Medicare’s Alzheimer’s drug plan lacks access to diversity

Racial minorities and others disproportionately affected by Alzheimer’s disease could continue to face barriers to treatment unless Medicare does more to facilitate access to research and safety studies, according to the political observers.

Medicare and Medicaid Service Centers plan finalized for Biogene Inc.‘s Aduhelm limits coverage to patients enrolled in certain clinical trials. The agency says approved studies must include a diverse group of patients representative of the nationally diagnosed population. But patient advocates say that doesn’t clarify how trial organizers can tackle geographic, financial and safety barriers to participation.

These vulnerable patients are “the ones who are going to bear the brunt of a bad decision first,” when you don’t have an agency to guarantee the drug actually works for them, said Reshma Ramachandran, a member of the National Clinician Scholars Program. from Yale University. .

The CMS made several changes to its original coverage determination in response to issues with advocacy groups accessing trials. The agency removed the requirement that approved clinical trials take place in outpatient hospital settings, as well as exclusion criteria that would have prevented Down syndrome patients from participating.

But hospitals may be the only places where the medical research teams needed to carry out these trials are located, even if some minority and rural populations may not live near these sites or have the resources to travel. The coverage plan also does not push researchers to conduct preliminary safety studies for patients with Down syndrome, which is necessary before including them in larger efficacy trials.

Policy watchers say the CMS could reimburse patients for the time and travel needed to participate in these trials, and also clarify to trial sponsors when additional safety data is needed on specific populations. The agency could also require that CMS-approved comparative studies using patient health databases meet certain diversity criteria.

Tamara Syrek Jensen, director of the CMS Centers Coverage and Analysis Group for Clinical Standards and Quality, said in a public call to stakeholders on April 11 that “diversity is extremely important in any trial approved by CMS, and this is a criterion, in any protocol or study submitted to CMS for approval.

CMS Administrator Chiquita Brooks-LaSure said in an emailed statement that the agency “is creating a pathway for people on Medicare to quickly access drugs that the FDA has found have shown benefit.” clinical”. She added that the pathway “encourages trial manufacturers and administrators to ensure that clinical trials recruit participants from diverse races.”

Access to the test center

Biogen’s Aduhelm won fast-track FDA approval in June 2021, even though a panel of external scientific advisors advised against it, citing mixed evidence on the drug’s effectiveness. The researchers identified several potential side effects of the treatment, including headaches, dizziness, falls and brain bleeds.

The CMS coverage determination would apply to all antibody drugs that target amyloid plaques — the abnormal protein sheets that accumulate in patients’ brains — in qualified clinical trials. The agency said manufacturers and sponsors of studies conducting approved trials must submit plans showing how they intend to enroll patients representative of the Medicare population, taking into account geographic, racial, and ethnic.

Patient groups had expressed concerns that the hospital’s outpatient center requirement of the original determination would have restricted access for certain minority and rural populations. Although the CMS has removed this requirement, political observers say that large hospitals and research sites may end up being the only places with the capacity to conduct these studies.

Subject to final coverage decision.

“It just seems like a lot of words said in a different way to refer to the outpatient hospital setting,” said Sue Peschin, president and CEO of the Alliance for Aging Research.

Ramachandran, who has repeatedly expressed concerns about Aduhelm’s fast-track approval, defended the importance of having requirements for study sites with clinical expertise and treatment infrastructure in place. “We want to be able to collect solid data on the actual effectiveness of the drug and its safety for patients,” she said.

She added, however, that tackling traditional barriers to accessing these research centers is key to achieving more adequate and representative results.

Trial sponsors must ensure that participants “are aware of these trials and can access them or be provided with means to facilitate access to medical centers,” said Esther Krofah, executive director of FasterCures and the Center. for Public Health from the Milken Institute. E-mail.

Reimbursements to trial participants for costs associated with travel, childcare and time off can help attract a more diverse group of trial participants, Ramachandran said. “It would be at least as a short-term solution”, until the CMS is “able to make investments in terms of increasing the infrastructure of rural hospitals or rural clinics, or other places where they might be able to distribute the drug.”

Patient Safety

Patient advocacy groups like the Alliance for Aging Research and UsAgainstAlzheimer’s, both of which receive funding from Biogen, have urged CMS to remove trial criteria that would have restricted access for people with Down syndrome. or other medical conditions that are “likely to increase significant adverse effects”. after taking the medicine.

But political observers argue that the Medicare agency should explicitly tell researchers that they must conduct safety studies of Alzheimer’s patients with Down’s syndrome and from minority groups before they are included in larger clinical trials. Safety is an important factor measured in phase 1 clinical trials, before studying the effectiveness, side effects and adverse effects of a treatment.

The CMS should inform sponsors of amyloid-targeting treatments whose clinical trials have already passed phase 1 if they now have to go back and do safety studies on patients who were not previously included, Peschin said. .

“There’s just going to be some kind of confusion about what type of evidence for this particular community is going to meet CMS standards,” she said.

At least half of people with Down syndrome will develop dementia due to Alzheimer’s disease as they age, according to estimates from the National Institute on Aging. This is because patients with Down syndrome contain an extra copy of chromosome 21, which carries a gene that produces amyloid.

Safety data is equally critical for other segments of the Alzheimer’s disease patient population, including black and Hispanic Americans, Ramachandran said.

In a letter to the CMS, she noted that early trials of Aduhelm only included 0.6% of participants who identify as black and 3% as Hispanic. About 18.6% of black Americans and 14% of Hispanic citizens age 65 and older have Alzheimer’s disease, compared to 10% of white adults in that age group, according to the advocacy group. WeagainstAlzheimer.

biogenic announcement in March that it would enroll at least 18% of patients in the United States in black and Latino communities in its confirmatory Phase 4 trial for Aduhelm.

Patient registers

The CMS decision also allows researchers to conduct prospective comparative studies using patient registries — or databases collecting clinical or medical data — instead of randomized controlled trials if a treatment is approved by the FDA. or if the drug has clinical benefits before approval.

Patient registries for certain amyloid-targeting drugs could be effective at analyzing a wide range of patient data, but only if they are representative of the true national Alzheimer’s population, policy analysts say.

“While the idea of ​​a patient registry sounds great on paper, they have a history of exacerbating health disparities,” Peschin said. “It takes a lot of time for patients to get assessed and kind of fill out everything in the registry, and that’s not available to everyone depending on their lifestyle and resources.”

The best way for CMS to ensure adequate representation is to work with the FDA to establish specific diversity criteria for patient registries as conditions for Medicare coverage, Ramachandran said, adding that explicit requirements might better incentivize researchers to incorporate these principles of diversity early in trial development. .

“When there’s nothing but encouragement, we really only hear promises from companies that they’ll actually adequately enroll patients in these trials,” she said.

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