Few drugs have triggered as much controversy and debate as those for Alzheimer’s Disease. So, it should come as no surprise that last week’s update from Centers for Medicare and Medicaid Services (CMS) on its coverage for these treatments would trigger a wide range of responses. Some outlets reported that CMS was broadening its coverage, even as other groups stated that the agency was limiting access. Others argued that the update heralded no change at all.
None of these takes are completely accurate and all miss a deeper concern.
CMS’ announcement anticipates the full approval of the second Alzheimer’s drug to the market, lecanemab. In its press release, the agency confirmed it would cover any new drug for Alzheimer’s Disease with full approval from the Food and Drug Administration (FDA) and that it was preparing a patient registry to collect data on these treatments. Currently, all new Alzheimer’s drugs have accelerated approval, which is based on measurable biological changes, not observable improvements in a patient’s condition. In a National Coverage Determination (NCD) issued last year, CMS committed to pay for these drugs when administered as part of a randomized controlled trial (RCT). The agency also noted that once a drug received full FDA approval based on an observable clinical benefit, it would extend coverage to beneficiaries enrolled, or “registered” in prospective observational studies.
Put another way, CMS confirmed its existing policy, but didn’t broaden it. Did it act to limit it instead?
Opponents argue that present coverage has been restrictive because RCTs randomly assign patients to treatment and control groups. By definition, this limits access to beneficiaries assigned to treatment. However, CMS will allow broader access by covering drugs with full approval when beneficiaries participate in prospective observational studies. In these studies, patients are tracked over time from the start of treatment; randomization to receive one treatment or another is not typically required. In other words, once a new Alzheimer’s drug receives full approval, patients can receive it as long as data are collected.
Some argue that any requirement for a clinical study – regardless of type – limits patients’ access to the drugs because providers must collect the data. In yesterday’s announcement, CMS established it was setting up a system for collecting the requisite data – called a registry – to ease the task of collecting the data. Participation in a “prospective observational study” need not be onerous if the agency streamlines processes to record the necessary information.
Some groups view registries as a barrier to access, but little evidence supports this stance. Consider transaortic valve replacement (TAVR), which is covered like Alzheimer’s drugs with full approval. Medicare will pay for TAVR as long as providers participate in a registry and meet certain infrastructure criteria. Although this has limited TAVR to certain treatment centers, most Americans undergoing the procedure receive it within their hospital referral region.
In the case of drugs for Alzheimer’s disease, the likelier barriers to access seem to be the requirements for treatment. Patients have to visit doctors’ offices or clinics for infusions on a regular basis. They also require frequent MRI scans to monitor for side effects of treatment, which includes swelling and bleeding of the brain. Scheduling and arranging transportation for these services has its own complexities for those living with the early stages of dementia. Those facing the greatest difficulties will likely be patients in rural and underserved areas with few healthcare providers and facilities with MRI machines, as well as lower quality of care for patients with dementia.
Although CMS neither broadened coverage nor limited it, yesterday’s announcement also doesn’t signal much about how it will apply the NCD. The threshold that drives CMS here – whether coverage of these treatments is ultimately “reasonable and necessary” – was set by Congress in 1965 when it created Medicare. Conforming with it means learning whether these treatments slow cognitive decline in the long run, whether different types of patients respond differently, and whether their responses change over time.
The agency has yet to clarify what sorts of observational study designs it will support to populate the registry. These details matter. To answer CMS’ questions, the data must allow for comparisons between diverse groups of Medicare beneficiaries, different drugs, and numerous treatment outcomes. Protocols must be developed and followed from the time patients elect to begin treatment until they stop. Seemingly small but important nuances, such as potential biases in treatment selection, must be considered and planned for.
Dr. Robert Califf, the FDA Commissioner, likens the transition from the FDA approving a drug to CMS covering it to passing the baton in a relay race. What one runner hands off, another should pick up. It’s important not to fumble it. But it’s also important to understand what race is being run, and who’s in it. In the case of Alzheimer’s, it appears to be a marathon and the other runner, biology. The standards CMS sets now will determine its performance in the race. Its best shot: to maintain a high standard for data that answer questions current clinical studies will leave open even after FDA approval.