Protocol for the development, dissemination and implementation of a globally relevant core outcome set for snakebite envenoming

Introduction
Snakebite causes 94,000 deaths per year and is associated with a varied range of complications that depend on the biting species. The only direct treatment currently available is antivenom, yet these products are rarely supported by clinical efficacy data from randomised controlled trials. We have conducted a systematic review that has identified significant heterogeneity in outcome measure use in snakebite clinical trials. In accordance with Core Outcomes Measures in Effectiveness Trials (COMET) initiative guidance, we plan to develop a globally relevant core outcome set.

Methods
The scope of this core outcome set is for it to be globally relevant, including for use in high and low-income settings, and adaptable to the type of envenoming. Core outcome measures will be categorised as: mortality, neurotoxicity, coagulopathy, haemorrhage, renal injury, local tissue damage, systemic myotoxicity, disability scale, and adverse events. Certain categories will be universally applicable to all snakebite trials (mortality, disability scale and adverse events). The other core outcome categories will be selected by trialists depending on the syndrome of envenoming of the study population. Reaching consensus on the core outcome measures will be a three-stage process. A stakeholder group will be formed which will include representatives from diverse geographic locations, including LMICs with a high burden of snakebite. Stakeholders will include clinicians, trialists, funders, statisticians and basic scientists.

During stage 1, a draft Information Pack will be prepared that will detail the evidence pertaining to the validity, reliability, feasibility and acceptability of the outcome domains identified during the systematic review. Via a videoconference with the stakeholder group, the draft Information Pack will be presented, and group members will be requested to provide feedback and recommendations of additional evidence to be included.

In stage 2, a questionnaire will be distributed to the stakeholders and respondents will be asked to score outcome domains from 1-9, and to provide comments for their rational. The questionnaire will be completed in conjunction with the Information Pack. The questionnaire and Information Pack will also be distributed to additional experts recommended by the stakeholder group, as well as all corresponding authors of snakebite clinical trials reported in the past 15 years. The results of the questionnaire will be used to shortlist the outcome domains.

For stage 3 the nominal group technique will be used to reach consensus amongst the stakeholders. This meeting will be held via videoconference. Anonymous online polling will be held, and =70% agreement will be required on each core outcome measure. The preliminary core outcome set will be prepared and presented to the stakeholder group for a final vote, requiring =70% agreement before final approval.

Dissemination
The final core outcome set will be uploaded to the COMET database, presented at scientific meetings and published in an open access peer-reviewed journal. The results will be directly shared with all experts that contribute to the questionnaire.

Contributors

Dr Michael Abouyannis - principal investigator (PhD student)

Dr Hanif Esmail - supervisor

Further Study Information

Current Stage: Ongoing
Date: November 2020 - April 2021
Funding source(s): Dr Michael Abouyannis is on a Wellcome Trust funded fellowship (grant number 203919/Z/16/Z)


Health Area

Disease Category: Public health

Disease Name: Snakebite

Target Population

Age Range: 0 - 120

Sex: Either

Nature of Intervention: Drug

Stakeholders Involved

- Charities
- Clinical experts
- Epidemiologists
- Methodologists
- Policy makers
- Regulatory agency representatives
- Researchers
- Service providers
- Statisticians

Study Type

- COS for clinical trials or clinical research

Method(s)

- Consensus meeting
- Literature review
- Nominal group technique (NGT)
- Semi structured discussion
- Survey
- Systematic review

The scope of this core outcome set is for it to be globally relevant, including for use in high and low-income settings, and adaptable to the type of envenoming. Core outcome measures will be categorised as: mortality, neurotoxicity, coagulopathy, haemorrhage, renal injury, local tissue damage, systemic myotoxicity, disability scale, and adverse events. Certain categories will be universally applicable to all snakebite trials (mortality, disability scale and adverse events). The other core outcome categories will be selected by trialists depending on the syndrome of envenoming of the study population. Reaching consensus on the core outcome measures will be a three-stage process. A stakeholder group will be formed which will include representatives from diverse geographic locations, including LMICs with a high burden of snakebite. Stakeholders will include clinicians, trialists, funders, statisticians and basic scientists.

During stage 1, a draft Information Pack will be prepared that will detail the evidence pertaining to the validity, reliability, feasibility and acceptability of the outcome domains identified during the systematic review. Via a videoconference with the stakeholder group, the draft Information Pack will be presented, and group members will be requested to provide feedback and recommendations of additional evidence to be included.

In stage 2, a questionnaire will be distributed to the stakeholders and respondents will be asked to score outcome domains from 1-9, and to provide comments for their rationale. The questionnaire will be completed in conjunction with the Information Pack. The questionnaire and Information Pack will also be distributed to additional experts recommended by the stakeholder group, as well as all corresponding authors of snakebite clinical trials reported in the past 15 years. The results of the questionnaire will be used to shortlist the outcome domains.

For stage 3 the nominal group technique will be used to reach consensus amongst the stakeholders. This meeting will be held via videoconference. Anonymous online polling will be held, and =70% agreement will be required on each core outcome measure. The preliminary core outcome set will be prepared and presented to the stakeholder group for a final vote, requiring =70% agreement before final approval.

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