Trial and error16 August 2022
Covid-19 transformed clinical trials practically overnight, with remote testing and quicker approvals suddenly becoming a reality the world over. These shifts aren’t hard to understand. Eager to defeat the pandemic as quickly as possible, researchers were happy to embrace change for financial and efficiency reasons. But with the pandemic finally passing into history, can we expect the revolutions of 2020 to transform clinical trials over the long term? Andrea Valentino talks to Professor Kenneth Getz, at the Tufts Center for the Study of Drug Development, to learn more.
Over the past few years, the pandemic has swept aside old ways of living – from how we work to how we see our friends. But change is not always a bad thing, and one silver lining has been the arrival of innovative new ways to work. Nowhere has this been more evident than in the sphere of clinical trials. Consider research timelines. Before Covid, trials typically took six months to implement and a year to recruit participants. Twelve months into the pandemic and those numbers were slashed in half. The same story can be told for drug approval. Less than a year after Covid was sequenced, EU and US regulators gave emergency approval to a trio of vaccines. To put that into perspective, it typically took around a decade for new medications to be greenlit pre-pandemic.
Nor, of course, are these shifts particularly hard to appreciate. With borders closed and economies tanking, it was imperative for researchers to understand the virus they were up against and hone vaccines to protect against it. And as those references to border closures imply, there were other pressures too. How could traditional clinical trials survive, for instance, when lockdowns stopped patients from physically visiting test sites? And with millions of new cases announced each day, how could researchers rely on official data alone? Beyond timelines, in other words, the profession has been forced to grapple with a plethora of new trial techniques – with vast consequences for doctors and patients alike.
Together with schemes like Operation Warp Speed, CEPI has invested this amount into Covid research.
Now that the pandemic seems to be receding, an even more interesting question will soon need to be broached: can these changes last? Though they started as knee-jerk reactions to a terrifying virus, after all, it’s quickly becoming apparent that greater speed and flexibility can be a boon to trials big and small. Not that totally abandoning traditions built up over decades is easy – or even possible. From regulatory challenges to worries around training staff, clinical trial insiders have plenty to do before the shifts wrought by Covid-19 can be made permanent. Succeed, however, and their field could be transformed forever.
If you want to understand how drastically clinical trials were changed by Covid-19, you could do worse than ask Professor Kenneth Getz. Executive director at the Tufts Center for the Study of Drug Development, Getz has worked in the clinical trials space for more than two decades. And as he emphasises, there is now a vast gulf between the pre- and post-Covid worlds. “The pandemic,” he explains, “has been the ultimate or ‘Grand Pilot Study’ demonstrating how multiple factors, well-mobilised, integrated and coordinated, can deliver remarkable innovation, speed and quality.”
Examine the dream-like story of the pandemic, and where exactly this occurred becomes obvious. Lockdowns and travel bans, for instance, prodded developments in home visits and wearable devices, with isolated patients monitored by researchers across the country. Technology also promoted a new appreciation of data sharing. With tools like Zoom and MS Teams making collaboration simpler than ever, Covid’s genome sequence was shared far and wide, while patient data was rapidly exploited too. In the US, for example, the National Covid Cohort Collaborative (N3C) began to systematically collect records on Covid patients. All this was echoed by new enthusiasm for experts. As politicians scrambled to limit the impact of Covid, bodies like the Coalition for Epidemic Preparedness Innovations (CEPI), founded in 2016, suddenly found new backers in governments the world over.
As these references to MS Teams and CEPI imply, it’d be wrong to suggest that this new reality was born overnight. On the contrary, Getz says “familiarity with nearly all of these factors” had “already been established” – with the pandemic merely acting as a starting gun on implementation. Whatever the cause, it is clear that Covid drastically changed the state of play. At N3C, for instance, researchers have already collated 6.3 million patient records from over 50 institutions. Together with schemes like Operation Warp Speed, CEPI has pumped $20bn into Covid research. With that kind of cash floating about, it is also unsurprising that research times have tumbled – by up to 70% according to one study.
That is shadowed by dramatic shifts in how clinical trials were actually run day-to-day. In 2020, 76% of clinical trial sponsors said they conducted most or all of their research monitoring remotely, up from just 18% in 2019. That obviously impacted patients themselves. Rather than physically travelling into clinics, many self-administered drugs from the comfort of their sofas. Naturally, this also meant patients and doctors had to become comfortable with new technology, for instance when it came to heart-rate monitors or smartphone applications. As Getz adds, that further involved close contact between trial organisers and external partners, notably contract service providers and investigative sites.
Brave new world?
For much of the Western world, the Covid crisis is finally spluttering to a halt. But the changes wrought by the pandemic are far from over. Though travel bans have mostly been consigned to history, to give one example, 91% of trial organisers expect to exploit the power of remote monitoring by the end of 2022. And as Getz notes, this is hardly surprising if you appreciate how much more efficient Covid-era trials could be. “This Grand Pilot has demonstrated that drug development conditions that have long plagued the pharmaceutical industry – high levels of inefficiency, long durations, suboptimal relationships with regulators, low success rates – can be eradicated when critical success factors are simultaneously well-coordinated and executed.”
Certainly, Getz’s point is amply reflected by the statistics. Beyond the remarkable speed of remote trials, after all, one 2019 study also found that dispensing with on-site monitoring can cut overall trial costs by 30%. Even better, no longer forcing patients to trek to trial sites can improve retention rates. Yet if the advantages of Covid-era trials are clearly understood – Pfizer and Merck are just two of the industry giants to investigate their potential even as the immediate crisis has eased – it would be wrong to assume that the industry can simply continue as it did in 2020. “It is too early to predict which approaches will become permanent,” warns Getz, adding that though the clinical community is obviously proud of its achievements, recreating the cocktail of conditions that sparked his ‘Grand Pilot Study’ is far from simple.
If nothing else, this hesitancy can be understood in terms of regulation. Put it like this: if the FDA was understandably happy to loosen the rules in the midst of a terrifying global pandemic, might it not return to a more cautious stance now that many Americans are vaccinated? The same could be said of data sharing. While the pandemic encouraged researchers to share what they knew for the good of humanity, are less serious threats likely to elicit the same goodwill? This is not an idle question: given the clinical trials sector is already worth $47bn, there’s plenty of money to be made by staying cynical. If getting patients to grips with remote medical equipment is one challenge, Getz highlights that training data scientists, able to parse mountains of sophisticated new information, is quite another. “Attracting, developing and retaining talent,” he says, “is considered one of the most important areas at this time – and one of the most challenging.”
Keeping at it
All the same, Getz seems optimistic about the future of clinical trials. When it comes to staffing, for instance, he notes that their increasingly remote nature means that “talent can be accessed and engaged anywhere”. At the same time, there is evidence that pharma companies are working hard to hire. GSK, for example, now makes a special effort to promote women in tech. Roche, for its part, showcases real world data scientists on its website. That is reflected by a warmer regulatory climate. The relaxed approach taken during the pandemic may have been gone forever, but bodies like the FDA are arguably becoming more accommodating – while ethical review committees are becoming more laid back too. Among other things, that could mean improving communication between researchers and reviewers, ensuring that new academic papers are published faster.
Dispensing with on-site monitoring can cut overall trial costs by this amount.
No wonder, then, that Getz expects to see clinical trials ultimately retain many of the accoutrements they gained during Covid-19 – in the more distant future anyway. “In the short-term,” he says, “many will add cost and time as pharma companies and their collaborators must learn how to juggle and adopt multiple approaches simultaneously. In the longer-term, we anticipate cost-efficiency and time savings. We also expect to see improvements in access to clinical trials among underserved patient communities.” A lot to be hopeful about, then, even as our bewildering experience with Covid gradually fades into memory.