How to Make Clinical Trial Site Start-up More Efficient

The process of starting up clinical trial sites can often be time-consuming and complex, leading to delays, extended study timelines, and increased costs. Goyal et al. (2021) assessed large cardiovascular randomized controlled trials (RCTs) in North America and the use of central vs. local institutional review boards (IRBs), one of many parameters which may contribute to the delay in trial start-up. The authors discovered that it took almost nine months for the first participant to enroll after delivering the study protocol, with the top-performing sites taking four months; however, using central IRBs can enhance efficiency. In this article, we will explore strategies to make clinical trial site start-up more efficient, ensuring that the journey from protocol design to patient enrollment is streamlined and effective.

Key Strategies for Efficient Clinical Trial Site Start-up

The site start-up phase is a pivotal juncture, acting as the foundation upon which the entire trial is built. It involves selecting and activating the sites where the study will be conducted, engaging with regulatory authorities, training site personnel, and establishing the groundwork for patient recruitment and data collection. Yet, despite its significance, this phase is notorious for causing delays, thereby impeding the overall trajectory of the trial.

Drug and device companies, along with researchers, often find themselves navigating a maze of challenges that can slow down progress and hinder the efficient initiation of trials. Below, we list eight challenges of clinical trial site start-up and key strategies to solve them.

1. Regulatory

Navigating the regulatory landscape can be a significant bottleneck in clinical trial site start-up. The regulatory submission process can take months, depending on the IRB and other factors. For global RCTs, Lai et al. (2021) identified six key drivers for regulatory delays, namely disparate regulations, submission delays, additional requirements after regulatory approval, use of a local ethics committee/IRB, infrequent ethics committee/IRB meetings, and regulatory backlogs/clock-stops.

Solutions to regulatory challenges with site start-up:

Comprehensive document management: Ensure compliance, quality, completion, and timely submission of required documentation by implementing a robust document management system that tracks and manages all regulatory documents.

Early regulatory engagement: Initiate early and transparent communication with regulatory authorities, presenting trial plans and seeking feedback. This proactive approach can streamline the approval process.

Regulatory expertise: Collaborate with regulatory experts who are well-versed in local and international regulations, ensuring accurate interpretation and efficient navigation of complex regulatory landscapes.

Strategic planning for document collection: Plan ahead for challenging-to-obtain documents such as executed site contracts and insurance policies, anticipating potential delays and addressing them proactively.

Global trial considerations: For global trials, meticulously account for disparate regulations and start-up processes in each country, strategizing for unique document requirements and challenges.

Utilize technology solutions: Embrace technology by utilizing electronic submission platforms for regulatory documents, reducing manual paperwork and expediting the approval process.

Regulatory compliance training: Provide comprehensive training to site personnel on regulatory requirements, ensuring their understanding and adherence to protocols, thereby minimizing regulatory hurdles

2. Site identification and selection

For site identification and selection, criteria for assessment include site experience with the study therapeutic area, access to eligible participants, and availability of appropriate resources, e.g., staff, facilities, training, and equipment. It has been found that selecting sites that have previously worked with a sponsor or clinical research organization (CRO) may reduce cycle times by 28% compared with newly selected sites.

Solutions to site identification and selection challenges:

Thorough site assessment: Conduct a comprehensive assessment of potential sites, considering patient demographics, site infrastructure, and investigator expertise to ensure suitability for the trial.

Utilize site selection tools: Leverage data-driven site selection tools that analyze historical performance data and site metrics to identify sites with higher probabilities of success.

Engage in early site engagement: Foster early engagement with potential sites to build rapport, understand their capabilities, and align expectations, reducing delays during start-up.

Establish site networks: Collaborate with established site networks or consortia that can provide access to a pool of pre-screened sites, expediting the selection process.

Streamlined contract negotiations: Simplify contract negotiations by adopting standardized templates and processes, facilitating quicker agreement finalization.

Implement risk-based site monitoring: Utilize risk-based monitoring strategies to identify sites with potential issues early, allowing for timely interventions and minimizing disruptions.

Promote site training and education: Offer thorough training to site personnel on protocol specifics, regulatory requirements, and trial procedures, ensuring consistent understanding and adherence.

3. Centralized document management

Efficient document management is essential for organizing and tracking various site-related documents. Stakeholders often grapple with the complexities of ensuring seamless access, version control, compliance, and security for an array of trial-related documents. Distributed teams, varying regulatory requirements, and the need for collaboration across different time zones can lead to delays, confusion, and potential errors.

Solutions to centralized document management challenges:

Implement electronic document management systems (eDMS): Utilize eDMS platforms to centralize document storage, enabling authorized stakeholders to access, review, and collaborate on documents in real-time.

Leverage cloud-based collaboration tools: Cloud platforms facilitate seamless sharing and collaboration on documents, eliminating geographical barriers and ensuring all parties work with the most up-to-date versions.

Establish standard operating procedures (SOPs): Develop SOPs for document creation, approval, revision, and archiving to maintain consistency and guide stakeholders through standardized processes.

Automate workflow processes: Implement automated workflows that notify stakeholders when documents require attention, reducing bottlenecks caused by manual coordination.

Maintain comprehensive version history and audit trails: Choose document management systems that offer detailed version tracking and audit trails, facilitating transparency and regulatory compliance.

Provide training and support: Offer training to all stakeholders on using the document management system effectively, ensuring smooth adoption and utilization.

Enhance data security: Prioritize data security through encryption and access controls to safeguard sensitive trial information from unauthorized access.

Efficiently addressing the challenges of centralized document management empowers stakeholders to navigate the intricate web of clinical trial site start-up with enhanced precision and efficiency.

4. Training and education:

Training and education constitute a critical pillar of clinical trial site start-up, aiming to equip investigators and site personnel with the knowledge and skills necessary to conduct the trial with precision. However, this phase presents its own set of challenges. Ensuring consistent and comprehensive training across geographically dispersed sites, addressing language barriers, and accommodating varying levels of expertise can pose obstacles. Moreover, the rapid evolution of trial protocols and regulatory updates necessitates frequent training updates, adding complexity to the process.

Solutions to Training and Education Challenges:

Develop comprehensive training programs: Create detailed training programs that encompass protocol specifics, regulatory requirements, and Good Clinical Practice (GCP) standards, ensuring site personnel are well-versed in all aspects of the trial.

Utilize multilingual resources: Provide training materials in multiple languages to accommodate diverse site locations, promoting a clear understanding of the trial requirements.

Implement virtual training: Leverage virtual training platforms and webinars to deliver consistent and standardized training to geographically dispersed sites, overcoming logistical challenges.

Engage key opinion leaders (KOLs): Collaborate with KOLs to conduct specialized training sessions, offering insights from experienced professionals and enhancing site personnel’s understanding.

Regular training updates: Establish a system for continuous training updates, disseminating new protocol information, regulatory changes, and best practices to keep site personnel informed.

Feedback and assessment: Incorporate regular assessments and quizzes to gauge comprehension and identify areas that may need further clarification.

Site visitations and support: Conduct site visits to provide hands-on guidance and address specific training needs, fostering a personal connection and clarifying any uncertainties.

Documentation of training: Maintain comprehensive records of training sessions, ensuring a clear audit trail for regulatory purposes and demonstrating site personnel’s preparedness.

By implementing these solutions, the challenges associated with training and education during clinical trial site start-up can be effectively managed, resulting in a well-informed and proficient team ready to execute the trial with precision and adherence to regulatory standards.

5. External vendor management

External vendors, including CROs and technology providers, play a pivotal role in clinical trial site start-up. However, orchestrating their contributions and ensuring seamless collaboration can present challenges. Coordinating timelines, aligning expectations, and maintaining effective communication with multiple external entities can lead to delays, misunderstandings, and potential disruptions in the start-up process.

Solutions to external vendor management challenges:

Clear scope and expectations: Establish clear scopes of work and expectations for each external vendor, ensuring a mutual understanding of roles and responsibilities.

Detailed communication plans: Develop communication plans that outline regular updates, reporting mechanisms, and channels of communication to maintain transparency.

Frequent progress check-ins: Schedule regular check-ins with external vendors to track progress, address any bottlenecks, and make necessary adjustments.

Centralized collaboration platforms: Utilize centralized platforms or project management tools that facilitate real-time collaboration, document sharing, and issue tracking among all stakeholders.

Vendor performance metrics: Define key performance indicators (KPIs) for external vendors and regularly assess their performance against these metrics to ensure accountability.

Risk management strategies: Collaborate with vendors to identify potential risks and develop contingency plans, minimizing the impact of unforeseen challenges.

Consistent documentation: Maintain consistent documentation of all vendor interactions, decisions, and agreements, providing a clear record for future reference.

6. Manual workflows and technology integration:

Manual workflows in clinical trial site start-up can be cumbersome and error-prone. Relying on paper-based processes or disjointed systems for data collection, monitoring, and reporting can lead to inefficiencies, data inaccuracies, and delays in decision-making. Integrating technology solutions is essential to overcome these challenges and optimize the start-up process.

Technical integration solutions:

Electronic trial master files (eTMFs): Adopt eTMFs for streamlined document management, offering centralized storage, version control, and access for all stakeholders.

Clinical trial management systems (CTMS): Utilize CTMS platforms to centralize trial-related data, manage site activities, track milestones, and provide real-time visibility into trial progress.

Electronic data capture (EDC) systems: Implement EDC systems for efficient data collection, minimizing manual data entry errors and enabling real-time data monitoring.

Real-time reporting dashboards: Develop customized dashboards that provide real-time insights into key trial metrics, facilitating informed decision-making and proactive issue resolution.

Automated workflows: Integrate automated workflows that trigger notifications, approvals, and document routing, reducing manual intervention and expediting processes.

Data security measures: Ensure robust data security measures, including encryption and access controls, to protect sensitive trial information while embracing technological advancements.

Leveraging these technology integration solutions empowers clinical trial site start-up processes with enhanced efficiency, accuracy, and transparency. Electronic trial master files (eTMFs), clinical trial management systems (CTMS), and electronic data capture (EDC) systems collectively optimize document management, data collection, monitoring, and reporting, paving the way for smoother trial execution and superior outcomes.

7. Site activation

Coordinating diverse site-specific requirements, training schedules, and documentation submissions can lead to discrepancies and delays. Additionally, managing the influx of information, protocols, and regulatory updates during onboarding poses a risk of miscommunication and site personnel overload. Finding effective solutions to navigate these challenges is essential to expedite site activation while maintaining adherence to protocols and regulations.

Solutions to site activation and onboarding challenges:

Digital site onboarding app: Implement a digital onboarding app that guides site personnel through the onboarding process, offering step-by-step instructions, document submission portals, and training modules.

Tailored onboarding plans: Develop customized onboarding plans for each site, considering site-specific requirements, investigator expertise, and language preferences.

Centralized information repository: Create a centralized repository for trial-related information, protocols, and regulatory updates, ensuring easy access for site personnel during onboarding.

Pre-onboarding webinars: Conduct pre-onboarding webinars that introduce site personnel to trial expectations, protocols, and training requirements, enabling them to arrive well-prepared.

Site liaison teams: Assign dedicated site liaison teams to assist site personnel during the onboarding process, addressing queries, and providing personalized support.

Clear communication channels: Establish clear communication channels for site personnel to reach out for guidance, ensuring that questions and concerns are promptly addressed.

Regular progress check-ins: Schedule regular check-ins with sites during onboarding to monitor progress, identify any challenges, and make necessary adjustments.

Feedback integration: Collect feedback from site personnel about the onboarding process, using their insights to refine and improve onboarding procedures for future trials.

8. Challenges of not partnering with a CRO

Not partnering with a CRO can pose significant challenges during clinical trial site start-up. The absence of a dedicated CRO can lead to fragmented efforts, resource constraints, and an increased burden on the sponsor’s internal teams to manage various aspects of trial initiation.

CRO solutions:

Expertise and experience: CROs bring specialized expertise in clinical trial operations, regulatory compliance, and site management, reducing the learning curve and streamlining start-up processes.

Site network access: CROs often have established site networks, enabling faster site identification, selection, and activation, while leveraging pre-existing relationships.

Resource optimization: Partnering with a CRO allows internal teams to focus on core functions, while the CRO handles site interactions, regulatory submissions, and documentation management.

Risk mitigation: CROs offer risk assessment and management expertise, identifying potential roadblocks and providing proactive solutions to minimize start-up delays.

Regulatory navigation: CROs are well-versed in navigating complex regulatory landscapes, ensuring that all necessary approvals and documents are obtained in a timely manner.

CROs like IQVIA, PPD, Medpace, and Vial have the experience, technology, and expertise to set up and activate clinical sites. CROs can assist sponsors in expediting the processes needed for start-up, including site selection, budget creation and contract negotiations between sponsors and sites, training site staff, patient recruitment through proprietary tech and platforms built to increase efficiency, completion, and submission of regulatory documents, and efficient ethics approval processes.

Understanding the Importance of Efficient Start-up

Efficient clinical trial site start-up is essential for several reasons:

1. Reduced Time to Market: Faster start-up processes mean that new drugs and treatments can reach the market sooner, benefiting patients and healthcare providers alike.

2. Cost Savings: Shorter start-up times lead to reduced operational costs, as resources are used more effectively, and the trial progresses at an optimal pace.

3. Improved Patient Access: Efficient start-up processes enable quicker patient enrollment, allowing individuals to access innovative therapies without unnecessary delays.

4. Enhanced Data Quality: By minimizing administrative burdens during start-up, research teams can focus more on data quality and patient safety throughout the trial.

Vial: Reimagining Clinical Trial Site Start-Up

Vial is a next-generation, technology-first CRO reimagining clinical trials to deliver faster, more efficient trial results at dramatically lower costs for biotech sponsors.

How do we do this? By offering accelerated site activation, with sites ready to initiate trials in 30 days or less. What sets us apart is our technologically empowered approach. Our comprehensive technology platform unifies an intuitive onboarding app, electronic data capture (EDC), electronic source (eSource), electronic trial master file (eTMF), and electronic patient-reported outcomes (ePRO) into a seamless, connected system.

We collaborate closely with some of the industry’s top-performing sites, enhancing site selection and patient recruitment strategies for optimal trial execution. As advocates for efficiency, we believe in transparency and cost-effectiveness, offering fixed-fee pricing that ensures value without compromise. With Vial, you’re not just embarking on a clinical trial journey; you’re embracing a transformative experience designed to accelerate progress, enhance data accuracy, and drive innovation in clinical research.

Partner with Vial for site start-up in under 30 days. Get in touch to find out how!