NAMI Highlights Concerns With ICER's Review of TRD

Seven percent of adults in the U.S. — an estimated 16 million people — experienced at least one major depressive episode in 2016 alone. Depression can be difficult to treat effectively because of variations in the level of severity and how a person responds to treatment. One in three people with depression have treatment-resistant depression (TRD), a devastating condition involving major depressive episodes with an inadequate response to therapy.

Seven percent of adults in the U.S. — an estimated 16 million people — experienced at least one major depressive episode in 2016 alone. Depression can be difficult to treat effectively because of variations in the level of severity and how a person responds to treatment. One in three people with depression have treatment-resistant depression (TRD), a devastating condition involving major depressive episodes with an inadequate response to therapy.

People living with TRD often experience months or even years of trial and error with different medications and combinations of therapies without relief. This challenge significantly increases the burden of the disease and disability on the individual and their caregivers, and increases the associated medical costs and economic losses, estimated at $64 billion a year.

Hope is on the horizon, given the FDA approval of a medication for TRD in March 2019.

Yet the treatment has already come under the purview of the Institute for Clinical and Economic Review (ICER), which has initiated a value assessment of this medication, comparing it with other antidepressants, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and an infusion therapy used off-label. With the exception of other antidepressants, none of these treatments has undergone the same rigorous review required of the FDA-approved medication for TRD, and these other treatments are not typically covered by most insurance plans.

Patient organizations, including the National Alliance on Mental Illness (NAMI), the nation’s largest grassroots mental health organization, have weighed in during ICER’s assessment process to ensure that the concerns of people living with TRD are considered. NAMI Director of Legislative Advocacy Andrew Sperling, who has participated in previous ICER assessments, most recently for one on tardive dyskinesia, shared NAMI’s experience with this latest ICER review and how his organization’s previous efforts influenced its approach.

NPC: Thank you for speaking with us, Andrew. First, tell us about TRD and what makes this treatment so important.

Depression can be very difficult to treat because it usually takes several weeks before the individual taking the medicine begins seeing clinical benefits. It could be 6-8 weeks before patients know whether it is working. If they need to try a different medicine, they need to wean off that first medicine before starting a new 6-8 week trial period to find relief. TRD is defined as having failed on three different antidepressants without symptom relief. The new medicine approved for TRD can provide relief of depressive symptoms as soon as 1-2 hours and was approved as an add-on therapy with antidepressants. That’s a huge improvement over waiting weeks or months.

NPC: This is your second involvement with an ICER review for treatments for mental illness. Based on your previous experience with the review for tardive dyskinesia treatments, did you change your approach in providing comments or how you engaged with ICER? If so, how?

Our approach was similar in that we engaged in every opportunity to provide comments to ICER. We also alerted NAMI members across the country to inform and educate them about new developments. NAMI has state and local groups who have experts come to their group meetings to discuss new treatments and breakthroughs. They are aware of the ICER review and may have local discussions on this and related topics.

For TRD, I presented at the May 23, 2019, public meeting where experts reviewed the ICER report and voted on questions relating to cost effectiveness and value. I have not done that before.

In terms of differences between this review and the previous one, we have seen some progress with ICER’s response to comments. For example, in response to NAMI and others in the mental health community, ICER agreed not to use a comparator that required people with TRD to keep trying and failing on different antidepressants.

NPC: Has ICER’s willingness to engage with NAMI and other patient groups changed?

Certainly, ICER has gotten better in talking with us. They are interested in demonstrating that they are listening to patients. For example, before ICER drafted their scoping document for TRD, they had a 45-minute call with doctors and patient groups about disease burden and treatments. Has this interaction shown any meaningful difference? The jury is still out.

Many of us in the patient advocacy community have raised issues with ICER’s use of quality-adjusted life years (QALYs) as a measure for value, but they continue to use it.

NPC: Let’s talk about QALYs for a minute. As you’ve done in the past, NAMI’s recent comments questioned the use of QALYs to measure value for diseases like depression, where extended life expectancy is not a primary outcome of treatment. What are the major drawbacks of QALYs when it comes to depression and other mental illnesses? What’s a better way to assess value from a patient perspective?

As I mentioned, we continue to find fault with ICER’s reliance on QALYs to assess the value of treatments for mental illness. Mental illness is a disability, and QALYs start by assuming a lower value for a person’s life when living with a disability. It is also hard to put a dollar value on a depression-free day, and QALYs are a blunt instrument when capturing the value of relief for patients. For TRD, patients have been through multiple treatments for months -- if not years -- without relief of their depression. Finding relief is extremely valuable for those individuals, but hard to quantify. QALYs fail to capture the frustration of having to wait weeks and weeks to see if something will work.

In terms of a better way, actually talking to patients and listening to their frustration with treatment as usual would be helpful to understand the tremendous burden involved and fully appreciating the challenges in having to wait to see if a medicine will work. We also should not ignore the growing public health burden of suicide. Death rates from suicide are greater than prostate and breast cancer. Depression is the leading risk factor for suicide.

NAMI is involved in an effort led by the National Health Council that is looking at ways to better integrate the patient voice and perspective in existing frameworks. It’s a relatively new effort and a work in progress, but shows promises and engages with patients up front to help design a better way to define and assess value.

NPC: ICER’s evaluation of TRD treatments included consideration of “other benefits or disadvantages and contextual considerations,” which the earlier assessment on tardive dyskinesia did not. NAMI raised important issues related to looking at the individual as a whole person, including the fact that many people living with TRD have other health conditions requiring attention that are adversely affected by depression. Why is looking at disease burden to include other conditions important with depression? How did ICER address this issue?

We were pleased to have the opportunity to include more contextual considerations to inform ICER’s analysis. With the tardive dyskinesia analysis, ICER placed no value associated with the social stigma of the disease and how limiting that is for people. The involuntary lip smacking and facial tics make finding and maintaining employment extremely difficult, and social interactions are limited. That’s devastating for the person affected, yet was not captured in ICER’s evaluation. Many people mistakenly assume that people with tardive dyskinesia have significant cognitive impairments, which again adds to the stigma and human burden of the condition.

With TRD, we did feel like ICER included some of the burden of depression in their analysis. The burden of depression also has a broader evidence base, which assisted in having that information included. How much it affected the final outcome isn’t clear.

NPC: ICER included off-label treatments as comparators in both value assessments for TRD and tardive dyskinesia. Is the inclusion of off-label therapies a positive or negative step in terms of value assessments? What are the risks for patients? How did your approach change in voicing your opinion on the off-label treatment comparator for TRD?

We did not change our approach with respect to ICER’s inclusion of an off-label infusion therapy, although we will continue to challenge them on their inclusion of interventions not approved by the FDA.

The inclusion of off-label comparators is troubling from the perspective of the lack of evidence and rigor some of these alternatives have undergone. FDA approval of new medicines is a rigorous, lengthy process that tests efficacy and safety through well-controlled clinical trials. We learn about appropriate dosing and potential side effects. With off-label treatments, we often don’t have clinical guidelines for those treatments and there haven’t been clinical trials testing the safety and effectiveness of these treatments. How can a patient, or insurer for that matter, tell if a doctor is administering the treatment appropriately without clinical guidelines or clinical trials?

We do not believe it’s likely that health plans will cover sending patients to a clinic to receive an off-label treatment that has no clinical research, clinical guidelines, or other strong evidence to support treatment protocols or results, despite ICER’s findings on the value of an off-label treatment.

NPC: After the latest review process, what would you change about your approach with ICER? Any new insights for other groups interested in engaging based on this experience?

The mental health community is fortunate in that there are many new treatments coming out, and that will likely mean more ICER reviews. There is a new drug for schizophrenia in clinical trials, for example. NAMI will continue to engage with ICER in good faith, but understand that there does not seem to be an interest to change their methods and recognize that QALYs fail to capture what is important to patients. That’s especially troubling with what’s available and what’s not available for treating mental illnesses. Many of these medicines have challenging risk profiles and side effects, so new treatments that address the challenges people with mental illnesses have can be significant breakthroughs for the community that are undervalued in ICER’s current framework.

NPC: Thank you, Andrew.