In the 1940s, the Royal Brompton Hospital was a cosy place. Photos from that time show rows of beds squeezed together with almost military discipline, their simple metal frames just a few feet apart. Nurses in plain white hats and skirts peered over their charges, and privacy is minimal. When Austin Bradford Hill came here in 1946 to conduct one of the first randomised clinical trials in history, he found himself nose to nose with his patients too. Hill wanted to test the efficacy of streptomycin on pulmonary tuberculosis, so proceeded the only way medical science knew back then: with x-rays, weight checks and sputum samples. This was science done intimately, the clinicians and their subjects spending long periods cooped up together.
Subsequent trials have been just as intimate. And how could they not be? With only rudimentary monitoring technology at their disposal, researchers have always had to get up close and personal to their patients. If nothing else, this is reflected by the statistics. As recently as 2020, work by Florence Healthcare found that nearly 80% of trial monitoring was conducted in person.
Yet, if this closeness has long been central to the success of clinical trials – and shaped their supply chains along the way – there are obvious downsides too. Forcing patients to come in for tests is hardly a good way of keeping them involved and hardly immaterial when up to 40% drop out before the trial ends. As with so much else, however, the pandemic appears to be sparking a revolution in how trials are conducted. Spurred on by new monitoring platforms, clinicians are increasingly experimenting with remote trials, delivering medicines to subjects in their homes, then monitoring their effects via sensors and computers. Not that the direct-to-patient model is necessarily easy to implement. Especially when it comes to the vexed question of supply chains, clinicians have plenty to do before remote trials can become the norm, forced as they are to organise hundreds or thousands of deliveries direct to private homes. Get it right, though, and pharmaceutical development could be changed forever.
In-person problems
In theory, direct-to-patient clinical trials have been around for years. As long ago as 2015, the FDA solicited feedback on using telehealth technology to improve trials. Yet, as Gaurav Agrawal explains, remote trials have traditionally struggled in practice. That begins, says the life sciences partner at McKinsey, with technology. To put it bluntly, sensors and monitoring devices just haven’t been sophisticated enough to be deployed in remote settings. Just take blood draws: until recently, they could only be done in hospitals and clinics. Órlaith Burke, the ‘data in health’ innovation portfolio lead at Accenture, makes a similar argument. “Traditionally, it has made sense to concentrate trials at investigator sites where experts can congregate to conduct the complex care and trial processes,” she says. “This has traditionally provided process, resource, and funding efficiencies for investigators.”
That’s shadowed by more practical considerations too, especially when it comes to supply chains. For years, the logistics network simply wasn’t robust enough to cope with a decentralised supply chain – something reflected in the fact that only small corners of the US and Europe have historically embraced them. Yet, with recruitment problems persisting, trial organisers are having to adapt. According to one 2019 survey, after all, 14,000 oncology trials were actively recruiting, even as they were able to secure just 5% of the subjects they needed. These recruitment struggles aren’t hard to understand; trekking to an in-person trial location is tiring, especially if someone is already sick, and it’s not like clinics are always nearby. In the US, 70% of potential participants live over two hours away from a trial site. To put it another way, hard-nosed questions around recruitment are fundamentally changing attitudes towards clinical trials. Rather than seeing trials purely in terms of costs and output, the phrase of the moment is ‘patient centricity’ – an attempt to cater trials to subjects themselves, ideally in the comfort of their own homes. Clearly, this is ethically desirable in principle. But what really makes it feasible in the real world is a proliferation of new technology, both in terms of data capture and logistics. “Advances in technology are one key enabler of this trend and include mobile technologies like smartphones, tablets, wearable devices, or web-enabled patient diaries,” says Agrawal. “Additionally, the establishment of electronic health records and advances in data management allows more seamless capture, processing and validation of data.”
“The pandemic has been the ultimate disrupter for all industries globally in the past century. We see so many innovations gaining momentum and increasing in popularity due to necessity. Direct-to-patient trials was a model used across the life sciences industry to keep numerous trials on their trajectory throughout the pandemic.”
Órlaith Burke, Accenture
Direct access
Over the past 18 months, from the workplace to the clinic, the realm of the possible has been pushed to its limits. That is just as true when it comes to clinical trials. If rapid developments in the field, from patient centricity to better technology, have revolutionised the process in theory, both Agrawal and Burke agree that Covid-19 has finally brought direct-to-patient trials centre stage. As Burke puts it: “The pandemic has been the ultimate disrupter for all industries globally in the past century. We see so many innovations gaining momentum and increasing in popularity due to necessity. Direct-to-patient trials was a model used across the life sciences industry to keep numerous trials on their trajectory throughout the pandemic.”
What does all this actually mean for patients themselves? For one thing, they no longer need to slog to trial centres for check-ups. For another, clinicians can use all those patient diaries and wearable devices to understand a drug’s effects remotely. More to the point, these innovations offer a number of practical benefits, from quicker results to cheaper medication. Decentralisation also makes it easier to recruit for trials. Yet, it’d be wrong to suggest that clinicians can click their fingers and expect direct-to-patient trials to simply happen. On the contrary, moving trials outside medical settings requires sophistication and nuance, especially when it comes to supply chains. While older models only need drugs to reach specific clinics, decentralised systems require them to land on the doormats of perhaps thousands of individual subjects – on time and without damage.
To be fair, there are signs that pharmaceutical companies are taking these challenges seriously. At World Courier, a global leader in medical supply chains, staff liaise closely with delivery companies to ensure shipments arrive promptly, using sophisticated GPS tracking to keep an eye on trucks. At Lash Group, another major player, clinicians frequently go to the homes of participants, preparing treatments and teaching them to administer injections properly. As so often in the world of supply chains, technology is proving remarkably useful here, and not just when it comes to established wizardry like GPS. Companies like GSK, for example, are using blockchain to ensure drugs get from the factory to the patient transparently. Roche, for its part, has experimented with big data to understand the optimum temperatures of different drugs, ensuring they reach their destination before they become unusable.
Beyond this physical chain, Agrawal highlights the importance of keeping virtual supply chains secure. Arming subjects with data watches is a good start, but ultimately means little if the information they send clinicians is inaccurate or incomplete. Burke makes a similar point. Accurate data is the ‘foundation’ of any successful trial, she says, and unreliable data risks corrupting the results. Yet here too, there are reasons for optimism. As direct-to-patient trials become more popular – one recent survey found 73% of respondents said they increased their use of decentralised trials during the pandemic – Agrawal expects data analysis to improve. “Broader adoption,” he suggests, “will increase efficiency for investigators and sponsors due to better digitalisation and data management.” There are signs this is happening already: heart monitors, for instance, can now offer accurate readings 24/7.
Remote control
Where does that leave direct-to-patient supply chains – and decentralised trials more generally? Agrawal, for his part, is sanguine. He argues decentralised – or at least hybrid – trials will become “more standard” as patient expectations shift towards staying at home. Burke agrees. “Advances in technologies have opened the door to broader applications of direct-to-patient trial designs,” she suggests, adding that telecommunications in particular have dramatically improved since the first lockdown. This is echoed by developments in how supply chains are managed. Among other things, pharmaceutical companies are promoting collaboration in their workflows, with companies battling hard to integrate people, technology and data into a single package.
Even so, both experts warn that difficulties remain. With all this data floating about – all from different sources – data protection is more challenging than ever. That inevitably raises regulatory questions too, not least given how quickly remote technology is advancing. Then there’s the issue of orchestrating a complex direct-to-patient supply chain across borders. “Trials conducted in more than one country are subject to additional cross-border data standards, as well as localisation and retention rules,” says Agrawal. “Therefore, it is essential for creators of a global trial to use a tailored approach, design an optimal country footprint at the outset, and account for complexities in trial-design planning.” These are all fair concerns. Yet, given how far clinical trials have come from the days of Austin Bradford Hill, there’s surely cause for optimism.
Decentralised trial elements
While most clinical trials are not likely to be entirely virtual, they will use one or more decentralisation elements based on suitability for their end points, patient populations, and treatments. Many such elements have been widely piloted, with 48–95% of sponsors reporting use in at least one phase 3 trial. A significant increase in uptake is expected because of experience gained during the Covid-19 pandemic.
Before the pandemic, an Industry Standard Research survey in December 2019 found that 38% of pharma and contract-research organisations (CROs) expected virtual trials to be a major component of their portfolios, and 48% expected to run a trial with most activities conducted in participants’ homes. When asked the same questions a year later at McKinsey’s Clinical Operations Roundtable, the responses were 100% and 89%, respectively.
Source: McKinsey & Company
