Reimagining the future

How together industry and regulators can change the clinical trial paradigm

The pandemic caused by COVID-19 has changed the way we live and work and not just for the short or medium term. For the biotechnology industry, it’s an opportunity to imagine how the world might be disrupted and the role that technology can play.

History has taught us that major events can have catalytic effects on society. The labor shortages caused by the bubonic plague in the 14th century forced lords to pay higher wages and create better working conditions. Serfdom almost disappeared after that.

Technology has also been catalytic throughout history. The Renaissance, for example, is due to some extent to the invention of the Gutenberg printing press, making it possible for ideas to spread quickly across Europe.1

More recently, the invention of the home computer and the internet have been described as the 4th technological revolution.

Our ability to adapt and leverage disruption, especially in the context of technology makes us wonder: What else is possible?” says Peter Bergethon, Vice President and Head of Digital and Quantitative Medicine at Biogen.  “This moment in time is the impetus for us to accelerate our digital plans and change the clinical trial paradigm.

Peter Bergethon, Vice President and Head of Digital and Quantitative Medicine at Biogen

The biotechnology industry cannot do this alone, however. The regulatory framework will also need to evolve in recognition of the increasing role digital technologies are playing in clinical trials.

In a whitepaper titled Transforming the Regulatory Landscape for Digital Health Technologies (DHT) in Drug Development, Biogen’s Global Regulatory Policy team calls for a modernized regulatory approach to these technologies and offers proposed solutions as industry and regulators move forward together.

“What we found is that while there are some regulatory frameworks for DHTs already in place they don’t fully address the regulatory needs of DHTs used in drug development,” said Priya Singhal, Senior Vice President (S.V.P.) and Head of Global Safety and Regulatory Sciences at Biogen.

“While they form a foundation for what could be, we found that the traditional drug and device frameworks are relatively siloed and do not address the unique regulatory needs of DHTs.

Priya Singhal, Senior Vice President (S.V.P.) and Head of Global Safety and Regulatory Sciences

We believe that DHTs hold tremendous promise for patients and drug development and this needs to be reflected in regulatory frameworks.

— Priya Singhal, Senior Vice President and Head of Global Safety and Regulatory Sciences

Impact on patients

The current model of identifying sites that could run the clinical trials, as well as finding and training investigators, is a lengthy process. More importantly, specific sites can limit access to patients due to geographic proximity and travel limitations.

“We hear from patients that participating in clinical trials places enormous demands on them. For many, participation could take up to a week out of their life as well as their caregivers. Considering that patients will have to do this a few times a year, it places a huge burden on them and their family,” says Peter.

This burden can translate into patients dropping out before the trial is completed. In fact, the industry has seen a 60% patient dropout rate from clinical trials over the past few years, especially if a trial is complex and lengthy.

A digital trial recognizes these components and decentralizes several activities thus removing the burden of travel on the patient and their families. Additionally, doing things remotely could potentially mean reaching more patients, something that would be particularly important with rare diseases. Ultimately this could mean getting to a potential treatment faster.

“Decentralizing clinical trials and moving to digital is by no means a novel idea. As an industry we have been using digital technologies to collect data for some time. And we have made some headway, especially in clinic,” says Peter.


Improving understanding

One area where digital tools have made significant impact is that of movement disorders. In Parkinson’s disease, for example, Biogen is currently using movement sensors in clinical trials that can measure and monitor the changes in the way a patient moves, including how fast or slow as well as gait (i.e. walking verses shuffling).

Outside of the clinic, as a member of the Critical Paths Consortium for Parkinson’s Disease, Biogen has been collaborating with other organizations in order to optimize the efficiency of ways to develop digital tools for Parkinson’s disease, investigating the role  electronic  devices such as mobile phones, ECGs, movement sensors, GPS and others can play in decentralizing clinical trials. 

In fact, as part of this work, Biogen and other members of the consortium are working with regulators on advancing digital measures for Parkinson’s pre-competitively – working with peer companies to address shared industry challenges.

“It is important as we move forward with digital measures that we engage with regulators early on in the process, bringing their perspective in as we look at study design which in turn will help them advance their own approach,” says Priya.

While the possibilities seem to hold great promise for the future, there are still some key considerations that will need to be addressed in order for the industry to make this transformational shift.

“We have to ensure that we have the right technology in place that people feel comfortable using and interacting with it. When we talk about digital in clinical trials, we have a clear objective: measuring what matters to the patient in order to make clinical trials smaller, faster and better,” says Peter

Ultimately, the scientific community will have to answer the following:

How do we ensure that data collected outside of the clinic are as rigorous? How do we sift through the large volume of data generated by devices in order to determine the efficacy of a treatment?


A hybrid model

But there are still ways to change the paradigm, even as we continue to evaluate remote digital measures. According to Yusuf Ghadiali, Senior Director at Biogen’s Global Clinical Operations, the company’s approach to this has been that of a fit for purpose hybrid model:

“We started this work about two years ago,” says Yusuf, “and it came down to an exercise of identifying what could be done remotely, in the patient’s home, while supporting/protecting scientific rigor, and what should be done in clinic, in a controlled environment. The key to doing so successfully is to consider these questions early on while the study is being designed,” he says. 

This approach could improve the experience for patients, while also maintaining continuity in clinical trials.

Yusuf Ghadiali, Senior Director, Global Clinical Operations

“If we can reduce the number of visits, participation can become less cumbersome and time consuming, helping us get to potential treatments faster,” says Peter.

Beyond clinical measures, digital can play an important role in identifying patients using genetic databases and data from Electronic Medical and Health records will help avoid duplication and real-world data can reveal new insights.


The future is now

“Two years ago, we had a handful of studies considering this hybrid model.  Since the pandemic, that number has risen to two digits in order to maintain data integrity, which could be jeopardized if patients missed visits. We implemented remote patient visits to mitigate for COVID-19 and plan to do so even after the pandemic is over. At the same time, we continue to explore suitability of other decentralized models such as telemedicine, patient downloaded mobile applications for our patient and clinical study needs,” says Yusuf.

The ecosystem has caused the world to be open to new ways of working, turning what was once a hypothetical into reality.

Without other options, patients and physicians are now being asked to get used to this way of working, helping them adapt to what is possible for the future.

— Yusuf Ghadiali, Senior Director, Global Clinical Operations

Adoption of temporary new policies for remote patient monitoring and telemedicine have accelerated adoption of DHTs in studies overnight.

“Ultimately, it will be up to regulators and industry to decide what can become the new normal and what didn’t quite work,” says Priya.

But to prepare for this future industry, patients, health care providers and regulators must find new ways to work together to advance joint guidance by drug and medical device regulators as well as an evidence framework that clarifies requirements for acceptance of DHT-generated data.

Continuous advances in hardware and a shortened development cycle of software and algorithm-based technologies means that innovation in DHTs advances much more rapidly than traditional medical devices. This needs to be reflected in more agile regulatory approaches that create the necessary flexibility for future innovation.

“With everything that happens there is a lesson learned. COVID-19 has given our industry, and indeed the world, the impetus to start thinking about how we can prepare for the next global crisis. Accelerating our digital capabilities, anticipating new disruptors in the world of technology, and being prepared to adapt to them will help us do so,” says Peter.

Read the whitepaper: Transforming the Regulatory Landscape for Digital Health Technologies in Drug Development