Overview

Pivotal programs in upper gastrointestinal indications (including gastroesophageal reflux disease [GERD], peptic ulcers, gastritis, eosinophilic esophagitis [EoE], H. pylori gastritis, and Barrett’s esophagus) present a unique set of operational challenges. Sponsors must navigate complex diagnostic requirements, evolving regulatory expectations, and increasing competition for eligible patients.

Across multiple global programs, we regularly see:

  • Strict diagnostic and procedural requirements (i.e., endoscopy)
  • Variability in regional pathways
  • Overlapping site networks competing for the same patient populations

These factors can significantly impact enrollment timelines and overall study predictability.

The challenge

Across several late-stage upper GI studies, sponsors faced a combination of operational risks that threatened enrollment performance, and adherence to timelines:

  • Regulatory changes mid-study, requiring rapid adaptation of country strategies
  • High screen failure rates, often linked to infection-related exclusion criteria
  • Patient burden from procedures, including repeat diagnostics
  • Site variability, with inconsistent screening and rescreening practices

Challenges occurring individually are manageable, however in combination, they can create a compounding effect, leading to slowed recruitment and increased operational complexity.

Strategic approach

To address these challenges, a coordinated, cross-functional strategy was implemented across programs, focusing on three core approaches.

Feasibility processes were designed to anticipate regulatory and operational variability across regions. This enables:

  • Rapid reallocation of countries and sites when conditions change
  • Activation strategies that align with real-world site capabilities
  • Subsequent early identification of potential enrollment bottlenecks

Screen failures are felt strongly in upper GI trials. We placed particular emphasis on improving patient flow through the screening process:

  • Structured rescreening strategies capture patients (following resolution of exclusion criteria keeping them from enrolling at first screening)
  • Clear guidance provided to sites for optimal timing of screening procedures
  • Enhanced collaboration with local providers, with local knowledge to streamline diagnostic workflows

We implemented operational adjustments to increase site efficiency (leading to improving the patient’s overall experience)

  • Coordination with vendors to minimize unnecessary repeat procedures – where relevant, endoscopy was kept to the minimal level required by the protocol
  • Alignment of protocol requirements with routine clinical practice, where possible
  • Targeted site support to reduce administrative burden, and maintain engagement

Outcomes across programs

Applying these three strategies consistently across multiple studies led to measurable impact: Stabilized enrollment trajectories despite variation at the site level and during the early stages of the trials; improved screening conversion rates; greater site engagement; and delivery of milestones in line with, or ahead of, expectations.

These outcomes were not driven by a single intervention (just like how operational complexity is not derived from a single challenge). They were made possible by integrated feasibility and operational expertise throughout the life cycle of these trials.

Sponsor takeaways

Upper GI trials benefit from a specialist CRO. The complexities of operational challenges requires effective collaboration between the sponsor and CRO, so that processes and protocols can be refined and trials accelerated. A partnership-driven approach ensures greater predictability and operational problem-solving in a complex therapeutic area.

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Abbreviations

GI, gastrointestinal.