Reuters Events | Pharma

Thought leadership and innovation for the Pharmaceutical Industry

Clinical research has long been due an overhaul, with advocates pushing for leaner, more nimble, decentralised trial formats to improve access and retention. It’s something which has been lacking widespread adoption – until 2020. 

 

As the world moved online due to COVID-19, so clinical trials, where possible, pivoted to remote delivery to enable research to continue. It has prompted pharma to reconsider the norm and move virtual trials up the agenda. What will this mean for physical trial sites? 

 

“What COVID-19 taught us was that things we thought of as risky, such as using new research sites, turned out to be actually very de-risking,” says Irfan Khan, CEO of clinical research organisation Circuit Clinical. “Using the same old, same old turned out to be exceptionally risky, because if something happens to that ecosystem, you don't have any elasticity.

 

“The spectrum is, ‘Can it all happen at home?’ to ‘Can we get back to businesses as usual?’ The domino has fallen and pretending we are not in a new normal is a recipe for extinction.”

 

Beyond the clinical research centre

“This is accelerating something that needs to happen already, which is allowing different designs, whether it be synthetic controls rather than placebo or virtual sites as opposed to a physical location,” says Michael Norton, VP Medical Affairs at AbbVie (formerly head of US Medical Affairs). 

 

Decentralised trials harness technology to facilitate remote research – often in a patient’s home – using wearables and remote monitoring to collect digital endpoints. Improving virtual trial platforms also makes it easier for patients to connect with one another and stay engaged, part of the process as active rather than passive participants in two-way conversations. Such features also allow valuable real-time feedback to be collated and prove favourable on retention rates – a long-standing challenge for pharma.

 

However there remains a clear limit on what can be researched wholly remotely. Some diseases will lend themselves to the virtual trial, where others feel more challenging. “I just can't envision a world where cancer or dementia trials are not going to rely on sites,” says Norton. “There is such an important role for the investigator, the doctor and the family and the hub is that investigator physical location. I don’t think physical locations go away.”

 

This leaves space for innovation alongside virtualisation. “Circuit is a rethink of where the site should be,” says Khan. “We're interested in making it easier for patients to participate right at their doctor's office. That’s where site management is going – how do you turn other places into research sites?” 

 

Such site-in-a-box trial models bring research closer to the patient by opening up different sites, from local hospitals and GP practices through to mobile sites offering outreach research visits, perhaps to draw blood. It could see sites collaborate with firms like Uber Health or Lyft to bring patients door-to-door where brief face-to-face visits are necessary. 

 

Virtual trial planning also needs to be cognisant of the fact that not everyone has equal access to digital technologies. “Internet access and technological know-how is going to be a big hurdle to overcome or you're going to wind up leaving those groups behind,” says John Linnell, an experienced patient advocate in the COPD space. 

 

This is particularly pertinent to conditions like COPD, which are often much more prevalent in lower socio-economic areas. Moving from a physical to virtual site without providing pre-paid phones, internet plans and digital training may in fact reduce, rather than improve, access. 

 

As decentralised as you choose

So what of the traditional clinical research site? “If pharma decentralises too fast and sites can’t absorb it, it could run good sites out of business and when we need them later, we won’t have the infrastructure,” says Khan. “Adding decentralised platforms makes sense and the sites are going to have to think about how to proactively change their model to stay competitive.” 

 

He sees the traditional site economy remaining, but “evolving to something more flexible, with the networks layering in new services”. 

 

Norton too favours an evolution of the clinical research site. “I think it’s going to be a minority of trials that are solely virtual, for a long time, but more will perhaps offer virtual as an option. This is going to be an add-on, not a replacement.”

 

In a clinical-trial-plus scenario, decentralised trials are less of a binary proposition, and part of a pick-and-mix selection of pieces which make up a flexible research package, offering varying levels of decentralisation chosen by participants and facilitators. 

 

“The solutions that provide the most optionality for pharma are going to be the ones that resonate, scale and succeed,” says Khan. “It’s the ability to turn to a client and say, ‘If you want these visits at home, in the office, at a traditional site or an academic centre, we can make that happen’.”

 

This diverse research landscape with more sophisticated engagement models is likely to lead to greater collaboration with external partners, who offer expertise which pharma lacks collaboration with external partners. “They still want it to be simple for them. People are looking for turnkey solutions,” says Khan. “They’d like to solve this complicated problem with solutions providers.”

 

At AbbVie, clinical development operations are currently in house rather than sitting with clinical research organisations (CROs), but virtualisation may challenge it to broaden its approach, says Norton. To manage the complexity of the new virtual space, and internal workloads, it makes sense to consider contracting some of this work, at least in the interim. 

 

“If you have 10 physical trial sites, either private practices or academic institutions, that requires a certain infrastructure, with or without a CRO,” says Norton. “Virtual adds another dimension. A pharma company could do that, but more often than not, I think that’s something you’re going to contract.” 

 

This might not be just a CRO but could be integrated research organisations (IROs) or the actual trial sites themselves who take the lead on virtual. “My sense is you're either going to have a pharma company or a state take the lead on who's going to enrol virtually and have a central institutional review board (IRB) that takes on responsibility that goes beyond just national protocol, but actually takes responsibility for actual patients and probably adjudicate data and oversight of virtual patients,” says Norton.

 

Harnessing the human element

Any shift towards virtual interactions must factor in patient needs, with an appreciation of the value of the human element. “Do you really want to participate in a clinical trial where you never meet a doctor face-to-face?” asks Khan. “I'm not convinced the answer is always yes. In a heart failure trial, it doesn’t seem very consistent with how we make decisions.” 

 

Bookending a virtual trial with in-person meetings, such as a nurse visit, or even virtual, but personal video calls, like quality time with an investigator via Zoom, could provide sufficient touchpoints and aid a sense of connectivity. 

 

“I like at least the beginning and the end to be face-to-face,” says Norton, noting its value when it comes to informed consent. “You want to get a sense as to whether somebody understands what they're signing up for. And at the end we have an obligation to report back to participants, in their language, helping them understand what their contribution has been. That's an important part that we need to get better at.”

 

Communication with trial participants isn’t something pharma has traditionally got right, however. “What trials often overlook to help the patient is giving the patient a specific name and person at the trial centre that's their contact if they have a question, issue or need reassurance,” says Linnell. 

 

When dialling in, not having a dedicated point of contact can leave patients repeatedly rerouted from department to department. “I'm not a customer, I'm a partner in searching for the cure,” he explains. “Treat me like a partner, not like a number or a name, because I'm trying to help make a difference. Patients that volunteer in trials aren’t given enough credit for the fact that they want to help.” 

 

Streamlined and ready for what comes next

If the previous paradigm was focused on doing one thing well, the new normal is about flexibility, says Khan. “It’s about multiple strategies, high elasticity and the ability to configure the solution to meet the needs.”

 

After all, COVID-19 isn’t likely to be the only ‘black swan’ event healthcare will face. Solutions solving for the present should be built with future pandemics, and other projected challenges, in mind, says Khan. “Everybody could imagine a virus coming, but no one expected that to shut down the entire global site economy,” he says. “The next one will be different, so how do you de-risk the whole research proposition? You do it by being flexible in your interpretation of what the site is and by looking for new places for research to happen in.”

 

A reassessment of the clinical research proposition also offers the chance to streamline processes to make trials less onerous for all parties. “Oftentimes we build in all of the bells and whistles into trials, and that is not very appreciated, not by sites, not by patients,” says Norton. “How many scans really are necessary? Previously if you didn’t participate in, for example, 20 events over two years, you were out of the trial. All of sudden, nobody could do that, because of COVID-19.

 

“I'd love to see this as a time when we expand our offerings of how one can engage and participate in a clinical trial and for our learnings to be that trials need to have the minimum number of visits or time commitment from patients, to lower the bar for getting more people in.”