PHARMExcel – Lessons learned from UK CRO partnering on a landmark NHS vaccine clinical trial

PHARMExcel is a UK CRO with extensive experience in vaccine clinical trials, this experience was successfully mobilised and tested during the COVID-19 pandemic, when the CRO was selected to manage the Covid-19 vaccine booster study.

This case study takes a closer look at the lessons learned in managing the COVBoost trial and how the agile project management and complex clinical trial execution that was demanded at this time, have set a new benchmark for clinical trial delivery that remains relevant for driving innovations forward into the future.

When the COVID-19 pandemic created an urgent need for booster vaccine data, the UK government turned to leading research partners to deliver fast, reliable results. PHARMExcel, a specialist UK CRO for vaccine studies, was selected to manage this Phase II, Investigational Medicinal Product (IMP) study, which evaluated seven different COVID-19 vaccinations given as a third booster doses. The participants were individuals who had previously received either two doses Pfizer–BioNtech or the Oxford–AstraZeneca vaccines.

Time was of the essence for this vaccine study, because data needed to be made available to the Joint Committee on Vaccination and Immunisation (JCVI) by a strict deadline, to allow the Government time to analyse and decide the policy strategy for an Autumn booster programme. As one can imagine, there was immense pressure to deliver, and in this instance, PHARMExcel excelled demonstrating how a UK CRO for vaccine clinical trials can accelerate timelines while maintaining quality and compliance.

The process from initial feasibility, essential document development, through to approvals (including further amendments), and all site activations took just four weeks, which is an unprecedented delivery time. A study of this nature would normally require at least 6 months for study start up. The whole vaccine trial was implemented from start to finish over a 5-month period so that data could be made available to the Joint Committee on Vaccination and Immunisation (JCVI) timeously, which is remarkable. How did UK vaccine CRO PHARMExcel achieve this? We unpack the details below.

The commitment from every PHARMExcel team member to delivering this vaccine trial was evident in the incredible teamwork and dedication to the project, the team worked round the clock. To learn more about how we worked towards delivering this vaccine trial, watch this video, where our Head of Clinical Operations Margaret Irwin describes how everything came together.

Rapid start-up: approvals to site recruitment within 4 weeks

PHARMExcel managed to take the study from the approvals stage all the way through to site recruitment in just four weeks — a much shorter timeline than usual, for a trial of this type.

Regulatory approvals secured quickly

Regulatory approvals from Ethics, HRA and MHRA were granted within 7 days. PHARMExel implemented rolling reviews to facilitate a fast, smooth approval process. Rolling reviews: submitting documents as they were complete ready rather than waiting for complete document packs; regulators provided ongoing feedback to work towards approval.

High recruitment throughput and data readiness to inform policy

Between 1st-30th June 2021: ~3,498 people were screened; ~2,878 found eligible and dosed. Reactogenicity / safety data (for day 28) was monitored, cleaned, analysed so it could be submitted to the Joint Committee on Vaccination and Immunisation (JCVI) in time for policy decisions.

The stand out learnings from this Vaccine Study are encapsulated in the key innovations introduced by PHARMExcel, including.

• Agile, collaborative approach to planning, working and communications, optimising as the trial progressed.
• Regulatory efficiency through rolling submissions/reviews.
• Rapid site activation and participant recruitment.
• Virtual site initiation visits.
• Real-time, seamless communication with NHS sites and sponsors.
• Quality-driven processes to save time and ensure data integrity.

There were extraordinary constraints in place for this clinical trial: a short 5- month window to plan the trial, secure sites, secure regulatory approvals and conduct the research before the deadline, with UK citizens waiting for a booster program to protect the most vulnerable potential COVID patients.

As a CRO that is used to delivering complex clinical trials and working efficiently, PHARMExcel was up for the challenge. With no room for error or delay, we streamlined our typical CRO processes and replaced them with collaborative, cross-functional working that allowed the study team to move quickly without compromising data integrity.

Key to saving time was ensuring that multiple parties and stakeholders could work together seamlessly, without bottlenecks. The agile ways of working which were implemented are highlighted below:

PHARMExcel proposed a system of rolling reviews to help navigate the regulatory requirements and expedite approvals. What this meant was that we were able to submit individual documents as they were finalised, rather than waiting for a complete document pack before submission, which led to significant time savings. All questions were addressed from the authorities in an expedited manner. The result was that approvals by the EC/HRA and Medicines and Healthcare product Regulatory Agency (MHRA) were granted within seven working days.

Rapid site start-up and recruitment in vaccine clinical research

PHARMExcel mobilised rapidly, demonstrating its strength as a CRO for vaccine clinical research. Key start-up elements were delivered in record time through clear efficient daily communications, decision making and the allocation of action items to the relevant, dedicated member of the project team. These start-up elements included: CRO project tracking, the development of study specific and operational documents, for example: site activation processes, Quality Control (QC) activities, the Quality Management Plan and the Safety Management Plan.

Remote site initiation and activation was one of the agile innovations proposed by PHARMExcel for this project which assisted in accelerating the start-up of the trial. Remote site initiation visits (SIVs) were conducted by our team of CRAs via virtual meetings. This was necessary because on-site visits were not permitted by many NHS Trusts due to the pandemic and it made it possible initiate all 18 sites within a five-day timeframe.

The diagram below outlines the fast-paced activation process that was implemented by PHARMExcel in four stages, to allow the sites to undertake certain activities such as advertising and pre-screening/telephone screening activities before booking a vaccine visit in a stepped wise manner. The COVBoost CRA, CTA and QA teams collaborated closely to gather, review and Quality Control (QC) documentation throughout the stages. Our clinical study/project manager (CSPM), CRAs and QA team worked collaboratively with the sponsor and the lead site’s (UHS) project team, to develop and release new study specific processes during this process.

Successfully recruiting candidates for this vaccine clinical trial was of the utmost importance. PHARMExcel’s experience and industry relationships were key to every aspect of this vaccine study, but particularly essential in achieving the recruitment target within the short time frame. PHARMExcel has an excellent, long-standing partnership with the Sponsor, UHS, from multiple previous studies. The UK CRO leveraged this relationship as well as relationships with other NHS Trusts to facilitate rapid recruitment for this trial. Between the 1^st June and 30^th June 2021, 3498 people were screened. 2878 participants met the eligibility criteria and received one dose of a Covid-19 vaccine or a control. This was an extra ordinary achievement, particularly given that initial screenings had to be done remotely via telephonic interviews. For a detailed breakdown of the recruitment process and rollout process read this article which includes a flow chart describing every step.

Partnering with the NHS on infectious disease research

The success of this trial depended on close collaboration with the NHS. PHARMExcel leveraged its long-term NHS relationships and its thorough understanding of the inner workings of the NHS system and clinical realities to successfully execute this vaccine clinical trial. Arguably having a CRO partner with the relationships and deep systemic knowledge of the NHS system, meant that the innovations proposed were actionable within the NHS environment and constraints, which made the rapid planning, trial start-up, recruitment and delivery possible within the timeframe. Time wise, there was no leeway to go back and forth on how this trial should be executed, so having PHARMExcel as a trusted NHS CRO partner ensured that solutions could be identified and implemented fast and efficiently.

Delivering reliable data to inform public health decisions

The vaccine clinical trial strengthened PHARMExcel’s position as a CRO for infectious diseases, showcasing its ability to work effectively with national healthcare systems on time-sensitive public health research. As such this case study is a valuable example of how a CRO for NHS studies can partner with government and work successfully to inform public health decisions.

Speed was vital, but so was accuracy, which is why agile methodologies were required to ensure both. The Electronic Data Capture (EDC) was reviewed by the COVBoost CRA team as a rolling remote activity using a study-specific EDC tracker – devised and implemented specifically for this trial. All documentation was reviewed centrally by the COVBoost CRAs. The day 28 reactogenicity data from all participants had to be monitored, cleaned and analysed, ensuring that it was submitted to the Joint Committee on Vaccination and Immunisation (JCVI) by August to allow for policy development of the booster vaccination programme.

For sponsors seeking a UK CRO for vaccine studies, PHARMExcel’s approach in the COVBoost vaccine trial demonstrates how dedication combined with expertise and tailored, agile solutions deliver results that really make a difference.

In this instance, turnaround times were exceptional, but they were achieved through implementing the best possible working practices possible and then managing it all with determination and expertise. This is essentially what the journey of working with PHARMExcel is like: we partner with our clients to really understand their research and then we work hard to steward them through the clinical trial process, using our exceptional knowledge and expertise to guide them seamlessly past every milestone. There are so many valuable learnings from this case study. For our organisation these exceptional achievements also come with a sense of validation that our ways of working and passion for what we do hold tremendous value.

Government Stakeholders

• National Institute for Health Research (NIHR)
• Vaccine Taskforce

Academic Clinical Trial Sponsor

• University Hospital Southampton NHS Foundation Trust -UHS