Clinical trials involve many moving parts—protocol design, site performance, patient engagement, regulatory timelines, vendor coordination. While strong planning is essential, missed milestones often trace back to misaligned feasibility assessments, under-supported sites, or lack of adaptability to arising challenges once the trial is underway. Running trials effectively isn’t just about planning well—it’s about anticipating challenges and staying responsive throughout execution.

When that responsiveness is missing—or when early signals of trouble go unaddressed—studies begin to stall. That’s when a strategic, experienced intervention can make the difference between recovery and failure.

At Confidence Pharmaceutical Research, we specialize in restoring momentum to underperforming studies. Whether we’re stepping in midstream or assuming full operational oversight, our approach is rooted in data-driven feasibility, focused site engagement, and operational excellence.

This blog series, Rescue Studies, offers an inside look at how Confidence successfully takes over stalled trials and implements tailored strategies to revitalize them. In this first installment, we explore the common causes of enrollment failure, our feasibility re-assessment methodology, the step-by-step takeover process, and the rejuvenation strategies executed by our dedicated Patient Recruitment and Site Engagement Task Force.

Why Are Some Studies Struggling to Enroll Patients?

Patient enrollment delays are among the leading causes of trial failure and are typically the first indicator that a study may be underperforming. From our experience, the root causes often include:

• Overly optimistic enrollment projections during initial feasibility that don’t reflect site realities.
• Site selection based on outdated or inflated metrics, without recent validation of actual performance or appropriate modeling that would take into account differences between the reference studies.
• Limited site engagement, with blurry motivation structures and poor communication or support from the CRO.
• Protocol complexity—lengthy visit schedules, extensive data collection, or burdensome eligibility criteria—that deters both investigators and patients and limits patient retention.
• Operational inflexibility, where rigid structures make it difficult to respond to site or patient feedback in real-time.

If not addressed early, these problems can quickly build up—slowing down enrollment, causing data delays, and leading sites to lose interest. As momentum fades, sponsors may start to question whether the study can succeed. Without timely action, a study that could have been saved may become too far off track to recover.

Performance Analysis and Feasibility Re-assessment

Before launching any corrective action, Confidence begins with a thorough performance and feasibility audit. This step is essential for diagnosing the precise challenges impacting study delivery.

Our process includes:

• Reviewing site-level metrics, such as actual vs. projected enrollment, pre-screening data, screen failure rates, protocol deviations, and monitoring findings.
• Reassessing regional feasibility assumptions, incorporating recent recruitment trends, site activation timelines, and therapeutic area benchmarks (local SoCs).
• Engaging with site staff to gather direct feedback on barriers to enrollment and study execution.

This detailed analysis provides clarity on what’s working, what isn’t, and why. We ask targeted questions such as:

• Were enrollment projections anchored in realistic site capacity and patient availability?
• Are there high-potential sites–and countries–that were overlooked or deprioritized during initial feasibility?
• What operational gaps—communication, training, logistics—are limiting performance?
• Are there any protocol changes that may improve patient enrollment and retention?

The answers inform our tailored recovery plan, ensuring that our rescue strategy is not based on assumptions, but on actionable insights grounded in data and frontline feedback.

Confident Study Take-Over Process

Taking over an ongoing study requires deep operational insight and careful execution. Transitions must be managed in a way that safeguards data integrity, regulatory compliance, and site relationships. At Confidence, we’ve developed a structured, multi-phase takeover framework designed to minimize disruption and restore study performance with speed and stability. We have Standard Operating Procedures (SOPs) guiding every step of the process and a variety of forms to document the transition. We try to ensure that no piece of valuable information is lost in transition. 

1. Sponsor Alignment and Transition Planning. 

We begin with a structured planning phase in collaboration with the sponsor. This includes:

• Defining the scope and depth of the transition
• Identifying known risks and mitigation strategies
• Aligning on revised timelines, deliverables, and roles across both organizations
• Reviewing current vendor contracts, system configurations, and site statuses

2. Data and Document Transfer

We coordinate a secure transfer of all essential documents and systems, including:

• Trial Master File (TMF) materials
• Site and vendor contracts
• Clinical systems (e.g., EDC, IRT, CTMS) and their associated data
  When system handoff isn’t possible, we develop transition plans to rebuild or migrate platforms while minimizing data loss and downtime.

3. Regulatory and Contractual Amendments

Our regulatory and legal teams ensure seamless compliance updates. This may involve:

• Revised site contracts and clinical trial agreements
• Core study documents amendments (as needed)
• Country-specific submissions (notifications) to ethics committees or competent authorities.

4. Site Engagement and Re-Onboarding

Rebuilding trust with sites is critical. Confidence initiates personal, coordinated outreach to each participating site, providing:

• Study updates and transition rationale
• Retraining on protocol and operational changes
• Direct access to CRAs and study leadership
  This phase is essential for reinforcing our commitment to supporting site needs while resetting expectations and timelines.

5. Functional Integration and Reforecasting

Internally, our cross-functional leads—clinical operations, monitoring, regulatory, medical affairs, data management—convene to:

• Integrate study oversight tools and SOPs, perform gap analysis
• Redefine recruitment targets and study milestones
• Establish escalation plans and performance tracking systems

By the end of this phase, the trial isn’t just back on course—it’s recalibrated with renewed clarity and aligned leadership.

Study Rejuvenation Processes (Implemented by Patient Recruitment and Site Engagement Task Force)

Rescuing a trial doesn’t stop at stabilization. True recovery happens when sites are re-motivated, patient pipelines are re-opened, and progress becomes sustainable.

That’s where our Patient Recruitment and Site Engagement Task Force steps in. This cross-functional unit is deployed specifically for enrollment turnarounds and works in tandem with project managers, CRAs, and medical monitors to execute targeted interventions.

Key rejuvenation tactics include:

• Site retraining on key protocol elements, enrollment procedures, and documentation standards
• Introduction of Sub-Investigators or referring physicians to expand patient reach
• Changes to site contracts and introduction of referral agreements to incentivize patient enrollment and retention
• Reactivation or replacement of sites based on engagement, performance, and recruitment viability
• CRA coaching and consistent site communication, including regular check-ins, monitoring and discussion around pre-screening activities, newsletters, and issue escalation
• Development of customized recruitment toolkits, often including translated patient-facing materials, outreach templates, and local referral strategies

These efforts are highly collaborative, with sponsor teams often participating in site webinars, co-hosting meetings, or supporting recognition programs to sustain engagement.

Together, these interventions help re-establish momentum, improve data quality, and equip the sites to meet updated expectations.

What Comes Next

Rescue isn’t about reacting—it’s about rethinking. At Confidence, every turnaround is an opportunity to rebuild a study around what works: realistic forecasting, collaborative oversight, and meaningful site partnerships.

In the next installment of our Rescue Studies series, we’ll explore what happens when performance issues are concentrated in specific regions—and why replacing a CRO in one or several countries can be a more effective solution than closing them down.

“Regional Rescue: Changing CROs in Underperforming Regions” will offer practical insights into how country-level course corrections protect global timelines, budgets, and study integrity.

Stay with us as we share what it truly takes to rescue, restructure, and reaccelerate clinical trials—confidently.