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Published on: February 27, 2019
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Consensus Report on Shigella Controlled Human Infection Model: Clinical Endpoints
Calman A MacLennan1, Mark S Riddle2, Wilbur H Chen3
1Bill & Melinda Gates Foundation, London, United Kingdom.
Summary
A standardized clinical endpoint for Shigella controlled human infection models (CHIM) was established to ensure vaccine efficacy assessment comparability. This harmonized endpoint defines shigellosis based on diarrhea severity and accompanying symptoms for consistent clinical trial outcomes.
Area of Science:
- Infectious Diseases
- Vaccinology
- Clinical Trials
Background:
- The Shigella controlled human infection model (CHIM) is crucial for evaluating vaccine candidates and expediting regulatory processes.
- Current Shigella CHIM studies utilize specific strains (Shigella flexneri 2a strain 2457T, Shigella sonnei strain 53G) across multiple US sites.
- Shigellosis symptoms vary, ranging from watery diarrhea to dysentery, often with fever, cramps, and malaise.
Purpose of the Study:
- To establish a harmonized primary clinical endpoint for Shigella CHIM studies to ensure comparability.
- To develop a consensus definition of "shigellosis" for consistent assessment in clinical trials.
- To standardize methods for evaluating clinical outcomes and safety in Shigella CHIM studies.
Main Methods:
- An expert working group convened to review existing Shigella CHIM clinical data.
- A consensus primary endpoint was developed, defining shigellosis based on severe/moderate diarrhea or dysentery, with specific criteria for fever and symptom severity.
- Standards for early antibiotic administration and symptom assessment were established.
Main Results:
- A consensus definition for "shigellosis" was established: severe diarrhea, or moderate diarrhea/dysentery with concurrent fever (≥38.0°C), vomiting, or moderate/severe constitutional/enteric symptoms.
- A blinded, independent committee will adjudicate the primary endpoint for subject comparability.
- Standardized criteria for early antibiotic administration were defined, balancing volunteer safety with outcome assessment.
Conclusions:
- The consensus primary endpoint provides a standardized measure for Shigella vaccine efficacy trials.
- Harmonization of clinical endpoints in Shigella CHIM studies will improve data comparability and accelerate vaccine development.
- Standardized safety and treatment protocols enhance the reliability and ethical conduct of Shigella CHIM studies.
