From the rise of digital medicine and fast-tracked vaccine development to the upscaling of devices manufacturing, healthcare as the world knew it in 2019 is gone forever. Covid-19 has irrevocably altered the pharmaceutical landscape – and nowhere is this more evident than in the clinical trials space. As the world locked down and vaccine research ramped up, other trials ground to a halt as sponsors looked online for digital solutions to not only salvage existing research, but also safeguard future studies. One company better placed than most to adapt to the changing landscape was Lundbeck – the Danish pharma was at the forefront of digitalising its clinical development when Covid-19 hit.

“You cannot be everywhere with everything, so we had to concentrate our resources, and one of the things we decided to zoom in on and prioritise was the decentralisation of trials,” explains Mads Dalsgaard, senior vice-president, head of experimental medicine and clinical development at Lundbeck.

That was five years ago – and a corporate digital strategy followed. All processes were put under the microscope and reviewed in terms of their potential for digitalisation – from site selection to monitoring and oversight, population selection and refinement, and back end development.

“Around the same time, we started to look at vendors that allowed decentralisation,” says Dalsgaard. “It’s one thing to have the patient at home, but there’s a whole infrastructure around getting the data and understanding how to analyse it. And then, of course, also having assessments and interactions that can be done remotely. We started to do all this gradually and slowly.”

Then Covid-19 hit. Lundbeck’s preparation and research came into play, and “gradually and slowly” went out the window. While other companies were starting from scratch, Lundbeck set about putting existing plans into action.

“First, we had to make workarounds and do what we could to get trials going. We were forced to change from physical visits to some remote visits, and some of the outcome assessments that were previously done by the physician and the patient interacting were replaced by phone calls or remote assessments,” says Dalsgaard. “We knew before that there was potentially a lot of value in this way of working, but we didn’t really have the data. Now, we were forced to do it and it really enabled some trials to get going.”

The new ‘norm’

As the Covid-19 emergency eases, the company is now pushing ahead with its decentralisation agenda in an effort to make virtual trials the ‘norm’.

“We have identified the first trials to not fully decentralise but to ‘hybrid decentralise’. We take each trial and say, ‘which are the visits that would normally require the patient to come into the clinic? Can we enable this within the home of the patient?’

“With our earlier preparation work, we already had a good understanding of vendors, we already had elements of the infrastructure, we had already worked with digital inputs. So, we had a head start. Now, we’ve done formal mapping around it. There are still a few gaps – for example, around consent – but we know what the ecosystem will need to be in order for us to be 100% virtual. We are using trials one at a time as vehicles to drive closure of those gaps.”

“My sense is that all our clinical trials will now more or less have elements of decentralisation in them.”

Dalsgaard says each trial is used to build knowledge in this way. “We had one trial that was struggling with enrolments, so we did a deep dive – almost an anthropological approach – and, working with a vendor, mapped the journey for patients, caregivers and investigators. We mapped the pain points and the motivating aspects of the trial for these key stakeholders, and it was really revealing.”

He says the benefits to patients of virtual trials are clear, especially in terms of cutting logistics and travel time. This is significant given the high number of trials that fail to recruit enough patients for day one. “Enrolment is nuanced in terms of access to patients, especially in rare diseases, where the likelihood that you have a high enough concentration around a few sites is low. It’s also about retainment within the trial – ensuring that patients are not surprised by the burden,” he says.

Push forward

Dalsgaard is also excited about improving the quality of data, especially given the push from both industry and regulators towards patient-reported outcomes.

“You could argue that a patient-reported outcome better captures the benefits to the patient,” he says. “How accurate is assessment number five after a long day if you’re assessing memory or mood? With decentralisation, instead of just relying on that one single time point, you can assess something three times a day. Some of these measures can almost be continuous. There’s a lot more burden on the analysis, but that gives you a wealth of information and much more richness in terms of what the molecule can do.”

The move to an online or home-based environment is not, however, without its challenges, particularly in terms of investigators. “For some investigators, it may not be easier. It may in fact be easier for them if the patient was there physically, rather than having to use a more cumbersome approach through video or other interactions,” says Dalsgaard.

“We have had examples where some investigators have declined to join a trial or where some of the hybridisation or decentralisation needs to be optional for the investigators in order to keep them. I think there needs to be a lot of learning on our side and in collaboration with investigators to find a good model where they also get the benefit of that extra work.”

He said finding a balanced approach would be key. “I hope and I expect that we’ll see more decentralisation, but we still need to refine the model. We need to ensure that we’re not relieving burden on patients and then unloading it on top of the investigators.”

Even so, Dalsgaard says virtual trials in the post- Covid-19 world have moved beyond the point of no return. “My sense is that all our clinical trials will now more or less have elements of decentralisation in them.” He predicts, however, that few trials will become fully decentralised. “Depending on the phase of the trial and the nature of the disease or the molecule, we will need to sometimes have the patients come to the clinic – we’re using home nursing to take blood samples, but there are obviously assessments like PET scans and MRIs, and things like that where you need the patient to come to the clinic.

“I think if I look within our own portfolio, the likelihood, at least in the earlier phases, that you can do 100% decentralised – I think that is far-fetched. It’s the hybrid model, which, in my mind, gives a good balance between really taking care of the safety and minimising risk, but at the same time also relieving the burden from the patient. To find a hybrid model [that works for everyone], I think is absolutely key.”

Digital support

Also key is the need to consider the ability of each patient group to manage technology. Patients with neurological or degeneration symptoms, for example, are a case in point for Dalsgaard, given Lundbeck’s focus on brain health.

“Some devices you have to wear – maybe it’s an app on a phone, you may need two devices or to install it on different platforms. There are of course challenges to that. If it’s a severe Alzheimer’s patient, you cannot ask them to sit down with an application and go through a cognitive test. So, there are very practical issues around tech.” However, he says exciting devices are constantly coming to market that offer solutions to support patients with even the most challenging symptoms. “We work with a company that has a sole in the shoe that measures gait. The assessment is independent of the patient, so you can have it even if you’re impacted cognitively. So, it’s a very broad picture in terms of technology.”

The advent of this kind of wearable and app-based tech means that the amount of data collected over a 24/7 period is greater than that during outpatient visits. Dalsgaard says e-diaries, sleep trackers and other wearable and non-wearable tech can provide valuable data if integrated into an effective trial design.

“There are some things you can do in the home that you cannot do in a clinic,” he says. “You can sample it much more frequently. You can control the variation and get a much more precise picture. You don’t necessarily want to replicate what you’re already doing – you want to really tailor it and make it exploit the opportunity in a decentralised setting. It would be a way of measuring data that you would not get through normal conversations.

“Digital devices are currently supplementary – they are not carrying the whole load of the trial yet.”

Move in the right direction

Further integration is the next inevitable step. That next push will largely depend on buy-in from regulators – and Dalsgaard remains upbeat about future approvals for trials that rely primarily on virtually collected data.

“It’s a moving target, but it’s moving in the right direction. I think, generally, everybody is sensing that this is a direction we’re moving in and we have to work together to make it happen. Regulators are approving digital therapeutics – if they’ve come that far in embracing digital, I don’t think that the distance to acknowledging that an element of a trial can be a digital device that can provide a primary endpoint is that far away.”

Dalsgaard says, ultimately, this should all lead to getting treatments to market faster – and possibly more cost-effectively. “You can deduce the logic out of it. If you are not limited to a few clinical trial sites, but you can access a broader patient group who then stay in the trial because it’s easier for them and you get better data that can be objectively assessed, then all that ties together to drive more efficient and effective clinical trials,” he says.

“You still have to go through the same steps, the regulator will require you to de-risk and replicate, and so forth, but on the whole that adds to the probability of success and speed, and maybe even cost savings.”