LONDON – In a potent demonstration of how COVID-19 is transforming the U.K. clinical trial landscape, 47,000 patients have been recruited to studies investigating potential treatments for the infection in a little over two months.
Every hospital in the country treating COVID-19 patients is taking part.
“Bureaucracy has been steamrollered down,” said Angela McFarlane, market development director at the contract research organization Iqvia UK.
That raises a controversial question: “Could adversity be a catalyst for U.K. clinical research transformation?” McFarlane said.
Iqvia is running the phase II Accord trial that is testing drugs in development and repurposed products. The first patient joined the study last week. “Our ambition is that within three weeks we will have 12 compounds in Accord,” said McFarlane.
As soon as there are results, compounds will move to the phase III Recovery trial, which has now recruited 8,937 patients at 173 sites.
In other studies to have seen accelerated approval, the U.K. arm of Gilead Sciences Inc.’s remdesivir trial recruited the full 147 patients in 12 days; in the 330-patient global trial assessing the use of Roche Holding AG’s rheumatoid arthritis drug, Actemra (tocilizumab), in patients re-randomized after failing on another therapy, the U.K recruited its 36-patient total in 12 days.
Meanwhile, from making the first approach to conduct the study in March, the 100-patient trial of Synairgen plc’s inhaled formulation of interferon-beta commenced dosing at the start of April and has recruited 75 people to date. The company subsequently received approval to extend the trial to patients at home, with the objective of initiating dosing earlier in the infection cycle.
In life before COVID-19, a lack of coordination meant study start up in the U.K. was 42% slower than in the U.S., McFarlane said. “How do we take this learning forward and get to a new normal? If we don’t, we should be ashamed of ourselves,” she told attendees of a Bioindustry Association (BIA) webinar examining the effect of COVID-19 on commercial clinical research in the U.K.
The sea change came about as a result of an edict from the government’s chief medical officer (CMO), Chris Whitty, to prioritize COVID-19 research. But it also builds on work done over recent years to make the U.K. a more attractive location for clinical research, said Divya Chadha Manek, head of business development at the National Institute of Health Research (NIHR) clinical research network.
“We have a single system, including the funding element, to ensure we have got a complete picture of urgent public health research,” Manek said.
NIHR is appealing to companies to submit COVID-19-related projects. More than 700 have been received and are being assessed by an urgent public health review panel. “It looks at the scientific rationale, capacity to do the study and competition with other studies,” said Manek.
Selected studies are referred to the CMO and, once approved, expedited to the clinic. To date, 32 trials have been approved through that route.
Accelerated recruitment is not just a factor of the high number of patients. All parties from regulators to ethics committees are taking a pragmatic approach, said Manek. This experience should not be wasted post COVID-19. “We’re in wartime, but lessons must be learned,” she said.
Other trials are delayed
But while COVID-19 studies are racing ahead, the industry has taken a significant hit on trials in every therapeutic area that were up and running before the pandemic took hold.
Data from clinical trials data specialist Medidata, show that globally there was a 75% decrease in the average number of new patients entering trials per study site in the first two weeks of April, compared to the same two week last year. “There was also a 65% decrease in March,” said Fiona Maini, global program director at Medidata.
That indicates the damage to patient enrollment in most countries continues to grow, with only China, South Korea and Italy seeing a decrease in the impact.
There has been a 17% decrease in the number of visits per subject per study between October 2019 and March 2020. In response to the difficulties of patients going to hospitals for assessments, regulators including the FDA and the EMA have updated their guidance. There has been a sudden increase in the use of technology for remote monitoring, study drugs are being posted or couriered to patients’ homes and regulatory agencies are taking a flexible view in order to mitigate impacts where possible.
“It’s absolutely astonishing – only [in March] WHO declared a pandemic and we have all these updates from the regulators,” Maini said. “There is great alignment and collaboration between regulators.”
Across the U.K., 2,700 projects have been halted and thousands of staff transferred over to carry out COVID-19 research, or onto the medical front line. Of commercial research studies, Manek said only 57% are continuing as planned. Of those on hold, she said, “It is really important to keep on top of this because at some point the pause button has to be lifted. NIHR is thinking about how to do this.”
NIHR also is considering if it can apply the accelerated COVID-19 approval process for non-COVID trials in the future. “It’s a big question,” said Manek. “We’ve got a task force looking at it.”
For Steve Bates, chief executive of BIA, the world has already changed. “I don’t think we will be going back. Some of the pressure points in the dam have now gone. We’ve got to show in this period of time why it’s better.”
The experience of COVID-19 shows the industry can link together with the U.K.’s integrated health care system. “COVID-19 is terrible, but in research terms some really exciting innovation is happening here,” said Bates.