Highlights
- HCTs are important tools in assessing vaccine efficacy.
- HCTs in LMICs are ethical and scientifically justified.
- There is consensus on the lack of standard regulatory guidelines on HCTs in LMICs.
- Informed consent was the most important success factor in conducting HCTs in LMICs.
- The identified critical success factors cannot be viewed in isolation.
Abstract
Background
Owing to the globalization of vaccine clinical trials, as well as advances in technologies, improved research accountability, and robust regulatory and ethical scrutiny, the choice to perform human challenge trials has become evident, and one of the most significant applications of human challenge trials is the assessment of vaccine efficacy. While human challenge trials have largely been conducted in high-income countries, the concept is relatively new in many low- and middle-income countries. Thus, the aim of this study was to identify the critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries.
Methodology
Using a two-step methodology, we first carried out a systematic literature review that was centered on identifying low- and middle-income countries that are either establishing a framework for, have conducted, or are conducting human challenge trials for vaccine development; secondly, we conducted a descriptive cross-sectional survey using a standardized semi-structured online questionnaire administered to eligible stakeholders, to identify the critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries. Seventeen low- and middle-income countries were identified and included in the survey.
Results
The most cited critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries were Informed Consent, Risk Compensation and/or Reimbursement, Participant Safety and/or Public Protection, Community Engagement, Infrastructural Capacity, and Ethical and Regulatory Frameworks.
Conclusion
From an empirical perspective, this study provides a list of critical success factors that form the basic structure to guide the design and implementation of further human challenge trials in low- and middle-income countries. Further studies are needed to establish a standardized conceptual framework to aid in the review, approval and overall conduct of human challenge trials in low- and middle-income countries.
Keywords
Human Challenge Trial, Controlled Human Infection Model, Vaccine Development, Low-and Middle-Income Country
Abbreviations
CHIM: Controlled Human Infection Model
CHMI: Controlled Human Malaria Infection
EMA: European Medicines Agency
FDA: Food and Drug Administration
GMP: Good Manufacturing Practice
HCT: Human Challenge Trial
HIC: High-Income Country
LMIC: Low- and Middle-Income Country
NRA: National Regulatory Authority
QA: Quality Assurance
REC: Research Ethic Committee
WHO: World Health Organization