Garbage from NYU Langone
A Response to Caplan and Moch
While Matt has been wandering the microcontinent of New Zealand, the article “Breakthrough Therapies Act: Good idea, wrong solution” dropped. In the piece, authors Caplan and Moch take on the Breakthrough Therapies Act, a bill recently introduced by Senators Booker and Paul.
Full disclosure: We consulted on the text of the Act. This is our response.
One can conceive of valid critiques to the Breakthrough Therapies Act. One may, for example, believe that decriminalization ought to take precedence over or go hand-in-hand with medicalization. Such a person might criticize the bill because it does squat for criminal justice reform. Or, one could identify a technical issue: a theoretical bifurcated scheduling that could arise after breakthrough therapy approval. These are criticisms one could make after reading the bill’s text.
Sadly, Caplan’s and Moch’s criticisms are not of this ilk. Indeed, we doubt they read the bill they deem a “wrong solution.” Before we get to that, let’s start with a tale of the tape.
Arthur Caplan is a world-leading bioethicist stationed at NYU Langone. His credentials could fill an auditorium. You can see his March 2022 long form disclosure here. Recently, he has stirred up controversy when he asserted that those who do not get the COVID vaccine “should pay for their poor choices that hurt others.” Guy is no stranger to browbeating.
Kenneth Moch is a graduate of Stanford School of Business and works in the Department of Medical Ethics at NYU with Caplan. He has served or currently serves as an executive or advisor for numerous pharmaceutical companies. He is currently the president of Euclidean Life Science Advisors, LLC. He advises Zynerba Pharmaceuticals, “an orphan-focused, neuropsychiatric, biopharmaceutical company taking a different and exciting transdermal approach to cannabinoids.”
Us? As noted above, we assisted with the bill. We support it. We’re currently litigating many of the same CSA issues now in federal court. We’ve been doing so for some time. So we aren’t as adorned as Caplan. And yes, we’re biased. (For a less biased/interested view, we encourage reading Mason Marks’ take on his newly launched Substack.1) But we certainly have read the bill. We know the issues. And yes, we know the law. Other than the litigations we’ve been involved in, we have no affiliations.
Based on their credentials, you would think these gentlemen would know what they are talking about. They don’t.
Start with their claim that the bill’s sponsors’ “misunderstand[ ] what is required to achieve FDA Breakthrough Therapy designation.” A bold claim, for sure. Divining what other folks do or do not understand—let alone from behind a keyboard with no personal interaction—is a difficult task. We seriously doubt the authors interviewed the sponsors or their staffs to figure out what they understand. Beyond that, what is particularly troubling about Caplan and Moch’s claim is they provide no evidence to substantiate the claimed lack of understanding.
They proceed to describe the process required to achieve a Breakthrough Therapy designation. They call it difficult. True enough. Later, they say it doesn’t make sense for “two federal agencies to simultaneously be regulating the clinical development process for the same experimental medicine.” Maybe so. This seems to be a fundamental gripe: the bill doesn’t do enough because it doesn’t recalibrate the distribution of delegated authority between DEA/FDA. A more “appropriate approach,” they say, “would be to allow the FDA to itself review the release parameters for any Schedule I drug to assure there is no abuse or misuse during the course of the clinical development process.”
They could be right. It is a perfectly appropriate viewpoint and valid criticism. But so what? The authors claimed that the sponsors “misunderstand[ ] … what is required to achieve FDA Breakthrough Therapy designation.” They never seem to prove that claim or seriously consider the possibility that, maybe, the sponsors do understand all this—and that knowing all this, this legislation is not trying to reinvent the wheel, fix every structural defect in one fell swoop, or fix the pet issue the authors care about most.
Equally important, is this a flaw in the bill? The purpose of this bill may not be to fix all the DEA-FDA issues at the preclinical and Phase I clinical trial level, where, according to the authors, most delay occurs. Not every bill is a Civil Rights Act of 1965, after all. Maybe, for example, this bill is an incremental change and is not hand-designed by pharma to serve pharma.
To say the sponsors “misunderstand[ ]” the FDA Breakthrough Therapy designation simply because the bill doesn’t fix the specific issues the authors care about is at best sloppy and irresponsible writing. This wouldn’t the first time Caplan and Moch have gone over the top with rhetoric or overstated a position. A fairer criticism—one that avoids unnecessary and unsubstantiated claims—might simply assert that the bill doesn’t address what the authors perceive to be the more significant issues with clinical research.
And that assertion might be fine in the abstract. Except here, it would be dead wrong. Section 2 of the bill—starting on line 6—is entitled “REGISTRATION REQUIREMENTS RELATED TO RESEARCH.”
This section puts forward numerous fixes that would expedite aspects of the very approval process that the authors complain of. These are fixes that all agencies, including FDA and DEA, have blessed. It is designed to pass. You can’t miss this part of the bill (if you read it). Not only is it up front, but it consumes 15 of the bill’s 18 pages. Would this fix the process wholesale or exactly as the authors propose? Perhaps not. But it does address some issues.
Indeed, when one looks at the entire bill, it is evident that there is no “misunderstanding of what is required to achieve FDA Breakthrough Therapy designation.” First, Section 2 of the Breakthrough Therapies Act—which Caplan and Moch do not discuss—makes it easier to complete Phase I trials with all Schedule I substances. Second, Section 3 follows and provides a mechanism to reschedule drugs that were shown to be safe in Phase 1 trials and have shown exceptionally promising end-points so that they can be used in expanded access or other severely restricted access programs with certain populations.
This second part isn’t even novel. FDA itself said that drugs far enough in the development process may qualify as having a “currently accepted medical use with severe restrictions” and could be rescheduled. All this bill does is say that a Breakthrough Designation—a designation reserved for drugs shown to be safe and with a favorable risk/reward profile—is one such circumstance.
Their second bold claim takes us even further off the reservation:
allowing an experimental medicine to be used through the expanded access process, or via the utterly ill-conceived Right to Try process that both Senators tried to “clarify,” does not advance the potential approval process for psychoactive medicines or, in fact, for any experimental medicines
Again, assuming one has read the bill, this is a difficult claim to make. The bill streamlines rescheduling “a drug or other substance that is an active moiety or active ingredient (whether in natural or synthetic form) of an investigational new drug” for which a breakthrough designation or intermediate expanded access has been achieved. Rescheduling, of course, not only makes drugs more easily used in expanded access protocols, it also makes it easier to research those substances, including for drug developers conducting Phase III clinical trials (among others). This would have a ripple effect of automatically rescheduling in around half the states in the country with “parity” laws that require consistency with federal drug scheduling.
In other words, once a Schedule I drug (present or future) progresses far enough in the clinical trial process to show safety and a potentially advantageous risk-reward profile for those with life-threatening conditions, we’re going to relax CSA barriers (just barely) to make it easier for physicians to use in controlled, restricted expanded access settings and for others to research the promising compound. Common sense, right?
The authors appear to approach the issue not from the viewpoint of either the patients or even the industry/research as a whole, but from a single pharmaceutical company developing a proprietary IND. And that should surprise no one. This isn’t their first rodeo with expanded access programs.
They then add: “expanded access is not clinical development. It does not advance the research or drug approval processes.” But again, so what? The authors ignore three points: (1) even if correct, this portion of the bill might be designed to do something different, (2) rescheduling from Schedule I to II does, in fact, advance research or drug approval products, and (3) the front-line section of the bill entitled “REGISTRATION REQUIREMENTS RELATED TO RESEARCH.” They also ignore a more fundamental point: expanded access isn’t clinical development but can be used to develop infrastructure and best practices—something psychedelic assisted therapy movement sorely needs.
Finally, note what the authors did not say. They never really explain why enacting the Breakthrough Therapies Act would be a bad idea and isn’t progress, other than vaguely discussing how these controlled access programs could delay completion of clinical trials. Taking what they say as true (which one need not do), one is left with a single potent point: the bill does not do enough. A half-step measure is worse than complete reform. But maybe that’s a feature, not a bug. Maybe, for example, narrowly tailoring small reforms can achieve bipartisan consensus—and pass.
We get that the authors want more daring fixes. And vigorous debate is always good. But this short hit piece appears to be built on strawmen—and dare we say—“misunderstanding.” Caplan, who has gone on tour combatting vaccine misinformation and is a leading medical ethicist, should know better.
While you are at it, his Wired article and post on data privacy issues in Oregon are also worth reading.