Chain of command

Clinical trials have been an established part of medical life for 1,000 years. As long ago as the 11th century, after all, Chinese physicians carefully evaluated the efficacy of Shangdang ginseng, testing whether it helped patients run faster (it did). In the 18th century, Dr Caleb Parry investigated whether expensive Turkish rhubarb was a better laxative than its cheaper English counterpart (it wasn’t). And by the 1940s, Sir Austin Bradford Hill, an English epidemiologist and statistician, was pioneering randomised controlled trials across several London hospitals.

All the same, it’s hard to confuse modern tests with their antique cousins. That’s primarily thanks to their scale. While Parry and Sir Austin’s samples numbered in the dozens, most contemporary trials typically test between several hundred and 3,000 people. The latest vaccine trials are larger still. It goes without saying that getting regular drug deliveries to that many people, sometimes for years at a time, isn’t easy. No wonder, too, that the clinical trial supply chain industry has become such a huge business. According to one estimate, it’s a market that was worth $10.9bn in 2019 and one that’s expected to enjoy a CAGR of 6.6% until the middle of this decade.

And if anything, it’s a field that has only increased in value over the past 18 months. With governments and pharmaceutical companies scrambling to secure a vaccine for Covid-19, they’ve had to rely on supply chains more than ever. Nor has it been simple. From instituting at-home trials to keeping drugs secure at scale, the pandemic has stretched traditional supply chains to their limits. Yet the pandemic and its consequences also offer opportunities. With agility as their watchword, some of the industry’s biggest players have used the recent upheavals to sharpen flexibility and customer choice – with benefits up and down the supply chain.

Trial by fire

In certain ways, the demands of clinical trials differ little from the pharmaceutical industry more broadly. As Javier Garcia Vela, a transport and logistic services team lead at Roche, explains, practically all his company’s work requires close collaboration with suppliers and hospitals, doctors and patients. Yet in some important ways, continues Vela, the struggles around supply chains for clinical trials are even tougher. One problem is managing the cold chain for trial drugs without much data.

“I think one of the biggest challenges in the clinical trial supply chain,” explains Vela, “is the temperature monitoring and maintaining the temperature ranges for a delivery of products, which usually don’t have stability data available to stand for excursions, even if they are small.” Another difficulty particular to trial supply chains is patient anonymity. As Vela puts it, it can be a “big challenge” to keep the data of thousands of trial patients organised and secure. That’s doubly true given data security is now such a mantra across industry and serious fines for data breaches aren’t unheard of.

These are undoubtedly questions that have vexed trial experts for years. But you get the sense that they’ve also been exacerbated by the scale of the pandemic and people’s response to it. Consider the statistics. Since April 2020, there have been over 5,000 registered Covid-19 studies worldwide. Patient numbers are similarly impressive. A far cry even from the 3,000 typically mandated by the FDA, Pfizer’s vaccine trial included 43,998 people. Merck’s effort topped 65,000. In the US alone, AstraZeneca enrolled around 30,000 patients across 80 sites. It goes without saying that the logistics of such an operation are bewilderingly complex – and that’s before you even factor in that many trial participants were legally banned from leaving their homes.

How, then, have major pharmaceutical companies like Roche reacted? When it comes to a big picture response, Vela suggests that agility has been key. “The pandemic made us realise that we need to be more flexible in some situations, and that not following the usual path can result in new and successful approaches,” he explains. “Sometimes, taking some risks is necessary when you need to implement something in an agile way: not having the perfect approach first, but implementing something that works and then you will have time to improve it.” Vela and his Swiss employer are certainly not alone here. In the UK, for instance, scientists working on the AstraZeneca vaccine unusually conducted several stages of their trial at once. Across the Channel, regulators were happy to waive some of the more onerous reporting requirements around clinical trials – at least until first doses were safely in European bloodstreams.

Never break the chain

This talk of flexibility is well and good for understanding how clinical trials have changed in general, but what does it actually mean for their supply chains? It’s a question that can be answered, Vela suggests, beginning with patients themselves. For the first time ever, 2020 saw Roche take some of its trials remote – with drugs delivered to patients at home, rather than waiting for them at a clinic. Unless someone had been living in the woods for the past 18 months, they would understand how this became a necessity in a world driven by lockdowns. More to the point, says Vela, having patients test medication from the comfort of their own homes helps put them at “the centre” of the trial experience. Given this model can boost patient recruitment by up to 60%, and maintain patient retention at over 95%, there are clearly benefits here for trial organisers too.

None of this would have been possible without new technology. That’s especially true with blockchain. Being able to track and trace every order on a digital ledger not only gives patients peace of mind that their medication is being kept safe, it also allows trial scientists to ensure that doses are getting to their destinations without problems. The same is true of instantaneous temperature and status monitoring. With trial organisers now able to use the internet of things to check even the speed of a drug delivery truck, the sorts of colossal trials we’ve seen for Covid-19 vaccines will obviously become easier going forward, and at a stroke, secure precious data for researchers as trials progress. Beyond Roche, other companies are clearly interested in sliding new technology into their trial chains too. Even before the pandemic, Pfizer and Biogen had developed a working group to prove that blockchain could keep supply chains secure. And since ‘social distancing’ and ‘self-isolation’ have entered our common vocabulary, Bayer, Transgene and several UK NHS hospitals have all decided to go down a similar path in terms of these regulations.

Of course, relying on technology inevitably raises the possibility of hacks or other data breaches. At Roche, Vela is clearly conscious of these dangers. “All the systems that work within the Roche network are properly tested and validated from our IT department,” he says. “Talking in more detail about patients’ [personal data] in home delivery, for example, transport and logistical companies, which have a wide expertise in this field, give us the operational support, so no data from the patients is transferred directly to Roche. Once implemented, we just need to ensure proper information and monitoring the service level are performing well.” This is shadowed by similar developments across the industry.

Tech you out

Now that the pandemic is finally subsiding, how might experiences of Covid-19 impact the development of the clinical trial supply chains more broadly? Vela is unequivocal. “These innovative projects,” he says, “means changing the way we worked in the past”. In particular, he cites Roche’s home delivery initiative that, he suggests, provided a “proper solution” in record time. According to one 2020 survey, around half of clinical trial investigators expect clinical trial decentralisation approaches – including home delivery and online recruitment – to increase.

Beyond that, it seems clear that digitalisation will continue to trickle down the supply chain in other ways. Once again, the numbers are instructive. The market for electronic trial master files is expected to grow by 16.5% CAGR from 2019 to 2027, while 70% of trials will use wearable sensors to track patient progress by 2025. “Evaluating what is better for the patient, and the success of a clinical trial,” summarises Vela, “makes you implement new ideas following an agile methodology that makes the innovation possible.” If only Parry, Hill and their anonymous Chinese forebears could come back and see it.