The FDA’s recent announcement signals that, in many cases, one well-designed pivotal trial may serve as the default pathway for approval. Regulators have framed this shift as enabled by advances in precision medicine and better trial design, arguing that for targeted therapies and high unmet need populations, a single rigorous study can generate sufficient evidence for decision-making.

In practice, this trajectory has already been unfolding. Over 60% of new drug approvals in the past five years have relied on a single pivotal study, often through accelerated pathways. What changes now is not the existence of the model, but its expansion across therapeutic areas beyond oncology and rare disease.

This is a consequential change.

For decades, development was structured to distribute scientific and financial risk across discrete phases. Sponsors established safety in small cohorts, explored signal and dosing in intermediate studies, and confirmed efficacy in larger, global trials. Each transition introduced a pause: new site activations, new patient recruitment, protocol amendments, budget resets, and renewed regulatory interaction. And over time, trial oversight systems were built around those natural inflection points.

A one-trial framework blurs and even eliminates many of those boundaries without sacrificing evidentiary standards. Early safety cohorts expand into confirmatory populations within the same protocol. Interim analyses become central governance mechanisms rather than supplemental checkpoints. Capital is deployed earlier, and scientific decisions occur while the trial remains live. All of this serves to reduce overall budgets, timelines, and site burden and accelerate the delivery of new and improved medicines to patients.

‘One Trial’ Requires Continuous Oversight

The ‘One Trial’ shift exposes the absence of a seamless operational layer between trial execution and regulatory engagement. Several structural gaps stand out:

• First, capital compression. Under a staged model, investment scaled with evidence. In a one-trial paradigm, larger commitments may occur earlier. Sponsors will not deploy tens of millions of dollars without embedded decision gates supported by real-time safety, enrollment, and endpoint monitoring.
• Second, operational continuity. If cohorts expand seamlessly and interim decisions occur within a single study, there is no room for episodic oversight. Waiting for periodic reconciliations across EDC, CTMS, labs, imaging, and safety systems introduces avoidable risk and delays.
• Third, regulatory defensibility. When approval rests on a single pivotal study, transparency becomes paramount. Interim adaptations, safety signals, and execution decisions must be explainable, audit-ready, and supported by unified data at any moment.
• Fourth, post-approval expectations. The FDA is signaling a larger role for real-world evidence both during trials via synthetic control arms as well as post-approval. If residual uncertainty is addressed through longitudinal monitoring, sponsors must operate across a continuous evidence lifecycle, from first patient in through post-market follow-up without isolation between pre- and post-approval environments.

The Path Forward

In a ‘One Trial’ world, periodic interim analyses and database lock cannot be the sole moments of clarity in a trial. Evidence must be continuously captured and translated into knowledge in real time.

To accomplish this, sponsors need more than dashboards. They need unified, analysis-ready data streams that are continuously monitored. They need automated detection of safety imbalance, enrollment drift, endpoint risk, and operational deviation while corrective options remain viable. They need predictive insights, not retrospective summaries. And they need succinct, interpretable evidence that is defensible in regulatory dialogue.

This is precisely what we designed Vivo to accomplish.

Vivo harmonizes trial data across the clinical ecosystem and applies agentic AI to monitor execution in real time. It surfaces emerging risk, interprets underlying drivers, and enables leadership to make staged, evidence-based decisions inside a compressed development model.

Vivo is ready to support sponsors ready to pursue a ‘One Trial’ approach. Contact us to learn more.