Updated cost-effectiveness of MDMA-assisted therapy for the treatment of posttraumatic stress disorder in the United States: Findings from a phase 3 trial

This study (2022) builds on previous research assessing the cost-effectiveness of MDMA-assisted therapy (MDMA-AT) for the treatment of PTSD by assessing the data from a recent phase III trial. MDMA-AT as conducted in the phase III trial costs $11,537 per patient. Compared to the standard of care for 1,000 patients, MDMA-AT generates discounted net health care savings of $132.9 million over 30 years. Ultimately, MDMA-AT for severe or chronic PTSD is cost-saving while delivering substantial clinical benefit.

Abstract

“Background: Severe posttraumatic stress disorder (PTSD) is a prevalent and debilitating condition in the United States. and globally. Using pooled efficacy data from six phase 2 trials, therapy using 3,4-methylenedioxymethamphetamine (MDMA) appeared cost-saving from a payer’s perspective. This study updates the cost-effectiveness analysis of this novel therapy using data from a new phase 3 trial, including the incremental cost-effectiveness of the more intensive phase 3 regimen compared with the shorter phase 2 regimen.

Methods: We adapted a previously-published Markov model to portray the costs and health benefits of providing MDMA-assisted therapy (MDMA-AT) to patients with chronic, severe, or extreme PTSD in a recent phase 3 trial, compared with standard care. Inputs were based on trial results and published literature. The trial treated 90 patients with a clinician-administered PTSD scale (CAPS-5) total severity score of 35 or greater at baseline, and duration of PTSD symptoms of 6 months or longer. The primary outcome was assessed 8 weeks after the final experimental session. Patients received three 90-minute preparatory psychotherapy sessions, three 8-hour active MDMA or placebo sessions, and nine 90-minute integrative psychotherapy sessions. Our model calculates the per-patient cost of MDMA-AT, net all-cause medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We reported results from the U.S. health care payer’s perspective for multiple analytic time horizons, (base-case is 30 years), and conducted extensive sensitivity analyses. Costs and QALYs were discounted by 3% annually. Costs were adjusted to 2020 U.S. dollars according to the medical component of the U.S. Bureau of Labor Statistics’ Consumer Price Index (CPI).

Results: MDMA-AT as conducted in the phase 3 trial costs $11,537 per patient. Compared to the standard of care for 1,000 patients, MDMA-AT generates discounted net health care savings of $132.9 million over 30 years, accruing 4,856 QALYs, and averting 61.4 premature deaths. MDMA-AT breaks even on cost at 3.8 years while delivering 887 QALYs. A third MDMA session generates additional medical savings and health benefits compared with a two-session regimen. Hypothetically assuming no savings in health care costs, MDMA-AT has an ICER of $2,384 per QALY gained.

Conclusions: MDMA-AT provided to patients with severe or extreme chronic PTSD is cost-saving from a payer’s perspective while delivering substantial clinical benefit.”

Authors: Elliot Marseille, Jennifer M. Mitchell & James G. Kahn

Summary

Background Posttraumatic Stress Disorder (PTSD) affects 11.8 million Americans and is associated with a wide range of comorbid health conditions. Current pharmacological and psychotherapeutic treatments have limited effectiveness for many patients. Six phase 2 randomized, placebo-controlled, multi-site clinical trials showed that MDMA-assisted therapy (MDMA-AT) was safe and effective for treating PTSD. The cost-effectiveness analysis indicated that third party healthcare payers would save $103.2 million over 30 years. The first of MAPS’ two phase 3 trials added substantial evidence for the benefits of this new therapy. This economic study re-calculates the cost-effectiveness of MDMA-AT based on the results of this new trial. Overview A Markov process model was used to portray clinical benefits, MDMA-AT costs, and net medical costs in a hypothetical cohort of 1,000 patients reflecting the distribution by PTSD severity of 90 patients treated in the MAPS-sponsored randomized, placebo-controlled, multi-site phase 3 trial. Patient population 90 subjects with PTSD participated in the trial; the mean duration of PTSD was 14.1 years, and the mean Clinician-Administered PTSD Scale (CAPS-5) total score was 44.1 (SD, 6.04). The majority of subjects were females and white, and the majority of subjects had received previous therapy. Treatment protocol After recruitment, randomization, and three non-drug 90-minute therapy sessions, participants received blinded doses of MDMA or placebo. Three 90-

Background

Posttraumatic Stress Disorder (PTSD) affects 11.8 million Americans and is associated with a wide range of comorbid health conditions. Current pharmacological and psychotherapeutic treatments have limited effectiveness for many patients.

Six phase 2 randomized, placebo-controlled, multi-site clinical trials showed that MDMA-assisted therapy (MDMA-AT) was safe and effective for treating PTSD. The cost-effectiveness analysis indicated that third party healthcare payers would save $103.2 million over 30 years.

The first of MAPS’ two phase 3 trials added substantial evidence for the benefits of this new therapy. This economic study re-calculates the cost-effectiveness of MDMA-AT based on the results of this new trial.

Overview

A Markov process model was used to portray clinical benefits, MDMA-AT costs, and net medical costs in a hypothetical cohort of 1,000 patients reflecting the distribution by PTSD severity of 90 patients treated in the MAPS-sponsored randomized, placebo-controlled, multi-site phase 3 trial.

Patient population

90 subjects with PTSD participated in the trial; the mean duration of PTSD was 14.1 years, and the mean Clinician-Administered PTSD Scale (CAPS-5) total score was 44.1 (SD, 6.04). The majority of subjects were females and white, and the majority of subjects had received previous therapy.

Treatment protocol

After recruitment, randomization, and three non-drug 90-minute therapy sessions, participants received blinded doses of MDMA or placebo. Three 90-minute psychotherapeutic integration sessions were provided following each experimental session.

Representation of treatment effects

We modeled the costs and benefits of the active treatment group after receiving MDMA-AT with the same group at baseline assuming no change in their treatment.

Patients transitioned to death according to the relative risk of mortality by severity category. The intervention effect was captured as the difference between baseline and follow-up in the distribution of patients by severity categories.

The model was implemented in Excel1 and used @RISK1 for sensitivity analyses. Costs were discounted at 3% per year.

Health state utility values

The EQ-5D-5L questionnaire was administered to phase 3 trial participants, and scores were converted to utilities. Adverse events were transient.

Intervention costs

Using micro-costing, MDMA-AT service delivery costs were estimated for eight metropolitan areas using FAIR Health Consumer data or Medicare allowable reimbursement.

Medical care costs

We updated our previous estimate of all-cause medical costs borne by U.S. medical care payers for patients with PTSD by applying the medical care component of the Consumer Price Index for 2020.

Mortality, analytic time horizon, and outcomes

We used the age-specific background U.S. mortality rate as a referent and calculated the relative mortality risks for patients with PTSD. We calculated the costs and health consequences for 30 years and found that net payer costs break-even after 10 years.

For the probabilistic, multi-way sensitivity analyses, we ran 10,000 Monte Carlo simulations with beta distributions specified for probabilities, gamma distributions for costs, and lognormal distributions for relative risks.

We performed scenario analyses to determine the long-term durability of MDMA-AT benefits and calculated an ICER comparing the cost and health consequences of two MDMA-AT protocols.

Base-case

MDMA-AT cost $11,537 per patient, was 90.7% clinicians’ compensation, generated 4,856 discounted QALYs, and saved $132.9 million in combined mental health and general medical care costs, compared with standard of care. It breaks even in costs at 3.8 years.

Sensitivity and scenario analyses

In one-way sensitivity analyses, the mean age of the patient cohort, the cost of treating severe and extreme PTSD, and the relative mortality risk associated with severe and extreme PTSD affect net savings.

MDMA-AT ceases to yield net savings if the medical care costs associated with PTSD are assumed to be 22.3% of the base case values.

A 10,000 iteration Monte Carlo analysis showed that the MDMA-AT cohort would save $69.8 million and gain 3,018 QALYs after 5 years.

Estimate of the incremental cost-effectiveness of three versus two MDMA sessions

The third 8-hour session plus three accompanying 90-minute integration sessions generates 26 additional QALYs at an incremental net cost of $1.8 million for 1,000 patients, and is cost-effective.

Discussion

A study using phase 3 trial data found that providing MDMA-AT to severely affected PTSD patients would save the health care system money while generating substantial health benefits.

The results of the two studies vary in consequential ways, but the phase 3 trial showed a higher rate of patients with severe or extreme PTSD, and more patients were averted from death.

In the current study, the health benefits associated with less severe PTSD were lower than in the previous study, because the utilities associated with less severe PTSD were measured using a consistently-applied method in the most directly-relevant patient population.

The addition of a third MDMA session was likely responsible for the greater efficacy seen in the phase 3 trial, as evidenced by the large drop in CAPS-5 scores between sessions 2 and 3, and the favorable ICER of the three-session regimen.

The phase 3 trial utilized a centralized assessment core and used EQ-5D-5L data drawn directly from the trial subjects. The sensitivity and scenario analyses reinforced confidence in the validity of these findings and suggested that MDMA-AT would have an attractive ICER of $2,384 per QALY over 30 years.

This is the first study to estimate MDMA-AT cost-effectiveness using phase 3 data. If the results of a second phase 3 trial demonstrate comparable benefits, MDMA-AT should be approved by the FDA and made available to the public.