Before the pandemic forced remote work, school and research to the forefront, decentralized clinical trials were probably on the horizon. Now, they’re here in earnest.
This week, precision psychiatry startup Alto Neuroscience and Cerebral, an online mental health provider, announced that they’ve joined forces for a decentralized Phase 2 clinical trial for Alto Neuroscience’s depression drug candidate — ALTO-300. The study will largely take place in patients’ homes.
Specifically, the project will recruit an estimated 200 volunteers from the Cerebral platform who are currently struggling with depression, and have seen no benefit from existing treatments. Alto Neuroscience, aside from providing the new drug, will also look to validate its approach to drug development: using patient biomarkers to predict which drugs patients will (or will not) respond to.
“The idea that you would do deep phenotyping on a patient population and find out which subgroups of patients really benefit from the drug before you end up spending a billion dollars in clinical trials made all the sense in the world, but no one was doing it,” David Mou, the chief medical officer at Cerebral told TC.
“In a way it was a match made in heaven. We had what they needed, and I trust that their vision is going to be what’s most workable.”
What’s interesting about decentralized clinical trials?
Definitions of a “decentralized clinical trial” vary slightly, but in essence, it means that care is brought to the patient in some form, either virtually or thanks to mobile clinicians. Data is also typically collected where patients are, rather than through regular visits to a study center.
Bringing clinical trials to patients does have the potential to solve major problems currently facing clinical trials by making the process less cumbersome for patients. Nearly 70% of clinical trial participants live more than two hours away from a study center, for instance. Enrollment is also common reason trials are terminated, and an estimated 80% of clinical trials fail to enroll patients on time. Finally, experts have suggested that bringing trials to patients might help improve the diversity and accessibility of drug research.
This trial is far from the first decentralized clinical trial ever, but it does come during an inflection point for the field.
Before the pandemic only 38% of pharma and contract research organizations (CROs) told McKinsey that decentralized clinical trials would be a major part of their portfolios.
When McKinsey surveyed those same organizations again in 2020, 100% expected decentralized trials to play a large role.
What this trial can tell us
This trial has the potential to reveal a lot about the strength of data collected at home, the FDA’s attitude toward that data and whether decentralized clinical trials really solve problems site-based trials have faced for years in real life.
Collecting in-depth data is especially important for Alto Neuroscience’s drug development strategy. That’s because the company is based on developing unique, biomarker-driven portraits of patients with mental health diagnoses, from EEG measurements to mood and emotion questionnaires.
“We’re developing new drugs for various psychiatric disorders, with a focus on identifying who the right patient would be using brain tests or brain biomarkers,” Amit Etkin, founder and CEO of Alto Neuroscience told TC.
“What that means in this case, is that a core part of everything we do is try to make sure that our biomarkers identify, in the most generalizable way, the patients who will respond to our drugs.”
Cerebral became an attractive partner for Alto Neuroscience’s upcoming trial for a few reasons. The first was that the company was able to quickly find a population that fit the specifics for the clinical trial: “We pulled out those 200 patients within an hour,” Mou said.
But the key piece was that Cerebral had already compiled a huge amount of data on patients and their clinicians — suggesting that they had capacity to collect the high quality of data that Alto Neuroscience needs. That includes data on patients who suffer from severe forms of depression (a category who are often not served by apps that fall into wellness categories).
For example, Cerebral patients already regularly fill out questionnaires on symptoms and mood. The company also has data on physician prescribing patterns, which could provide insight into what’s working and what isn’t.
“Because we’ve focused so much on high-quality care, it forced us to create a data infrastructure on the back end to know much more about our patients and our clinicians than any other mental health provider in existence right now,” said Mou.
One lingering question is how the FDA will view data collected in a decentralized, even remote, way. That’s process is in development. In April, for instance, the agency required oncology decentralized trials to label their data sets to distinguish which data was collected in-person, and what was collected remotely, for instance.
This trial may offer a good point of comparison. Alto Neuroscience is actually currently running two similar clinical trials on ALTO-300: one with Cerebral, and another in the traditional site-based format.
The strategy there, says Etkin, isn’t just to evaluate the effectiveness of ALTO-300. It tests the whole concept of a decentralized precision psychiatry clinical trial.
“Part of what we’re trying to do is also validate our approach for FDA so that we can show that what we’re getting in a decentralized approach is equivalent to what we’re getting in a site-based approach,” said Etkin.
Finally, there’s some evidence that this trial overcomes barriers associated with traditional clinical trials — like enrollment issues. But it’s not perfect. The patients in the Cerebral trial, for example, are still based in New York, Dallas or Atlanta, not exactly populations that live hours away from major medical centers.
“Does it solve the problem of representation? Not completely,” notes Mou. “But I would say it’s a higher fidelity group: The chances they have true depression is much higher than going out there in the classic way and recruiting patients through brick and mortar clinics.”
From trial to commercialization
Both founders noted that decentralized trials could also pave the way for drug commercialization. For instance, Mou notes that Cerebral could easily help deploy a drug to the patients who might benefit from it post-approval.
From Alto Neuroscience’s perspective Cerebral could be a conduit to helping bring mental health biomarkers into clinical practice — a longstanding issue when it comes to diagnosing mental health conditions. (Historically, mental health diagnoses have been made through observing behavioral symptoms, rather than medical tests. Though some researchers, and commercial companies like Alto Neuroscience have been seeking to turn the field toward diagnosis based on validated biomarkers.)
“A partner like Cerebral would be ideal for bringing our biomarkers, once approved, for medication into clinical practice, because their clinical care is so structured and well-tracked.”
As for this current trial, the companies expect to get a first readout by the end of 2022.
