The Pfizer/BioNTech COVID-19 vaccine trial was one of the largest and fastest clinical trials ever conducted. ICON, a global provider of outsourced drug and device development and commercialisation services to the pharmaceutical, biotechnology and medical device industries and government and public health organisations, provided clinical trial services to Pfizer and BioNTech at the time.
Here, Dr Nuala Murphy, President of Clinical Services at ICON plc, talks exclusively to Pharmafield about what it really takes to conduct a vaccine trial at such scale and the implications this has on the future of drug development.
Top 5 Takeaways:
- Pfizer/BioNTech COVID-19 vaccine trial one of the largest and fastest clinical trials ever.
- Submitting data as it was generated to the regulators was crucial to speed and success.
- Collaboration with sponsors and regulators helped to shorten timelines.
- Decentralised and hybrid clinical trial designs allows greater participation.
- New mRNA technology appears to be very effective, opening the door to new treatments in other clinical areas, such as immuno-oncology.
What does it really take to conduct one of the largest clinical trials in history?
From the get-go, we knew the world was watching and waiting for the results of this trial. Therefore, we had to deliver at speed and also with the highest possible standards of safety and quality. The Pfizer/BioNTech COVID-19 vaccine trial was one of the largest and fastest clinical trials ever conducted: we had 44,000 volunteers across six countries and four continents. This required sophisticated planning in setting up the trial, and designing an operational plan that allowed us to recruit a diverse patient population.
Given the nature of pandemic, approximately 90% of the trial monitoring was conducted remotely – at over 150 study sites set up in the U.S., Latin America, Europe and South Africa. We took a global approach to solve this challenge – for example utilising a team in Japan to provide remote monitoring capabilities to cover sites in the Americas.
ICON played a key role in selecting suitable sites, and ensuring that each clinical setting was appropriate and that investigators could deal with the volume of subjects that were required from a trial of this magnitude. There were also the operational considerations of conducting a trial in the midst of a pandemic – ensuring patient and staff safety through the use of PPE and other protective measures.
How could it happen so quickly?
Collaboration with our sponsors and regulators helped us remove a lot of the white space from the trial process, shortening timelines as much as possible. This was particularly noticeable with regulators. As an illustration, typically in Latin America, it can take six to 12 months to have study protocols approved. During the pandemic, we had protocols approved there in three weeks.
Another example would be the U.S., where we had a protocol submitted on a Saturday, reviewed on Sunday and approved on Monday. The FDA played an incredible role in ensuring the trial was reviewed in a rapid fashion, despite regulatory standards remaining exactly the same. The fact we submitted for emergency authorization in 248 days marks record time.
To further expedite the trial, we also carried out rolling submissions – submitting data to the regulators as it was generated. This of course brought challenges – the data had to be monitored and cleaned each day, meaning that for a trial of this scale, we had over 1,000 ICON personnel assigned to the trial – managing the collection and quality of the data. We could not have taken this approach without the full support of regulatory authorities and sites.
What are the wider industry implications of this?
Technology has played an enormous role in making what we achieved possible, in terms of both scale and speed. We’ve already mentioned the vital part played by remote monitoring in this trial, and I think that the pandemic has accelerated existing trends towards decentralised and hybrid clinical trials. This approach can both accelerate drug development, and make research and development less costly – R&D is the single biggest cost involved in bringing new drugs to market and this cost has increased over the last ten years and we need to take an innovative approach to bring that down.
Hybrid trials combine some element of home visits, and seeing patients in traditional clinical settings. This has the advantage of allowing more focus on ensuring a patient-centric trial design. By decentralizing trials with a focus on making them faster and easier for patients, investigators and the industry, we have been able to reap benefits for all involved. It is also worth noting that some indications don’t always lend themselves to a remote situation, whereas others do. Vaccines definitely lend themselves to being remote and decentralized, not least because in a pandemic situation, it’s simply safer, both for the patients and the investigators. This trial and others like it have acted as a proof point, and helped the industry see that largescale remote trials are not only possible, but in many cases, desirable and advantageous.
This has been further supported by the FDA’s unequivocal endorsement of the quality of the data that’s come in under these settings: “the Pfizer-BioNTech COVID-19 Vaccine development has ensured the highest compliance and quality standards while progressing expeditiously to address this urgent and unmet medical need.” This endorsement should help the industry overcome any reservations and begin to apply this thinking in more settings.
To anyone who believe that steps must have to be skipped to meet accelerated study timelines – how would you reassure them?
Regulatory standards across the globe remained exactly the same for this trial as they do for any other. The data we submitted has been subject to the same stringent interrogation as any other vaccine.
More importantly, the vaccine has proved both safe and efficacious – the data indicates a vaccine efficacy rate of 95%, which is good news for everyone in terms of saving lives, and ultimately beating this pandemic. As more people see the beneficial effects of vaccination programmes around the world, allowing society to open up and people to meet and socialise again, I think we will likely see concerns diminishing to an extent.
It’s worth noting that there is still an education process that needs to happen around vaccines and perhaps medicines more generally. Vaccines can cause mild side effects – all medicines cause side effects – but this has to be weighed against the risk of COVID-19, which as we’ve sadly all seen. Vaccines are a key element in reducing that threat and getting back to doing the things we all enjoy.
What other areas in healthcare could benefit from the COVID-19 model of trial management and speed?
There have been a number of positive potential transformations to come out of what has been an incredibly difficult year for everyone. Firstly, there is real potential for us to enter an era of expedited drug development with new cutting edge drug synthesis – for example, new mRNA technology appears to be very effective, opening the door to new treatments in other clinical areas, such as immuno-oncology. Decentralised and hybrid clinical trial designs also open the possibility of greater participation in clinical trials and the potential to improve diversity in patient populations.
Finally, the application of digital technology to clinical trial monitoring and management has taken a leap forward in terms of acceptable. This provides an important opportunity to integrate these approached into our normal processes and therefore move the industry forward. When the pandemic is brought under control, I hope we can all apply the same spirit and drive to speed up drug development and help to bring other much-needed treatments to market faster.