Prioritising high-quality expedited COVID-19 vaccines

Prior to the COVID-19 pandemic, vaccine studies formed a relatively niche area in clinical research. The COVID-19 pandemic rapidly transformed the perception, understanding, and involvement of vaccine studies from a niche to a high-priority area.

From the off-set small biotech companies were key to pushing forward their research on mRNA and associated technologies and adapting candidate vaccines to combat COVID-19. Our proven experience in the small biotech space ensured ICON was ideally placed to partner with these sponsors on COVID-19 vaccine trials.

Conventionally, vaccine trials can take 5-10 years to ensure safety and efficacy, but the urgency of the COVID-19 situation necessitated the unprecedented acceleration and compression of trial set-up and conduct timelines without jeopardising patient safety or analysis, resulting in creative solutions to manage these high intensity programs.

Many operational and statistical challenges were encountered. The emergence of new COVID variants of concern throughout the course of the trials necessitated changes to planned immunogenicity and efficacy analyses. As other COVID-19 vaccine trials were published, new adverse events of special interest emerged as important for surveillance.

A particularly unique challenge was the availability to the market of alternative vaccinations. This posed ethical concerns regarding participants in placebo arms and resulted in the need to unblind participants partway through the study to partake of a licenced vaccine as and when applicable.

To meet unprecedented timelines, existing resources were prioritised for COVID 19 trials, ensuring a rapid turnaround of deliverables at all phases of development. A dedicated statistician and programming team were assigned full-time, with a transition of individuals between study phases and consistent oversight for statisticians and programmers.

Phase 1, 2, 2b and 3 studies were run in close succession, with a fast transition between phases. Statistical analysis plans were developed in parallel with to the finalisation of the protocols. We initiated a program of accelerated dose escalation with dose administration at the site to data safety review meetings in less than 48 hours and deliveries to the independent safety review committee provided on the same day as the data was available.

To expedite the production of outputs shortly after the first patient was in, the set-up of SDTM and ADaM specifications commenced on draft protocols, and programming was initiated on mock data. The programming team proactively prepared materials for submissions to markets with different CDISC/data requirements in readiness for potential EMA, FDA, and /or PDMA submissions. Standard Adverse Event reporting procedures were revised to include vaccine-specific requirements for reactogenicity, solicited and unsolicited events.

Many sub-group and sensitivity analyses were added to account for baseline serology, age groups, gender, region, and dosing schedule.

Several protocol amendments were also required to adapt to changing COVID-19 landscape. Statistical analysis plans, datasets, and associated programming were updated in a short period of time to adapt to the new requirements.

All deliveries were on time to high quality, including several dry-runs, interim analyses, rolling safety submissions and independent safety review committees. Overall, the portfolio included greater than 40,000 participants, over 50 sites, approximately 2.1 million forms, and over 700,000 data queries were raised.

Our involvement has broadened and strengthened our vaccine experience. We have used this experience to become more agile and efficient on the vaccine and non-vaccine trials alike and to establish a vaccines academy training program.