Background:
Malaria is one of the most important parasitic infectious diseases worldwide. Severe or complicated malaria is the most life-threatening and potentially fatal manifestation of the disease, and most cases will develop severe neurological deficit or death in the absence of prompt and effective management. Despite the scale-up of effective antimalarials, mortality rates from severe malaria remain significantly high; thus, numerous trials are investigating both antimalarials and adjunctive therapy.
A critical component in measuring and evaluating antimalarial or adjunctive treatment efficacy is the selection of appropriate outcomes for the RCTs. However, to date there is no agreed uniform method to assess the efficacy of antimalarials or adjunctive treatments and no conclusive analysis of outcomes being used in this area has been published. A systematic review published in August 2022 showed a large amount of heterogeneity with 101 different outcome measures reported in 27 trials between 2010-2020.
A standardized minimum set of outcomes, known as a Core Outcome Set (COS), would help define clinically meaningful outcomes for the treatment of severe malaria, facilitate transparency and reduce outcome reporting bias, whilst enhancing the credibility and validity of future trials. It could also enable more meta-analysis of trials in this area and support the development of evidence-based treatment guidelines.
Aim:
To develop a core outcome set for trials in the treatment of severe malaria.
Objectives:
1. To update the systematic review undertaken in 2020 looking for any additional published or registered trials in severe malaria. Severe malaria has a varied clinical presentation including several complications, that require a range of targeted adjunctive treatments which poses a challenge to standardising outcomes. Each complication of severe malaria may need its own primary core outcome for any phase II trials, and this would need to be considered alongside an overarching core outcome set. Work following the review would look to group the outcomes into domains linked to the complications.
2. To undertake a review of outcome measurement instruments in this area following guidelines from COSMIN (Consensus-based Standards for the Selection of health Measurement Instruments)
To develop a study protocol that would be registered on the COMET Initiative website or published to be publicly available. This would describe the scope, interventions, setting, methods, and people and organisations involved.
3. To work with key stakeholders and experts to prioritise outcomes with a Delphi survey. This would include consideration of how to involve community groups linked to hospitals that treat children and adults for severe malaria in this process and in trial research.
4. To continue working with the stakeholders and expert group to achieve consensus as to the core set using a semi-structured group discussion or a consensus development conference/meeting.
5. To prepare an implementation plan to include both the intended audience and users of the COS and the pathways to reach them.
6. To action some of the implementation plan through dissemination work with publications and visibility at conferences to ensure those designing and setting up severe malaria treatment trials use the newly developed COS.
Relevance the study:
Although previous studies have addressed COS in Malaria, specifically in the context of vaccine trials (Malaria vaccine research and development: the role of the WHO MALVAC committee” study), there is currently no established COS for Trials in the treatment of Severe Malaria, particularly with 'adjunctive therapies.' This absence poses a significant global health concern, given the devastating impact of Severe Malaria. It is imperative that this issue be promptly addressed. Implementing a COS for severe Malaria treatment will enable researchers to ensure that outcomes are precisely defined, consistently measured, standardised, and easily comparable across different studies, ultimately enhancing patient care and informing clinical decisions.
Gideon Darko Asamoah (PhD Student)
Professor Daiana Gibb (Supervisor)
Dr Elizabeth George (Supervisor)
Dr Sharon Love (Supervisor)
Professor Kathryn Maitland (Supervisor)
Disease Category: Infectious disease
Disease Name: Malaria
Age Range: 0 - 120
Sex: Either
Nature of Intervention: Device, Drug
- Clinical experts
- Patient/ support group representatives
- Pharmaceutical industry representatives
- Policy makers
- Researchers
- COS for clinical trials or clinical research
- COS for practice
- Recommendations for outcome measures (measurement/how)
- Delphi process
- Survey
- Systematic review
The primary objective of the project is to develop a Core Outcome Set (COS) for clinical trials aimed at treating severe malaria. To achieve this, the process will entail conducting a systematic review to identify the relevant outcomes (in this case updating the systematic review conducted by Dr. George and Lamprini), followed by collaboration with stakeholders and expert groups to reach a consensus on core sets for severe malaria treatment using the Delphi method. Lastly, appropriate knowledge translation methods will be employed to disseminate the findings and encourage the use of the tool by the intended audience and end-users.