Backwards about moving forwards

The work put into modern clinical trials is extraordinary. Consider the numbers: taking seven years to complete, the average phase one trial costs anything up to $6m and can require the labour of 3,000 people – and that is just the beginning. With the growth of remote operations, especially in the wake of the pandemic, contemporary trials can be organisationally complex at each step of the process, from getting medications to patients to sending data back to researchers. It is no wonder the market for clinical trial logistics is currently hovering around the $19bn mark – and is expected to reach $28bn by 2026.

Yet if clinical trials have scaled unimagined heights, prodded along by the rush for Covid-19 vaccines, there is one area where the sector is arguably stuck at basecamp: reverse logistics. The practice of collecting unused and reusable materials, then either reconciling or discarding them, is theoretically a part of every trial. But explore the specifics and it quickly becomes obvious that practical reverse logistics enjoy far less attention. From cultural and regulatory challenges to the simple fact that the end of an experiment is less exciting than the optimistic start, reverse logistics has traditionally been shunned by the trials industry.

At the same time, ignoring reverse logistics can have serious real-world consequences. With strict rules in place about how unused medications need to be handled, snubbing reverse logistics can get the organisers and sponsors of trials into legal trouble. From a financial perspective, meanwhile, being disorganised at the close of a trial often means unnecessary costs and delays. At worst, this can even impact the data painstakingly gathered over months and years. Even so, the situation is far from hopeless. Buoyed by new technology, which makes tracking components easier, trial insiders are finally embracing reverse logistics in all its variety.

End of the line

Few people are better placed to appreciate the sophistication of modern clinical trials than Kimberly Finn. A veteran in the field for nearly 30 years, she’s worked everywhere from cardiovascular metabolism to oncology. Since 2018, meanwhile, Finn has been vice president of global patient centric services at Marken, a Chicago clinical supply chain firm and subsidiary of UPS. What Finn has to say, in other words, is worth listening to – and she is clearly keen to stress the importance of reverse logistics, at least in theory. “It is quite important,” she says. “Most institutions will have SOPs regarding the proper destruction of medications – because we can’t just throw them in the receptacles most of the time.”

As this last comment implies, the need for reverse logistics can be understood in two ways: the vast surplus clinical trials frequently end up with, and the regulatory obligations that accompany them. To take the surplus first. From storage conditions to expiry dating, to say nothing of patients that leave a trial early, planning the minutiae of a trial in advance is often impossible. Naturally, this means that clinicians are often left with leftover drugs – either reusable or which have to be disposed of safely. Combined with the rise of digital accoutrements – think wearable devices for monitoring vital signs, especially important in our new era of lockdowns – and the materials trials have to contend with soon balloon. It similarly follows that all this comes with a serious dose of regulation. Beyond individual SOPs, regulators like the European Medicines Agency have robust guidelines for how to deal with unused drugs. Nor is this very surprising: dumping pills in the bin is fine until they are sold on the black market or discovered by a curious teenager.

Yet speak to the experts and it soon becomes clear that the theory of reverse logistics has traditionally clashed with the reality. For Edward Groleau, clinical supply chain director for North America at PCI Pharma Services, reverse logistics is “very much” underappreciated across the sector. Perhaps most fundamental here are the vagaries of human nature. “The exciting part of the trial is over and everyone is anxious to see the results plus planning the next phase of the development programme,” is how Groleau puts it. “Dotting the final I’s and crossing all the T’s is not what people want to do.” That’s shadowed by the frustrating complexity of the whole process. Tracking trial materials is generally a shared responsibility, involving different stakeholders across different locations. As Groleau bluntly says: “Wading through mounds of paperwork to count trash is not an exciting task anyone looks forward to doing.”

Whatever the reasons for lapses, it is indisputable that ignoring reverse logistics has a number of drawbacks. One issue involves data. As Finn explains, a trial will inevitably be less accurate if crucial patient statistics are left on devices forgotten in a corner. Information matters in other ways. “The people completing the reverse logistics are forced to chase down the information needed,” says Groleau. “This can be happening years after the trial started, so documentation can be lost, and with personnel changes it may be impossible to recover the information.” Apart from again damaging the informational integrity of a trial, this risks leaving researchers with an unfavourable audit review. Of course, all this messing about can be expensive – hardly ideal when drugs already typically cost an eye-watering $985m to develop.

Working backwards

Given the convoluted nature of reverse logistics, it is probably unsurprising that any solution requires what Finn calls a “strategic” approach. Her work at Marken is a case in point. When her team has an opportunity to supply medications to trial sites, for instance, she emphasises that reverse logistics is examined right at the start. Among other things, that covers regulation and trade compliance: Marken boasts a regulatory database that trial planners can use to understand exactly what needs to happen when medications go to the big warehouse in the sky. Nor is the Chicago firm alone. Like Marken, Groleau’s PCI Pharma Services is moving in a similar direction, using a client portal to give customers a detailed overview of where exactly materials are in the reverse supply chain.

As these references to client portals hint, technology can be a real boon here. Groleau, for his part, emphasises that many so-called ‘interactive response technologies’ (IRTs) have modules that can document the information needed for reverse logistics. “The better systems available have extended the capabilities to include the final reverse logistics activities.” Finn makes a similar point, noting that GPS tracking is just one way of keeping abreast of medications and other materials both during a trial and after it ends.

More to the point, there are signs that these multipronged efforts are paying off. As one recent study notes, the global reverse logistics market is now enjoying a CAGR of 5.6%, even if only 20% of medical device firms have yet to fully embrace it. Examine the benefits of reverse logistics and you have to imagine this figure will rise sharply over the coming years. As Groleau says, “efficiency and thoroughness of completing the reverse logistics for a trial is the biggest impact proper planning will have,” adding that avoiding a post-trial paperchase will save money too. Finn agrees. With enough pre-planning, she envisages a situation where test sites can periodically receive used or expired medications from remote patients, before passing it all on to a centralised destruction facility. Preparing for a global recall of a product, or for trials that terminate abruptly, is another part of the jigsaw. All told, in fact, Finn speculates that serious reverse logistics could ensure efficiency savings of up to 50%.

The final frontiers?

All the same, it would be wrong to imply that a path to the reverse logistics uplands is debris free. For starters, researchers and their external partners must increasingly contend with the spectre of accountability. Think about it like this: new gadgets make it simpler than ever to follow drugs from the trial site to the incinerator. But in a world where trial patients are often left to self-administer drugs remotely at home, how can trial insiders know how much is being left in an IV drip? Bans on international transfers from some jurisdictions are another issue. Again, regulatory databases and the like can mitigate much of the confusion. But that is not the whole story. “Sometimes your hands are tied,” warns Finn, “and you have to have country-level solutions and handle everything very individually.”

Despite these challenges, however, both Groleau and Finn argue that reverse logistics is here to stay. Once again, Groleau suggests that technology will be the major driver of adoption, explaining that the integration of “technologies involved in the supply chain will be the biggest leap in simplifying the reverse logistics process”. Finn, meanwhile, comes at the question of the future from a different angle. For her, the growing internationalism of clinical trials, cross-border trickery notwithstanding, means reverse logistics is more crucial than ever. Fair enough: now that global borders are again open for business, trial organisers should once more expect patients to start globetrotting. It goes without saying that their drugs surely will too – ideal territory for reverse logistics experts who want to see the world.