Vanguard Trials

A vanguard trial—also referred to as a pilot trial embedded within a larger trial, i.e., internal pilot—is a type of feasibility study conducted as the initial phase of a definitive randomized controlled trial (RCT). Its purpose is to test the feasibility of the main trial’s methods before fully launching it. Unlike standalone pilot trials, the data collected in a vanguard trial can be incorporated into the main trial if predefined criteria are met. This design promotes efficiency, minimizes redundancy, and supports adaptive learning early in the trial process.

Purpose of a Vanguard Trial

The primary goal of a vanguard trial is to assess whether the full-scale trial is feasible and worth pursuing as planned. Key feasibility domains include recruitment capability, participant retention, adherence to the intervention, protocol fidelity, and data completeness. For example, a research team might ask: "Can we recruit 50 patients with heart failure within 6 months for a physical activity intervention?"

Objectives and Success Criteria

Before launching a vanguard trial, researchers should define clear feasibility objectives and success thresholds. These criteria determine whether the trial will proceed without change, require modifications, or stop entirely.

Examples of success criteria include:

Recruiting 80% of the targeted participants within 6 months
Achieving ≥85% adherence to the intervention
Maintaining less than 5% missing data in the primary outcome

Study Design

The vanguard trial should closely mirror the design of the planned full trial to ensure the results are generalizable. Design options may include parallel-group RCTs, cluster randomized trials, or stepped-wedge designs, depending on the larger trial’s framework. While the duration is typically shorter, the design should still include all key trial procedures.

Sample size is based on feasibility metrics rather than statistical power to detect treatment effects. A common approach is to enroll approximately 10–20% of the full trial’s intended sample during the vanguard phase.

Feasibility and Clinical Outcomes

Primary outcomes in a vanguard trial focus on feasibility. These might include:

Recruitment rate
Retention at follow-up
Adherence to the intervention
Protocol compliance

Secondary outcomes may include preliminary clinical data that help refine sample size estimates or assess variability in outcome measures. For example, recruitment might be tracked as 12 participants per month, with a retention goal of ≥90% at six months and primary outcome completeness of ≥95%.

Feasibility Analysis Plan

The analysis of feasibility outcomes often involves descriptive statistics and visual summaries. Qualitative methods such as interviews with participants and staff can offer insights into logistical challenges or barriers to protocol implementation.

Researchers may also use graphical analyses to track patterns in clinical outcomes or operational metrics over time. These visual tools can guide adaptations in trial procedures before moving to the full-scale phase.

Predefined Stopping Rules

To ensure transparency and guide decision-making, stopping rules should be established in advance. These rules typically outline conditions for proceeding, modifying, or stopping the trial based on feasibility results.

Example stopping rules:

Proceed: Recruitment exceeds 85% of the target within the planned timeline
Modify: Recruitment falls below 70%; protocol adaptations required
Stop: Adherence below 50% or emergence of serious safety concerns

Integration with the Main Trial

If the vanguard trial meets its feasibility criteria, the data collected may be incorporated into the full trial’s final dataset. This integration increases the overall efficiency and reduces the need to repeat early-phase activities. For example, 50 participants enrolled during the vanguard phase could be counted toward the main trial’s sample size and included in the final analysis.

Ethical Considerations

Ethical approval must reflect the phased nature of a vanguard trial. Participants should be fully informed that the trial is being conducted in two stages and that their data may be included in a larger study if feasibility targets are met. Transparency regarding trial transitions is essential for maintaining ethical integrity.

Dissemination and Reporting

The results of the vanguard trial should be reported according to the CONSORT extension for pilot and feasibility studies. Reporting should include recruitment and retention statistics, any modifications made to the trial protocol, and key lessons learned that informed the full trial.

Example: Vanguard Trial Design

Research Question: Can we recruit and retain patients with chronic kidney disease for a 12-month dietary intervention?

Design: Parallel-group RCT with 100 participants in the vanguard phase.

Feasibility outcomes: Recruitment rate, retention at 6 months, dietary adherence, and missing data rates.

Success criteria: Recruit at least 80 participants in 6 months, retain ≥85% of participants, and achieve ≥90% completeness of dietary intake data.

Bibliography

Eldridge SM, Chan CL, Campbell MJ, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239.
Thabane L, Ma J, Chu R, et al. A tutorial on pilot studies: the what, why and how. BMC Medical Research Methodology. 2010;10:1.
Arain M, Campbell MJ, Cooper CL, Lancaster GA. What is a pilot or feasibility study? A review of current practice and editorial policy. BMC Medical Research Methodology. 2010;10:67.
Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. Journal of Psychiatric Research. 2011;45(5):626–629. Highlights the strategic use of vanguard trials.
National Institutes of Health (NIH). NIH Definition of a Clinical Trial and Requirements for Registering and Reporting. Guidance on vanguard and feasibility phases. Available from: https://grants.nih.gov

Adapted for educational use. Please cite relevant trial methodology sources when using this material in research or teaching.

Vanguard trials

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