Endpoint selection framework:

Public consultation

We have launched a public consultation on a framework that has been developed to support the selection of endpoints in clinical trials for outbreak-prone infectious diseases. This draft has undergone multiple rounds of expert review.

The survey closes on 31 January 2024.

Background

Finding safe and effective treatments for high consequence infectious diseases (HCIDs) – such as Lassa fever, mpox, and plague – is challenging. Reasons include low numbers of sporadic cases, the unpredictable nature of outbreaks, geographical dispersion, and limited healthcare and research facilities in affected areas. As a result, few therapeutics are available on the market and accessible to those who need them.

To accelerate product development there is a critical need for clinical trials that are designed to withstand these difficulties in recruiting and monitoring patients and measuring treatment effects.

One of the key elements of a robust trial design is the selection of the primary endpoint and the tools with which they are measured. For HCIDs, this selection is made difficult by a lack of systematically collected and comparable clinical research data, a lack of agreed-upon methodologies, and practical site-level challenges.

Purpose, Scope and Application

The aim of this work is to support the selection of robust endpoints from which clinically-meaningful and reliable evidence can be generated in these settings.

We have developed a framework to aid the selection of:

Robust endpoints,
Outcome measurement tools

The scope of the framework is primary endpoints in Phase III superiority trials for outbreak-prone infectious diseases that aim to identify a new treatment where no other treatment exists or where the current standard of care is inadequate. The focus is on endpoint selection for trials in low-resource settings, but it may also be applied in any setting.

Public Consultation

In this public consultation we will seek feedback from a wide range of stakeholders with an interest in clinical trials for difficult-to-study infectious diseases.

Key stakeholder groups include, but are not limited to:

Researchers from public and private sectors
Representatives from regulatory authorities
Ethics committee members
Patient and community engagement organisations
Representatives from national research councils

We would like to receive feedback on what the framework does well, what could be improved and the limits of its potential applications. You can provide your comments via an online form or you can arrange a short meeting with a member of the project team.

The feedback we collect will be used to revise the framework and ensure it adequately represents the requirements of the research community and has a clear practical utility.

The deadline for the submission of your feedback is Wednesday, 31 January 2024.

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Timeline

Frequently Asked Questions

1. What is the aim and scope of this framework?

This framework aims to support the selection of primary endpoints for Phase III superiority treatment trials for outbreak-prone infectious diseases to identify a new treatment where no other treatment exists or where the current standard of care is deemed sub-optimal or ineffective. The framework is endpoint- and disease-agnostic.

2. What are outbreak-prone infectious diseases?

Outbreak-prone infectious diseases are those that can be characterised as follows:

having outbreak, epidemic or pandemic potential
but can have low numbers of sporadic cases,
are often widely geographically dispersed,
can occur in locations where there may be limited clinical research facilities in areas with endemic transmission,
for which there is currently limited evidence to support the selection of clinical trial endpoints
and are often under-researched

Examples include bubonic plague, mpox, CCHF and Lassa fever.

3. How did this project arise?

Identifying meaningful and measurable outcomes for outbreak-prone infectious diseases is complicated by several methodological and operational challenges, including:

Few clinical research studies having taken place, meaning there is a lack of systematically collected and comparable clinical research data on which to support endpoint selection
Few or no agreed-upon endpoints or methodologies to support evidence generation
The limited number of validated tools available to assess potential outcomes
The limited research and healthcare infrastructure in some settings where some outbreak-prone infectious diseases arise most frequently

After witnessing these challenges directly, we aimed to develop a tool that could support researchers navigate the complexities of endpoint selection in Phase III clinical trials for outbreak-prone infectious diseases

4. How could the framework be applied?

It is meant to act as a guide to assist researchers to identify:

An endpoint that is clinically meaningful and reliably measured to generate good quality evidence
The limitations or biases that may arise from the trial which could be addressed or minimised in other ways before the trial or analysis begin

5. What is the structure of the framework?

The framework is structured in four sections:

Domains: the top-level descriptive category that summarises the characteristics it contains

Critical characteristics: The “must-have” characteristics of an endpoint and one that all endpoints need to possess to be viable for selection.

Ideal characteristics: Other characteristics that endpoints should possess to generate meaningful evidence for trials (but acknowledging they may not be reasonably achieved in all scenarios for these diseases)

Additional considerations: Other important considerations that shouldn’t necessarily affect endpoint selection, but are good to bear in mind

6. What does the framework do?

The framework aims to support the selection of primary endpoints in Phase III superiority trials for outbreak-prone infectious diseases to identify a new treatment where no other treatment exists or where the current standard of care is deemed sub-optimal or ineffective.

While the framework has been developed with a specific focus on primary endpoints for outbreak-prone infectious diseases, it could be broadly applied to other diseases and would be particularly helpful for diseases that are poorly characterised.

It can also be applied to secondary and exploratory endpoints, where appropriate.

It also identifies areas of potential bias, weakness or operational challenge that researchers may encounter when using an endpoint to evaluate their trial data.

The framework has been developed with a focus on trials taking place in resource-limited settings. This is particularly important to the domain relating to “feasibility”.

7. What does the framework NOT do?

The framework does not confirm whether any specific endpoint is appropriate for a specific trial taking place in a specific context. The research team must take in to account their particular scenario to determine the overall appropriateness of their endpoint and how they might mitigate any challenges relating to its use in the trial.

The framework is not designed to be restrictive. It is designed to be a guide, which researchers can adapt to their own needs and contexts. Other considerations may be needed for non-inferiority or equivalence trials.