficiently by individual studies or aggregate data meta-analyses.

Examples of impactful meta-analyses that informed improvements in the treatment of uncomplicated malaria with the following artemisinin-based combination treatments:

• Dihydroartemisninin-piperaquine: Improved dosing recommendations in young children;
• Artesunate-amodiaquine: The enhanced efficacy of the fixed dose combination relative to loose tablets; and
• Artemether-lumefantrine: Sub-optimal lumefantrine exposure in malnourished children.
  

A research question can be proposed by anyone, and researchers from malaria endemic countries may be best placed to identify important knowledge gaps. These study groups not only benefit from pooling the individual patient data shared, but also from skill-sharing of the expertise of each of the primary researchers and technical and statistical support provided through the WWARN data platform. Depending on each study group member's level of engagement in the secondary analysis, the members are authors, collaborators, or acknowledged in resulting publications.

3) Increasing capacity building efforts to enable researchers from malaria-endemic LMICs to be able to access and use secondary data to answer questions of importance to malaria and other NTD control and elimination efforts. These include online open access resources, training workshops conducted in East, West and Southern Africa, and to date hosting ten EDCTP/TDR career development fellows from LMICs to gain the skills required to lead future efforts to make the best use of available data to inform policy and practice. As a part of the Infectious Diseases Data Observatory (IDDO), WWARN also contributes to work with other research communities to replicate this model for other neglected, poverty-related diseases and emerging infections.