Coming of age in Berkeley during the height of the counterculture, it would perhaps be a more surprising story if a young Elliot Marseille (now, Dr. Marseille) had managed to avoid encountering psychedelics. Well, not if his parents had anything to say about it: his father, a Freudian psychoanalyst, employed LSD in the treatment of his patients and was open about his own experiences. His mother, a psychotherapist, also took an interest in psychedelic therapy in her own practice.
Today, Marseille’s carrying on the “family business”, he says, albeit via Monte Carlo simulations, QALYs and ICERS: such is the lingo of the health economist. In his position as Director of the Global Initiative for Psychedelic Science Economics (GIPSE), Marseille is preparing for the next major hurdle that psychedelic therapies will need to avoid tripping over: demonstrating cost effectiveness.
We sat down with Marseille to discuss the importance of the health economist’s toolkit and contributions in these considerations, as well as some of the ethical and practical challenges that arise from this work.
To begin, tell us a little about your interest in psychedelics. Is this a recently-developed one, spurred by the so-called ‘psychedelic renaissance’, or is there a richer psychedelics-related personal history here that you would be happy to share?
My roots in psychedelics precede the current renaissance and even the previous one. My father was a Freudian psychoanalyst. In the early 60s when it was still legal, he obtained a supply of LSD, presumably from Sandoz, and used it in the treatment of some of his patients. He also experimented on his own, and told me about some of his experiences.
For example, he had a huge print of a Bruegel painting in the living room called “The Peasant Dance”. Under the influence, he told me that the celebrating peasants appeared to him as Napoleon’s army retreating from Moscow. The red banner festooning the building in the upper half of the painting, appeared as flames from the battle. I was 7 or 8 years old and found this fascinating. From that time on I understood that LSD could be magical.
Growing up in Berkeley during the 60s and 70s it is also not entirely inconceivable that I did some explorations of my own. In 1980, a friend of mine introduced me to Leo Zeff (aka “The Secret Chief”). Through working with Leo I deepened my understanding of the transformative potential of these materials. Through an entirely unrelated route my mother, a psychotherapist, also got to know Leo, and she occasionally conducted sessions with her clients. Until recently, I couldn’t have imagined that I would continue the “family business”, so to speak, albeit in a different form. Life is full of surprises.
Can you briefly sum-up the Global Initiative for Psychedelic Science Economics (GIPSE) for us?
Certainly. Until recently, research on psychedelic-assisted therapy (PAT) has focused almost exclusively on safety and efficacy. This is appropriate. Why put resources into developing service delivery models, or into economic analyses until safety and efficacy are established? At GIPSE we believe that this rationale has exceeded its expiration date. There is now a sufficient body of favorable clinical results, that it makes sense to answer the next set of questions which will need to be addressed if PATs are to be accessible at scale.
Among these are economic questions such as, “Intervention “X” appears to be effective for psychiatric indication “Y”; but is it cost-effective? That is, for a given amount of money, does it deliver superior clinical outcomes versus the current standard of care?” Other questions concern the cost per person and for society; the potential savings from reduced psychiatric morbidity; and other economic benefits such as productivity effects. Yet other questions pertain to how these therapies should be priced so as to maximize overall social benefit; and the design of reimbursement mechanisms that would allow PATs to be integrated into the mental and behavioral health care systems. Research has lagged on these and other economic considerations, yet addressing them is indispensable if psychedelic therapies are to make their full contribution to the health of the public.
At a high level, why is it so important to demonstrate the cost-effectiveness of psychedelic therapies?
It’s simple. If health care payers, both private and public, are going to support these services, they need to know how their budgets will be affected. They also need to know whether these new therapies are good value for the money.
This is an imperfect analogy, but perhaps serviceable for this discussion: No company puts a new product on the market without estimating how this will affect their bottom line. This may be particularly true for stigmatized and previously illegal materials, and for therapies which, like MDMA-assisted therapy (MDMA-AT), have high initial costs. In Europe there is perhaps an even greater emphasis on value for money. For example, NICE in the U.K. makes cost-effectiveness an explicit criterion for acceptance, something the U.S. FDA does not. (Editor’s note: see Bulletins from August 2021 and June 2022 for our coverage of this topic through the lens of Janssen’s esketamine nasal spray, Spravato.)
To make this more concrete for our readers, can you briefly describe the findings of your cost-effectiveness analyses of MAPS’ MDMA-assisted therapy for PTSD phase 3 data?
We used clinical results from the MAPS phase 3 trial, early estimates of the cost of MDMA-assisted therapy, and costs of medical care, excess mortality and other parameters from the published literature to model the costs and cost-effectiveness of MDMA-assisted therapy over various time horizons. For a hypothetical cohort of 1,000 patients, compared to standard of care for 1,000 patients, MDMA-AT generates discounted net health care savings of $132.9 million over 30 years, accrues 4,856 quality-adjusted life-years (QALYs), and averts 61.4 premature deaths. It is thus not merely cost-effective but cost saving to the health care payer.
If one conservatively assumes that benefits ceased after 3.8 years, MDMA-assisted therapy breaks even on costs while still delivering 887 QALYs. Another important finding of our study is that the third active MDMA session of the phase 3 trial yielded both additional savings and additional benefits compared with the two-active session regimen of the Phase 2 trials.
An important proviso: These estimates are based on the best estimates of the cost of MDMA-assisted therapy available at the time. However, MAPS Public Benefit (PBC) Corporation is considering a wide range of prices for MDMA which could result in much higher costs for MDMA-assisted therapy, and thus less favorable cost-effectiveness outcomes. We are now formalizing our analysis of the effect of a wide range of parameter values affecting the economics of MDMA-assisted therapy, including the cost of the MDMA itself.
The participants in MAPS’ phase 3 trials were suffering from especially severe and intractable cases of PTSD, right? What does that mean for broadening MDMA-AT to people with ‘mild’ PTSD diagnoses: do you expect MDMA-AT to remain cost-effective, and what might the break-even period look like in these less severe cases?
This is an important point. The favorable clinical results from the MAPS trials pertains to people with severe or extreme treatment-resistant PTSD who had lived with the diagnosis for an average of 14 years or 18 years for the phase 3 and phase 2 trials, respectively. How people with milder or less chronic forms of the disorder will respond is unknown. However, for multiple reasons, from a cost-effectiveness perspective, the results are likely to be less favorable, and probably much less favorable.
First, patients who go into remission from mild or moderate PTSD, by definition, get less benefit than those who go into remission from more severe forms of PTSD. There is simply less health benefit to be obtained.
Second, early PTSD, resolves for many people without specific treatment within a year or so. For those people, MDMA-assisted therapy offered as a first line treatment is, in effect, wasted. That’s on the benefit side.
On the cost side, less money is spent on medical care for people with less severe PTSD; thus, there is less money to save as patients’ PTSD status improves. Finally, relatively inexpensive standard therapies work for a substantial portion of people with early PTSD. This pessimistic view regarding the cost-effectiveness of MDMA-AT for less severe PTSD could turn out to be wrong, if it turned out to be spectacularly effective for these milder cases. We should try the therapy with a sufficient number of such patients and find out.
On a similar note, are there challenges in relying on clinical trial data to make these cost-effectiveness and cost-benefit analyses, given that we might expect the effectiveness of an intervention to be reduced in ‘real-world’ settings? Are there ways of accounting for that (e.g., discounting or otherwise scaling down efficacy predictions) in your analyses?
Right. As you point out, ‘real-world’ effectiveness is often lower than the ‘efficacy’ reported from clinical trials. There is no substitute for actual data from real-world settings to see how large the difference is in the case of psychedelic therapies. But in the interim, in order to get some idea, we can look for published data on that difference for other psychiatric interventions. We have not done this yet, but it is in our “to-do” list.
In this regard, does Oregon’s Psilocybin Services (which will allow for legal psilocybin therapy in many areas of the state from next year) represent a natural experiment for researchers like you?
Yes. We are interested to see how exposure to psilocybin in both clinical and non-clinical settings affects health care utilization, and how it affects depression, anxiety, substance use disorders and other measures of mental and behavioral health. Much depends on the willingness of participating facilities and their clients to provide the relevant information.
I would like to see agreement on a core set of data forms that would be completed not just for diagnosed patients but also for clients who are not seeking treatment per se but are availing themselves of psilocybin for less specific personal development. This is an important opportunity, and one which deserves intense focus over the next few months.
Beyond payers, could it be argued that your economic analyses might be used to aid drug developers in making their prices as high as the market would tolerate? Is that an ethical concern that folks in your field grapple with?
I do think there are ethical dimensions to these questions, and it is difficult to chase down all of the consequences. Let’s say an intervention is highly cost-effective or cost-saving. This can, as you say, encourage higher prices for the drug itself than would be the case if the intervention were found to be less cost-effective. Two points here: First, there is a logic to more effective and more cost-effective therapies commanding a higher price. As long as they are not so high that they discourage payers from accepting them, this is a sensible alignment of incentives. But secondly, what is the alternative? In the absence of credible economic analyses, payers will be reluctant to make the treatment available at all. How is that ethical? Analysts can’t choose which results to make public based on their assessment of the downstream consequences. That would undermine trust in the entire enterprise of transparent, rigorous analysis for the allocation of health care resources.
Now let’s take the opposite case and suppose that a PAT is found to be a poor use of money compared with feasible alternatives, i.e., that money could better be deployed on more effective (or less cost) interventions. In that case, society benefits from that knowledge both financially and in health outcomes. But undoubtedly there would be some people who would have benefited from that uneconomical PAT. As is the case in public health generally, we should usually (but emphatically not always!) be guided by utilitarian principles that look to maximizing overall societal net benefit.
We have talked a lot about mental health indications like PTSD, but are there other conditions that you believe might be very clearly cost-effective when it comes to psychedelic therapies?
I don’t want to get ahead of the more definitive clinical data which will be coming out on a variety of psychedelic treatments over the coming months and years, but the interim findings from Matthew Johnson’s work at JHU on psilocybin for smoking cessation look extremely promising from a cost-effectiveness point of view. The superior cessation rates compared with standard-of-care nicotine patches, combined with the huge disease burden associated with smoking, suggests likely favorable cost-effectiveness.
The same may be true for alcohol use disorder based, in particular, on the recent paper from Michael Bogenschutz at NYU. (Editor’s note: we covered this study in a recent Bulletin.)
To end, can you share one thing that you’re concerned about re: the future of psychedelic medicine, and one thing that makes you especially excited?
Via exposure to psychedelic therapies, and also via the thoughtful use of psychedelics in non-clinical settings, millions of people in the U.S. and elsewhere will make contact with the numinous. This is indeed exciting. It will have consequences that are impossible to predict; but they will be profound and, in my view, are likely to be positive.
One of the things I’m concerned about is how we will care for people who, despite appropriate screening and post-trip integration sessions, are destabilized by the psychedelic experience. This may be a small portion of people exposed to psychedelics in clinical settings, but a small portion of a very large number is a large number. We have an ethical obligation to provide additional support to these people. And as a practical matter it may take only a few such incidents to be covered in the media, to shift the currently favorable climate of public opinion on psychedelics in a more negative direction. I am not a clinician and have no practical suggestions to offer, but I have heard too little discussion of this potential problem, and believe we need to get ahead of it.
You can learn more about the Global Initiative for Psychedelic Science Economics (GIPSE), and contact Elliot Marseille, via the network’s webpage.