VBT was aware of a number of ongoing studies in skin and skin structure infections, thus patient enrollment would potentially be affected by competing trials. Therefore, it was imperative that both our Sponsor and our internal team generate enthusiasm for this particular protocol. We began by enabling a comprehensive and targeted feasibility study to identify and evaluate upcoming competing studies, followed by an educative session with the Investigators on the biologic attributes of the study drug specifically with regard to its rapid bacteriacidal activity, potentially faster rates of resolution, and its potential to limit the development of resistance due to its multiple mechanisms of action. And finally, we recommended that the Sponsor offer more competitive Investigator grants. All these proactive steps resulted in targeted high enrollment rates for the majority of participating research sites.

VBT was aware of a number of ongoing studies in skin and skin structure infections, thus patient enrollment would potentially be affected by competing trials. Therefore, it was imperative that both our Sponsor and our internal team generate enthusiasm for this particular protocol. We began by enabling a comprehensive and targeted feasibility study to identify and evaluate upcoming competing studies, followed by an educative session with the Investigators on the biologic attributes of the study drug specifically with regard to its rapid bacteriacidal activity, potentially faster rates of resolution, and its potential to limit the development of resistance due to its multiple mechanisms of action. And finally, we recommended that the Sponsor offer more competitive Investigator grants. All these proactive steps resulted in targeted high enrollment rates for the majority of participating research sites.

During the development of the protocol, VBT’s scientific team foresaw that maintaining the blind would pose a potential risk for the study, as we assumed the study drug and the comparator were not blinded. Also, the requirements for the study drug level monitoring varied, and many institutions required that the study drug levels be reviewed by either a pharmacist or a physician. Sites needed to ensure that systems were in place so that study drug levels are not inadvertently revealed to blinded study staff. Therefore, our team proposed the use of unblinded monitors who would be responsible for the following:

• Ensure correct dose of study drug was dispensed
• Ensure proper storage of study drug
• Ensure proper return of used and unused vials
• Verify and retrieve study drug accountability pages
• Ensure that study drug levels are appropriately monitored, if applicable, and blinded from blinded study staff

We previously had experience with a very similar study and worked closely with sites to develop site specific plans that outlined how the blind would be maintained at each site prior to the site enrolling subjects.

Challenge

A biotech sponsor conducting a Phase II study in patients with acute variceal bleeding faced a significant enrollment and evaluability risk.

Due to the urgent nature of the condition, potentially eligible patients frequently presented through emergency departments or other hospital units requiring immediate medical intervention. Once certain non-study therapies were administered as part of standard clinical care, patients became ineligible for study participation.

Without effective identification and referral processes, eligible subjects could be lost before study teams were notified, negatively impacting enrollment rates, patient evaluability, and overall study timelines.

Vantage BioTrials Approach

Vantage BioTrials conducted an early operational assessment of the patient care pathway and identified patient identification and referral processes as critical success factors for study execution.

To mitigate enrollment risk, Vantage BioTrials implemented a multi-faceted strategy focused on site selection, staff education, and internal communication workflows.

First, participating sites were carefully selected based on their demonstrated ability to coordinate patient care across multiple hospital departments and maintain effective internal referral networks. Particular emphasis was placed on institutions with established communication pathways between emergency medicine, gastroenterology, hepatology, critical care, and research personnel.

Recognizing that eligible patients could present through several clinical departments, Vantage BioTrials recommended comprehensive study-specific training for investigators, coordinators, emergency department personnel, and other frontline healthcare providers responsible for the initial assessment and treatment of patients with variceal bleeding.

To further strengthen site readiness, Vantage BioTrials collaborated with sites to develop customized referral plans outlining: 

• Department-specific patient identification procedures
• Escalation pathways for potential study candidates
• Roles and responsibilities of clinical and research personnel
• Processes for rapid notification of study staff prior to administration of disqualifying therapies

 In addition, Vantage BioTrials introduced study-specific enrollment support tools, including abbreviated eligibility reference cards containing key inclusion and exclusion criteria along with direct contact information for study coordinators and principal investigators. These tools were distributed across relevant hospital departments to facilitate rapid patient identification and referral.

To ensure consistent implementation across the study, all participating sites completed protocol-specific eligibility and referral pathway training prior to activation, and site-specific referral plans were finalized and approved before enrollment commenced.

Outcome

The implementation of structured referral pathways and targeted site education strengthened communication across participating institutions and improved identification of potentially eligible patients prior to treatment decisions.

One hundred percent (100%) of participating sites completed eligibility and referral pathway training prior to site activation, ensuring that clinical and research personnel were prepared to identify and refer potential study candidates appropriately.

In addition, 100% of participating sites implemented site-specific referral plans before enrolling their first patient, creating standardized processes for patient identification and rapid study team notification across participating institutions.

Most importantly, zero major protocol deviations related to patient eligibility or administration of disqualifying therapies were reported during study conduct, demonstrating the effectiveness of the proactive enrollment and referral strategy.

Collectively, these measures reduced the risk of missed enrollment opportunities, protected patient evaluability, and supported consistent recruitment performance throughout the study.

Key Takeaway

For acute care studies, successful enrollment depends not only on identifying appropriate research sites, but also on understanding how patients move through complex healthcare systems before reaching the research team.

Vantage BioTrials applies a Quality by Design approach to evaluate patient pathways, identify operational risks, and implement site-specific mitigation strategies that protect patient eligibility, improve recruitment efficiency, and support the successful execution of complex clinical trials.

With the extensive knowledge and experiences gained from the multitude of Phase I / Bioequivalence studies VBT has monitored for clients over the years, we began offering Training Courses for our clients’ scientific and operational teams, focusing on GCPs and practical ways to monitor these type of studies while maintaining the highest levels of quality. The response we received after each of these training sessions was tremendously positive, with feedback such as “Very insightful and detailed review. I learned a lot of new aspects about the source document review process,” and “Excellent job with the training provided. I have never seen my team so engaged in any training session before. We definitely learned a lot!”