Turning Innovation into Execution in CNS Trials
By Dr. Rachna Saralkar, MD, MS, Principal Investigator, Flourish Research
At SCOPE 2026, I had the opportunity to chair an engaging discussion on the evolving landscape of CNS and mental health clinical trial execution. In recent years, my own focus (along with much of the industry conversation) has centered on the role of technology and innovation in improving research. What I appreciated most about this session, however, was its focus on the operational fundamentals: the site teams, the patients, and the real-world workflows that ultimately determine whether a trial succeeds or stalls.
Across speakers and perspectives, one theme emerged clearly: progress in mental health research will depend not only on new tools, but on strong planning and execution and trial designs that reflect the realities of clinical care. Some topics touched on include:
- The role of iterative testing in innovation
- Mock visits in optimizing protocol feasibility and site workflows
- PAs and expanded investigator roles
- Patient engagement as a core protocol component
- Updated AE frameworks in psychedelic trials
1. Innovation Requires Iteration and a Willingness to Fail Forward
One of the early speakers emphasized that meaningful innovation does not happen in a straight line. Instead, it requires a cyclical, iterative approach, one that accepts setbacks as part of progress.
It is always encouraging to hear sponsors speak openly about dedicating the time, resources, and people needed to innovate responsibly, while also recognizing that failure is often a necessary step toward scalable solutions.
2. Improving Mental Health Clinical Trial Execution Through Mock Visits
A standout operational takeaway came from a clinical leader from a European pharma. Their approach to protocol design: conducting mock visits at the sponsor level before launching a study.
By running through screening or baseline procedures internally, teams can identify bottlenecks, unrealistic timelines, and workflow challenges early, at a point when adjustments are relatively easy to implement.
Building on that idea, the discussion also raised the value of a “Patient Zero” model at the site level: allowing sites to conduct a full mock run-through with a volunteer before enrolling the first real participant. This creates space to uncover practical issues (from lab logistics to scheduling windows) without compromising the integrity of study data.
Hearing this approach articulated at the sponsor level was particularly heartening. Testing assumptions early and being open to what those tests reveal is critical to improving mental health clinical trial execution and may allow studies to launch with stronger workflows and fewer downstream inefficiencies.
At Flourish, we already conduct site-level mock walkthroughs for key operational components of a study, from screening and baseline visit SOAs to lab processing and pharmacy workflows. These exercises are critical for identifying protocol or lab manual inconsistencies early, as well as the practical hurdles that site teams are often left to navigate once a trial is underway.
It was especially encouraging to see sponsors adopt this same level of detailed planning before protocols ever reach sites. Many site teams would welcome the opportunity to participate in a collaborative “patient zero” mock-up or to engage even earlier in protocol development, helping sponsors identify where assumptions in the schedule of activities may fall short in real-world practice.
3. Expanding the Investigator Model: Recognizing the Role of PAs
Another important conversation focused on the growing role of Physician Assistants (PAs) in clinical research and the need for sponsors to more fully recognize their potential as investigators. Many PAs are deeply embedded in the day-to-day conduct of trials, consenting patients, supporting rater assessments, coordinating care, and providing consistent, hands-on oversight.
Historically, however, sponsors have often limited PI opportunities to highly credentialed MDs and DOs, frequently prioritizing academic experience or extensive publication histories. While experience and training matter, this raises an important question: is the defining factor the pedigree on paper, or the quality and consistency of PI oversight in practice?
In some CNS studies, full-time PAs may be better positioned to provide continuous oversight than physicians with limited on-site availability. The value lies not only in credentials, but in presence, engagement, and accountability.
This is an area where site networks are uniquely positioned to lead. With centralized infrastructure, standardized training, and built-in oversight, networks can create the guardrails that allow PAs to step into expanded investigator roles while maintaining sponsor confidence and study integrity.
4. Patient Engagement Must Be Built into Protocol DNA
We also heard compelling examples of sponsors taking patient engagement beyond advisory boards, investing in structured, one-on-one feedback to understand what participation truly feels like.
This level of intentionality helps ensure that protocols reflect the lived experience of patients, not just operational feasibility on paper. As mental health trials continue to evolve, embedding the patient voice into protocol development will be essential for both enrollment and retention.
5. Defining Adverse Events in Psychedelic Trials
The session also touched on the growing relevance of psychedelic research and other emerging approaches in psychiatry.
These trials introduce unique challenges, including how adverse events are defined and captured. In psychedelic studies, even positive perceptual or emotional shifts may be classified as adverse events. These include visual or perceptual distortions and feelings of euphoria or transcendence experiences that participants may find meaningful yet still represent deviations from baseline, requiring documentation. More typical negative events such as anxiety, nausea, and headaches are also commonly reported.
This requires investigators and sponsors to adapt traditional safety frameworks to new therapeutic contexts.
What Comes Next for Mental Health Clinical Trials
The conversations at SCOPE reinforced that the future of CNS and mental health clinical trial execution will continue to be shaped by how well we get the basics right, aligning protocols with real-world practice, supporting site teams, listening to patients, and building investigator models that match today’s research environment.
As we look ahead to 2026, the path forward will require practical collaboration between sponsors, sites, and investigators to ensure that trials are not only innovative, but truly executable and meaningful for the communities they aim to serve.
At Flourish, we partner with sponsors to ensure CNS and mental health clinical trials are efficient, patient-centered, and operationally executable, delivering high-quality data from first-patient-in to last visit. If you’re planning a study, we’d welcome the opportunity to collaborate.