When a global clinical trial falters, the consequences ripple across continents. Recruitment slows in multiple regions, data flow becomes irregular, monitoring gaps widen, and the trial’s scientific and financial integrity is placed at risk. Unlike localized underperformance, which can often be corrected with targeted adjustments, global studies require something far more comprehensive: a full rejuvenation strategy.

Abandoning a global trial is often seen as the last resort. Yet the cost of doing so is staggering. A single Phase III oncology program can exceed $200–300 million in direct costs [1], and termination not only wastes years of investment but also deprives patients of a potential therapy. The good news: global rescues are possible.

At Confidence Pharmaceutical Research, we specialize in bringing struggling studies back to life. Our structured methodology – Reengage, Reorganize, Retrain, Replace, and Repeat – offers sponsors a disciplined, evidence-based approach to restoring trial performance while maintaining compliance and patient trust.

Reengage: Restoring Trust and Rhythm

Global studies rely on rhythm: predictable site interactions, steady enrollment, and consistent data submission. When that rhythm falters, momentum can be lost quickly.

FDA Bioresearch Monitoring (BIMO) inspections from 2021–2023 highlight deficiencies in communication and oversight as recurring root causes of global trial delays [2]. Likewise, a 2022 analysis in Clinical Trials identified investigator disengagement as a leading predictor of enrollment failure in multi-regional oncology programs [3].

To restore rhythm, our first step is direct reengagement:

• Deploying highly experienced CRAs who can quickly identify friction points, rebuild trust, and establish consistent oversight.
• Implementing structured, proactive communication plans – weekly check-ins, data flow dashboards, and escalation pathways.
• Establishing “site health checks” that combine enrollment metrics, monitoring reports, and site-reported challenges into an early warning system.

Reengagement is not just about increasing calls or visits. It is about rebuilding trust so that investigators, coordinators, and country teams feel supported, valued, and empowered to perform.

Reorganize: Reshaping the Study Framework

When trials are designed, assumptions about feasibility and capacity often look different once execution begins. A 2020 EMA reflection paper emphasized that misaligned feasibility and over-concentrated site footprints are frequent contributors to delays in multinational oncology studies [4].

Reorganization in a global rescue means realigning the architecture of the trial itself:

• Redistributing enrollment targets across regions and sites to better match actual patient pools.
• Activating new geographies when certain countries prove saturated, over-regulated, or logistically unworkable.
• Clarifying and recalibrating vendor roles – ensuring central labs, imaging providers, and CRO partners are aligned under a single governance framework.
• Establishing task-force governance that unites global, regional, and country leadership under shared KPIs and reporting cadences.

This structured reorganization prevents overreliance on “hero sites,” reduces bottlenecks, and ensures that the trial’s footprint reflects real-world patient availability.

Retrain: Elevating the Team

Training gaps are one of the most underappreciated drivers of study underperformance. A DIA survey published in Therapeutic Innovation & Regulatory Science reported that over 50% of global delays were linked to inadequate training or turnover of site personnel [5].

Rescue retraining is more than repeating the investigator meeting slides. It involves:

• Re-education of current teams focused on protocol-critical endpoints and monitoring trends.
• Onboarding of new staff (sub-Is or referral partners) with customized training modules.
• Direct senior team involvement, where medical monitors and clinical leads personally connect with sites to discuss protocol nuances, safety signals, protocol deviation trends, and endpoint definitions.
• Country-level reinforcement, ensuring local leadership provides regulatory and cultural context to training.

This layered approach creates alignment across the network, prevents protocol drift, and ensures that the trial is conducted consistently despite regional variations.

Replace: Strengthening the Site Network

Not all sites can be salvaged. Chronic underperformance, repeated protocol deviations, or lack of resources can compromise both enrollment and data integrity.

An analysis in Contemporary Clinical Trials demonstrated that replacing the lowest-performing quartile of sites accelerated enrollment timelines by 25–35% in global oncology programs [6]. The challenge is making these decisions fairly, transparently, and with minimal disruption.

Our structured replacement process involves:

• Objective performance review using metrics such as enrollment contribution, data query resolution, and monitoring findings.
• Support-first philosophy – underperforming sites are offered retraining, CRA reinforcement, and leadership escalation before replacement is considered.
• Compliant transition planning, ensuring ongoing patients are protected, regulatory bodies are informed, and documentation is complete.
• Selective onboarding of new sites with proven capability, supported by feasibility data and historical performance.
• 24/7 support to the sites 

This balanced approach respects existing partnerships while safeguarding the sponsor’s investment and the trial’s scientific validity.

Repeat: Building Sustainable Recovery

Global rescues are not solved by a single intervention. They are sustained through iteration. Each cycle of reengagement, reorganization, retraining, and replacement builds greater stability until the program regains its intended trajectory.

Confidence implements repeatable cycles through governance structures:

• Monthly global rescue dashboards that track KPIs across sites and  geographies.
• Cross-functional task forces that include sponsor, CRO, and site representatives to review progress and troubleshoot.
• Rolling retraining schedules to prevent regression after turnover or protocol amendments.
• Adaptive feasibility reviews, ensuring that any new site or geography is continuously assessed for contribution.

By institutionalizing these cycles, rescue efforts evolve into sustainable quality systems, ensuring resilience beyond the initial recovery.

The following case illustrates how this methodology is applied in practice when a global program requires full-scale rejuvenation.

Case Study: Diabetic Foot Infection (DFI) Rescue 

This Phase III DFI study was conducted across more than 25 countries spanning Europe, Latin America, the United States, and China. In November 2023, approximately two years into execution, the sponsor transferred full project management responsibilities from an incumbent global CRO to Confidence Pharmaceutical Research.

At the time of transfer, roughly 40 sites had been activated and initiated enrollment. The study faced extended start-up and site activation timelines, investigator demotivation due to prolonged inactivity, low recruitment rates at open sites, and the absence of a reliable forecast for activating the remaining majority of planned sites. Recruitment was materially behind initial projections, placing overall timelines at risk.

Confidence assumed responsibility without interrupting ongoing trial activities. Within a short timeframe, a fully operational global project organization was established, including blinded and unblinded teams, comprehensive project-specific execution plans, and a globally distributed medical monitoring function providing 24/7 coverage across all participating regions.

In parallel, feasibility and project teams implemented a structured site engagement and recruitment recovery plan. Site-level enrollment potential was reassessed, targeted re-motivation measures were introduced, and underperforming sites were objectively evaluated. Several sites were closed and replaced with locations better aligned to patient availability and operational readiness.

Each active site participated in dedicated meetings to assess realistic recruitment prospects. Individualized patient recruitment plans were developed and formally agreed upon with principal investigators. Recruitment performance was tracked continuously by a dedicated specialist, enabling near real-time oversight and rapid escalation when needed.

Ongoing recruitment discussions with the sponsor were supported by structured incentive mechanisms linked to consistent patient identification activities, including pre-screening documentation, frequent remote engagement, and targeted motivational booster visits. These measures were implemented as permanent, cyclical interventions rather than one-time actions.

To support global execution, a dedicated logistics function was established with regional hubs in the United States, Latin America, and Europe, ensuring reliable storage and distribution of study materials.

The rescue effort required simultaneous management of complex transitions, including regulatory delegation of authority, site contract resolution, transfer of trial master files (TMFs), reconciliation of site payments, personnel retraining, establishment of blinded and unblinded access controls, vendor qualification and audits, and regional and global governance alignment.

Despite the scale and complexity of the transfer, operational control was restored, a credible recruitment forecast was established, and execution progressed in line with the recovery plan. This case demonstrates Confidence’s ability to assume control of an ongoing, large-scale global study, reengage and remotivate sites, restore enrollment predictability, and stabilize execution under demanding conditions.

Rejuvenation Is Achievable

Global trial abandonment is costly — financially, scientifically, and for the patients waiting for new therapies. But abandonment is rarely the only option. With a structured methodology, transparent governance, and disciplined iteration, struggling programs can be brought back on course.

At Confidence, our philosophy is simple: rescue is not a one-time intervention but a sustainable cycle. By reengaging sites, reorganizing study frameworks, retraining teams, replacing when necessary, and repeating until stability is achieved, we deliver full study rejuvenation — restoring confidence where it matters most.

References

1. Sertkaya A, et al. “Key cost drivers of pharmaceutical clinical trials in the United States.” Clin Trials. 2016;13(2):117–126.
2. U.S. Food and Drug Administration (FDA). Bioresearch Monitoring (BIMO) Inspection Data. 2021–2023.
3. Getz KA, et al. “Predictors of enrollment failure in multi-regional oncology studies.” Clin Trials. 2022.
4. European Medicines Agency (EMA). Reflection Paper on Risk-Based Quality Management in Clinical Trials. 2020.
5. DIA. “Training and site readiness in multinational programs.” Therapeutic Innovation & Regulatory Science. 2023.
6. Smith J, et al. “Impact of site replacement on global oncology enrollment performance.” Contemp Clin Trials. 2022.