BMJ Open Protocol Targets Vaccine Trial Inequities Across Low- and Middle-Income Countries
Vaccine development depends on clinical evidence that travels well beyond the country where a trial begins. This BMJ Open protocol is designed to examine a long-running fault line in that evidence base: whether low- and middle-income countries are adequately represented in vaccine clinical trials, and how that representation varies by sponsor, funding source, trial phase, vaccine platform, and time.
The question is not abstract. LMICs carry a disproportionate share of vaccine-preventable disease, and they are often the settings where immunisation programmes must perform under the most difficult logistical and epidemiologic conditions. If pivotal trials are concentrated in higher-income regions, the resulting data may be less transferable to the places where vaccine impact is most urgently needed. Even when the biological target is the same, the surrounding reality is not: background immunity, circulating strains, access to follow-up, and health system infrastructure can all shape how trial results are interpreted at the bedside and in national policy.
This protocol is built around a systematic review and meta-epidemiological analysis intended to quantify that imbalance with trial-level data rather than assumption.
Trial Geography Will Be Measured Against a Global Burden That Remains Uneven
The review will include published and unpublished phase I through phase IV interventional vaccine trials in humans, without restrictions on disease area, vaccine platform, language, or publication status. That broad scope matters because inequity can emerge anywhere in the development pipeline. Early-phase trials may cluster near academic hubs, while late-phase efficacy studies may follow market access priorities or regulatory strategies that leave LMIC participation inconsistent from one product class to another.
Several bibliographic databases will be searched, including MEDLINE via PubMed, Embase, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials. Trial registries will also be queried, with coverage extending to the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, the EU Clinical Trials Register, the Pan African Clinical Trials Registry, and ISRCTN. That design gives the analysis a better chance of identifying trials that never made it into the published literature, where reporting bias can hide geographic concentration behind selective visibility.
Two reviewers will independently screen titles, abstracts, and full texts. Trial-level extraction will capture geographical location, trial phase, vaccine type, study design, sponsor type, funding source, participant distribution, and publication status. The primary unit of analysis is the individual clinical trial, an appropriate choice for a question centered on where research is actually conducted rather than where it is summarized.
A Meta-Epidemiological Lens May Separate Structure From Chance
The primary outcome is straightforward: the proportion of vaccine clinical trials that include at least one LMIC study site. From there, the review moves into more granular territory. Secondary outcomes will map geographic distribution by income group and region, representation by phase, vaccine category and platform, sponsor and funding source, and temporal trends in LMIC participation. Reporting transparency will also be assessed through concordance between registry records and published reports.
A strong signal may emerge from sponsorship patterns. Industry-led programs, public funders, and mixed partnerships do not always recruit sites in the same way, and trial geography often reflects strategic priorities as much as scientific need. Vaccine platform may matter too. Some technologies require specialized infrastructure, cold-chain capacity, or frequent monitoring, all of which can narrow the pool of feasible sites. Other platforms may be easier to deploy across a wider set of countries, making international representation more realistic if sponsors choose to pursue it.
The planned multivariable logistic regression analyses will be used, where appropriate, to identify trial-level factors associated with LMIC participation. In practical terms, that approach can help distinguish broad geographic trends from the specific design or funding variables that may be shaping them.
One site location can change how a vaccine trial is read by regulators, ministries, and clinicians.
Reporting Gaps May Be as Informative as Site Counts
The protocol gives unusual attention to concordance between registry entries and published reports. That choice reflects a familiar problem in clinical research: trial geography may be described one way in a registry and another way, or not at all, in the final manuscript. For vaccines, where policy decisions often depend on confidence in external validity, incomplete reporting is more than a clerical flaw. It can obscure whether evidence was generated in populations that resemble those receiving the product later.
By including unpublished trials and registry data, the review should better capture the full universe of vaccine development activity. It also places pressure on a more difficult question: whether the current research system is generating evidence in the same regions that bear the heaviest infectious disease burden. If LMICs are underrepresented, the issue is not simply numerical. Underrepresentation can shape dose selection, immunogenicity expectations, safety surveillance, and even the operational assumptions used when vaccines are rolled out at scale.
Why This Protocol Matters Before the Results Arrive
No outcome data are being reported yet, because this paper is a protocol rather than a completed review. Even so, the design itself sends a clear signal about the field’s priorities. The investigators are not limiting the question to one pathogen, one platform, or one funder. They are asking whether the architecture of vaccine research matches the geography of vaccine need.
Ethical approval is not required, since the work uses publicly available data and includes no human participants. Dissemination is planned through peer-reviewed publication and presentations at scientific and policy forums. The review is registered in PROSPERO under CRD420261295568.
If the eventual analysis confirms a shortfall in LMIC representation, the implications will extend beyond academic equity debates. Regulators, trial sponsors, and global health funders would face a concrete evidence gap: vaccine data may be least representative exactly where disease burden is highest. If representation has improved over time, the review may identify which funding models, trial phases, or sponsor structures have helped close that gap. Either way, the result will be a map of how global vaccine science is currently distributed — and where its blind spots still sit.