Vaccine clinical trials in low- and middle-income countries: a brief review of standard, newer and proposed approaches

ABSTRACT

Introduction

Vaccine clinical trials are necessary in low- and middle-income countries (LMICs) because new vaccine candidates are developed against diseases found mainly in these settings, the results of trials done in industrialized countries may not be generalizable to LMICs and more institutions in middle-income countries are producing vaccines for use in LMICs.

Areas covered

We searched PubMed and conducted a narrative review on standard, newer and proposed approaches toward obtaining data supportive for vaccine licensure, with a special focus in LMICs.

Expert opinion

Of the vaccine trials done worldwide, only a small proportion is conducted in LMICs, but this is likely to increase as more research experience and infrastructure is developed. At present, the majority of vaccine trials follows the standard paradigm of fixed phase 1 to 3 trials, the latter with clinical endpoints, or immunobridging studies when a valid immunocorrelate of vaccine protection exists. Other study designs may help facilitate the generation of data toward licensure of and recommendations for needed vaccines. Increased international collaboration is needed for local capacity building and regulatory oversight to ensure that all studies are conducted under good clinical practice.

KEYWORDS:

• vaccine
• vaccine clinical trials
• vaccine licensure
• vaccine pre-qualification
• clinical development pathway

Article highlights

• Vaccine clinical trials in low- and middle-income countries (LMICs) are important to generate population-specific data that can help inform public health decisions on the licensure and deployment of new vaccines.

• We provide an overview of standard, newer and proposed vaccine trial designs toward obtaining data supportive for vaccine licensure, with a special focus in LMICs.

• The standard clinical development of candidate vaccines toward licensure involves fixed phase 1 to 3 trials, with the latter measuring vaccine safety and clinical protection. Alternatively, when there is an immune correlate of protection, immunobridging studies may be done in lieu of Phase 3 trials with clinical endpoints.

• Other study designs that may provide supportive data include human challenge studies, adaptive vaccine trials, and cluster-randomized trials.

• Proposed study designs include biomarker investigations, the delayed-start randomised controlled trial design and the immunobridging approach followed by observational studies.

• As the vaccinology field in LMICs continues to develop, more of the newer study designs may be implemented to facilitate the licensure of candidate vaccines.

• For any of the study designs, the first and foremost priority should be the protection of human rights and welfare. All studies should be conducted in accordance with the Declaration of Helsinki and adhere to Good Clinical Practice guidelines.

• Conducting vaccine trials is logistically difficult and resource intensive; increased partnerships to share expertise among institutions may help overcome some of these challenges.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

We confirm that all authors should have (1) substantially contributed to the conception and design of the review article and interpreting the relevant literature, and (2) been involved in writing the review article or revised it for intellectual content.

Additional information

Funding

This paper was not funded.