Lessons in logistics

Three years after the first vaccines were approved, Covid-19 is increasingly seen as the defining clinical moment of our century. Forcing conveners to dramatically shift how trials occurred – expediting testing with the help of regulators – it feels reasonable to agree with one senior clinician at Rutgers University that the pandemic “challenged the traditional approach” to how clinical research was done. The same is true, we’re often told, of where trials took place. In a world of lockdowns and social distancing, conducting central hubs risked doing more harm than good, with researchers instead opting for a decentralised trial model to provide investigational medicinal products (IMPs) directly to participants.

It would be foolish to suggest that the pandemic and its consequences had no impact on the rise of decentralised clinical trials (DCTs). Just consider the statistics: according to work by Veeva Systems, the implementation of decentralised clinical studies skyrocketed by 59% compared to the pre-Covid age. Yet talk to the experts and it soon becomes apparent that decentralisation ultimately represents far more than merely a response to the exigencies of the pandemic. “While there was already a move towards DCTs before 2020,” says Tero Laulajainen, head of global clinical science and operations at Belgian pharma giant UCB, “the Covid-19 pandemic accelerated the adoption of remote approaches.”

Its a fair point: higher patient diversity and lower costs are just two of the benefits of embracing a decentralised style. Yet if DCTs offer organisers and patients plenty of advantages, the years since the pandemic haven’t been entirely happy. Especially around the knotted question of supply chain management, but also around keeping patient data organised, the clinical trial sector is still battling to fully decentralise. But with the rapid spread of new technology, as well as the parallel sharpening of industry partnerships, genuine success looks closer than ever.

A growing trend

Laulajainen is quite right to note the pre-pandemic march towards DCTs. Even before anyone had heard of Covid-19, after all, 28% of sponsors and contract research organisations were already integrating digitalisation into their trials. Nor is this trend particularly hard to understand – if nothing else from a financial perspective. As recent work by the Tufts Center for the Study of Drug Development uncovered, decentralised phase 3 trials can be completed significantly faster than their on-site counterparts, a situation that could ultimately lead to net benefits 14 times greater than the initial investment. That’s shadowed by other cost-saving opportunities. Decentralised trials require fewer expensive review boards, for example, even as protocol changes can be prodded through without fuss.

But for Kevin Ketels, assistant professor of teaching in global supply chain management at Wayne State University in Michigan, to focus entirely on the bottom line is to miss the point. “Because decentralised trials are more convenient,” explains Ketels, who spent nine years as CEO of clinical research site management organisation KMED Inventory before taking on his academic role. “You could potentially increase the number of research subjects.” This intuitively makes sense. Allowing patients to test new drugs from the comfort of their own homes, trial organisers are more likely to secure a range of subjects from different backgrounds, potentially bolstering results – nothing to sniff at when only 5% of eligible patients currently sign up for clinical research.

Examine the sector for long, however, and it becomes obvious that for every benefit, DCTs can also pose a number of difficulties. “There are several challenges with the DCTs inherent to the supply chain,” emphasises Antonio Tramontano, a life science supply chain specialist at Genpact – a global IT firm that supports clinical trials. For one thing, Tramontano says that getting drugs to hundreds or thousands of individual locations can be hard, especially when some drugs need to be stored in temperature-controlled conditions until they reach their destinations.

At the same time, Tramontano notes that the virtual supply chain is severely impacted by decentralisation. True enough: if hub-based trials meant patient data could be collated from a single building, securing quality information from countless smart watches or online video sessions can be a muddle. More to the point, the consequences of getting any of this wrong can be fatal to a trial’s progress. In 2021, a number of Stanford researchers admitted terminating a trial into virtual cardiac rehabilitation after suffering technological snafus, including the inability to get the relevant data-collection app to work on subjects’ smartphones. Naturally, failures like this risk undercutting whatever financial benefits digital trials offer in theory, even as Laulajainen warns that patient outcomes risk being hampered too.

Tracking changes

In a sense, failures like the Stanford trial are unsurprising. Only fully entering the mainstream in the wake of Covid, it was always going to take time for trial conveners to get to grips with DCTs in all their complexity. Yet listen to industry insiders and it’s equally apparent that the years since lockdown have seen a number of improvements; for Laulajainen, one of the biggest is technology. “Technology,” he says, “can play a significant role in enhancing the supply chain process. Logistics trackers and temperature trackers have been widely used for some time. However, emerging technologies such as artificial intelligence or tokenisation could revolutionise supply chain

management by improving transparency, traceability and real-time monitoring of shipments.”

Certainly, such enthusiasm is shadowed by the statistics. Helping researchers understand clinical results from a range of physical sources, the global market for AI in clinical trials is expected to reach $4.8bn by 2027. Technology can have an equally significant role in ensuring drugs reach far-flung trial centres to order. In Genpact’s case, Tramontano and his colleagues ensure shipments are logged digitally. In the case of deviations during and after the delivery, he says that damaged goods can be returned and replaced promptly. In a similar vein, the Genpact executive says that external partnerships with logistics firms are vital too, explaining how lacing the same data and processes from one end of the supply chain to the other can help avoid mistakes. Ketels agrees, noting that the technology trackers used to follow medical shipments have become “much more sophisticated” over recent years.

Regulators, for their part, are doing their best to make things as straightforward for investigators as possible. “While organisations build up experience of running decentralised trials, we encourage them to approach the MHRA for regulatory advice, especially where supply chains or the dispensing process are likely to be complicated,” a spokesperson from the British regulator says, an openness that is echoed on the other side of the Atlantic aswell. Piggybacking on the industrywide gusto for technology, meanwhile, the MHRA is also using data to make other parts of the DCT process simpler. Liaising with academics from the University of Birmingham, for instance, the MHRA’s Clinical Practice Research Datalink service uses NHS data to track the health outcomes of patients with irregular heartbeats.

$4.8bn
The forecasted global market value for eClinical trial solutions (including AI) in 2027
ASDReports

Decentralised ascent

In short, it seems clear that if post-Covid DCTs got off to a wobbly start, the future looks increasingly positive. Not that anyone would say the sector is there quite yet. For Tramontano, one continuing issue involves the lack of international cooperation, stressing that a “common roadmap” for large multinational DCTs has yet to emerge. This is doubtless causing problems in practice; in March the South Korean government totally blocked decentralised trials in their country. In a broader sense, meanwhile, Tramontano suggests that, present cooperation notwithstanding, the industry must still do more. “A broad expansion of DCTs,” he says, “will require a ‘tipping point’ of collaboration and coordination among all the stakeholders, including patients, in order to model the multi-party commitments that a full-scale implementation will take.”

To be fair, the industry is battling to overcome these hurdles too. As always in these situations, specialised vendors seem eager to fill the breach, offering specialised tracking technologies to ensure decentralised medications reach homes and clinics alike. “As technology continues to evolve,” says Laulajainen, “we must leverage emerging tools and platforms to enhance our supply chain capabilities. This includes utilising advanced data analytics and leveraging AI and machine learning.” There are certainly exciting developments on the horizon here. At Merck, for example, managers are starting to use machine learning to understand where in the DCT supply chain drug shortages might occur. UCB, for its part, is going down a similar path, unveiling non-intrusive sensors that can measure a patient’s vital signs without them needing to ever disrupt their daily schedule. There are doubtless improvements to be made, but decentralised trials continue to transform how drugs are tested and approved.