Through the spring of 2020, it became evident that the Covid-19 pandemic would have a dual impact on the clinical research sector. For commercial organisations with the resources and flexibility required to quickly shift research, the pandemic provided an opportunity to lead in new and potentially lucrative markets for vaccines, treatments and diagnostic testing. But for other disease areas, Covid-19 was a major disruptive force, halting trials in their tracks and exacerbating existing fragilities within the sector.
This dynamic of feast and famine was perhaps most evident in UK clinical trials. The country’s clinical research sector has been heralded for its quick response to the pandemic, which has led to the development of the Oxford/AstraZeneca vaccine and the establishment of the NHS’s RECOVERY platform trial, but it has also seen one of the largest reductions in non-Covid-19 trial activity.
When Covid-19 first hit in the second quarter of 2020, the UK initiated 55% fewer commercial clinical trials than in Q2 of 2019, according to analysis of data from GlobalData. And while commercial trial activity has since recovered to pre-pandemic levels in Australia and the USA, the UK remains behind, commencing 18% fewer commercial trials during the first three quarters of 2021 than over the same period in 2019.
Slow recovery in trials activity has prompted the UK’s Association of the British Pharmaceutical Industry (ABPI) to call for the “revitalisation” of the clinical research sector. The group’s recent annual report focusing on clinical research argues that the UK needs to apply lessons from the successes of its own Covid-19 research more broadly, and learn from other countries that weathered the pandemic with greater ease.
According to ABPI head of research policy Dr Jennifer Harris, the pandemic added pressure to areas of the research process that were already fragile.
“The one thing we were talking about pre-pandemic that was then amplified by Covid-19 was NHS resourcing and capacity to deliver research,” Harris says. “Prior to the pandemic we consistently mentioned that research needs to be more deeply embedded in the NHS, we needed protected time for research, we needed research to be a part of everybody’s day jobs rather than a separate thing.”
Harris says that since clinical research was not a central focus within the NHS, once the pandemic placed strain on the health services, non-Covid-19 research had “fallen to the wayside.”
“Because clinical research in interventional studies is conducted within secondary care settings and needs to have access to the same clinical facilities as frontline care, that means that if you’ve got a complete shift of resources towards Covid-19 and clearing waiting lists, it then means that it’s difficult to get clinical research onto people’s agendas,” Harris says.
The UK had been slipping down global rankings of clinical trial activity prior to the pandemic. The country has traditionally been regarded as a world leader on cancer research and during the first half of the decade, one in every seven oncology trials included participation within the UK. But by 2019, that figure had fallen to just one in 12.
The UK also saw a precipitous decline across Phase I trials before Covid-19, with this stage’s share of commercial trials falling from 8.4% in 2016 to 3.6% in 2019. In both cases, China’s dramatic growth in trial activity explains some of the UK’s reduced share but the country also compares unfavourably to other high-income economies. Australia and Spain, for example, have doubled their rate of new Phase I commercial trials since 2010, whereas the UK initiated the same number of new trials in 2020 as ten years earlier.
Some countries have benefitted from a lower prevalence of Covid-19 – Australia, for example, did not see the closure of trial sites during the early stages of the pandemic as it pursued a zero-Covid strategy. But many countries that, like the UK, experienced prolonged lockdowns and pressure on health services saw strong recoveries. The ABPI’s report highlights Spain, arguing that the Spanish Government’s commitment to investment in research and development in future years and the streamlining of approvals and site set-up processes had made the country a destination of choice for clinical research.
There are signs that the UK could follow in Spain’s footsteps. In March, the government stated that more deeply embedding clinical research within the NHS was a key theme in its vision for the future of the sector, and the Health and Care Bill, currently making its way through parliament, could prove a timely legislative lever for making the goal a reality. In addition, at the Autumn Budget Chancellor Rishi Sunak announced a commitment to £5bn in health-related research and development spending by 2024/25.
Meanwhile, Harris believes the successes of the UK’s Covid-19 research following the MHRA’s pragmatic approach to the regulation of Covid-19 research and the Urgent Public Health badging process for prioritising studies have demonstrated the potential impact of reforming procedures for non-Covid-19 trials.
“During the pandemic we’ve showcased what we can do when we work together more closely and are more pragmatic and we now have a UK-wide vision for clinical research,” she says. “If we continue to work collaboratively with the Department of Health on that vision I see us being able to drive forward these new ways of working in other disease areas. But a caveat to that is if the NHS cannot recover then we’re going to be stuck in this rut of an NHS that can’t do much research for years to come.”
Harris says streamlining regulatory processes would not only make the UK a more attractive destination for clinical research, it would also allow the UK to improve enrolment levels – an area in which it currently lags behind other countries.
“One of the things we’ve seen in other countries is that they have incredibly streamlined processes for getting regulatory ethics approval through to a site being ready for the first patient visit,” Harris said. “At the moment we’ve got quite protracted timelines for that whole process, which for a multi-country international global study, if you’re spending so much of your window on setup then you don’t have much time for recruitment.”
The UK’s average enrolment levels were already comparatively low before the pandemic and while Covid-19 had only a slight impact on enrolment in Australia, China and the US, enrolment in the UK fell further. Since the pandemic began, the UK’s average participants in Phase I trials has been less than half of both the US and China’s.
As a result, UK trials are more likely to fall far short of their target enrolment levels. Since 2018, the UK has had the highest share of trials fail to reach 50% of target enrolment out of all the major clinical research markets. In the UK, low participation has been a particular challenge for Phase II and III trials, with 13.7% of these trials recruiting fewer than half of their target enrolment levels.
Harris believes the UK’s Covid-19 trials demonstrated another opportunity to boost enrolment. During the pandemic, sophisticated data tracking, combined with a proactive approach within the NHS combined to allow for more effective identification of “the right patient at the right time to get involved in the right trial”.
“I think the attitude in the NHS was, ‘we need to do this because it’s really important,’ and that led to an approach where a lot of sites basically spoke to every single Covid patient that came in and asked about research participation,” Harris says. “We do not have that for other disease areas, so opening up that dialogue with patients and asking ‘do you want to get involved?’ is really valuable.”