07 Jun FDA Advisory Committee Defends Status Quo
This this post was originally posted here
Much has been written about Tuesday’s meeting of the Psychopharmacologic Drugs Advisory Committee.
About the matter of blinding, expectancy, the culture of MAPS, the impact of psychotherapy, the choice of psychotherapy, sexual misconduct by a study therapist, the impact on the field, the likelihood of subsequent approval, the heartfelt stories from people whose lives had been torn apart by PTSD, etc.
I have to imagine this is the most emotionally charged, controversial, and consequential FDA Advisory Committee Meeting in recent history.
I have only three points to make:
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Comments from Advisory Committee members—despite training and credentials as medical professionals—reveal that their day-to-day involvement in patient care is limited or non-existent. As a result, they are personally shielded from the on-the-ground reality of treating patients with PTSD—and the consequences for patients, families, communities, and healthcare providers. As committee member Melissa Barone—a VA psychologist, no less—noted “we already have evidence-based treatments for PTSD.”
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If the advent of Randomized Controlled Trials (RCTs) that began in the 1960s inflicted a mortal blow to psychedelic research at the time—the reverse is now playing out—the return of psychedelic clinical trials highlights the shortcomings of an epistemology over-reliant on RCTs.
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Finally, this Advisory Committee outcome—handed down by a detached group of administrators ill-equipped to wrangle with the complexity of a novel, paradigm-breaking treatment approach for a desperate patient population—has accomplished something unexpected: it awakened and activated a broad coalition of stakeholders—including the veteran community, politicians, investors, activists, philanthropists, scientists, clinicians, patients, and family members—that will spend the next two months highlighting the unmet need, the strength of available data and epistemological shortcoming of the current paradigm that could ultimately render this advisory meeting a mistrial.
Let’s get into it.
“We already have evidence-based treatments for PTSD”
Last Fall, the 2023 National Veteran Suicide Prevention Annual Report by the U.S. Department of Veterans Affairs revealed that 6,392 veterans died by suicide in 2021 (the latest year records are available).
The report also found that the suicide rate among veterans had increased 11.6% from the year before.
The suicide rate among female veterans increased 24% from the year before.
And yet, during Tuesday’s Meeting of the Psychopharmacologic Drugs Advisory Committee, a committee member—psychologist Melissa Barone from the Department of Veterans Affairs in Maryland—said:
“The other thing I think about is that we already have evidence-based treatments for PTSD. And yes, you know, they do have dropout rates, but they do have really strong outcomes and those treatments usually take around 12 hours of therapy. They’re, you know, covered by insurance. So lots of people have access to them, and they do have strong outcomes. And so, when you think about that, compared to a treatment that’s, you know, 42 hours of treatment, I mean, how do you even compare them…”
To hear this from someone at the VA was breathtaking.
Amidst the discourse on functional unblinding, expectancy bias, disentangling the effect of the drug from the psychotherapy, and alleged misconduct, it was this comment that stuck with me more than anything else.
“We already have evidence-based treatments for PTSD…It only takes twelve hours” reveals a truly untenable perspective.
It is the perspective of someone who is shielded from the reality of treating mental illness, shielded from the reality of provider burnout, and shielded from the reality of moral injury.
Advisory Committee members were overwhelmingly comprised of professionals who appear to have left clinical practice for research, industry, and administrative roles and are, therefore, too detached from the lived experience of patients, families, providers, and healthcare staff in the trenches.
This detachment in the name of objectivity affords them a luxury their colleagues in clinical practice do not have—to hide behind groupthink and the status quo.
In other words, Dr. Barone might have said,
“What are we even doing here? We already have an effective treatment. It only takes twelve hours. It’s covered by insurance.”
RCTs vs Psychedelics
In 1962, the Kefauver Harris Drug Amendments marked the advent of the Randomized Controlled Trial era.
In the wake of the Thalidomide disaster and other instances of pharmaceutical injuries, the new law mandated proof of efficacy through controlled clinical trials before a drug could be approved for sale.
The RCT is the best way to evaluate a treatment—if the treatment can be blinded.
While a boon for public health and affording medicine a more reliable way to scrutinize treatments and establish a rigorously tested toolkit, it had the collateral effect of stifling clinical research on psychedelics as the obviously altered state could not be adequately blinded.
Fast-forward more than sixty years, and Lykos Therapeutics’ New Drug Application brings this epistemological paradigm full circle: A promising new (old) treatment has accumulated evidence, catalyzed cultural demand, and piqued interest from patients and providers, but it doesn’t fit into the paradigm established in 1962.
As industry consultant Harry Tracy noted in an excellent summary aptly titled The Blind Leading the Unblinded:
“…the same conventional thinking dominated, with only one reviewer (from UCLA, a former VA psychiatrist, who made the effort to put on his “clinician hat”) pointing out that the reported effect size was so robust that, even if ‘diluted’ by some undefined expectancy factor, it most likely would still have demonstrated efficacy. The others seized on the functional unblinding issue, and upon Lykos’ report that 37% of PhIII subjects had reported previous MDMA exposure, which in their view further skewed patient expectations and report of benefit, as if rendered automatically invalid.”
This is, of course, not unique to psychedelics, as many psychiatric treatments are plagued by the same confounding factor, but could this high-profile instance mark the beginning of a new era—the post-RCT era?
A Sleeping Giant Awakens
Finally, Tuesday’s outcome—unexpected by most—has activated a multistakeholder coalition that, under ‘peace times’ may be more inclined to nitpick ideological differences but against a newly emergent existential threat, is galvanized, aligned, and motivated.
Over the next two months—until the August 11th deadline the FDA has to make a decision—we are going to see a wide range of stakeholders—politicians, investors, activists, philanthropists, scientists, clinicians, patients, family members, and of course, veterans—apply pressure to lawmakers and regulators and make the case to the American public that the time has come for MDMA-assisted therapy.
Lives depend on it.
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