Clinical trials for breakthrough treatments are pivotal in shaping the future of mental health care. If you’ve ever wondered about the ins and outs of running trials, you’ll want to read on. We interviewed Dr. Michael Banov. He’s the Medical Director of PsychAtlanta and PsychAtlanta Research Center in Atlanta, Georgia.

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Triple-board certified in adult, adolescent, and addiction psychiatry, he’s conducted over 150 clinical research trials, marking a journey that spans from the groundbreaking Clozapine trial for depression to the recent advancements with implanted vagus nerve stimulators (VNS). His unique perspective offers practical guidance on the evolution and challenges of psychiatric clinical trials.

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Expect to Learn:

• The historical significance and impact of the Clozapine trial for depression.
• The evolution of psychiatric clinical trials and the transition from traditional methods to modern approaches.
• The role of professional patients and the representation of real-world scenarios in clinical trials.
• The challenges and complexities of recruiting for psychiatric clinical trials.
• The ethical considerations and the importance of oversight in clinical trials.
• The challenges and promises of psilocybin and vagus nerve stimulators in clinical trials.

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The Evolution of Psychiatric Clinical Trials

Dr. Banov's first clinical trial with Clozapine for depression was a landmark in psychiatry, introducing second-generation antipsychotics for mood disorders. He recalls, "It's really the first time that antipsychotics were actually used to help with depression in that way." This trial, conducted at a time when treatment options for refractory illnesses were desperately needed, marked a significant shift in psychiatric treatment approaches. Banov emphasizes the importance of conducting research alongside an active clinical practice, as it allows for drawing patients from the practice and ensures a representation of real-world scenarios, contrasting with sites solely dedicated to research.

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The Changing Landscape of Psychiatric Clinical Trials

Starting his career with trials conducted in academic settings and private practices, Banov witnessed a significant shift in the research landscape. He notes, "There were basically two groups that did research: academic facilities... or clinicians who had this sort of side gig going on."

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He describes the early days of clinical trials as being more intuitive and hands-on, with everything recorded on paper and pen. However, the landscape began to change due to high placebo responses and the need for more stringent oversight. This led to a more regulated environment where trials were closely monitored, sometimes losing the nuanced understanding that comes from direct patient interaction. Banov reflects, "There's something lost... you're not sitting with the patient. You don't know what happens right before the recording started or something they said to you after."

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This increased regulation, while necessary for ensuring the integrity of trials, also brought challenges. Banov discusses how the clinical trial environment has become more corporate, with many research organizations now being owned by private equity. He observes, "It's taken a little bit of that human touch out of it... sometimes the pendulum just goes too far in one direction."

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Recruitment Challenges and Trial Complexities

Recruiting for clinical trials in psychiatry is a multifaceted challenge, particularly when dealing with drugs like Clozapine, known for their difficult side effects. Banov reflects on the past, "You didn't have the internet so people didn't know what was available and what wasn't available and didn't know about side effects." This lack of information sometimes made recruitment easier, as patients were eager to try new treatments unavailable outside of trials.

Today, the inclusion and exclusion criteria for trials have become highly restrictive, and the demands on patients are significant. Banov notes, "Some of these study visits can be four, six hours, once a week... who in the real world could commit that kind of time to these trials?"

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The Challenges of Recruitment and Technology's Role

Recruiting participants for clinical trials is challenging, and technology is a double-edged sword. Banov points out, "Social media has helped with recruitment but not necessarily enrollment." This observation reflects the complexity of recruiting suitable participants, where technology casts a wide net but often brings in many ineligible candidates, making the process inefficient.

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Misinformation and heightened public interest complicate the process. He says, "You've got so much on the internet that talks about psilocybin and all the wonders... but the vast majority of people don't qualify." This influx of unqualified candidates strains resources and complicates the recruitment process.

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Blinding for placebo controlled trials in Psilocybin is Challenging

Clinical trials are complex enough without multi-hour psychedelic effects to factor in. With placebo control in trials like psilocybin, blinding is difficult due to the drug's distinct effects. He explains the necessity of a "placebo script" to manage patient expectations and maintain the integrity of the trial. This script is a crucial tool to ensure unbiased results, but it also reflects the intricate balance required in psychiatric clinical trials between providing care and maintaining scientific rigor.

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The challenges extend to the regulatory aspects as well. Banov highlights the importance of consent forms, which can be daunting in their length and detail, yet are essential for ethical compliance. He remarks, 'These consent forms are 40 pages long... anyone who reads through and still signs them is indeed a brave soul.'"

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CRO and FDA Audits for Clinical Trials: What to Expect

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Role of CROs in Clinical Trials

Contract Research Organizations (CROs) play a crucial role in clinical trials. He explains, "If Pfizer wants to look at a new medication, they might go to a CRO like IQVIA to design the trial, find sites, and oversee everything." This insight highlights the comprehensive role of CROs, from conducting initial site checks to ensuring that research sites have the necessary infrastructure and ethical standards for conducting trials.

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"After enrolling one or two subjects, the monitor will come to ensure we're on the right track." This regular monitoring is crucial to maintain the trial's integrity and ensure compliance with the protocol.

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FDA Audits in Clinical Trials

Imagine the FDA telling you they need to audit your site. Nervewracking indeed. Banov recalls, "You might be audited if you're a high enroller or if there's suspicion of misconduct." He describes these audits as thorough and potentially daunting, with the FDA requiring access to all trial-related documents and data. His experience with three audits over 25 years highlights the rarity but seriousness of these events.

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"When the FDA audited us, they were the least friendly people you'd ever met. They would not talk to you, they wouldn't give you eye contact." However, at the end of the audit, the tone would often change, "They were the nicest people you could imagine. It was like they were there to do their job, not make friends." Nothing is personal in clinical trials; just make sure you dot your i’s and cross your t’s!

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Vagus Nerve Stimulators: A New Frontier in Treatment-Resistant Depression

In the realm of psychiatric treatment, particularly for treatment-resistant depression, Vagus Nerve Stimulators (VNS) are emerging as a promising option. Dr. Banov highlights the transformative benefits of VNS implants for patients who previously relied on treatments like ketamine. Unlike quicker-acting alternatives, VNS may take months to show results, but these results tend to be long-lasting, offering a stable solution for those with chronic depression.

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Discussing a specific VNS study, Dr. Banov notes its liberal protocol that allows participants to continue their existing medication regimens. This flexibility has facilitated successful enrollment from their treatment-resistant population. The trial's design is particularly noteworthy: in the first year, while half of the participants receive an active device, the other half are given a sham device. After a year, the sham devices are activated, ensuring all participants eventually benefit from the treatment.

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The mechanism and placement of the VNS device resemble that of a pacemaker, implanted just under the skin and connected to the vagus nerve. The device emits electrical pulses at regular intervals, subtly stimulating the nerve. This innovative approach, with its patient-centered trial design, makes VNS a beacon of hope in the challenging landscape of mental health treatment.

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Conclusion: Harnessing the Power of Clinical Trials

The landscape of psychiatric clinical trials is both challenging and rich with potential. From the pioneering days of the Clozapine trial to the cutting-edge vagus nerve stimulator studies, we’re excited to see how psychiatric research will continue to evolve.

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Key Takeaways:

• Historical Milestones: The Clozapine trial's impact in introducing second-generation antipsychotics for mood disorders cannot be overstated. It marked a pivotal shift in treatment approaches for refractory illnesses.
• Evolving Research Landscape: The transition from traditional, intuitive methods to modern, regulated approaches has reshaped clinical trials. This evolution, while ensuring integrity and ethical compliance, also brings new challenges and complexities.
• Recruitment Challenges: The intricate process of recruiting suitable participants, compounded by technological advancements and misinformation, highlights the nuanced nature of modern psychiatric research.
• Regulatory Oversight: Insights into CRO and FDA audits underscore the importance of meticulous compliance and ethical conduct in clinical trials.
• Innovative Treatments: The promising results of vagus nerve stimulators and psychedelics in treating treatment-resistant depression exemplify the potential of new technologies and approaches in psychiatric care.

You’re now better equipped with the knowledge and insights to navigate the complexities of running your own clinical trials. Let’s chart the future of mental healthcare together!

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Timestamps:

• [00:00:00] Introduction to the podcast and mention of ketamine treatments and vagus nerve stimulators.
• [00:01:00] Introduction of Dr. Michael Banov and his background in clinical trials.
• [00:02:00] Discussion on the challenges of recruiting for psychiatric clinical trials.
• [00:03:00] Insights into the evolution of clinical trial landscapes and the role of social media in recruitment.
• [00:04:00] Introduction to the trial of vagal nerve stimulation for depression.
• [00:05:00] Discussion on the potential of vagal nerve stimulator trials for treatment-resistant depression.
• [00:06:00] Dr. Banov's career highlights and how to get involved in clinical trials.
• [00:07:00] Dr. Banov's first clinical trial experience and the use of Clozapine.
• [00:08:00] The transition from academic research to industry and the ethical considerations.
• [00:09:00] Challenges faced in starting clinical research and the importance of experience.
• [00:10:00] The shift in psychiatric treatment approaches and the role of industry professionals.
• [00:11:00] Insights into the pharmaceutical industry and the development of medications.
• [00:12:00] The process of recruiting for a Clozapine trial and the challenges involved.
• [00:13:00] The key role of recruitment in clinical research and the evolution of patient protection.
• [00:14:00] The increasing challenges in recruiting for clinical trials.
• [00:15:00] The impact of clinical trials on real-world treatment scenarios.
• [00:16:00] The unique aspects of running psilocybin clinical trials.
• [00:17:00] Challenges in placebo control and patient interaction in psilocybin trials.
• [00:18:00] The necessity of a placebo script in clinical trials.
• [00:19:00] The regulatory aspects of clinical trials and the importance of consent forms.
• [00:20:00] Reflections on the changing landscape of psychiatric clinical trials.
• [00:21:00] The shift towards more regulated clinical trials and the loss of nuanced patient interaction.
• [00:22:00] The impact of private equity on research organizations and clinical trials.
• [00:23:00] The role of technology in modern clinical trials.
• [00:24:00] The challenges introduced by technology in clinical trials.
• [00:25:00] The use of technology for monitoring patient compliance in trials.
• [00:26:00] The importance of oversight in clinical trials.
• [00:27:00] The process of being monitored and audited in clinical trials.
• [00:28:00] The role of Contract Research Organizations (CROs) in clinical trials.
• [00:29:00] The process of site initiation and monitoring in clinical trials.
• [00:30:00] The reasons for FDA audits in clinical trials.
• [00:31:00] The consequences of FDA audits and the importance of ethical conduct.
• [00:32:00] The challenges of being a high enroller in clinical trials.
• [00:33:00] The role of technology in patient recruitment and enrollment.
• [00:34:00] The challenges of recruiting patients in active clinical practice.
• [00:35:00] The implementation and mechanism of vagal nerve stimulators.
• [00:36:00] The contrast between VNS and other treatments like ketamine.
• [00:37:00] The design of the VNS trial and its benefits.
• [00:38:00] The steps to become a site researcher in clinical trials.
• [00:39:00] The importance of experience and connections in starting clinical research.
• [00:40:00] The necessity of oversight in clinical trials for patient safety.
• [00:41:00] The role of technology in facilitating patient identification and enrollment.
• [00:42:00] The challenges of using social media for recruitment in clinical trials.
• [00:43:00] The practical aspects of running a VNS study in a clinical practice.
• [00:44:00] The process and placement of the VNS unit.
• [00:45:00] The sustained response of VNS compared to other treatments.
• [00:46:00] The sponsor of the VNS study and the cost considerations.
• [00:47:00] The trial design of VNS and its real-world applicability.
• [00:48:00] Advice for clinicians interested in becoming involved in clinical trials.
• [00:49:00] The importance of gaining experience and certifications in clinical research.