Adapting the future of DTx clinical trials – Woebot Health

Following DTx West 2023 in San Mateo, California, back in February, Woebot Health’s chief clinical officer Athena Robinson spoke with pharmaphorum about the conversations had at the event, exploring the practices, barriers, and market changes that affect digital therapeutics (DTx) clinical trials and what the future holds.

Overall, DTx West itself provided “a great opportunity”, Robinson said, to “learn about how things are progressing” in the digital therapeutics area. 

“I think DTx West is a great way to understand the pace of the field’s advancement,” Robinson mused. “Woebot Health is at the forefront of the way the way the field is thinking, and we are leaders in the space in terms of how we are liaising with our clinical research organisations and how we're taking into consideration our communications with regulatory.”

“Clinical trials have always been the cornerstone of how safety and efficacy get tested and proven out for a wide variety of products,” she explained, “and that continues to remain true in digital mental health interventions as well. 

“I think where we are now is [we’re] seeing an arc of adaptation as we move from more traditional brick-and-mortar, physical site-based, and use of these clinical trials, all the way through fully decentralised online trials.”

Going towards the light at the end of the tunnel

But the question is, are DTx trials at the point that those in the field would expect them to be, given what barriers exist and the market changes that have been taking place?

“There is an understanding across many companies about the importance of moving into decentralised clinical trials,” Robinson said. “It is commonly utilised as a means of testing products among many trials, and many people have also worked on the different elements of a study. For example, recruitment, participant journey, and survey and measurement capture.”

“In many regards, we understand all that we need to do in order to get to the light at the end of the tunnel with fully decentralised, well-functioning, and finessed clinical trials,” she explained. “For example, a lot of people have made adaptations to fully online recruitment, leveraging social media or other outlets that allow them to recruit into these trials.”

Additionally, Robinson said, they’ve seen a lot of clinical research organisations or CROs increase the ‘menu’ of services they offer to manufacturers.

“We can leverage their services in order to run these trials,” she explained. “For example, they might offer remote principal investigators. They might offer electronic data captures, data analysis, etc. In many ways, we’ve seen the field advance in this regard.”

Innovation and improvements yet to come

However, the state of affairs of the development of DTx trials is not quite finessed to its end goal state, and improvements remain.

“We’re all learning together,” Robinson admitted. “All the companies are learning about how to best run these decentralised clinical trials, and the CROs are learning as well, and so as we continue to make progress towards that light at the end of the tunnel, that North Star, we’re learning how to best refine the processes along the way.”

Innovation – a buzzword at the moment, not just in the digital health space, but throughout pharma and healthcare generally – is key, of course.

“We have really invested in a rigorous science team internally,” Robinson stated. “Both our clinical operations team and our science research associate team facilitate managing the clinical research organisation in a way that ensures all of the elements are in place – so, really tight and clear protocols, operations manuals, and oversight of the CRO.”

“Also, our company has implemented and continues to refine all of the various quality control processes to ensure that, for example, our electronic data captures – which are the survey administrations – flow just right, that each question leads to the next as you’re supposed to,” she said. “The participant’s journey, from the participant’s shoes, is really quite smooth.”

Making the patient part of the journey, equitably

The pharma and healthcare sectors are, after all, about the patients for whom research and development is essentially undertaken, and more and more the importance of access and equitability becomes a necessary central focus.

“We've also facilitated making sure that the patient feels part of the study,” Robinson said. “Sometimes at site-based, brick-and-mortar studies, they are able to build that relationship, and we want to be able to continue that relationship in a decentralised way, ensuring that we have adequate patient-facing materials that are well written, really transparent about all the procedures that the patient will go through, and very warm and welcoming to ensure that the participant feels indeed a part of the trial, a meaningful part of the trial throughout their journey.”

Innovation and – it goes without saying – clinical trials must encompass health equity.

“This is a really important topic in digital mental health innovation and clinical research therein,” Robinson noted. “Our company has taken a number of steps towards not only beginning the conversation about this, but keeping channels of communication open to keep learning and keep growing therein. One example of this is in recruitment.

“When we talk about scientific methods, it begins with recruitment,” she explained. “One of the methods that we've used is Qualtrics panels or setting goals for how we want to target sufficient enrolment of particular groups. It's hard to know exactly how to target those numbers. We use US census-based data, as well as other studies and vetting with clinical experts and research experts against that, and we learn as we go, knowing that there's always room to improve. We work really hard on recruitment, using ads that are appropriate for a wide variety of self-identities; using language that's accessible and welcoming.”

Health equity and a surveyable question of socio-demographics

Beyond patient recruitment, though, Robinson mentioned that Woebot Health had polished its self-identity sociodemographic battery.

“That’s our baseline survey that just asks who you are and how you self-identify,” she explained. “We’ve invested quite a lot of work in updating that. We did this a few years ago and now it’s been deployed in all of our clinical research trials and has really set the stage for how we welcome people to self-identify in a wide variety of ways.”

This is not a question of merely elected pronouns but utilising national standards – such as those from the Centers for Disease Control and the National Institutes of Health, as well as ongoing discussions with its clinical diversity advisory board. 

“Another way that we’ve considered health equity through research,” Robinson explained, “is through our statistical analysis. I work very closely with my biostatisticians to try to understand how we can use our participant population to take a look at how folks of different identities are responding.” 

Additionally, Woebot Health is trying to get its findings back into communities.

“We use standard opportunities to get things out into the world,” Robinson said. “Such as peer-reviewed scientific publications [or] scientific conferences, but, more than that, we do blogs and videos, and we […] leverage our clinical diversity advisory board to facilitate identifying opportunities for dissemination back into the community. These are all the different pillars that we are evergreen in, in terms of how we are working to adapt our trials and continue to learn.”

Investment internally, growing talent, and navigating regulatory changes

Diversity and equitability begin within a company itself, however, and Woebot Health is no exception.

“We've hired from academia, from clinical research organisations, from brick-and-mortar sites that conduct clinical trials as well,” Robinson noted. “And, with this cornucopia of experience and talent, we've really been able to understand what we need to do to continue to grow and to continue to move and to conduct the trials we've been successful in conducting to date.”

“We have standard onboarding procedures around educating our clinical research staff on core elements of running clinical trials as well,” she continued, “and that education is ongoing in terms of both running clinical trials and regulatory elements too.”

In terms of regulation, the path to compliance has recently undergone changes that can help reshape digital therapeutic clinical trials.

“Regulatory is learning more and more about Software as a Medical Device and about wellness applications,” Robinson said. “They are putting guidance documents out into the field for manufacturers to review. At the same time, though, the core of the regulatory requirements remains the same. They want very rigorous clinical and scientific evidence that your product is safe and efficacious.

“Towards that end, it's the manufacturers and the CROs that need to adapt to meet this ever-steady standard. In that regard, I think we are going to continue to aim for that, and our, currently, live pivotal trial is a nice example of how we were able to talk with the FDA and agree upon our research design and safety parameters for that particular product.”

Nevertheless, a particularly unique area of concern for DTx trials is the question of fraudulent responses.

“[We must ensure] ways to mitigate fraudulent participants in research trials,” Robinson made clear. “Because people aren't showing up in person, it's really helpful to make sure we have ways of confirming the identity of our research participants, so that the decentralised clinical trial is thoughtful about not inadvertently enrolling fraudulent participants who might be aiming to just participate in order to gain survey compensation.”

An ongoing, hybrid trial into postpartum depression

The trial Robinson referred to is for Woebot Health’s WB001, a Software as a Medical Device (SaMD) based Cognitive Behavioural Therapy (CBT) program for the treatment of mild to moderate postpartum depression (PPD), granted Breakthrough Device designation by the US Food and Drug Administration (FDA) in 2021, and for which in January it announced its first patient had been enrolled. 

Actively recruiting women aged 22 to 45 years old who have given birth in the last three months and are experiencing mild to moderate PPD, the purpose of the study is to determine if, for women diagnosed with PPD, WB001 as an adjunct to Treatment as Usual (TAU) can reduce symptoms of depression, compared to an educational control with adjunctive TAU at the end of eight weeks of treatment – as measured by clinically validated HAM-D6 scale, which is an assessment of symptoms of depression, such as depressed mood, guilt, psychomotor retardation, psychic anxiety, and general somatic symptoms.

“That trial is live right now,” Robinson said. “It is a national decentralised clinical trial recruiting women who have postpartum depression and we are offering our intervention, as well as a control condition as part of that. We will have between 15 to 20 sites live nationwide, and it is a hybrid decentralised trial. What a hybrid means is it's in between a traditional brick-and-mortar site and a fully decentralised site.”

“In a hybrid site, as you can imagine, there are just maybe one or two visits,” she explained. “In our pivotal trial for postpartum depression, we have one: the baseline. The first visit is in person, on site, and then the rest are fully decentralised. The reason we picked this approach is because we wanted to facilitate that relationship between the patient and the investigator on site for the first visit and then make it very easy for our participants to complete the remainder of their surveys and their questions from the comfort of their own home without needing to come in.”

For such a deeply personal mental health issue for a woman, the hybrid decision is a well-founded and practical one, in terms both emotional and physical.

“For women who have recently given birth and who have a young infant at home, it can be difficult to travel into sites on a regular basis,” Robinson said. “Also, because we will not be collecting any labs, for example, blood work or urinanalysis from these women, it makes the completion of their questionnaires much easier [when] remote.”

The three-part future for DTx trials

When asked about where she considered the DTx trial development journey to be heading next, Robinson was clear in her mapping out towards that horizon.

“I do think that companies will continue to need to understand, number one, how to best work with clinical research organisations, understanding that, as I mentioned, they're learning as well, and so the level of oversight from internal to that research organisation should be quite astute and reliable,” she said. 

“Number two, I do think that companies will continue to need to be openhearted and handed when it comes to health equity and really understand the different investments they need to make on an ongoing basis, to ensure representative samples to the best of their degree,” she explained. “After all, that's one of the benefits of accessing remote trials and of accessing digital therapeutics.”

“Number three, I think we'll continue to iterate towards the level of rigor required by the FDA and use a lot of FDA correspondence to ensure that we have done just that,” she concluded.

About the interviewee

As Chief Clinical Officer at Woebot Health, Dr. Athena Robinson directs the Clinical Research and Development team. Her research and clinical expertise is in technology-leveraged methodologies for implementing evidence-based psychotherapeutics. Specifically, Dr. Robinson has extensive experience in implementation science and research-focused intervention development employing evidence-supported theory and treatment (e.g. Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), Interpersonal Psychotherapy (IPT)), and has facilitated the delivery of such interventions via various in-person or technology leveraged formats. At Woebot Health, she oversees the company's program of research and has crafted and executed several successful clinical trials investigating Woebot's efficacy, acceptability, and feasibility among various clinical indications, symptoms of interest, and populations. She also led the initiative to and then established the Woebot Health Clinical Diversity Advisory Board and is co-chair of the Woebot Health Scientific Advisory Board. Dr. Robinson has been NIH funded for several years, starting in 2001. She has been Principal Investigator (PI) on various trials and successfully completed research funded by the National Institutes of Mental Health, National Institutes of Drug Abuse (NIDA), National Cancer Institute, National Collegiate Athletics Association, and Stanford University. Dr. Robinson has supervised and collaborated with research partners (industry, academic, government, research organizations) and staff on all aspects of designing, administering, and running clinical trials within the digital therapeutics field. She has written, edited, and published peer-reviewed articles and other book chapters on a wide variety of topics relevant to mental health care. Dr Robinson is also Adjunct Clinical Associate Professor at Stanford University School of Medicine where she continues teaching, and is a licensed and practicing psychologist who has provided mental health care to adolescents and adults for more than 20 years.
 
About Woebot Health

Woebot Health is the mental health ally for people and businesses, with products that put personal growth in people’s hands, wherever they are. Our pipeline of prescription digital therapeutics and behavioral health products combine natural language processing, decades of clinically-proven techniques and a relational agent called Woebot, which together form the foundation for mental health solutions that engage at scale and fit right into people’s lives. Woebot Health has been recognized for its safety, efficacy and privacy standards by One Mind PsyberGuide and the Organization for the Review of Care and Health Apps (ORCHA), meeting the organizations’ rigorous criteria that evaluate the security and effectiveness of digital health technologies worldwide