Vaccine efficacy (VE) trials play a critical role in assessing how well vaccines prevent infection or disease. These Phase 3 trials measure VE as the proportionate reduction in infection rates between vaccinated and unvaccinated groups. For decades, VE trials have been instrumental in the development of safe, life-saving vaccines, forming the cornerstone of public health policies. Their importance grew exponentially during the race to develop COVID-19 vaccines.

Designing robust VE trials is essential to generating reliable, actionable results. This is where tools like East Horizon^TM – Explore can make a significant impact by empowering researchers to design, simulate, and analyze these types of trials effectively.

Commonly used metrics for vaccine efficacy trials

Commonly used metrics to evaluate outcomes in vaccine efficacy trials include risk ratios, hazard ratios, and odds ratios:

• Risk ratios: The risk of an event happening in one group vs. the risk of the same event happening in another group.
• Hazard ratios: The relative risk of the complication based on comparison of event rates.
• Odds ratios: The likelihood that an outcome will occur given a particular exposure vs. in the absence of that exposure.

These metrics enable researchers to evaluate outcomes with precision.

Special considerations for vaccine efficacy trials

VE trials have a unique set of characteristics that set them apart from other late-phase clinical trials. These characteristics include a large number of study participants, often in the tens of thousands of study subjects, specific follow-up and event requirements, unique testing rules, and super-superiority thresholds, which set a higher standard of efficacy for these products as they are targeted at a relatively small expected number of events. These features address the ethical, logistical, and public health demands of evaluating vaccines for healthy populations. Many of these aspects are shaped by regulatory guidelines (e.g., FDA, EMA) and global health priorities.

Some examples of these unique aspects include:

• Fixed follow-up times: Standardized observation periods that ensure consistency in data collection and improve the reliability of trial results.

• Targeted event counts & stopping boundaries: Setting target case numbers and stopping boundaries enhances trial efficiency by focusing resources on meaningful outcomes.
• Unique testing methods for measuring vaccine efficacy

• • 1 – Ratio of proportions: This approach compares infection rates between vaccinated and unvaccinated groups to estimate VE.
  • 1 – Ratio of Poisson rates: Designed for time-to-event data, this method accommodates varying follow-up times among participants.

• Super-superiority testing: Evaluate cases where vaccine efficacy significantly exceeds standard expectations.

• Futility boundaries: Facilitate early termination of trials if interim results indicate the vaccine is unlikely to meet efficacy goals.

Generating and analyzing VE data using advanced simulation software

East Horizon – Explore enables precise trial design by simulating binary endpoints and time-to-event data and offers a powerful tool for analysis and data visualization. The solution allows users to model randomization and enrollment times, replicating realistic trial scenarios, and modeling enrollment schedules and infection incidence.

Binary and time-to-event endpoints allow biostatisticians to model infection risks and represent participants avoiding infection during the trial period. Additionally, East Horizon – Explore allows for effect measures and hypothesis testing at ease. Users can utilize either 1 – Ratio of proportions or Poisson rates as straightforward and industry-standard formulas.

Advanced continuity correction and R integration capabilities allow users to address potential Type-I error inflation for larger event rates, while enabling advanced customization through R code integration.

Financial analysis: Beyond basic efficacy testing

East Horizon – Explore goes beyond traditional VE analysis by incorporating optional financial and operational modeling. Users may incorporate revenue and cost modeling, alongside traditional efficacy testing. For example, users can include variables related to potential market share and associated costs, based on expected treatment thresholds to generate an expected Net Present Value (eNPV) forecast. This option enables strategic decision-making with detailed financial forecasts tailored to vaccine development, which is especially sensitive to cost and market access pressures.

Tailored financial forecasts are particularly important for vaccines because they differ from other clinical products in key ways. Unlike therapeutic drugs, vaccines often require substantial upfront investment for large-scale manufacturing, face shorter market exclusivity periods, and must balance affordability with global accessibility. These unique challenges demand a specialized approach to financial modeling that ensures both economic viability and alignment with public health priorities.

Final takeaways

Vaccine efficacy trials are critical component of public health. A unique set of characteristics, however, set them apart from other late-phase trials, requiring special consideration. Advanced simulation software, like East Horizon – Explore, can help sponsors optimize trial designs and gain deeper insights into trial outcomes.

Interested in learning more?

East Horizon – Explore offers a comprehensive platform tailored for a variety of designs, including VE trials. The platform empowers researchers with flexible design capabilities, rigorous statistical methods, and decision-support tools. From robust VE analysis to financial modeling, Explore facilitates data-driven decisions that advance vaccine research and enhance public health outcomes.

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