What does a world-class research site look like from a CRO-Sponsor perspective?

It’s easy to feel disheartened at the current UK research landscape when we hear reports on 41% decline in trials initiated since 2017 and a 44% drop in the number of UK participants recruited. However, the UK still leads the world in discovery-led research, ranking first for research quality in the G7 for more than a decade. It has an unrivalled science infrastructure and is home to a network of best-in-class clinical trial sites.

Clinical trial sites play a vital role in increasing access to new treatments and healthcare innovations, providing widespread benefit to the whole healthcare ecosystem, including the NHS, academia, industry, and most importantly, patients.

What makes a research site world-class from a CRO and Sponsor perspective?

A world-class clinical trials site is characterised by several key factors that are highly valued by both Contract Research Organisations (CROs) and Sponsors.

1. Experienced and dedicated staff
   A world-class clinical trials site is staffed with experienced and knowledgeable professionals, including principal investigators, sub-investigators, research coordinators, and support staff who are dedicated to the success of the trials.
2. High patient enrolment and retention rates
   The site consistently demonstrates the ability to enrol patients efficiently and retain them throughout the entire study duration, ensuring timely completion of the trial.
3. Strong infrastructure and resources
   The site has robust infrastructure and resources, including adequate facilities, equipment, and technology necessary for conducting complex clinical trials. This includes state-of-the-art laboratories, imaging capabilities, and other essential amenities.
4. Adherence to quality standards and regulatory compliance
   The site strictly adheres to Good Clinical Practice (GCP) guidelines and other regulatory requirements, ensuring the highest standards of data integrity and patient safety.
5. Efficient data management systems
   A world-class site employs efficient data management systems that facilitate accurate and timely data collection, entry, and analysis. This ensures that the data generated is of the highest quality and can be readily accessed for review and reporting purposes.
6. Compliance with timelines and budgets
   The site consistently meets project timelines and budgets, demonstrating a high level of efficiency and cost-effectiveness in the conduct of clinical trials.
7. Patient-centric approach
   A world-class site prioritises the well-being and comfort of the patients participating in the trial, providing them with comprehensive support and information throughout the study.
8. Innovation and adaptability
   The site embraces innovation and is adaptable to changes in the industry, incorporating new technologies and methodologies to improve the efficiency and effectiveness of clinical trial operations.
9. Track record of success
   A proven track record of successfully completed trials and satisfied sponsors and CROs is a testament to the site’s excellence and reliability.

Clinical research in the NHS is responsible for some of the UK’s greatest success stories in science and medicine. The COVID-19 trials are just one example of the UK’s unique capacity to combine excellence in academic life science with the UK healthcare system.

However, the increasing burden on clinicians and healthcare professionals, lack of resourcing, and erosion of a professional workforce, are all factors contributing to the decline in UK clinical research.

Sponsors, CROs, and the research community all have a role to play to facilitate more clinical research and help maintain the momentum gained during the pandemic.

How can CROs and Sponsors unburden sites to empower clinical trial delivery?

Early engagement
Engaging with a proposed or selected site early on will help identify any critical risks factors allowing time to put mitigation measures in place. Key opinion leaders (KOLs) can play an important role in clinical trial strategies and trial management, but relying on KOLs in academic institutions may expose gaps in the process. Bringing the wider site team to the conversations early in the process and allowing it to feed into components of the protocol can be enormously beneficial in accelerating progress and setting realistic expectations from the outset. Equally, a Sponsor who involves its CRO in site feasibility can tap into the CROs previous experience with sites and gain valuable feedback in areas such as how well the proposed site delivers on its patient enrolment targets and other study targets.

Giving the site a voice
We have seen huge value when the CRO and Sponsor involve the site at the beginning of the process to ascertain its capabilities to fully support the trial requirements. Sponsors typically engage with the principal investigator to ensure the study is scientifically sound, but often the site is not fully evaluated to identify if the delivery requirements can be met within the timelines and budget. Often sites are selected by a Sponsor because they have worked with them or the KOL before. However, each study is different, so engaging with the right site early on to ensure they are aligned to the protocol and can successfully deliver the trial is paramount.

4 key recommendations for Site-CRO-Sponsor to achieve clinical trial excellence

1. Study design and set up
   • Sponsors and CROs need to ensure they present a clear, well thought out, scientifically and ethically sound protocol.
   • Set clear patient entry criteria and specify how visits are scheduled. Sites need to understand the patient pathway, ensuring ancillary services can also accommodate scheduling.
   • The site perspective is critical to advancing a standardised workflow throughout the entire clinical trial chain so involve your site early in the process.
   • Ensure the site and Research & Development department carry out a streamlined review of the study and provide an efficient contracting process. The new National Contract Value Review should support this process for trials in the UK.
   • Do an early feasibility study on the site, the CRO should be able to facilitate this.
2. Site resourcing
   • Don’t always target KOLs, emerging researchers are often engaged and visible. An invested Principal Investigator sets the tone for the study and the site teams.
   • Ensure sites have sufficient skilled resource to deliver the study. Undertake robust feasibility and establish if there are any competing studies. Consider if they have patient populations and sufficient numbers to recruit. Look at past activities from the sites – did they recruit to time and target?
   • Is there a dedicated research nurse involved? Do they have access to a Clinical Research Facility (CRF) for more complex trial delivery? Involve ancillary service providers (pharmacy, radiology, laboratory personnel).
   • Have they got staff to support the quality of documentation management? Maintaining Investigator Site File (ISF) is critical.
3. Clinical Research Associates (CRAs)
   Behind the scenes, a dedicated team of professionals ensures that the study runs smoothly, adhering to strict regulations and ethical standards. Among them, the Clinical Research Associate (CRA) emerges as a key player, shouldering the responsibility of overseeing various aspects of clinical trials.
   • An enthusiastic and competent CRA can give significant support for sites. Therefore, its important an open and trusting relationship is built between the site and the CRA.
   • Effectively communicating with investigators, site staff, and sponsors is essential. CRAs must be able to convey complex information clearly and concisely and build a quick rapport.
   • Sites should be able to reply on their CRAs to quickly resolve challenges when they encounter them. The ability to think critically and solve problems is a critical attribute of any CRA and invaluable to the site.
   • CRA turnover – it is sometimes unavoidable during the course of a clinical trial to have a CRA leave and a new one appointed. To avoid impacting the trial process, it’s important for the CRO to handle the communications clearly with the Sponsor and site and provide adequate training and onboarding for the new CRA, who can slot seamlessly in place.
4. Trust and communication
   • Clear lines of communication and support between site, CRO, and Sponsor throughout the entire life cycle of the study are essential.
   • Sites that are willing to adopt a more consultative relationship with their CRO can optimise shared expertise to drive operational efficiencies.
   • Foster and maintain strong and synergistic relationships. Explore effective communication strategies, conflict resolution techniques, and always ensure site and CRO/Sponsor align goals and expectations.
   • Ensure responsibilities are defined early and accountability maintained for deliverables of all parties.

In summary

Getting to really know your site and establishing a genuine partnership based on open communication and trust is essential in enabling sites to deliver a successful trial for the Sponsor and achieve world-class excellence.

Early engagement with the site by CRO and Sponsor and enabling the site to feed into the protocol design will undoubtedly avoid delays during the process and optimise the trial delivery. As well as discussion with the Principal Investigator/KOLs to ensure the study is scientifically sound, early dialogue with the site is important. It is the site and its team who are managing the trial on the ground and are fundamental to delivering the trial.

Naturally if a sponsor has already identified the sites it wants to use, it makes it easier for the CRO to carry out a site feasibility to ascertain that the site has the full resources and capabilities to deliver the trial successfully. Identifying sites early on in the trial set up process allows for the sites involved to feed into the protocol design to achieve the best possible outcome for the study. Complications arise when the sponsor develops the protocol without identifying specific sites. This means site feasibility may occur further along the process and there may be some disconnect between the PI/protocol requirements and realistic logistical deliverables from the chosen site.

Sponsors should lean on their CROs to help improve trial planning and accelerate research through the CRO’s existing relationships and on the ground experience with sites – they will often know the best centres to approach for resourcing, facilities, and patient access.

Finally, clinical trial leaders should recognise the need for standards to advance the professionalisation of the workforce and to continue to develop a clinically-competent, best-in-class workforce to advance world-class research.