EU-PEARL is promoting the uptake of ‘adaptive trials’, of the type currently being used in the WHO Solidarity study, because they can speed up drug development times
The record for the fastest vaccine ever developed is about four years from lab to patient. The new coronavirus vaccines are set to smash this record. In some cases, it will be thanks to the use of adaptive trial platforms, which are trials that run studies of multiple drugs at the same time and ‘pool’ the placebo group.
While adaptive trial design is extremely good at reducing drug development times, it is also very complex. That’s why in 2019, IMI launched EU-PEARL to help provide the evidence and support for those who want to design their own adaptive trials, with the ultimate aim of getting medicines more quickly to market.
Among EU-PEARL’s consortium partners are some of the world’s foremost experts in the design and statistical methodologies of adaptive platform trials. These experts were consulted by the World Health Organisation during the design phase of the Solidarity trial, a study to test multiple COVID-19 treatment, diagnostic and prevention options, including vaccines. The consortium members were asked to provide input on how best to make it a success.
What it is: more flexible, and more attractive for participants
The Solidarity trial is testing multiple compounds from multiple sources in an adaptive design. That means that different candidate compounds, belonging to different pharma companies, are being trialled simultaneously. The companies are ‘sharing’ the standard of care groups (a group that is treated with the same drugs they would receive for their condition were they being treated outside of a clinical trial) and operating under a master protocol.
New treatment groups can be added at any time, where necessary, and candidate compounds that don’t work can be dropped. This makes it more beneficial for participants. In the WHO Solidarity trial’s treatment component, for example, the lopinavir/ritonavir and hydroxychloroquine arms have already been dropped, while others have been added.
Though the concept has existed for years, there is still lack of uniformity and understanding as to what an adaptive platform means and how it works in practice. “The process of designing and running these trials is incredibly complex,” says Ann Van Dessel, Senior vice president and Head of global clinical and regulatory operations at Johnson & Johnson, and EU-PEARL project lead. “To support researchers who decide to take on the task, we are putting in place the tools that are necessary to make sure they succeed. The project will set up a new entity whose job it will be to help facilitate these very complex new studies, and to maintain the tools and guidelines developed during the project.”
Professor Joan Genescà, Chief of the Liver unit at Vall d’Hebron University Hospital and EU-PEARL’s project coordinator emphasises the scale of the collaboration of the project: ”Academic leaders, leading scientists, methodologists, regulators, patients and their representatives, among many other stakeholders, are all collaborating in a public-private endeavour. They are the core of the EU-PEARL project, which shares many similarities to what and how the WHO Solidarity trial is trying to accomplish,” he says.
Reducing the heavy burden on participants
“There have been some studies done in the past where multiple drugs from multiple companies have been tested against each other in an adaptive way,” says Ms Van Dessel. “We want to promote this and facilitate it, but we also want to put the patient at the centre because patient recruitment and retention in clinical trials is always a challenge. The burden on a patient in participating in a clinical trial is rather high.”
“The beauty of adaptive trials is that when you share the control group, the likelihood that the patient ends up in the placebo group is lower,” says Ms Van Dessel. Prof Genescà adds, “Another major and complementary advantage of adaptive designs to participants is that those arms doing better have more patients allocated and therefore the chances of a particular patient receiving an effective drug increase.”
The COVID-19 pandemic has been a case study
Explains Ms Van Dessel, “Pharma companies have traditionally been hesitant to conduct this kind of trial for multiple reasons. It’s difficult to get people to move away from the ‘gold standard’ of randomised trial design. But because of the severity of the COVID pandemic, the pharmaceutical companies and the regulatory authorities are collaborating, along with more than 400 hospitals in 35 countries, demonstrating to the sceptics that it is possible.” The experts group includes academics, regulators and WHO representatives.
According to Prof Genescà, “Although remarkable examples of platform trials during the COVID-19 pandemic are a good proof of concept, there are also many opportunities missed. Only a handful of the almost 4,000 trials on COVID-19 registered to date are following an adaptive, platform approach, therefore showing this is still a work in progress, and that is why the remit of EU-PEARL is so relevant.”
Ms Van Dessel adds, “In a way, Solidarity trial is a perfect case study, because it demonstrates that it can be done. At the end of our project, when all of the tools are available and the negotiations with health authorities are done and the resources for patients have been made available, we will be ready for the next crisis, and it might even go faster because it will be less ‘out of the norm’.”